Toshiyuki Yasui, Minoru Irahara and Toshihiro Aono : 排卵障害治療の実際 漢方療法, Nakayama-Shoten Co., Ltd., Tokyo, Jan. 2000.
14.
Toshiyuki Yasui, Minoru Irahara and Toshihiro Aono : The Management of the Menopause:The Millennium Review 2000, --- Effects of oral and transdermal hormone replacement therapy in relation to serum estrogen levels ---, The Parthenon publishing Group, London, Oct. 1999.
Academic Paper (Judged Full Paper):
1.
Yukie Matsuura, HoangNam Tran and Toshiyuki Yasui : Association between Menstruation-Related Symptoms and the Type of Stress in Japanese Female University Students: A Prospective Cohort Study from Admission to the Second Year, Women, Vol.4, No.3, 254-264, 2024.
(Keyword)
menstruation-related symptoms / fresh female university students / prospective cohort study / stress
Yukie Matsuura, HoangNam Tran, Nguyen Thanh Binh, Phan Ngoc Quang, Nguyen Trung Kien and Toshiyuki Yasui : Menstruation-Related Symptoms and Associated Factors among Female University Students in Vietnam, Youth, Vol.4, No.1, 344-356, 2024.
(Summary)
Menstruation and menstrual-related symptoms, stress, and lifestyle factors can significantly affect the health and academic lives of university students. This study aimed to explore menstruation-related symptoms and associated factors among female university students in Vietnam. This study used a cross-sectional design. Data from 349 students were analyzed for menstrual and menstrual-related symptoms using the Menstrual Distress Questionnaire (MDQ). We found that 92.0% and 98.9% of the students had menstrual-related symptoms in the pre- and intra-menstrual phases, respectively. The most common symptoms in each phase were backache (71.1%) in the pre-menstrual phase and fatigue (90.3%) in the intra-menstrual phase. Menstruation-related symptoms were associated with stress. These results contribute significantly to our understanding of menstrual health among Vietnamese university students. These findings imply the need to strengthen support systems for university students, especially by providing proper information about menstruation and managing stress.
(Keyword)
menstrual-related symptoms / female university students / MDQ / stress / Vietnam
Hiroko Sato and Toshiyuki Yasui : Differences in Changes in Game Usage Time and Game Use-Related Factors Depending on Parity in a Prospective Study of Pregnant Women in Japan, Healthcare, Vol.11, No.23, 2023.
(Summary)
Game usage has recently been increasing, but the actual situation of game usage and issues among pregnant women are not clarified. The purpose of this prospective longitudinal study was to examine changes in game usage, lifestyle, and thoughts about game usage during pregnancy depending on parity and to clarify the characteristics of pregnant women who continue to use games. We conducted three web surveys in early, mid- and late pregnancy in 238 pregnant women. For primiparous women who continued to use games, there was a significant increase in game usage time from early to late pregnancy ( = 0.022), and 25.0% of those women had anxiety that they might have a game addiction. For primiparous women in mid-pregnancy and multiparous women in early and late pregnancy, the proportions of women who thought that they could not use gaming sufficiently due to pregnancy and child-rearing were significantly higher in women who continued to use games. In both primiparous women and multiparous women, the proportion of partners who used games was significantly higher in women who continued to use games. It is necessary for midwives to discuss with pregnant women and their partners about game usage and to provide advice about control of game usage in daily life.
(Keyword)
pregnant woman / game usage / gaming disorder / prospective study
Yukie Matsuura, HoangNam Tran and Toshiyuki Yasui : The Changes in Menstrual and Menstrual-Related Symptoms among Japanese Female University Students: A Prospective Cohort Study from Three Months to Nine Months after Admission, Healthcare, Vol.11, No.18, 2557, 2023.
(Summary)
Menstrual and menstrual-related symptoms can significantly impact an individuals physical and psychological health. Understanding how these symptoms evolve over time is crucial to provide appropriate support and healthcare services to young women. This study aimed to investigate changes in menstrual and menstrual-related symptoms among first-year female university students. A prospective longitudinal design was used to compare the symptom profiles between two time points (three and nine months after admission). Out of 100 female university students, 30 responses were analyzed. Data on menstrual and menstrual-related symptoms were collected using standardized questionnaires focusing on menstrual status and the Menstrual Distress Questionnaire (MDQ); no notable changes occurred between the time points. Approximately half reported having irregular menstruation during the three time periods. Among the sub-scales, premenstrual impaired concentration showed a tendency to be lower, whereas menstrual water retention tended to be higher in timepoint 2 compared to timepoint 1. Distractible was found to be significantly lower in timepoint 2 compared to timepoint 1. There was a significant association between a sleep duration of <7 h and worsened MDQ scores. These findings may underscore the importance of providing comprehensive lifestyle and menstrual education to new university students, along with access to appropriate medical care.
(Keyword)
menstrual-related symptoms / female university students / three months and nine months after admission / prospective cohort study / lifestyle
Ayako Suto, Yuya Yano, Yuri Yamamoto, Hiroki Noguchi, Asuka Takeda, Shota Yamamoto, Tomohiro Kagawa, Kanako Yoshida, Kenji Hinokio, Akira Kuwahara, Toshiyuki Yasui and Takeshi Iwasa : Effects of activation with a Ca ionophore and roscovitine on the development of human oocytes that failed to fertilize after ICSI., The Journal of Medical Investigation : JMI, Vol.70, No.3.4, 321-324, 2023.
(Summary)
Sequential treatment with an Ca ionophore and roscovitine activates oocytes that remain unfertilized after ICSI. In TESE-ICSI, the activation rate tended to be increased by the co-administration of roscovitine with a Ca ionophore. J. Med. Invest. 70 : 321-324, August, 2023.
Yukie Matsuura, Yoko Abe, Yoshie Motoki, HoangNam Tran and Toshiyuki Yasui : Menstrual Abnormalities in Female International Students in Japan: Changes during Pre-Arrival, Difficult, and Current Periods, European Journal of Investigation in Health, Psychology and Education, Vol.13, No.7, 1362-1377, 2023.
(Keyword)
female international students in Japan / menstrual symptoms / menstrual abnormalities / difficult period / stress
Hiroko Sato and Toshiyuki Yasui : Comparisons of game usage time and game usage-related factors in Japanese women before pregnancy and during early pregnancy, International Journal of Nursing and Midwifery, Vol.15, No.1, 6-15, 2023.
(Keyword)
pregnant women / game usage / before pregnancy / early pregnancy
(Tokushima University Institutional Repository: 118292)
8.
Toshiyuki Yasui, Y Ideno, K Nagai and K Hayashi : Characteristics of HRT users in Japan: From the Japan Nurses' Study., Maturitas, Vol.173, 1-6, 2023.
(Summary)
Little is known about what type of women use hormone replacement therapy (HRT) in Japan. Based on the Japan Nurses' Health Study (JNHS), a large population cohort study, we determined the characteristics of HRT users by comparing the characteristics of new HRT users and the characteristics of women who did not use HRT during a 10-year follow-up period. Of the 15,019 JNHS participants, 4886 women reported an experience of menopausal transition during the 10-year follow-up period. Characteristics of new HRT users. The proportion of HRT users during the 10-year period was 8.5 %. Advanced age at menopause was significantly associated with a low rate of use of HRT. Past use of oral contraceptives, dysmenorrhea with disturbance in daily life and vasomotor symptoms were significantly associated with a high rate of use of HRT. The occupations of public health nurse and midwife and a history of bilateral oophorectomy were also significantly associated with a high rate of use of HRT. We determined the characteristics of new HRT users among middle-aged women during a 10-year follow-up period. Women who had sufficient knowledge about endocrinological hormones and women who had less reluctance to visit doctors for gynecological problems were likely to use HRT.
T Ishumaru, M Okawara, S Tateishi, Toshiyuki Yasui, S Horie and Y Fujino : Impact of menopausal symptoms on presenteeism in Japanese women, Occupational Medicine, Vol.73, No.7, 404-409, 2023.
(Summary)
Menopausal symptoms are common among middle-aged women. Working women with severe menopausal symptoms are more likely to experience presenteeism-a condition where employees continue to work despite feeling unwell. However, it remains unclear as to which specific symptoms women experience during the menopausal transition and postmenopausal periods that primarily contribute to presenteeism. To evaluate the associations between types of menopausal symptoms and presenteeism among Japanese women. A cross-sectional study of 4000 women aged 40-59 years who were currently working was conducted in Japan in September 2022. We used an online self-administered questionnaire that included items on demographic characteristics, the Menopause Rating Scale for measuring menopausal symptoms and the Work Functioning Impairment Scale for measuring presenteeism. Logistic regression analysis was performed. Women with severe overall menopausal symptoms had 12.18-fold (95% confidence interval [CI] 9.09-16.33, P < 0.001) increased odds of presenteeism compared with those without symptoms. Participants with psychological symptoms also had significantly higher presenteeism (severe: odds ratio: 9.18, 95% CI 6.60-12.78, P < 0.001). However, after controlling for psychological symptoms, there were no significant associations between somatic and urogenital symptoms and presenteeism. The results indicate that menopausal symptoms, especially psychological symptoms, have a significant impact on presenteeism among Japanese women. Organizations need to address menopausal symptoms in the workplace, with an emphasis on reducing work-related stress for women with menopausal symptoms.
Toshiyuki Yasui, T Ishimaru, M Okawara, S Tateishi, S Horie and Y Fujino : Impact of menopausal symptoms on presenteeism in Japanese women., Occupational Medicine, 1-5, 2023.
11.
Hiroko Sato and Toshiyuki Yasui : Game Usage in Pregnant Women at Early Gestation in Japan, Global Journal of Health Science, Vol.15, No.2, 1-11, 2022.
Yohei Takahashi, Takashi Kaji, Toshiyuki Yasui, Atsuko Yoshida, Naoto Yonetani, Naoto Suzue, Shinsuke Katoh, Kazuhisa Maeda, Koichi Sairyo, Minoru Irahara and Takeshi Iwasa : Ultrasonographic changes in quadriceps femoris thickness in women with normal pregnancy and women on bed rest for threatened preterm labor., Scientific Reports, Vol.12, No.1, 17506, 2022.
(Summary)
This study aimed to evaluate the changes in quadriceps femoris muscle thickness during the pregnancy and postpartum periods and to elucidate the effect of bed rest for threatened preterm labor on muscle thickness. In 26 women with normal pregnancy, quadriceps femoris thickness was measured at 11-13, 26, 30, and 35 weeks' gestation, and at 3-5 days and 1 month postpartum using ultrasonography. In 15 pregnant women treated with bed rest for threatened premature labor, quadriceps femoris thickness was measured at 30 and 35 weeks' gestation and postpartum. In women with normal pregnancy, quadriceps femoris thickness increased, peaking at 35 weeks' gestation, followed by a postpartum decrease. In women on bed rest, quadriceps femoris thickness showed no significant change during the pregnancy and postpartum periods, and the muscle was significantly thinner at 35 weeks' gestation than that in women with normal pregnancy. In conclusion, a significant increase in quadriceps femoris muscle thickness during normal pregnancy was found using ultrasonography. Meanwhile, in pregnant women on bed rest treatment, the quadriceps femoris was significantly thinner in the late third trimester than that in normal pregnant women. Prolonged bed rest can affect normal changes in the quadriceps femoris muscle thickness during the pregnancy and postpartum periods.
(Keyword)
Infant, Newborn / Humans / Female / Pregnancy / Bed Rest / Quadriceps Muscle / Obstetric Labor, Premature / Gestational Age / Pregnancy Trimester, Third
Rumi Ishihara, Keiko Nagamine, Yoshie Nishikawa, Mari Haku, Hirokazu Uemura, Yukie Matsuura and Toshiyuki Yasui : Associations of psychological status in the early postpartum period with resumption of menstruation and degree of menstruation-related symptoms, Journal of Obstetrics and Gynaecology, Vol.42, No.7, 2954-2961, 2022.
(Summary)
The aim of this prospective study was to clarify the associations of psychological status in the early postpartum period with resumption of menstruation and degree of menstruation-related symptoms. This study was conducted from February in 2017 to July in 2018 in Japan. We conducted self-administered questionnaire surveys for 229 postpartum women at 3 days postpartum, 2 weeks postpartum, one month postpartum, 3 months postpartum and 6 months postpartum. The proportion of women who resumed menstruation in the period up to 6 months postpartum was 38.8%. The Edinburgh Postnatal Depression Scale (EPDS) score at 6 months postpartum in women who resumed menstruation in the period up to 6 months postpartum was significantly higher than that in women who did not resume menstruation. EPDS scores during the postpartum period in women in whom menstruation-related symptoms became worse than those before pregnancy were significantly higher than those in women in whom menstruation-related symptoms did not change compared to those before pregnancy. In multiple regression analysis, there was no significant difference between EPDS score at 6 months postpartum and degree of menstruation-related symptoms. Additional research is needed to clarify the association of psychological condition during the postpartum period with resumption of menstruation. Impact Statement Postpartum psychological symptoms such as depression and anxiety during the postpartum period may affect degrees of menstruation-related symptoms after resumption of menstruation, and there also may be a bidirectional relationship between psychological symptoms and menstrual pain. Resumption of menstruation occurred in 38.8% of 121 women within 6 months postpartum, and poor psychological condition during the postpartum period was associated with early resumption of menstruation. The psychological condition in women with earlier resumption of menstruation might affect menstruation-related symptoms. Management of a stable psychological status during the early postpartum period should be implemented for women's health care in the future.
K Hayashi, Y Ideno, K Nagai, JS Lee and Toshiyuki Yasui : Complaints of reduced cognitive functioning during perimenopause: A cross-sectional analysis of the Japan Nurses' Health Study, Women's Midlife Health, Vol.8, No.1, 1-6, 2022.
(Summary)
Many women experience various symptoms during the period of menopausal transition, including complaints of reduced cognitive functioning. However, these complaints are not necessarily recognized as core menopausal symptoms. In this study, we sought to characterize subjective complaints of reduced cognitive functioning by analyzing cross-sectional data from the Japan Nurses' Health Study (JNHS). The JNHS 4-year follow-up questionnaire containing a 21-item climacteric symptom checklist, which included a question about "poor memory or forgetfulness", was mailed between 2005 and 2011 to all JNHS participants, regardless of their age at the time of the survey. We estimated the prevalence of slight and severe complaints in 5-year age-groups. We used principal component analysis to explore the underlying factors among the 21 symptoms during the menopausal transition period in women aged 45-54 years at the time of the survey. We also examined risk factors for complaints using multivariable modified Poisson regression analysis. In total, 12,507 women responded to the 4-year survey. The mean age at the time of the 4-year survey was 46.5 years (range 27-82). "Poor memory or forgetfulness" showed a peak prevalence of 81.7% (severe 27.9%; slight 53.8%) at 50-54 years, and gradually decreased after 55 years. Principal component analysis indicated that "poor memory or forgetfulness" belonged to somatic symptoms and was close to psychological symptoms in women aged 45-54 years. In women aged 45-54 years, the complaint was also significantly associated with hot flashes and sweats. Multivariable modified Poisson regression analysis showed that menopausal status (uncertain and postmenopausal), less sleep (sleep of < 5 h and sleep of 5- < 6 h), night-shift work, and severe vasomotor symptoms (VMS) were significantly associated with the prevalence of severe complaints of reduced cognitive functioning in women aged 45-54 years. We found that prevalence of "poor memory or forgetfulness" was highest during the menopausal transition period and among perimenopausal women. This subjective complaint was associated with somatic, psychological complaints and VMS. It may be useful for women with cognitive problems in the transition period to consider management of comorbid menopausal symptoms.
Yukie Matsuura, HoangNam Tran and Toshiyuki Yasui : Comparison of Menstruation-Related Symptoms Before and During Menstruation of University Students in Japan, a Year after the COVID-19 Pandemic, Global Journal of Health Science, Vol.14, No.4, 1-11, 2022.
(Summary)
<jats:p>The coronavirus disease 2019 (COVID-19) pandemic affected the daily lifestyle of people, including many aspects affecting young women. Subsequent to the COVID-19 pandemic stress and anxiety have been reported related to menstrual disorders (Takmaz, Gundogmus, Okten, & Gunduz, 2021). The purpose of this study was to investigate the intensity and to compare menstruation-related symptoms before and during menstruation among university students in Japan. We conducted an online cross-sectional study from May to July 2021 using a menstrual distress questionnaire (MDQ) to assess symptoms experienced before and during menstruation. Our results showed that of 141 students, five students (3.5%) did not report any symptoms before menstruation and one student (0.7%) had no symptoms during menstruation. We found that the most frequently experienced symptoms before menstruation were skin blemishes or disorder, mood swings, irritability, swelling, cramps, fatigue, take naps, stay in bed, feeling sad or blue, weight gain and difficulty concentrating. The most frequently experienced symptoms during menstruation were cramps, fatigue, irritability, mood swings, take naps, stay in bed, feeling sad or blue, backache, swelling, skin blemish or disorder, and poor school/work performance. The total MDQ score was significantly higher during menstruation than before menstruation. Among the MDQ eight scales, the scores of five scales including pain, autonomic reaction, impaired concentration, behavior change, and control were significantly higher during menstruation than before menstruation. The prevalence of increased appetite and craving for sweets were higher than MDQ symptoms before menstruation. The prolonged exposure to pandemic may have more effect on psychological symptoms than on physical symptoms.</jats:p>
Yukie Matsuura, HoangNam Tran and Toshiyuki Yasui : Differences in Menstruation-Related Symptoms of University Students Depending on their Living Status in Japan, Healthcare, Vol.10, No.1, 131, 2022.
(Summary)
Mothers and family members of young female students play important roles for guiding their self-care strategies for menstruation-related symptoms; which often affect their daily life and academic life. The aim of this study is to clarify the differences in menstruation-related symptoms before and during menstruation in university students living alone and university students living with their family in Japan. We conducted a cross-sectional online survey to assess menstruation-related symptoms before and during menstruation using the menstrual distress questionnaire (MDQ). Among 135 students; the proportion of students living alone was 60.7% and the proportion of students living with their family was 39.3%. Before menstruation; the MDQ total score and the scores for negative affect and behavior change were significantly higher in students living alone than in students living with their family. During menstruation; scores for negative affect and impaired concentration were also significantly higher in students living alone. In addition; before menstruation; scores for an increase in appetite and craving for sweets were significantly higher in students living alone. Thus; living alone affected the psychological aspects of menstruation-related symptoms in young women. The results suggest that university students who live alone should be aware of the importance of talking about their menstruation problems with family members and seeking their advice.
Sachiko Kubo, Toshiyuki Yasui, Yukie Matsuura and Masahito Tomotake : Differences in Male Climacteric Symptoms by Aging Males Symptoms Scale and Coping Strategies with Aging among Rotating Night Shift Workers, Global Journal of Health Science, Vol.14, No.3, 1-11, 2022.
Megumi Abe, Toshiyuki Yasui and Yukie Matsuura : Views Regarding Management Skills Required Currently and in the Future for Middle Managers in Perinatal Medicine: Their Differences Depending Working Position in Advanced Midwives, Open Journal of Obstetrics and Gynecology, Vol.12, No.1, 43-55, 2022.
Aya Kondo, Mari Haku and Toshiyuki Yasui : Development and Psychometric Testing of the Mental Health Scale for Childrearing Fathers, Healthcare, Vol.9, No.11,1587, 2021.
Moyo Ri, Kunihiko Hayashi, Takumi Kurabayashi, Jung Su Lee, Yuki Ideno, Kazue Nagai, Toshiyuki Yasui, Toshihiro Kubota and Kiyoshi Takamatsu : Hypertensive disorders of pregnancy increase risk of future menopausal hot flashes in Japanese women: results from the Japan Nurses' Health Study., Menopause, Vol.29, No.2, 164-169, 2021.
(Summary)
We aimed to investigate whether hypertensive disorders of pregnancy (HDP) are associated with problematic hot flashes in Japanese women. In this study, we included participants in the Japan Nurses' Health Study who were women aged 41 to 55 years at baseline, parous, and completed a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology. At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of HDP. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of HDP of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with HDP as compared with those without these disorders. In this prospective study, we found that women with a history of HDP have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of HDP.
(Keyword)
female / Hot Flashes / Humans / Hypertension, Pregnancy-Induced / Japan / Menopause / Nurses / Pregnancy / Prospective Studies
Takako Kawakita, Toshiyuki Yasui, Kanako Yoshida, Sumika Matsui and Takeshi Iwasa : Correlations of Androstenediol with Reproductive Hormones and Cortisol According to Stages during the Menopausal Transition in Japanese Women. J, The Journal of Steroid Biochemistry and Molecular Biology, Vol.214, 106009, 2021.
(Summary)
Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the menopausal transition may be different depending on the menopausal stage. The aim of this study was to determine the changes in circulating androstenediol during the menopausal transition in Japanese women and the associations of androstenediol with estrogen, androgen and cortisol for each stage of the menopausal transition. We divided the 104 subjects into 6 stages by menstrual regularity and follicle-stimulating hormone level: mid reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause and early postmenopause. Levels of dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and cortisol were measured. Serum androstenediol concentration was measured by using liquid chromatography mass spectrometry. There were no significant differences in androstenediol levels among the 6 stages. Levels of DHEA-S and testosterone showed significant and positive correlations with androstenediol in all stages. Estradiol levels showed negative correlations with androstenediol levels in the late menopausal transition and very early postmenopause (r=-0.452, p = 0.052 and r=-0.617, p = 0.006, respectively). Cortisol levels showed significant and positive correlations with androstenediol levels in the mid and late reproductive stages (r = 0.719, p = 0.003 and r = 0.808, p < 0.001, respectively).The associations of androstenediol with estradiol and cortisol were different depending on the stage of the menopausal transition. Androstenediol may play a compensatory role for estrogen deficiency from late menopausal transition to very early postmenopause.
Megumi Abe, Toshiyuki Yasui, Yukie Matsuura, Mari Haku and Hirokazu Uemura : Comparison of management skills that are required for middle managers at present and in the next generation in advanced midwives, International Journal of Nursing and Midwifery, Vol.13, No.3, 42-53, 2021.
Aya Kondo, Toshiyuki Yasui and Mari Haku : Relationship between maternal mental status and social supports during pregnancy and until one month after childbirth in a local city, The Journal of Medical Investigation : JMI, Vol.68, No.3,4, 265-270, 2021.
(Summary)
The aim of this study was to clarify the relationship between maternal mental status and social supports during pregnancy and until one month after childbirth in order to evaluate the actual situation in a local city. A survey was conducted on 78 pregnant women who completed the CES-D (depression score), STAI (anxiety score) and Social Support Scale. Data were collected four times : during the second trimester, the third trimester, postpartum hospitalization, and 1 month after childbirth. The CES-D and STAI scores were initially high during pregnancy and decreased during the postpartum period. The Social Support Scale score, however, was initially low during pregnancy and increased during the postpartum period. The CES-D and STAI scores was significantly and negatively correlated with The Social Support Scale score during all four time periods. Participants ≧ 35 years of age scored lower on The Social Support Scale than did participants < 35 years of age in the second trimester, third trimester, and 1 month after childbirth. These findings should assist with the implementation of a comprehensive support center and may be useful for a local city in Japan. J. Med. Invest. 68 : 265-270, August, 2021.
(Keyword)
Adult / Family / Female / Humans / Postpartum Period / Pregnancy / Pregnancy Complications / Social Support / Surveys and Questionnaires
Kiyoshi Takamatsu, Yuki Ideno, Mami Kikuchi, Toshiyuki Yasui, Naho Maruoka, Kazue Nagai and Kunihiko Hayashi : Validity of self-reported diagnoses of gynaecological and breast cancers in a prospective cohort study: the Japan Nurses' Health Study, BMJ Open, Vol.11, No.6, e045491, 2021.
(Summary)
To validate the self-reported diagnoses of gynaecological and breast cancers in a nationwide prospective cohort study of nursing professionals: the Japan Nurses' Health Study (JNHS). Retrospective analysis of the JNHS. Data were reviewed for 15 717 subjects. The mean age at baseline was 41.6±8.3 years (median: 41), and the mean follow-up period was 10.5±3.8 years (median: 12). Participants are regularly mailed a follow-up questionnaire once every 2 years. Respondents who self-reported a positive cancer diagnosis were sent an additional confirmation questionnaire and contacted the diagnosing facility to confirm the diagnosis based on medical records. A review panel of experts verified the disease status. Regular follow-up, confirmation questionnaires and expert review were validated for their positive predictive value (PPV) and negative predictive value (NPV). New incidences were verified in 37, 47, 26 and 300 cervical, endometrial, ovarian and breast cancer cases, respectively. The estimated incidence rates were 22.0, 25.4, 13.8 and 160.4 per 100 000 person-years. These were comparable with those of national data from regional cancer registries in Japan. For regular follow-up, the corresponding PPVs for cervical, endometrial, ovarian and breast cancer were 16.9%, 54.2%, 45.1% and 81.4%, and the NPVs were 100%, 99.9%, 99.9% and 99.9%, respectively. Adding the confirmation questionnaire improved the PPVs to 31.5%, 88.9%, 76.7% and 99.9%; the NPVs were uniformly 99.9%. Expert review yielded PPVs and NPVs that were all ~100%. Gynaecological cancer cannot be accurately assessed by self-reporting alone. Additionally, the external validity of cancer incidence in this cohort was confirmed.
Yukie Matsuura, Kiko Akamine, Ayumi Murakami, Tokimi Wada, Honoka Atsumi, Erina Kane, Mizuki Yano and Toshiyuki Yasui : Associations between sensitivity to cold, menstruation-related symptoms and handgrip strength in female university students in Japan, Health, Vol.13, 526-537, 2021.
Takumi Kurabayashi, Yuki Ideno, Kazue Nagai, Naho Maruoka, Kiyoshi Takamatsu, Toshiyuki Yasui and Kunihiko Hayashi : Validity of self-reported diagnosis of osteoporosis in Japan Nurses' Health Study, Clinical Epidemiology, Vol.13, 237-244, 2021.
(Summary)
Although the validity of self-reported osteoporosis is often questioned, validation studies are lacking. This study was performed to investigate how well self-reported diagnoses of osteoporosis agreed with validated clinical information in young and middle-aged women in the Japan Nurses' Health Study (JNHS), a nationwide prospective cohort study of nursing professionals. Data were reviewed for 15,717 subjects from the combined cohorts of the JNHS and a preceding pilot study (Gunma Nurses' Health Study). The subjects' mean age at the baseline (BL) survey was 41.6 ± 8.3 years, and the mean follow-up period was 11.5 ± 4.4 years. Participating nurses were mailed a follow-up questionnaire every 2 years. Respondents who self-reported a positive osteoporosis diagnosis during the study period were sent an additional confirmation questionnaire to corroborate the details. The number (proportion) of women with osteoporosis was 884 (5.6%) [primary osteoporosis, 812 (5.2%); secondary osteoporosis, 72 (0.5%)]. The cumulative incidence of osteoporosis at the age of 40, 50, 60, 70, and 80 years was estimated to be 0.1% (95% confidence interval, 0.1-0.2), 1.1% (0.9-1.3), 7.7% (7.0-8.4), 23.6% (21.6-25.7), and 54.2% (40.2-68.1), respectively. For BL and regular follow-up + expert review versus BL and regular follow-up + confirmation questionnaire + expert review, the positive predictive value (PPV) was 61.3% versus 85.6% and the negative predictive value (NPV) was 98.9% versus 98.2%, respectively. Self-reporting was associated with a high NPV for the incidence of osteoporosis. Although the PPV was slightly lower, additional corroborations by confirmation questionnaire might improve the PPV.
Toshiyuki Yasui, Yuki Ideno, Hiromitsu Shinozaki, Yoshikazu Kitahara, Kazue Nagai and Kunihiko Hayashi : Prevalence of the use of oral contraceptives and hormone replacement therapy in Japan: the Japan Nurses' Health Study, Journal of Epidemiology, Vol.32, No.3, 117-124, 2021.
(Summary)
There have been few community-based epidemiological studies in which the prevalence of exogenous hormone use, including the use of oral contraceptives (OCs) and hormone replacement therapy (HRT), has been accurately assessed in Japan. We have been conducting repeated surveys of participants in the Japan Nurses' Health Study (JNHS), as a nationwide prospective cohort study, since 2001. We determined the prevalence of exogenous hormone use at baseline and during a 10-year follow-up period. A total of 15,019 female nurses participated in the JNHS follow-up cohort. We determined the prevalence of OC use in 14,839 women <60 years of age at baseline and the prevalence of HRT use in 7,915 women, excluding premenopausal women, at the last time they answered a questionnaire. The duration of HRT use was estimated using the Kaplan-Meier method. Six percent of the participants used OCs. The proportion of HRT users who stopped HRT before the baseline survey, the proportion of women using HRT during the follow-up period, and the proportion of all of the participants who had used HRT were 3.2%, 10.6%, and 13.8%, respectively. The median duration of HRT use was 2 years. The lifetime prevalences of exogenous hormone use during this prospective study conducted in Japanese nurses were 6.0% for OCs and 13.8% for HRT. The information obtained in this study will be useful for clarification of the association between exogenous estrogen exposure and estrogen-related diseases as future research.
Megumi Abe, Toshiyuki Yasui, Yukie Matsuura and Mari Haku : Management skills required for nursing middle managers in the next generation in perinatal medical care, International Journal of Nursing and Midwifery, Vol.12, No.4, 151-157, 2020.
Sachiko Kubo, Toshiyuki Yasui, Reiko Okahisa, Yukie Matsuura and Masahito Tomotake : Differences in Male Climacteric Symptoms and Lifestyle Depending on the Duration of Working among Rotating Night Shift Workers, Health, Vol.12, 1598-1609, 2020.
Natsumi Yamaguchi, Toshiyuki Yasui, Takashi Kaji, Eishi Sogawa, Atsuko Yoshida, Naoto Yonetani and Minoru Irahara : Usefulness of measurement of proximal phalanx length by using ultrasonography in newborn infants., Journal of Obstetrics and Gynaecology, Vol.41, No.5, 739-745, 2020.
(Summary)
The purpose of this study was to compare digit lengths and proximal phalanx lengths in newborn infants by using ultrasonography (USG) and to examine sex differences between the ratio of the second digit (2D) and fourth digit (4D) of digit length and that of proximal phalanx length and the associations of digit length and proximal phalanx length with birth weight and birth height. Sixty newborn infants (28 males and 32 females) were recruited. Digit lengths were measured by using a transparent ruler and proximal phalanx lengths were measured by using USG. There were significant correlations between digit length and proximal phalanx length in the left and right hands. There was no significant correlation between 2D:4D ratios of digit lengths and 2D:4D ratios of proximal phalanx lengths measured by using USG. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males. Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.Impact statement The ratio of the second digit (2D) and fourth digit (4D) has been used postnatally to provide a retrospective indication of the foetal hormonal environment. Digit lengths have been measured by using a direct method, photocopies, digital scans and radiographs, but the results of a study on measurement of digit lengths by using ultrasonography (USG) have not been reported. Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males. Measurement of proximal phalanx length by using USG may be useful for a study on gender differences in foetal development and the foetal hormonal environment. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.
Rumi Ishihara, Keiko Nagamine, Yoshie Nishikawa, Mari Haku, Hirokazu Uemura, Yukie Matsuura and Toshiyuki Yasui : Transition of Depressive Symptoms and Anxiety Symptoms According to Parity and Associations of These Symptoms with Feelings for Involvement with Newborn Infants during a 6-Month Postpartum Period, Open Journal of Obstetrics and Gynecology, Vol.10, 1315-1330, 2020.
Yukie Matsuura, Honoka Atsumi, Erina Kane, Mizuki Yano, Kiko Akamine, Ayumi Murakami, Tokimi Wada and Toshiyuki Yasui : Relationships of Handgrip Strength with Menstruation-Related Symptoms in Female University Students in Japan, Open Journal of Obstetrics and Gynecology, Vol.10, 1056-1066, 2020.
Yukie Matsuura, Aoi Inoue, mizuki Kidani and Toshiyuki Yasui : Change in appetite and food craving during menstrual cycle in young students, International Journal of Nutrition and Metabolism, Vol.12, No.2, 25-30, 2020.
Yukie Matsuura, Kazuyo Matsuzaki and Toshiyuki Yasui : Menopausal Symptoms in Japanese Nurses: Differences between Smokers and Non-Smokers, Health, Vol.12, No.5, 474-485, 2020.
Yukie Matsuura, Takane Morita, Momoko Sekimoto, Ayaka Maeda and Toshiyuki Yasui : Differences in Physical and Psychological Condition, Sleeping Status and Menstruation-Related Symptoms before and after Smartphones Use in Young Female Students in Japan, Health, Vol.12, No.4, 407-424, 2020.
Rumi Ishihara, Keiko Nagamine, Yoshie Nishikawa, Mari Haku, Hirokazu Uemura, Yukie Matsuura and Toshiyuki Yasui : Prevalence and factors related to hot flashes and night sweats in postpartum women in Japan, International Journal of Nursing and Midwifery, Vol.12, No.1, 14-21, 2020.
Sachiko Kubo, Toshiyuki Yasui, Yukie Matsuura and Masahito Tomotake : Differences in male climacteric symptoms with aging among rotating night shift workers, The Aging Male, Vol.Aug 9, 1-9, 2019.
(Summary)
The aim of this study was to clarify the actual status of male climacteric symptoms in rotating night shift workers and how to cope with the symptoms. We planned a self-administered questionnaire survey in male rotating night shift workers. Male climacteric symptoms were evaluated by using the Aging Males' Symptoms (AMS) scale. Of 1891 questionnaires that were sent, 1561 were collected. There were significant differences in total AMS scores among the age groups. In all age groups, there were high proportions of men with increased need for sleep and often feeling tired (64.9%) and decrease in muscular strength (60.7%). There were significant differences in AMS scores for somatic symptoms between men in their 20 s and those in their 40 s or 50 s and between men in their 30 s and those in their 50 s and in AMS scores for sexual symptoms between men in their 20 s and those in their 30 s, 40 s, 50 s or 60 s, between men in their 30 s and those in their 40 s, 50 s or 60 s and between men in their 40 s and those in their 50 s or 60 s. Significant age-dependent differences are found in somatic symptoms and sexual symptoms in rotating night shift workers.
Eishi Sogawa, Takashi Kaji, Soichiro Nakayama, Atsuko Yoshida, Naoto Yonetani, Kazuhisa Maeda, Toshiyuki Yasui and Minoru Irahara : Seasonal variation of serum 25(OH)vitamin D levels in maternal and umbilical cord blood in Japanese women, The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 128-133, 2019.
(Summary)
We aimed to demonstrate that the serum 25-hydroxyvitamin D (25(OH)D) level in maternal and umbilical cord blood has a seasonal variation in Japanese women. The study cohort comprised 256 healthy Japanese women with a singleton pregnancy who delivered after 36 gestational weeks between 2012 and 2015. The season at delivery was categorized for 3 months and recorded as "spring", "summer", "autumn" and "winter". Subjects were divided into four groups according to season. A sample of peripheral venous blood at 35-36 gestational weeks and blood from the umbilical vein at delivery were taken. The mean serum 25(OH)D concentra tion (ng/mL) in maternal blood for each season (spring, summer, autumn and winter) was 18.0 (?6.7), 17.1 (?5.1), 21.6 (?8.0) and 16.0 (?5.1), whereas that for umbilical cord blood was 8.8 (?3.6), 8.6 (?2.6), 10.7 (?3.5) and 8.6 (?2.1), respectively. The mean serum 25(OH)D concentration of maternal and umbilical cord blood in autumn was higher than that for the other three seasons. In pregnant Japanese women, the mean serum 25(OH)D concentration in maternal and umbilical cord blood was affected by the season of delivery, with both being highest in autumn. Regardless of the season, the maternal serum concentration of 25(OH)D was low in Japan. J. Med. Invest. 66 : 128-133, February, 2019.
Sumika Matsui, Toshiyuki Yasui, Hirokazu Uemura and Minoru Irahara : Variation in follicle-stimulating hormone level and different associations of follicle-stimulating hormone level with body mass index over the menopausal transition in Japanese wome, The Journal of Japan Society for Menopause and Women's Health, Vol.27, No.2, 311-317, 2019.
Y Onizuka, K Nagai, Y Ideno, Y Kitahara, A Iwase, Toshiyuki Yasui, J Nakajima-Shimada and K Hayashi : Association between FSH, E1, and E2 levels in urine and serum in premenopausal and postmenopausal women, Clinical Biochemistry, Vol.73, 105-108, 2019.
Toshiyuki Yasui, Y Ideno, Y Onizuka, J Nakajima-Shimada, H Shinozaki and K Hayashi : Variation of urinary follicle-stimulating hormone level after menopause: From the results of Japan Nurses' Health Study, The Journal of Medical Investigation : JMI, Vol.66, No.3.4, 297-302, 2019.
(Summary)
The change in follicle-stimulating hormone (FSH) during the menopausal transition and associations of FSH with various diseases have been assessed by using blood samples. We examined cross-sectionally the variation of FSH levels, associations of estrone and estradiol with FSH, and associations of BMI with these hormones by using urinary samples from peri- and postmenopausal women in Japan. Of 4472 participants in the Urinary Isoflavone Concentration Survey of the Japan Nurses' Health Study, we analyzed urinary levels of estrone, estradiol and FSH in 547 women aged from 45 to 54 years. Urinary FSH levels varied widely in postmenopausal women and the pattern of change in urinary FSH levels seems to be similar to that in blood FSH levels in previous studies. There were no significant differences in age, body mass index (BMI), estradiol, estrone and estradiol/estrone ratio among three groups according to the tertile of FSH. In postmenopausal women, there were significant associations of BMI with levels of estrone and estradiol, but there was no significant association of BMI with FSH. Studies using urinary samples will allow us to establish a study project as a large-scale population-based study to determine associations between FSH and various diseases after menopause. J. Med. Invest. 66 : 297-302, August, 2019.
(Keyword)
Body Mass Index / Cross-Sectional Studies / Estradiol / Estrone / Female / Follicle Stimulating Hormone / Humans / Menopause / Middle Aged / Nurses
T Iwasa, T Matsuzaki, T Kawakita, K Kasai, K Yoshida, T Kato, S Matsui, Toshiyuki Yasui and M Irahara : The effects of androgens on metabolic functions and their underlying mechanisms in females of reproductive age, The Journal of Japan Society for Menopause and Women's Health, Vol.26, 128-134, 2019.
46.
Toshiyuki Yasui, Y Ideno, Y Onizuka, J Nakajima-Shimada, Lee Jung-Su, H Shinozaki, M Kishi, R Suzuki and K Hayashi : The association of urinary estrogen levels with urinary isoflavone levels: Difference between premenopausal women and postmenopausal women, Maturitas, Vol.121, 41-47, 2019.
(Summary)
Results of studies on the associations of soy food intake with urinary estrogen levels in premenopausal women and in postmenopausal women have been inconsistent. We examined the associations of urinary isoflavone levels as well as soy food intake with estrone (E1) and estradiol (E2) in pre- and postmenopausal women. In addition, we compared the levels of isoflavones, E1 and E2 across current hormone users such as those receiving hormone replacement therapy and those using oral contraceptives and non-users among both pre- and postmenopausal women. Urinary levels of isoflavones, E1 and E2 in 498 women (36 hormone users and 462 non-users) were analyzed. Premenopausal women with a higher frequency of soy food intake had higher urinary isoflavone levels, but there were no significant associations between E1 and E2 levels and urinary isoflavone levels. Levels of E1 and E2 in hormone users were significantly lower than those in hormone non-users among premenopausal women, but levels of E1 and E2 in hormone users were significantly higher than those in hormone non-users among postmenopausal women. Postmenopausal women with a higher frequency of soy food intake had higher urinary isoflavone levels, and postmenopausal women with high urinary isoflavone levels had significantly higher E1 and E2 levels. In conclusion, the associations of urinary isoflavone levels with urinary estrogen levels differed with menopausal status. Urinary levels of E1 and E2 were high in postmenopausal women with high urinary isoflavone levels but not in premenopausal women with high urinary isoflavone levels.
K Matsuzaki, Toshiyuki Yasui, S Matsui, M Fukuoka and H Uemura : Differences in menopausal symptoms and coping strategies according to personality in Japanese nurses., Journal of Obstetrics and Gynaecology, Vol.39, No.2, 242-247, 2018.
(Summary)
We examined the associations of type A personality with menopausal symptoms and strategies for coping with menopausal symptoms in Japanese nurses. Valid responses to health questionnaires were obtained from 1174 nurses aged 45-60 years Menopausal symptoms were assessed using Greene's climacteric scale, and a type A behaviour pattern was assessed using the type A rating scale developed for the Japanese. The mean score of psychological symptoms in nurses with a type A personality was significantly higher than that in the nurses with a non-type A personality. The proportion of the nurses who received hormone replacement therapy in the nurses with a type A personality was significantly higher than that in the nurses with a non-type A personality. The nurses with a type A personality had a sufficient understanding of treatments for menopausal symptoms. In conclusion, there were differences in the menopausal symptoms and coping strategies between the nurses who had a type A personality and the nurses who had a non-type A personality. Impact statement What is already known on this subject? Menopausal symptoms have been shown to be affected by lifestyle and by socioeconomic status as well as oestrogen deficiency, but there have been few studies on the associations of personality with menopausal symptoms and coping with the menopausal symptoms. The type A personality is associated with a greater risk for the development of several diseases. However, the association of a type A behaviour pattern with menopausal symptoms has not been clarified. What do the results of this study add? There were differences in the menopausal symptoms and the coping strategies between women with a type A personality and women with a non-type A personality. Psychological symptoms were found more frequently in the Japanese nurses with a type A personality. The proportion of nurses who received hormone replacement therapy in the nurses with a type A personality was significantly higher than that in the nurses with a non-type A personality. There were no significant differences in the proportions of nurses in the two groups with other coping strategies. What are the implications of these findings for clinical practice and/or further research? The management for coping strategies according to the type of personality should be considered.
(Keyword)
Adaptation, Psychological / Estrogen Replacement Therapy / Female / Health Knowledge, Attitudes, Practice / Humans / Menopause / Middle Aged / Nurses / Surveys and Questionnaires
Toshiyuki Yasui, K Hayashi, H Okano, M kamio, H Mizunuma, T Kubota and JS Lee : Uterine leiomyomata: aretrospective study of correlations with hypertension and diabetes mellitus from the Japan Nurses' Health Study., Journal of Obstetrics and Gynaecology, Vol.38, No.8, 1128-1134, 2018.
(Summary)
We performed a scrutiny survey of self-reported uterine leiomyomata (UL) to investigate the associations of parental history with hypertension and personal history of hypertension in the UL cases in Japanese women. Questionnaires that included items on the sites of UL determined by imaging techniques and surgical procedure were mailed to 2015 women with a self-reported UL at a baseline survey of the Japan Nurses' Health Study (n = 15,019). We found that women with a past history and a maternal history of hypertension had an increase in their risk of UL. A maternal history of hypertension was significantly associated with an increase in the risk of UL in women without a past history of hypertension but not in the women with a past history of hypertension. A past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. Women of reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL. Impact Statement What is already known on this subject? A positive association of uterine leiomyomata (UL) with a past history of hypertension has been found but the association of a parental history of hypertension with UL has not yet been clarified. What do the results of this study add? Maternal hypertension, as well as a personal history of hypertension, was associated with an increased risk of UL and a past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. What are the implications of these findings for clinical practice and/or further research? Women of a reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL.
Yuko Uemura, Toshiyuki Yasui, Kimiyo Horike, Kazuhisa Maeda, Hirokazu Uemura, Mari Haku, Reiko Saka and Keiko Matsumura : Association of Low Back and Pelvic Pain with Mental Health Condition during Pregnancy and Postpartum, Health, Vol.10, No.12, 1650-1660, 2018.
Yuko Uemura, Toshiyuki Yasui, Kimiyo Horike, Kazuhisa Maeda, Hirokazu Uemura, Mari Haku, Reiko Saka and Keiko Matsumura : Possible Predictive Factors for Low Back and Pelvic Pain at Three Months Postpartum -Assessed in a Prospective Study from Early Pregnancy until the Postpartum Period, Open Journal of Nursing, Vol.8, No.8, 552-566, 2018.
K Matsuzaki, M Fukuoka, H Uemura and Toshiyuki Yasui : Differences in strategies for coping with menopausal symptoms in full-time workers and part-time workers in Japan, International Journal of Nursing and Midwifery, Vol.10, No.1, 1-7, 2018.
牧田 和也, 岡野 浩哉, 倉林 工, 寺内 公一, Toshiyuki Yasui, 樋口 毅, 藤野 敬史, 茶木 修 and 久保田 俊郎 : 産婦人科医による骨粗鬆症診療の現状:第二報, The Journal of Japan Society for Menopause and Women's Health, Vol.26, No.1, 48-53, 2018.
53.
Yuko Uemura, Toshiyuki Yasui, Kimiyo Horike, Kazuhisa Maeda, Hirokazu Uemura, Mari Haku, Reiko Sakae and Keiko Matsumura : Association of Low Back and Pelvic Pain at the Second Trimester with that at the Third Trimester and Puerperium in Japanese Pregnant Women, Journal of Pregnancy and Child Health, Vol.4, No.5, 2017.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Circulating dehydroepiandrosterone-sulphate decreases even with a slight change in oestradiol., Journal of Obstetrics and Gynaecology, Vol.38, No.2, 231-235, 2017.
(Summary)
The aim of this study was to determine the effect of hormone replacement therapy (HRT) on changes in circulating dehydroepiandrosterone-sulphate (DHEA-S) with focus on the relationship between oestrogen level and change in DHEA-S. Forty-two women were enrolled in this longitudinal study. Nineteen women received oral oestradiol and twenty-three women received transdermal oestradiol continuously. Twenty women received progesterone continuously except for women who had undergone hysterectomy. Circulating oestradiol, follicle-stimulating hormone, luteinising hormone and DHEA-S levels before and at 3 months after commencement of HRT were measured. Circulating DHEA-S level was significantly decreased at 3 months (p < .001). Oestradiol level at 3 months ranged from 6.5 pg/ml to 159 pg/ml. There was no significant correlation of ΔDHEA-S (DHEAS level at 3 months-DHEA-S level at baseline) with Δoestradiol (r = 0.114, p = .471). Circulating DHEA-S level was significantly decreased at 3 months in all the four quartiles and divided according to Δoestradiol, and ΔDHEA-S did not show significant differences. In conclusion, circulating DHEA-S decreases even with a slight increase in oestradiol level. Impact statement What is already known on this subject: A transient increase in DHEA-S in women during the menopausal transition may be involved in the occurrence of menopausal symptoms and/or unfavourable metabolic changes. Hormone replacement therapy decreases circulating DHEA-S level. However, dose dependency of the change in DHEA-S on oestrogen has not been reported. What the results of this study add: Circulating DHEA-S decreases even with a slight increase in oestradiol level. What the implications are of these findings for clinical practice and/or further research: Adrenal function may respond to a small change in oestrogen.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kaoru Keyama, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol., Journal of Obstetrics and Gynaecology, Vol.37, No.5, 627-632, 2017.
(Summary)
Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 g) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 g) as a transdermal group. In addition, the women received dydrogesterone continuously (5g) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin- 2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.
Yuu Tanaka, Akira Kuwahara, Kenjiro Ushigoe, Yuya Yano, Yuka Taniguchi, Yuri Yamamoto, Toshiya Matsuzaki, Toshiyuki Yasui and Minoru Irahara : Expression of cytokine-induced neutrophil chemoattractant suppresses tumor necrosis factor alpha expression and thereby prevents the follicles from undergoing atresia and apoptosis., Reproductive Medicine and Biology, Vol.16, No.2, 157-165, 2017.
(Summary)
Cytokine-induced neutrophil chemoattractant (CINC/gro) is a CXC family chemokine, similar to interleukin-8 in rats, and is one of the factors that regulates ovulation. However, the mechanism that regulates atresia of the ovaries postovulation is not clearly defined. Whether antibody-blocking of CINC/gro can alter the number of ovulated oocytes and modulate neutrophil infiltration was investigated. The effect of the antibody on the level of inflammatory cytokine production and follicular atresia was examined. Apoptosis was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and via analysis of the messenger RNA expression of Bcl-2 and Bcl2-associated X (Bax). The anti-CINC/gro antibody treatment decreased the number of ovulated oocytes. The messenger RNA levels of cyclooxygenase-2 and interleukin-1 beta were decreased by the antibody treatment, whereas that of tumor necrosis factor (TNF) alpha was increased. The TUNEL analysis revealed a larger number of apoptotic cells in the antibody group, compared with those in the control group, as well as a significant increase in the Bax/Bcl-2 ratio 24 hours after human chorionic gonadotropin administration. These findings suggest that ovulation is accelerated by neutrophil infiltration into the theca layer. The CINC/gro appears to synergize with interleukin-1 beta for ovulation. By contrast, the data suggest that CINC/gro expression suppresses TNF alpha expression and that CINC/gro expression therefore prevents the follicles from undergoing atresia and apoptosis.
Kazuyo Matsuzaki, Toshiyuki Yasui, Miwa Fukuoka and Hirokazu Uemura : Differences in Associations of Menopausal Symptoms with Job-related Stress Factors in Full-time and Part-time Workers in Japan, International Journal of Women's Health Care, Vol.2, No.1, 1-6, 2017.
58.
Tomoki Tada, Kensaku Aki, Wataru Oboshi, Kazuyoshi Kawazoe, Toshiyuki Yasui and Eiji Hosoi : Evaluation of effects of various drugs on platelet functions using phorbol 12-myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells, Drug Design, Development and Therapy, Vol.10, 3099-3107, 2016.
(Summary)
The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions. The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions. Human erythroid leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca(2+) concentration ([Ca(2+)]i) mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs. There was a positive correlation between [Ca(2+)]i and platelet aggregation induced by thrombin. Aspirin (5.6-560 µM) and cilostazol (5-10 µM) significantly inhibited thrombin-induced increases in [Ca(2+)]i in a concentration-dependent manner. On the other hand, ibuprofen (8-200 µM) and sodium valproate (50-1,000 µg/mL) also significantly inhibited thrombin-induced increases in [Ca(2+)]i in a concentration-dependent manner. Furthermore, the interaction effects of the simultaneous combined use of aspirin and ibuprofen or sodium valproate were evaluated. When the inhibitory effect of aspirin was higher than that of ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced. The combination of aspirin and sodium valproate synergistically inhibited thrombin-induced [Ca(2+)]i. It is possible to induce HEL cells to differentiate into megakaryocytes, which are a useful model for the study of platelet functions, and the quantification of the inhibition of thrombin-induced increases in [Ca(2+)]i is applicable to the evaluation of the effects of various drugs on platelets.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kaoru Keyama, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Changes of liver enzymes and triglyceride during the menopausal transition in Japanese women., Journal of Obstetrics and Gynaecology, Vol.36, No.6, 806-811, 2016.
(Summary)
We examined detailed changes in liver enzymes as surrogate markers for metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) during the menopausal transition and the associations of liver enzymes with lipid profiles related to risk of metabolic syndrome and endocrinological hormones. We divided 393 women into seven stages by menstrual regularity, follicle-stimulating hormone level and years since menopause. Serum levels of alanine aminotranferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, lipid parameters, glucose, and endocrinological hormones were measured. Both levels of AST and ALT increased towards early post-menopause. AST remained high in late post-menopause but ALT decreased. The AST/ALT ratio decreased towards late menopausal transition and very early post-menopause and increased thereafter. This ratio was negatively correlated with triglyceride. Significant changes in ALT and AST/ALT ratio during the menopausal transition, which were associated with triglyceride, might be involved in the occurrence of metabolic syndrome and NAFLD in Japanese women.
Takeshi Iwasa, Toshiya Matsuzaki, Sumika Matsui, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Eri Takiguchi, Takako Kawakita, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : The sensitivity of adipose tissue visfatin mRNA expression to lipopolysaccharide-induced endotoxemia is increased by ovariectomy in female rats., International Immunopharmacology, Vol.35, 243-247, 2016.
(Summary)
Visfatin plays an important role in inflammatory and metabolic conditions. In this study, the effects of septic stress on the serum, white-adipose-tissue (WAT), and liver visfatin levels of male and female rats were examined. Both gonadally intact (sham) and ovariectomized (OVX) female rats were used in order to evaluate the effects of the gonadal hormonal milieu on visfatin responses. Under the saline-injected conditions, the serum visfatin levels and the hepatic, subcutaneous, and visceral WAT visfatin mRNA levels of the OVX and sham rats did not differ. The serum visfatin levels and the subcutaneous, visceral WAT, and hepatic visfatin mRNA levels of both male and female rats were increased by the injection of a septic dose (5mg/kg) of LPS. At 6h after the injection of LPS, the WAT visfatin mRNA levels of the OVX rats were higher than those of the sham rats, whereas the serum visfatin levels and hepatic visfatin mRNA levels of the two groups did not differ. In the cultured visceral WAT, visfatin antagonist (FK-866) attenuated the LPS-induced up-regulations of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). The pathophysiological roles of visfatin under septic conditions remain to be clarified. In addition, the precise mechanisms responsible for the increased WAT visfatin expression seen after ovariectomy and the effects of such changes should also be clarified.
Kazuyo Matsuzaki, Hirokazu Uemura and Toshiyuki Yasui : Differences in coping with menopausal symptoms in nurses and general workers in Japan., Maturitas, Vol.86, 45-52, 2016.
(Summary)
We examined the differences in coping with menopausal symptoms between nurses and general workers, and we examined the association of the differences with understanding of menopausal symptoms in Japan. Three hundred and ninety-seven nurses and 217 general workers aged 45-60 years who had experienced menopausal symptoms completed a health questionnaire including questions on coping with menopausal symptoms and an understanding of causes and treatment of menopausal symptoms. Approximately 50% of both nurses and general workers had experience in coping with menopausal symptoms. Both nurses and general workers who had a sufficient understanding of menopausal symptoms were likely to cope with the symptoms and to visit hospitals. For coping strategies, the proportions of women who used diversion and dietary supplements were high in nurses and general workers, and the proportion of nurses who used diversion was significantly higher than that in general workers. Nurses with a sufficient understanding of menopausal symptoms had received hormone replacement therapy, and general workers with a sufficient understanding of menopausal symptoms had received herbal medicine. The proportions of nurses and general workers coping with menopausal symptoms were similar, although nurses had better knowledge regarding menopausal symptoms. More efforts to provide information and appropriate education regarding menopausal medicine and coping strategies may be required for both nurses and general workers.
(Keyword)
Adaptation, Psychological / Dietary Supplements / Female / Health Knowledge, Attitudes, Practice / Hormone Replacement Therapy / Humans / Japan / Menopause / Middle Aged / Nurses / Surveys and Questionnaires
Yuko Uemura, Toshiyuki Yasui, Kimiyo Horike, Kazuhisa Maeda, Hirokazu Uemura, Mari Haku, Reiko Sakae and Keiko Matsumura : Factors related with low back pain and pelvic pain at the early stage of pregnancy in Japanese women., International Journal of Nursing and Midwifery, Vol.9, No.1, 1-9, 2016.
Y Uemura and Toshiyuki Yasui : Assessment of pelvic shape by a newly developed posture analyzer in young women in Japan., Journal of Women's Health, Issues & Care, Vol.5, 1-8, 2016.
Shoko Fuji, Tetsuya Tanioka, Yuko Yasuhara, Miki Satoh, Ken Saito, Marguerite J. Purnell, Rozzano De Castro Locsin and Toshiyuki Yasui : Characteristic Autonomic Nervous Activity of Institutionalized Elders with Dementia, Open Journal of Psychiatry, Vol.6, No.1, 34-49, 2015.
Anna Tani, S Yamamoto, Masahiko Maegawa, Koutaro Kunimi, Sumika Matsui, Kaoru Keyama, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Toshiyuki Yasui, M Kamada, Takeshi Soeki, Masataka Sata and Minoru Irahara : Arterial stiffness is increased in young women with endometriosis., Journal of Obstetrics and Gynaecology, Vol.35, No.7, 711-715, 2015.
(Summary)
Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.
(Keyword)
arterial stiffness / endometriosis / hs CRP / subclinical inflammation / young women
Takeshi Iwasa, Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : The advancement of the onset of vaginal opening in female rats subjected to chronic testosterone treatment occurs independently of hypothalamic Kiss1 and RFRP expression., Neuroendocrinology Letters, Vol.36, No.8, 767-770, 2015.
(Summary)
The neonatal and/or prepubertal androgen milieu affects sexual maturation. In rodents, neonatal chronic testosterone treatment, which is used as a model of polycystic ovary syndrome (PCOS), results in the onset of vaginal opening occurring earlier in the pubertal period. In the present study, the changes in hypothalamic Kiss1 (a gonadotropin-releasing hormone (GnRH)-stimulating factor) and RF-amide related peptide (RFRP; a GnRH inhibitory factor) mRNA expression induced by testosterone treatment were examined in order to clarify whether these factors are involved in the testosterone-induced acceleration of sexual maturation. The onset of vaginal opening occurred earlier and uterine weight was increased in female rats subjected to chronic (from postnatal day 23 to day 31) testosterone treatment. Contrary to our expectations, the rats' hypothalamic Kiss1 and Kiss1 receptor mRNA levels were not changed, and their serum luteinizing hormone (LH) levels were decreased. Although hypothalamic RFRP mRNA expression was decreased in the testosterone-treated rats, this change was not reflected in their serum LH levels. These results indicate that the advancement of sexual maturation observed in chronic testosterone-treated rats might be caused by a peripheral, rather than a central, mechanism.
Takeshi Iwasa, Toshiya Matsuzaki, Sumika Matsui, Munkhsaikhan Munkhzaya, Altankhuu Tungalagsuvd, Takako Kawami, Masahiro Murakami, Takeshi Katou, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : The effects of LPS-induced endotoxemia on the expression of adiponectin and its receptors in female rats., Endocrine Journal, Vol.61, No.9, 891-900, 2014.
(Summary)
Adiponectin (APN), secreted by white adipose tissue (WAT), acts as a protective factor against inflammatory conditions. However, the changes in the expression levels of endogenous APN and the two types of APN receptor (AdipoR1 and AdipoR2) induced by acute inflammatory conditions have not been fully elucidated. In this study, the changes in peripheral and/or central APN and AdipoR expression caused by lipopolysaccharide (LPS)-induced sepsis were examined in gonadal-intact (Sham) and ovariectomized (OVX) female rats. As it has been reported that APN and AdipoR suppress the production of inflammatory cytokines to prevent excessive inflammation, the mRNAs of these molecules were also examined. LPS injection induced increases in visceral WAT APN mRNA without affecting the serum APN level in both the Sham and OVX rats. OVX rats exhibited higher serum APN levels than Sham rats. LPS injection increased the subcutaneous WAT APN mRNA in OVX rats. In both Sham and OVX rats, LPS injection led to a decrease in hepatic AdipoR2 mRNA and an increase in hypothalamic AdipoR2 mRNA. Hypothalamic AdipoR2 mRNA was upregulated 24 h after LPS injection in OVX but not Sham rats. Serum TNF- level at 6 h after LPS injection and hypothalamic and hepatic IL-6 and TNF- mRNA at 24 h after LPS injection were significantly higher in Sham than OVX rats. These results suggest that APN and AdipoR play roles in modulating inflammation under septic conditions in female rats.
Miki Satoh, Tetsuya Tanioka, Yuko Yasuhara, Toshiyuki Yasui, Yukie Iwasa and Masafumi Miyake : Sensitive Test for Screening for Autonomic Neuropathy of Type 2 Diabetes, Information : an International Interdisciplinary Journal, Vol.17, No.1, 367-372, 2014.
(Keyword)
autonomic nervous system activity / type 2 diabetes / disturbed sleep / actigraphy / heart rate variability
Sumika Matsui, Toshiyuki Yasui, Kaoru Keyama, Anna Tani, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : High adiponectin level in late postmenopausal women with normal renal function., Clinica Chimica Acta, Vol.430, 104-108, 2014.
(Summary)
We examined whether high circulating adiponectin level is associated with renal function and is favorable for lipid and glucose metabolism in late postmenopausal women with normal renal function. We conducted a cross-sectional study in 115 postmenopausal women and divided the subjects into 2 groups (early postmenopausal women and late postmenopausal women). Serum levels of adiponectin, blood urea nitrogen, creatinine (Cr), glucose, insulin and lipid profiles were measured. Glomerular filtration rate (GFR) was estimated by age and Cr. Serum adiponectin level in late postmenopausal women was significantly higher than that in early postmenopausal women, and eGFR in late postmenopausal women was significantly lower than that in early postmenopausal women. Adiponectin level showed a negative correlation with eGFR and tended to have a negative correlation with eGFR after adjustments for age, BMI and bioavailable testosterone in all subjects, but adiponectin level did not show a significant correlation with eGFR in late postmenopausal women. Adiponectin level in late postmenopausal women showed a significant negative correlation with triglyceride (TG) and a positive correlation with high-density lipoprotein cholesterol (HDL-C) after adjustments for age and BMI. In late postmenopausal women with normal renal function, high adiponectin level is associated with favorable lipid profiles. High adiponectin level may be involved in not only eGFR but also other factors in late postmenopausal women.
Sumika Matsui, Toshiyuki Yasui, A Tani, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Kokichi Arisawa and Minoru Irahara : Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women., Climacteric, Vol.17, No.2, 191-196, 2013.
(Summary)
Abstract Background Ultra-low-dose estradiol is known to improve menopausal symptoms and increase bone mineral density. However, the effect of ultra-low-dose estradiol on vascular function has not been clarified. Objectives We examined the effects of ultra-low-dose estradiol on brachial-ankle pulse wave velocity (baPWV) and circulating markers of cardiovascular risk. Patients and methods Twenty-eight postmenopausal women were enrolled in this study. Fourteen women received oral estradiol (0.5 mg) and dydrogesterone (5 mg) every day for 12 months (ultra-low-dose group) as hormone replacement therapy (HRT) and 14 women as a control group did not receive HRT. The baPWV, lipid profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and vascular inflammatory markers were measured. Results The baPWV level significantly decreased in the ultra-low-dose group (p = 0.037), while the baPWV level did not significantly change in the control group. HOMA-IR tended to decrease in the ultra-low-dose group (p = 0.076). Systolic blood pressure and diastolic blood pressure did not change significantly in either group. Conclusion An HRT regimen using oral ultra-low-dose estradiol and dydrogesterone has an effect on arterial stiffness and insulin resistance.
Sumika Matsui, Toshiyuki Yasui, Anna Tani, Takeshi Katou, Kotaro Kunimi, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Difference in the Ratio of High-Molecular Weight (HMW) to Total Adiponectin and HMW Adiponectin in Late Postmenopausal Women., Journal of Endocrinological Investigation, 2013.
(Summary)
Objective: High-molecular weight (HMW) isoform level and HMW ratio have been shown to be better predictors of insulin sensitivity and metabolic syndrome than total adiponectin level. We examined the changes in circulating levels of HMW adiponectin and ratios of HMW to total adiponectin in women during the menopausal transition. Methods: We conducted a cross-sectional study in 217 healthy women and divided them into 4 stages: 58 women in premenopausal, 69 women in perimenpausal, 62 women in early postmenopausal and 28 women in late postmenopausal women. Serum levels of total adiponectin and HMW adiponectin were measured by an enzyme-linked immunosorbent assay. Results: In late postmenopausal women, HMW adiponectin level was significantly higher than that in perimenopausal women and the HMW to total adiponectin ratio was significantly lower than that in early postmenopausal women. In perimenopausal women, HMW adiponectin level was significantly lower than that in premenopausal women and HMW to total adiponectin ratio was significantly lower than the ratios in premenopausal and early postmenopausal women. Conclusion: The ratio of HMW to total adiponectin is low in late postmenopausal women, though both levels of total and HMW adiponectin were high after menopause in our cross-sectional study.
Sumika Matsui, Toshiyuki Yasui, Anna Tani, Kotaro Kunimi, Hirokazu Uemura, Satoshi Yamamoto, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Associations of estrogen and testosterone with insulin resistance in pre- and postmenopausal women with and without hormone therapy., International Journal of Endocrinology and Metabolism, Vol.11, No.2, 65-70, 2013.
(Summary)
Estrogen deficiency due to natural menopause or surgical menopause has been suggested to have an adverse effect on insulin resistance. Testosterone and sex hormone-binding globulin (SHBG) as well as estrogen are also associated with insulin resistance in women. However, to date, the associations of estradiol, testosterone and SHBG with insulin resistance according to estrogen level have not been clarified. We examined the associations of estradiol, testosterone and SHBG with insulin resistance in pre- and in postmenopausal women and postmenopausal women who had received hormone therapy to clarify whether the associations differ depending on the estrogen status. Twenty premenopausal women and thirty-two postmenopausal women were enrolled in this study. Fifteen postmenopausal women received oral conjugated equine estrogen (CEE) (0.625 mg) everyday for 12 months. Serum levels of estradiol, testosterone, SHBG and insulin and plasma levels of glucose were measured. Serum estradiol levels tended to have a negative correlation with homeostasis model assessment of insulin resistance (HOMA-IR) in premenopausal women but not in postmenopausal women. On the other hand, free testosterone levels tended to have a positive correlation with HOMA-IR in postmenopausal women but not in premenopausal women. Serum SHBG levels showed significant negative correlations with HOMA-IR in both pre- and postmenopausal women. SHBG level was significantly increased, free testosterone level was significantly decreased and HOMA-IR was significantly decreased at 12 months after CEE administration. However, there were no significant correlations of changes between estradiol, SHBG or free testosterone and HOMA-IR. The associations of sex steroid hormones with insulin resistance are different depending on the estrogen status.
Miki Satoh, Yuko Yasuhara, Tetsuya Tanioka, Yukie Iwasa, Toshiyuki Yasui, Masafumi Miyake, Haruo Kobayashi, Waraporn Kongsuwan and Rozzano C. Locsin : Changes before and after improvement of subjective sleep state of a man diagnosed with pre-diabetes and sleep disorder, Health, Vol.5, No.3A, 504-511, 2013.
(Keyword)
Actigraphy / Heart Rate Variability / Autonomic Nervous System / Function / Disturbed sleep
Takeshi Iwasa, Toshiya Matsuzaki, Riyo Kinouchi, Ganbat Gereltsetseg, Masahiro Murakami, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Developmental changes in the responsiveness of hypothalamic ER alpha mRNA levels to food deprivation., Neuroendocrinology Letters, Vol.34, No.6, 543-548, 2013.
(Summary)
Estrogen plays an important role in feeding and energy balance, and the critical role of estrogen in the control of appetite and energy balance is mediated by hypothalamic estrogen receptor (ER) alpha. In undernourished rodents, hypothalamic ER alpha mRNA expression are decreased. Responses of some hypothalamic factors to negative energy balance develop during the early neonatal period. In this study, we examined the developmental changes of fasting-induced alterations in hypothalamic ER alpha mRNA expression in female rats. ER alpha mRNA expression was reduced after a 12-h or 24-h fast at postnatal days 15 and 25, but not at day 5. Serum estradiol levels in postnatal day 25 rats were not changed by fasting. Although serum leptin levels were suppressed by fasting at all ages, hypothalamic ER alpha mRNA expression at postnatal day 25 was not changed by leptin administration after a 24-h fast. These data show that the sensitivity of hypothalamic ER alpha to negative energy balance may not be established in the early neonatal period, and that it develops by postnatal day 15. Decreased leptin levels might not be involved in the alterations of hypothalamic ER alpha mRNA expression in the undernourished condition.
Toshiyuki Yasui and T T Kuramoto M Imamura M Kishida S Yasui Takata : Differences in knowledge of and attitudes regarding complementary and alternative medicine among health care profession students in Japan, Japanese Journal of Complementary and Alternative Medicine, Vol.10, No.2, 87-97, 2013.
(Summary)
Objective: The aim of this study was to evaluate and compare levels of knowledge of and attitudes toward complementary and alternative medicine (CAM) in different groups of health care profession students. Methods: The subjects of this study were 1465 students of nursing, medicine, radiologic science, laboratory science, nutrition, dentistry, oral health and welfare, and pharmaceutical science. We used a questionnaire to obtain information on knowledge, sources of information, interest, personal use, willingness to take lectures, opinions regarding effectiveness and willingness to recommend for 17 different CAM modalities. Results: Knowledge of CAM differed depending on the CAM therapy in all students. Nursing students had high levels of interest in massage, aromatherapy, yoga and chiropractic. The proportions of nursing students with high levels of interest in these CAM therapies were significantly higher than the proportions in other groups of health profession students (p < 0.05). In addition, proportions of nursing students who had positive opinions regarding the usefulness of massage, chiropractic, psychotherapy, yoga and aromatherapy were significantly higher than the proportions in other groups of heath care profession students (p < 0.05). Conclusions: Nursing students tend to have positive and favorable attitudes toward CAM compared to other groups of health care profession students. If nursing students receive lectures on CAM in their curriculum, they may use CAM in clinical care and thereby contribute to an accumulation of evidence on the benefits of CAM as well as to improvement in the quality of medical service.
(Keyword)
complementary and alternative medicine / nursing students / knowledge / education
Riyo Kinouchi, Toshiya Matsuzaki, Takeshi Iwasa, Ganbat Gereltsetseg, Hiroshi Nakazawa, Kotaro Kunimi, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Prepubertal exposure to glucocorticoid delays puberty independent of the hypothalamic Kiss1-GnRH system in female rats., International Journal of Developmental Neuroscience, Vol.30, No.7, 596-601, 2012.
(Summary)
Secretion of glucocorticoids is widely known as a key endocrine response to stresses. Prenatal dexamethasone administration induces intrauterine growth retardation and delayed onset of puberty in female rats independent of the hypothalamic Kiss1-gonadotropin-releasing hormone (GnRH) system. The aim of this study was to evaluate the influence of chronic intracerebroventricular (central, CD) or subcutaneous (peripheral, PD) dexamethasone administration to prepubertal female rats on the onset of puberty and body weight change. Rats administered dexamethasone from day 25 to day 34 (CD and PD) showed significantly reduced body weight gain throughout the experimental period and delayed onset of vaginal opening compared with rats administered saline centrally (CS) or peripherally (PS). At 34 days old, hypothalamic Kiss1r mRNA levels were significantly lower with CD than with CS. No significant differences were seen between rats administered saline and rats administered dexamethasone with regard to hypothalamic Kiss1, GnRH and NPY mRNA levels or serum LH levels. Serum leptin concentrations were higher in CD and PD than in the controls (CS and PS). These results suggest that the delayed onset of puberty induced by prepubertal dexamethasone administration occurs independent of the hypothalamic Kiss1-GnRH system.
Sumika Matsui, Toshiyuki Yasui, Anna Tani, Takeshi Katou, Kotaro Kunimi, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Association of circulating adiponectin with testosterone in women during the menopausal transition., Maturitas, Vol.73, No.3, 255-260, 2012.
(Summary)
We examined (1) the change in circulating adiponectin in women during the menopausal transition and (2) the associations of adiponectin levels with estrogen, androgen and sex hormone-binding globulin (SHBG) in women during the menopausal transition. We conducted a cross-sectional study in 235 healthy women and divided them into 7 stages by menstrual regularity and follicle-stimulating hormone (FSH) level. Serum levels of adiponectin, estradiol, total testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and SHBG were measured. Levels of free and bioavailable testosterone were calculated by using total testosterone, albumin and SHBG. Serum adiponectin levels showed a U-curve, levels being low in early and late menopausal transition and gradually becoming higher after menopause. Adiponectin levels were negatively correlated with levels of free testosterone, bioavailable testosterone and DHEA-S and were positively correlated with SHBG in postmenopausal women for whom more than 1 year had passed since menopause. Adiponectin level was not correlated with estradiol level. Circulating adiponectin level shows a U-curve during the menopausal transition and adiponectin level is associated with levels of free and bioavailable testosterone and DHEA-S in postmenopause.
Sumika Matsui, Toshiyuki Yasui, Anna Tani, Kotaro Kunimi, Hirokazu Uemura, Satoshi Yamamoto, Akira Kuwahara, Toshiya Matsuzaki, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Changes in insulin sensitivity during GnRH agonist treatment in premenopausal women with leiomyoma., Clinica Chimica Acta, Vol.413, No.11-12, 960-965, 2012.
(Summary)
The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity. Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined. In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased. Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment.
Tomomi Iba, Yuya Yano, Mayumi Umeno, Kenji Hinokio, Akira Kuwahara, Minoru Irahara, Shuji Yamano and Toshiyuki Yasui : Roscovitine in combination with calcium ionophore induces oocyte activation through reduction of M-phase promoting factor activity in mice., Zygote, Vol.20, No.4, 321-325, 2011.
(Summary)
SummaryThe aim of the present study was to determine oocyte activation and change in M-phase promoting factor (MPF) activity induced by treatment with calcium ionophore and roscovitine in comparison with those induced by treatment with roscovitine alone and treatment with calcium ionophore and puromycin in mice. Freshly ovulated oocytes obtained from 6-8-week-old mice were divided into five groups (no activation treatment; 5 μM calcium ionophore A23187; 50 μM roscovitine; 5 μM calcium ionophore and 10 μg/ml puromycin; and 5 μM calcium ionophore and 50 μM roscovitine) and were incubated for 6 h. Oocyte activation, assessed by morphological changes, and changes in MPF activity in the five groups at 0, 2, 4 and 6 h of incubation were examined. Activated oocytes were defined as oocytes with at least one pronucleus. Oocytes treated with roscovitine alone were not activated during the 6-h incubation period. All of the oocytes in the calcium ionophore with puromycin group and in the calcium ionophore with roscovitine group were activated. The percentage activity of MPF in oocytes treated with roscovitine alone was decreased after 2 h and increased after 4 h of incubation. The percentage activity of MPF in oocytes treated with calcium ionophore and roscovitine was significantly decreased with suppression of MPF activity being maintained for 6 h, and this change was similar to that in oocytes treated with calcium ionophore and puromycin. Roscovitine with calcium ionophore is effective for induction of oocyte activation through suppression of MPF activity in mice.
Toshiya Matsuzaki, Takeshi Iwasa, Riyo Kinouchi, Shinobu Yoshida, Masahiro Murakami, Ganbat Gereltsetseg, Satoshi Yamamoto, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Fasting reduces the kiss1 mRNA levels in the caudal hypothalamus of gonadally intact adult female rats., Endocrine Journal, Vol.58, No.11, 1003-1012, 2011.
(Summary)
Kisspeptin, which is the product of the kiss1 gene and its receptor kiss1r, have emerged as the essential gatekeepers of reproduction. The present study used gonadally intact female rats to evaluate fasting-induced suppression of the KiSS-1 system of anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) under normal physiological conditions. Starting on the day of estrous, one group of rats was subjected to 72 h of food deprivation, while the other group of rats was able to continue feeding ad libitum. The length of the estrous cycle was significantly longer in the food-deprived rats as compared to the feeding rats. At the end of the 72-h food deprivation period, all of the food-deprived rats were at the diestrous phase, with their serum concentrations of LH and leptin significantly lower than that observed in the feeding rats. In addition, as compared to the feeding rats, the expression levels of kiss1 mRNA were significantly lower in the food-deprived rats in the posterior hypothalamic block, which contained the ARC, but not in the anterior hypothalamic block, which contain the AVPV. However, both the kiss1r mRNA expression levels in the anterior and posterior hypothalamic blocks and the neurokinin B and neurokinin 3 receptor mRNA expression levels in the posterior hypothalamic block were not significantly different between the feeding and food-deprived rats. Thus, lower kiss1 mRNA levels in the ARC appear to be responsible for the fasting-induced inhibition of gonadotrophin secretion and subsequent prolongation of the estrous cycle.
Takeshi Iwasa, Toshiya Matsuzaki, Riyo Kinouchi, Ganbat Gereltsetseg, Masahiro Murakami, Hiroshi Nakazawa, Shinobu Fujisawa, Satoshi Yamamoto, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Effect of immune stress on body weight regulation is altered by ovariectomy in female rats., Journal of Reproductive Immunology, Vol.91, No.1-2, 41-47, 2011.
(Summary)
It has been suggested that obesity and loss of ovarian function alter the inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used as a model of human menopause, exhibit both hyperphagia-induced obesity and gonadal steroid deficiency. To evaluate the effects of ovariectomy on inflammatory responses, we compared the anorectic response to LPS in OVX rats and gonad intact female rats. As leptin and hypothalamic interleukin-1β (IL1β) play pivotal roles in the anorectic response to immune stress, these factors were also measured. It was found that the OVX rats exhibited an increased anorectic response to LPS compared with the sham-operated rats. The OVX rats showed higher serum leptin concentrations and a greater increase in hypothalamic IL1β mRNA expression after LPS injection. In addition, in order to determine whether gonadal steroid deficiency contributes to the changes in the inflammatory responses of OVX rats, we compared responses between OVX rats treated with gonadal steroids and untreated OVX rats. There were no differences in appetite, the serum leptin level, and hypothalamic IL1β mRNA expression between the two groups after LPS injection. These findings suggest that the loss of ovarian function increases the induction of leptin and hypothalamic IL1β synthesis and consequently increases the anorectic response under immune stress conditions. It is possible that these alterations are caused by OVX-induced obesity rather than the direct effects of gonadal steroid deficiency.
Sumika Matsui, Toshiyuki Yasui, Hirokazu Uemura, Satoshi Yamamoto, Toshiya Matsuzaki, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Induction of circulating monocyte chemoattractant protein-1 in women with gonadotropin-releasing hormone agonist., Journal of Reproductive Immunology, Vol.90, No.2, 227-234, 2011.
(Summary)
The aim of the present study was to determine the influence of acute estrogen deficiency induced by administration of a gonadotropin-releasing hormone (GnRH) agonist on circulating levels of cytokines and chemokines. Eighty-three women with uterine leiomyoma were assigned in open, parallel-group fashion to a no-treatment (control) group and a GnRH-agonist group. Serum levels of nine cytokines and chemokines as well as vascular inflammatory markers were measured. Serum levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-α (TNFα) in the GnRH-agonist group were increased significantly at 6 months. There were also significant differences in percentage changes in interleukin (IL)-6, IL8, MCP1, and macrophage inflammatory protein-1β (MIP1β) between the control and GnRH agonist groups. Soluble intercellular adhesion molecule-1 (sICAM1) and E-selectin levels showed significant increases in the GnRH agonist group at 6 months. Serum MCP1 concentrations showed weak correlations with levels of sICAM and E-selectin. We conclude that a hypo-estrogenic state due to administration of a GnRH agonist increases circulating levels of cytokines and chemokines, especially MCP1.
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Murakami, Riyo Kinouchi, Ganbat Gereltsetseg, Hiroshi Nakazawa, Satoshi Yamamoto, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Changes in responsiveness of appetite, leptin and hypothalamic IL-1β and TNF-α to lipopolysaccharide in developing rats., Journal of Neuroimmunology, Vol.236, No.1-2, 10-16, 2011.
(Summary)
In addition to its role as a regulator of energy homeostasis, leptin plays a pivotal role in some immune/inflammatory responses. Synthesis and secretion of leptin are increased under immune stress conditions, and increased leptin may participate in the development of anorexia and fever. These actions are partially mediated by up-regulation of hypothalamic IL-1β. Leptin also protects against immune stress-induced lethality. On the other hand, the response and roles of leptin to immune stress conditions in the neonatal period have scarcely been examined. We hypothesized that 1. the response of leptin to immune stress would be suppressed in the early neonatal period, 2. hyporesponse of leptin in the early neonatal period would attenuate the anorectic response and increase the lethal rate under immune stress conditions and 3. supplementation of leptin in the early neonatal period would increase the anorectic response, whereas it would decrease the lethal rate under immune stress conditions. To test these hypotheses, we first examined the developmental changes in the responses of leptin and hypothalamic proinflammatory cytokines, i.e., IL-1β and TNF-α, to LPS-induced immune stress in female rats. We also examined the developmental changes in the anorectic response and lethality rate under LPS-induced immune stress conditions. Five- and 15-day-old rats showed no leptin response and a weak hypothalamic IL-1β response to LPS when compared with 25- and 42-day-old rats. Fifteen-day-old rats showed low anorectic responses and high lethality rates when compared with 25- and 42-day-old rats under LPS-induced immune stress conditions. We then examined whether administration of leptin affected the response to the anorectic and lethal effects of LPS in 15-day-old rats. Administration of leptin further attenuated body weight after LPS injection, but not after saline injection. On the other hand, administration of leptin did not affect survival rate. In addition, hypothalamic IL-1β mRNA levels were not affected by leptin administration. In conclusion, the absence of a leptin response may act to prevent immune stress-induced anorexia during the early neonatal period.
Souichiro Nakayama, Toshiyuki Yasui, Masanori Suto, Miki Sato, Takashi Kaji, Hirokazu Uemura, Kazuhisa Maeda and Minoru Irahara : Differences in bone metabolism between singleton pregnancy and twin pregnancy., Bone, Vol.49, No.3, 513-519, 2011.
(Summary)
The objective of this study was to examine the influence of twin pregnancy on calcium metabolism, including bone turnover markers and calcium-regulating factors, by comparison between singleton pregnancy and twin pregnancy in women during pregnancy and puerperium in cross-sectional and longitudinal studies. Women with singleton and twin pregnancies were recruited from the outpatient clinic of Tokushima University Hospital. In both cross-sectional and longitudinal studies, bone formation and resorption markers, mineral metabolism and calcium-regulating factors were measured at 10, 25, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum in women with singleton and twin pregnancies. Urinary levels of cross-linked type I collagen N-telopeptides and C-terminal telopeptides of type I collagen in women with twin pregnancy were significantly higher than those in women with singleton pregnancy and those high levels were observed earlier than those in women with singleton pregnancy. In the cross-sectional study, serum levels of bone-specific alkaline phosphatase, calcium and phosphate in women with twin pregnancy were higher and the levels of 1,25-(OH)2 vitamin D and 25-(OH) vitamin D in women with twin pregnancy were lower than those in women with singleton pregnancy. Changes in bone metabolism in women with twin pregnancy are different from those in women with singleton pregnancy. Early and large increases in bone turnover markers allow women with twin pregnancy to meet high fetal demand for calcium during pregnancy.
(Keyword)
Adult / Alkaline Phosphatase / Biological Markers / Bone Remodeling / Bone and Bones / calcium / Collagen Type I / Cross-Sectional Studies / Female / Gestational Age / Humans / Longitudinal Studies / Parathyroid Hormone / Peptide Fragments / Phosphates / Postpartum Period / Pregnancy / Pregnancy, Twin
Ayako Kobayashi, Masahiko Maegawa, Satoshi Yamamoto, Natsuyo Ugumori, Yuka Kasai, Anna Tani, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Toshiyuki Yasui, Hiroyuki Furumoto, Masaharu Kamada and Minoru Irahara : The role of blood in early endometrial-peritoneal interactions in a syngeneic mouse model of endometriosis, Reproductive Medicine and Biology, Vol.10, No.1, 15-20, 2011.
(Keyword)
Blood / Coagulation / Endometriosis / Fibrinolysis / Murine model
Yuka Kasai, Masahiko Maegawa, Satoshi Yamamoto, Masaharu Kamada, Toshiyuki Yasui, Hirokazu Uemura, Ayako Kobayashi, Masayo Kaneyama, Anna Tani, Sumika Matsui, Akira Kuwahara, Toshiya Matsuzaki, Hiroyuki Furumoto and Minoru Irahara : Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies., The Journal of Medical Investigation : JMI, Vol.58, No.1-2, 110-117, 2011.
(Summary)
The aims of this study were to determine the effects of raloxifene therapy on production of cytokines and in vitro effects of raloxifene on production of cytokines by whole blood cultures. We obtained samples of peripheral blood from 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months of raloxifene therapy and 10 postmenopausal women who did not receive raloxifene therapy. Whole blood from raloxifene-treated women was stimulated with lipopolysaccharide (LPS) or phytohemeagglutinin (PHA). Whole blood from postmenopausal women who were not treated with raloxifene was preincubated with raloxifene at concentrations of 10(-10)-10(-7) M and then stimulated with LPS or PHA. Concentrations of IL-1β, IL-4, IL-6, IL-12p40, IL-12p70, TNF-α and IFN-γ in the supernatant were measured by respective ELISAs. In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated production of IL-1β, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated production of IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10(-9) M) inhibited LPS-stimulated production of IL-1β, IL-6 and IL-12p40 and PHA-stimulated production of IFN-γ. Raloxifene therapy decreases the production of IL-1β, IL-6, IL-12 and TNF-α but not that of IL-4 and IFN-γ, suggesting that modulation of cytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene.
(Keyword)
Aged / Bone Density Conservation Agents / Bone Diseases, Metabolic / Cell Survival / Cytokines / Female / Humans / Leukocytes, Mononuclear / Menopause / Middle Aged / Raloxifene / Selective Estrogen Receptor Modulators / Time Factors
Toshiyuki Yasui, Sumika Matsui, S Yamamoto, Hirokazu Uemura, N Tsuchiya, M Noguchi, M Yuzurihara, Y Kase and Minoru Irahara : Effects of Japanese traditional medicines on circulating cytokine levels in women with hot flashes., Menopause, Vol.18, No.1, 85-92, 2011.
(Summary)
The effects of the Japanese traditional medicines keishibukuryogan and kamishoyosan on circulating cytokines were examined to clarify the difference in the actions of Japanese traditional medicines in women with hot flashes. Seven premenopausal, 51 perimenopausal, 45 spontaneously postmenopausal and 17 surgically postmenopausal women who had complained of hot flashes were enrolled in this study. Eighty women who hoped to receive Japanese traditional medicines were randomly assigned in open, parallel-group fashion to a keishibukuryogan group or kamishoyosan group. Forty women who did not want any treatment for hot flashes were followed up for 6 months as a control group. Serum levels of cytokines were measured using a multiplexed human cytokine assay. The proportions of responders in women treated with keishibukuryogan and kamishoyosan were 73.7% and 69.2%, respectively. Serum monocyte chemotactic protein-1 level in women treated with keishibukuryogan decreased significantly (P = 0.0037). On the other hand, concentrations of interleukin (IL)-6 and macrophage inflammatory protein-1β in women treated with kamishoyosan decreased significantly (P = 0.019 and P = 0.039, respectively). In both keishibukuryogan and kamishoyosan responder groups, serum IL-8 concentrations were reduced significantly (P = 0.021 and P = 0.014, respectively). Both treatments with keishibukuryogan and kamishoyosan reduce the circulating IL-8 level, which is involved in thermoregulation in perimenopausal women with hot flashes. In addition, keishibukuryogan decreases circulating monocyte chemotactic protein-1 level in postmenopausal women.
Toshiyuki Yasui : Gneder differences in attitudes regarding complementary and alternative medicine among health care profession students in Japan, Japanese Journal of Complementary and Alternative Medicine, Vol.11, No.2, 81-88, 2011.
Takeshi Iwasa, Toshiya Matsuzaki, Riyo Kinouchi, Shinobu Fujisawa, Masahiro Murakami, Machiko Kiyokawa, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Neonatal LPS injection alters the body weight regulation systems of rats under non-stress and immune stress conditions., International Journal of Developmental Neuroscience, Vol.28, No.1, 119-124, 2010.
(Summary)
It has been reported that prenatal immune stress induced by lipopolysaccharides or cytokines increases food intake and leads to obesity and other features of metabolic syndrome in adulthood. Using Sprague-Dawley rats, we evaluated whether neonatal LPS injection altered their body weight regulation systems under non-stress and immune stress conditions. On Day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) (PND(10)LPS) or saline (PND(10)Saline). After weaning, body weight was significantly elevated in PND(10)LPS compared with PND(10)Saline. Thereafter, the rats were injected with LPS (100 microg/kg, i.p.) or saline (used as a basal condition) from 7 to 8 weeks of age. Under basal conditions, cumulative food intake were significantly higher, serum leptin concentration was significantly increased, and hypothalamic NPY mRNA expression was significantly decreased in PND(10)LPS compared with PND(10)Saline. Under adult LPS injected conditions, body weight gain and cumulative food intake were suppressed in both the PND(10)LPS and PND(10)Saline groups compared with those observed under basal adult saline-injected conditions. The suppressive effects induced by adult LPS injection were less evident in the PND(10)LPS group than in the PND(10)Saline group. Adult LPS injection increased the serum leptin concentration in the PND(10)Saline rats, but not in the PND(10)LPS rats. In addition, adult LPS injection increased the mRNA expression of anorexinergic factors (IL-1beta, and TNF-alpha), and decreased that of the orexinergic factor NPY in both groups. However, the influence of adult LPS injection upon these factors was less evident in the PND(10)LPS group than in the PND(10)Saline group. These results suggest that neonatal LPS injection alters body weight regulation under both non-stress and immune stress conditions in male rats. Changes in the endocrine, neuropeptide, and cytokine regulation systems might be involved in these alterations.
Toshiyuki Yasui, Sumika Matsui, Ayako Saijo, Takashi Kaji, Satoshi Yamamoto, Hirokazu Uemura, Toshiya Matsuzaki and Minoru Irahara : Association of N-terminal pro B-type natriuretic peptide and sex hormone-binding globulin in non-obese peri- and postmenopausal women., Clinica Chimica Acta, Vol.411, No.3-4, 280-284, 2010.
(Summary)
BACKGROUND: The relationships between N-terminal fragment proBNP (B-type natriuretic peptide) (NT-proBNP) and sex steroid hormones have not been fully elucidated. We examined these associations in pre-, peri- and postmenopausal women without known cardiovascular disease. We also examined the change in circulating NT-proBNP caused by a gonadotrophin-releasing hormone (GnRH) agonist in order to clarify the effect of acute hormone deficiency on NT-proBNP. METHODS: Forty-nine premenopausal women, 101 perimenopausal women and 108 postmenopausal women were enrolled in one study. Forty-four premenopausal women with leiomyoma were recruited for another study, and 22 of those women were treated with a GnRH agonist. Serum levels of NT-proBNP, estradiol, testosterone and sex hormone-binding globulin (SHBG) were measured. RESULTS: NT-proBNP concentrations showed significant inverse correlations with body mass index (BMI) in peri- and postmenopausal women. Serum NTproBNP concentrations showed significant positive correlations with SHBG in peri- and postmenopausal women. These significant correlations remained after adjustment for age and BMI. Serum NT-proBNP concentration was significantly decreased after GnRH agonist administration, while NT-proBNP concentration in the control group did not change significantly. Serum SHBG level was also significantly decreased after GnRH agonist administration. CONCLUSION: Circulating NT-proBNP levels are positively associated with SHBG levels in non-obese peri- and postmenopausal women, and this relationship was found under the condition of acute hormone deficiency induced by GnRH agonist treatment.
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Murakami, Shinobu Fujisawa, Riyo Kinouchi, Ganbat Gereltsetseg, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Effects of intrauterine undernutrition on hypothalamic Kiss1 expression and the timing of puberty in female rats., The Journal of Physiology, Vol.588, No.Pt 5, 821-829, 2010.
(Summary)
Recent studies have suggested that intrauterine undernutrition is closely associated with the pathogenesis of diseases after birth. Perinatal undernutrition is known to disturb the development of reproductive function and delay the onset of puberty in some species. Using a rat model, we determined the effects of prenatal undernutrition on the development of the hypothalamic kisspeptin system and evaluated whether the alteration of the kisspeptin system contributes to the delayed onset of puberty induced by prenatal undernutrition. We also evaluated the effects of prenatal undernutrition on the developmental changes in serum leptin levels because leptin was a putative positive regulator of the hypothalamic kisspeptin system. We compared the timing of vaginal opening (VO) and the developmental changes in body weight, hypothalamic Kiss1 mRNA levels, and serum leptin concentrations between offspring with prenatal undernutrition (UN offspring) and normal nutrition (NN offspring). After birth, the UN offspring showed rapid growth and had caught up to body weight of the NN offspring by postnatal day 12. After postnatal day 16, the UN offspring showed significantly lower Kiss1 mRNA levels than the NN offspring, despite their significantly higher serum leptin levels (at days 20 and 28). The timing of VO in the UN offspring was delayed compared with that in the NN offspring, and chronic central injection of kisspeptin normalized the timing of VO in the UN offspring. These results suggest that decreased hypothalamic kisspeptin action contributes to the delayed onset of puberty in prenatally undernourished female rats. Increased leptin resistance in the kisspeptin system might be involved in these alterations.
Rie Ogata, Toshiya Matsuzaki, Takeshi Iwasa, Machiko Kiyokawa, Naoko Tanaka, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Hypothalamic Ghrelin suppresses pulsatile secretion of luteinizing hormone via beta-endorphin in ovariectomized rats., Neuroendocrinology, Vol.90, No.4, 364-370, 2009.
(Summary)
OBJECTIVES: Ghrelin, an endogenous growth hormone secretagogue, is a known accelerator of feeding behavior and suppresses pulsatile secretion of luteinizing hormone (LH) in ovariectomized rats. However, the mechanisms underlying this action remain unclear. We examined the effects of naloxone (NAL), a specific opioid antagonist, on the suppression of pulsatile LH secretion by ghrelin to determine whether beta-endorphin (beta-END) is involved in this suppressive effect. METHODS: Ghrelin was administered intracerebroventricularly, and NAL was injected intravenously in ovariectomized rats; then, serum LH concentrations were measured by radioimmunoassay in blood samples drawn every 6 min for 2 h to analyze pulsatile secretion. RESULTS: Administration of ghrelin significantly reduced mean LH concentration and pulse frequency. Coadministration of NAL with ghrelin significantly restored mean LH concentration and pulse frequency. CONCLUSION: Suppressive effect of intracerebroventricular injection of ghrelin on pulsatile LH secretion was mediated by beta-END, suggesting that hypothalamic ghrelin suppressed pulsatile gonadotropin-releasing hormone secretion via beta-END in female rats.
Toshiyuki Yasui, Ayako Saijo, Hirokazu Uemura, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Interleukin-7 is associated with monocyte chemoattractant protein-1 and soluble E-selectin levels in peripheral blood of newly post-menopausal women., Journal of Reproductive Immunology, Vol.81, No.1, 97-102, 2009.
(Summary)
Interleukin (IL-7), which is a regulator of development and homeostatic maintenance of T and B cells, is implicated in the induction of leukocyte-endothelial cell adhesion during inflammatory events. We hypothesized that circulating IL-7 is associated with cytokines and chemokines, vascular inflammatory markers and lipid profiles involved in regulating cell adhesion in post-menopausal women. Serum levels of 8 cytokines and chemokines were simultaneously measured in 200 post-menopausal women using a multiplexed human cytokine assay. C-reactive protein, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule and soluble E-selectin were measured as inflammatory markers. Serum IL-7 concentration was significantly correlated with serum MCP-1 concentration and the correlation remained after adjustment for age and body mass index (BMI). Serum IL-7 levels also showed significant positive correlations with serum levels of IL-10 and IL-6. In addition, the serum IL-7 concentration showed significant positive correlations with levels of soluble E-selectin and triglyceride after adjustment for age and BMI. We conclude that there is a relationship between circulating IL-7, MCP-1 and soluble E-selectin, and that IL-7 may be involved in regulating inflammatory cell adhesion together with MCP-1 and E-selectin in post-menopausal women.
(Keyword)
Age Factors / Body Mass Index / C-Reactive Protein / Cell Adhesion / Chemokine CCL2 / E-Selectin / Female / Humans / Inflammation / Intercellular Adhesion Molecule-1 / Interleukin-10 / Interleukin-6 / Interleukin-7 / Middle Aged / Postmenopause / Triglycerides / Vascular Cell Adhesion Molecule-1 / Vascular Diseases
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Murakami, Fumi Shimizu, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Reproducibility of luteinizing hormone hypersecretion in different phases of the menstrual cycle in polycystic ovary syndrome., The Journal of Obstetrics and Gynaecology Research, Vol.35, No.3, 514-519, 2009.
(Summary)
AIM: We evaluated the reproducibility of an elevated luteinizing hormone (LH) level or elevated LH/follicle-stimulating hormone (FSH) ratio in different phases of the menstrual cycle in patients with polycystic ovary syndrome (PCOS). Furthermore, we evaluated the influence of cycle days and body mass index on LH levels using different days from menses or withdrawal bleeding. METHODS: Forty-three patients with PCOS and 37 controls were enrolled. All patients with PCOS had elevated LH levels and LH/FSH ratio, polycystic ovarian morphology and chronic anovulation at diagnosis. After their diagnoses, we measured serum LH and FSH in the early period and/or late period of the follicular phase. RESULTS: The rate of patients with elevated LH levels and LH/FSH ratio were significantly higher in the late phase than in the early phase in PCOS. In the early phase, only 52% of patients had elevated LH levels and LH/FSH ratio. We failed to demonstrate an inverse relationship between the LH level and BMI. Conclusions: LH levels of patients with PCOS were strongly influenced by the days from menses or withdrawal bleeding. In the early period, the reproducibility of elevated LH levels or LH/FSH ratio was poor even in patients previously diagnosed with them.
(Keyword)
Adult / Body Mass Index / Female / Follicle Stimulating Hormone / Humans / Luteinizing Hormone / Menstrual Cycle / Polycystic Ovary Syndrome
Toshiyuki Yasui, Ayako Saijo, Hirokazu Uemura, Toshiya Matsuzaki, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Effects of oral and transdermal estrogen therapies on circulating cytokines and chemokines in postmenopausal women with hysterectomy., European Journal of Endocrinology, Vol.161, No.2, 267-273, 2009.
(Summary)
OBJECTIVE: The aim of the present study was to determine the different effects of oral estrogen therapy (ET) and transdermal ET on changes in circulating levels of cytokines and chemokines in relationship to changes in markers of inflammation in postmenopausal women with hysterectomy. METHODS: Fifty-five postmenopausal women with hysterectomy were randomly assigned in open, parallel-group fashion to an oral ET group and a transdermal ET group. Serum levels of cytokines and chemokines were simultaneously measured using a multiplexed human cytokine assay. Serum concentrations of high-sensitive C-reactive protein, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, and E-selectin were measured as vascular inflammation markers. RESULTS: Both oral ET and transdermal ET significantly decreased serum interleukin (IL)-7 concentrations at 12 months (P=0.020 and P=0.015 respectively). Transdermal ET decreased serum concentrations of IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1beta (P=0.05, P=0.019, and P=0.029), but oral ET increased IL-8 level (P=0.025). There were significant differences in percentage changes in IL-8 and MIP-1beta between the oral and transdermal ET groups. Oral ET significantly decreased E-selectin level after 12 months. CONCLUSION: Transdermal ET reduces circulating levels of IL-8, MCP-1, and MIP-1beta, while both oral ET and transdermal ET reduce circulating level of IL-7.
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Murakami, Riyo Kinouchi, Rie Ogata, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Neonatal lipopolysaccharide exposure attenuates the homotypic stress-induced suppression of LH secretion in adulthood in male rat., International Journal of Developmental Neuroscience, Vol.27, No.4, 345-349, 2009.
(Summary)
Neonatal immune challenges have a long-lasting influence on immune response. Using male Sprague-Dawley rats, we examined whether neonatal lipopolysaccharide (LPS) challenge alters the sensitivity of male reproductive function to adult LPS challenge and at which level (central or testes) the alteration occurs. We also examined the mRNA expression of proinflammatory cytokines in the hypothalamus and testes because they have a pivotal role in immune stress-induced suppression of gonadotropin secretion and testosterone synthesis. On day 10 after birth, all the pups were injected with LPS (100 microg/kg, i.p.) or saline. Thereafter, LPS (100 microg/kg, i.p.) or saline was injected in adulthood at 8 weeks of age. The serum LH concentration was decreased by LPS injection during adulthood in the neonatal saline-injected rats. This suppressive effect was not seen in the neonatal LPS-injected rats. The serum testosterone concentration was decreased by adult LPS injection in both the neonatal LPS-injected and neonatal saline-injected rats. The expression levels of KiSS-1, which encodes kisspeptin, known to have a crucial role in the regulation of gonadotropin secretion, and GnRH mRNA in the hypothalamus and LHbeta mRNA in the pituitary were not influenced by neonatal or adult LPS injection. On the other hand, the expression levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA in the hypothalamus and testes were increased by adult LPS injection in both the neonatal LPS-injected and neonatal saline-injected rats. Furthermore, the expression levels of these factors in the hypothalamus after adult LPS injection were significantly lower in the neonatal LPS-injected rats than in the neonatal saline-injected rats. These findings indicate that neonatal LPS challenge reduces the sensitivity of male reproductive function to the suppressive effects of LPS, mainly at the central level. Attenuation of proinflammatory cytokine synthesis in the hypothalamus might be involved in this alteration.
Toshiyuki Yasui, Masayo Yamada, Hirokazu Uemura, Shu-Ichi Ueno, Shusuke Numata, Tetsuro Ohmori, Naoko Tsuchiya, Masamichi Noguchi, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitor and Japanese traditional medicine., Maturitas, Vol.62, No.2, 146-152, 2009.
(Summary)
OBJECTIVE: The aim of the present study was to compare the effects on serum cytokine concentrations of paroxetine, a selective serotonin re-uptake inhibitor, and kamishoyosan, a Japanese traditional medicine, in midlife women with psychological symptoms. METHODS: Seventy-six women with psychological symptoms such as anxiety and mild depression as menopausal symptoms were enrolled in this study. Thirty-eight women received oral administration of 10mg paroxetine every day, and 38 women received oral administration of kamshoyosan every day for 6 months. Overall climacteric symptoms were assessed using Greene's climacteric scale. Serum levels of cytokines were measured using a multiplexed human cytokine assay. RESULTS: Greene's total scores in both women treated with paroxetine and in women treated with kamishoyosan decreased significantly. Percentage decreases in Greene's total, psychological and vasomotor scores during the 6-month period in the paroxetine group were significantly greater than those in the kamishoyosan group. Serum IL-6 concentration in women treated with paroxetine decreased significantly. Serum concentrations of IL-8, IL-10, macrophage inflammatory protein (MIP)-1beta and monocyte chemoattractant protein-1 in women treated with paroxetine decreased significantly. On the other hand, serum IL-6 concentration in women treated with kamishoyosan decreased significantly, but other serum concentrations did not change significantly. CONCLUSION: Decrease in IL-6 concentration may be involved in the mechanism of the actions of both paroxetine and kamishoyosan in women with psychological symptoms, and IL-6 may therefore be useful as a marker of treatment. The action of paroxetine may also be associated with decreases in IL-8, IL-10, MIP-1beta.
(Keyword)
Administration, Oral / Angiosperms / Climacteric / Cytokines / Depression / Drugs, Chinese Herbal / Hot Flashes / Humans / Medicine, East Asian Traditional / Middle Aged / Paroxetine / Phytotherapy / Plant Extracts / Serotonin Uptake Inhibitors
Toshiyuki Yasui, Hirokazu Uemura, S Hyodo, M Yamada, Satoshi Yamamoto, M Maegawa, N Tsuchiya, M Noguchi, M Yuzurihara, Y Kase and Minoru Irahara : Raloxifene reduces circulating levels of interleukin-7 and monocyte chemoattractant protein-1 in postmenopausal women., Atherosclerosis, 2009.
(Summary)
OBJECTIVE: The aim of the present study was to determine the effects of raloxifene on changes in circulating levels of cytokines and chemokines in relation to changes in lipid profiles and markers of inflammation in postmenopausal women. METHODS: Fifty-three postmenopausal women aged 45-65 years old were randomly assigned in open, parallel-group fashion to a control group or raloxifene group. Twenty-six women received oral administration of 60mg raloxifene every day and 27 women did not receive any drugs for 12 months. Serum cytokines levels were simultaneously measured using a multiplexed human cytokine assay. RESULTS: Serum IL-7 concentrations in women who received raloxifene were decreased significantly (p=0.014), and serum monocyte chemoattractant protein (MCP)-1 concentrations in women who received raloxifene were decreased significantly (p=0.0003) at 12 months. In the control group, serum levels of MCP-1 and IL-7 did not show significant changes. There were significant differences (p=0.032 and p=0.0024, respectively) in percentage changes in IL-7 and MCP-1 in the control group and in the raloxifene group. Levels of low-density lipoprotein cholesterol (LDL-C) and E-selectin were decreased significantly in women who received raloxifene, but the percentage changes in LDL-C and E-selectin over a period of 12 months were not significantly correlated with percentage changes in IL-7 and MCP-1 over the same period. CONCLUSION: Circulating levels of IL-7 and MCP-1 decrease in postmenopausal women who received raloxifene.
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Murakami, Riyo Kinouchi, Fumi Shimizu, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Neonatal immune challenge affects the regulation of estrus cyclicity and feeding behavior in female rats., International Journal of Developmental Neuroscience, Vol.27, No.1, 111-114, 2008.
(Summary)
A single immune challenge with lipopolysaccharide (LPS) in the neonatal period has a long-lasting influence on immune response. Using female Sprague-Dawley rats, we examined whether neonatal LPS challenge influences the life-long neuroendocrine sensitivity of reproductive function and feeding behavior to LPS, and whether stress-related neuropeptides and their receptors are involved in neonatal LPS-induced physiological change. On day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) or saline. Then, in Experiment 1, LPS (100 microg/kg, i.p.) or saline was injected at diestrous in adulthood, and the length of the estrous cycle, 24h food intake and body weight change were recorded. In Experiment 2, the mRNA expression levels of corticotropin-releasing hormone (CRH), urocortin (UCN), urocortin 2 (UCN2), CRH receptor type 1 (CRH-R1) and CRH receptor type 2 (CRH-R2) in the hypothalamus were measured using real-time PCR. LPS injection in adulthood prolonged the estrous cycle in neonatal LPS-injected rats. LPS injection in adulthood decreased food intake and body weight in both neonatal LPS- and saline-injected rats, more so in the latter. Basal expressions of UCN2 and CRH-R2 mRNA were higher in neonatal LPS-injected rats than in saline-injected rats. These findings indicate that neonatal immune challenge influences the anti-stress regulation of the estrous cycle and feeding behavior in adulthood. Increased expression of UCN2 and CRH-R2 might enhance the sensitivity of the estrous cycle in suppressing the effects of LPS.
Toshiyuki Yasui, Hirokazu Uemura, Minoru Irahara, Makoto Arai, Noriko Kojimahara, Ryugo Okabe, Yasutomo Ishii, Shin-Ichi Tashiro and Hiroshi Sato : Associations of endogenous sex hormones and sex hormone-binding globulin with lipid profiles in aged Japanese men and women., Clinica Chimica Acta, Vol.398, No.1-2, 43-47, 2008.
(Summary)
BACKGROUND: The associations of endogenous estrogen with lipid profiles and insulin resistance were conflicting in both men and women. We determined the associations of serum estradiol level and free estradiol index (FEI) with lipid profiles and insulin resistance in aged Japanese men and women. METHODS: One hundred seventy-four men and 208 postmenopausal women aged from 50 to 85 y were included in this study. Lipid profiles, fasting glucose and insulin as well as estradiol, testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and sex hormone-binding globulin (SHBG) in serum were measured. RESULTS: Serum estradiol concentration in men showed a significant and negative correlation with high density lipoprotein-cholesterol (HDL-C) concentration and a significant and positive correlation with triglyceride (TG) after adjustment for age and body mass index (BMI). In addition, estradiol level was positively correlated with insulin and HOMA index. In women, serum levels of estradiol and testosterone were not correlated with lipid profiles and insulin resistance. SHBG concentration was negatively correlated with TG after adjustment for age and BMI in women. CONCLUSION: Endogenous estradiol level is associated with unfavorable lipid profiles and insulin resistance in aged men. In aged women, SHBG level is associated with favorable lipid profiles.
(Keyword)
Aged / Aged, 80 and over / Androgens / Body Mass Index / Cholesterol, HDL / Dehydroepiandrosterone Sulfate / Estradiol / Female / Gonadal Steroid Hormones / Homeostasis / Humans / Insulin / Insulin Resistance / Japan / Lipids / Male / Middle Aged / Sex Hormone-Binding Globulin / Testosterone / Triglycerides
Masahiro Murakami, Toshiya Matsuzaki, Takeshi Iwasa, Toshiyuki Yasui, Minoru Irahara, Tomohiro Osugi and Kazuyoshi Tsutsui : Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats., The Journal of Endocrinology, Vol.199, No.1, 105-112, 2008.
(Summary)
Gonadotropin-inhibitory hormone (GnIH), a newly discovered hypothalamic RFamide peptide, inhibits reproductive activity by decreasing gonadotropin synthesis and release in birds. The gene of the mammalian RFamide-related peptides (RFRP) is orthologous to the GnIH gene. This Rfrp gene gives rise to the two biologically active peptides RFRP-1 (NPSF) and RFRP-3 (NPVF), and i.c.v. injections of RFRP-3 suppress LH secretion in several mammalian species. In this study, we show whether RFRP-3 affects LH secretion at the pituitary level and/or via the release of GnRH at the hypothalamus in mammals. To investigate the suppressive effects of RFRP-3 on the mean level of LH secretion and the frequency of pulsatile LH secretion in vivo, ovariectomized (OVX) mature rats were administered RFRP-3 using either i.c.v. or i.v. injections. Furthermore, the effect of RFRP-3 on LH secretion was also investigated using cultured female rat pituitary cells. With i.v. administrations, RFRP-3 significantly reduced plasma LH concentrations when compared with the physiological saline group. However, after i.c.v. RFRP-3 injections, neither the mean level of LH concentrations nor the frequency of the pulsatile LH secretion was affected. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 on LH secretion was not clear, but when GnRH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that RFRP-3 does not affect LH secretion via the release of GnRH, and that RFRP-3 directly acts upon the pituitary to suppress GnRH-stimulated LH secretion in female rats.
Yuka Miyatani, Toshiyuki Yasui, Hirokazu Uemura, Masayo Yamada, Toshiya Matsuzaki, Akira Kuwahara, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Associations of circulating adiponectin with estradiol and monocyte chemotactic protein-1 in postmenopausal women., Menopause, Vol.15, No.3, 536-541, 2008.
(Summary)
OBJECTIVE: The aim of the present study was to clarify the association of serum adiponectin concentrations with serum 17beta-estradiol concentrations in pre-, peri-, and postmenopausal women. In addition, the associations of serum adiponectin with serum concentrations of proinflammatory and anti-inflammatory cytokines were examined in women during the menopausal transition. DESIGN: A total of 197 women were enrolled in this study: 33 premenopausal women, 80 perimenopausal women, and 84 postmenopausal women. Serum adiponectin concentration was measured by an enzyme-linked immunosorbent assay. Serum concentrations of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha, anti-inflammatory cytokine IL-10, and the chemokines IL-8, macrophage inflammatory protein-1beta and monocyte chemotactic protein-1 were measured by using a multiplexed human cytokine assay. RESULTS: Serum adiponectin concentration showed a significant negative correlation with serum estradiol concentration (r= -0.400, P=0.001) in postmenopausal women but not in pre- and perimenopausal women, and this correlation was significant after adjustment for age and body mass index. Serum adiponectin concentration also showed a significant negative correlation with serum monocyte chemotactic protein-1 concentration (r= -0.244, P=0.05) in postmenopausal women. CONCLUSION: An increase in adiponectin level due to a decrease in estradiol results in a reduction in monocyte chemotactic protein-1 level in postmenopausal women, suggesting that adiponectin may be associated with a protective role against insulin resistance and atherosclerosis, which occur in the postmenopausal stage.
Fumi Shimizu, Toshiya Matsuzaki, Takeshi Iwasa, Naoko Tanaka, Masahiro Minakuchi, Akira Kuwahara, Toshiyuki Yasui, Hiroyuki Furumoto and Minoru Irahara : Transition of leptin receptor expression during pubertal development in female rat pituitary., Endocrine Journal, Vol.55, No.1, 191-198, 2008.
(Summary)
Leptin is thought to play important roles in pubertal development and reproductive function in the female. Leptin receptor is expressed in various tissues including the pituitary and hypothalamus. We investigated the transition of leptin receptor (Ob-R) expression in female rat pituitary during pubertal development. Real-time RT-PCR was performed for long-form leptin receptor (Ob-Rb) and short-form leptin receptor (Ob-Ra) in the pituitary and cerebrum of the rats aged 4 (juvenile), 6 (pubertal), and 8 weeks (adult). Double immunohistochemical colocalization of Ob-R and luteinizing hormone (LH) was performed in pituitaries from 4-week-old female rats. Serum leptin concentrations of 4-, 6-, and 8-week-old rats were measured by radioimmunoassay. In the pituitary, expression of Ob-Rb mRNA in 4-week-old rats (1.00 +/- 0.16) was significantly higher than in 8-week-old rats (0.61 +/- 0.07, p<0.05), although expression of Ob-Ra mRNA did not differ among 4-, 6-, and 8-week-old rats. In cerebrum, Ob-Ra and Ob-Rb mRNA expressions did not differ significantly among 4-, 6-, and 8-week-old rats. Intense staining of Ob-R and colocalization of Ob-R and LH were seen in 4-week-old rat pituitary. On the other hand, serum concentrations of leptin in 6- and 8-week-old rats were significantly higher than those in 4-week-old rats (p<0.05, p<0.01, respectively). In conclusion, since the pituitary gonadotroph is a potential target of leptin, the juvenile rat pituitary might prepare for a subsequent increase of serum leptin concentration by expressing Ob-Rb.
Hirokazu Uemura, Toshiyuki Yasui, Y Miyatani, M Yamada, Mineyoshi Hiyoshi, Kokichi Arisawa and Minoru Irahara : Circulating profiles of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in post-menopausal women., Journal of Endocrinological Investigation, Vol.31, No.2, 163-168, 2008.
(Summary)
OBJECTIVE: The aim of this study was to elucidate the detail profiles of circulating osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappaB ligand (sRANKL) in post-menopausal women. METHODS: Eighty Japanese post-menopausal women were enrolled in this cross-sectional study. Circulating OPG and free fraction of sRANKL (free sRANKL), PTH, calcium and phosphorus, age, years since menopause, body mass index, bone mineral density of the vertebral bodies (LBMD) and bone turnover markers were determined in each subject. RESULTS: In rank order correlation analysis, serum OPG concentrations had a significant positive correlation with age (r=0.291, p=0.024) and a marginal significant negative correlation with LBMD (r=-0.247, p=0.062). However they did not have correlations with LBMD or other parameters after adjustment for age. Serum free sRANKL concentrations had a significant positive correlation with age (r=0.332, p=0.010) and a significant negative correlation with LBMD (r=-0.608, p<0.001). This correlation with LBMD persisted after adjustment for age. In a multiple regression analysis with a stepwise model, the main determinants of LBMD were age and serum free sRANKL (p=0.015 and p=0.006, respectively). CONCLUSIONS: We found the increase in circulating OPG and sRANKL with age and a robust negative correlation between circulating free sRANKL and LBMD after adjustment for age. The increase in circulating free sRANKL may reflect directly or indirectly the conditions coexistent with bone loss in post-menopausal women.
(Keyword)
Alkaline Phosphatase / Bone Density / Calcium / Collagen Type I / Female / Humans / Middle Aged / Osteoporosis, Postmenopausal / Osteoprotegerin / Parathyroid Hormone / Peptides / Phosphorus / Postmenopause / RANK Ligand / Solubility
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18362509
Toshiyuki Yasui, Hirokazu Uemura, Masayo Yamada, Toshiya Matsuzaki, Naoko Tsuchiya, Masamichi Noguchi, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara : Associations of interleukin-6 with interleukin-1beta, interleukin-8 and macrophage inflammatory protein-1beta in midlife women., Cytokine, Vol.41, No.3, 302-306, 2008.
(Summary)
OBJECTIVE: The aim of the present study was to determine the associations of interleukin (IL)-6 with other cytokines and chemokines and to compare these associations in peri- and postmenopausal women. METHODS: Ninety-nine perimenopausal and 92 postmenopausal women were enrolled in this study. Serum concentrations of IL-6, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor (TNF)-alpha, interferon gamma, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, macrophage inflammatory protein (MIP)-1beta and monocyte chemotactic protein (MCP)-1 were measured simultaneously using a multiplexed cytokine assay. RESULTS: Among the 17 cytokines, IL-6, IL-1beta, IL-5, IL-7, IL-8, IL-10, MCP-1 and MIP-1beta were detected in serum in more than 50% of the women. Serum levels of IL-4 and MCP-1 in postmenopausal women were significantly higher than those in perimenopausal women. Serum IL-6 concentrations showed significant and positive correlations with serum concentrations of IL-1beta, IL-8, MIP-1beta, IL-7 and MCP-1 in women regardless of menopausal status, and these correlations were still significant after adjustment for age and body mass index. CONCLUSION: Serum IL-6 concentration was found to be closely associated with serum concentrations of IL-1beta, IL-8, MIP-1beta, IL-7 and MCP-1 in women regardless of menopausal status, suggesting that these cytokines act in concert with the progression of several symptoms and various diseases.
Sawako Kinouchi, Junichi Iga, Shu-ichi Ueno, Ken Yamauchi, Shusuke Numata, Hongwei Song, Satsuki Sumitani, Sumiko Shibuya-Tayoshi, Mari Haku, Toshiyuki Yasui, Minoru Irahara, Kyoko Morita, Kazuhito Rokutan and Tetsuro Ohmori : FKBP5, SERT and COMT mRNA expressions in the peripheral leukocytes during menstruation cycle in healthy reproductive females., Neuroscience Letters, Vol.434, No.1, 124-128, 2008.
(Summary)
There have been several evidences that the mRNA expressions in the peripheral leukocytes may indicate not only physical but also psychological states. The purpose of this study is whether the mRNA expressional changes in the leukocytes are related to the mental states across the menstrual cycle in reproductive healthy female subjects. Thirty-eight female subjects (22.4+/-1.4 year-old) were participated in this study at three menstruation cycle periods (menstrual, follicular and luteal phase). The FKBP5 (FK506-binding protein gene), SERT (serotonin transporter gene) and COMT (catechol-o-methyltransferase gene) mRNA expressions in the leukocytes were determined with hormonal data. The psychological changes were assessed with self-rating hospital anxiety and depression scale (HADS). Only one thirds of subjects (n=12) had regular menstrual cycles during the experiment. So we analyzed the data from these 12 subjects. The anxiety score of each subject was changed across the menstrual cycle (Friedman test: P<0.05). The FKBP5 mRNA expression was significantly lower in the follicular phase than in the other phases but no changes were seen in either SERT or COMT mRNA expressions among the phases. In conclusion, there are differences of HADS anxiety score and FKBP5 mRNA expression in the leukocytes across the menstrual cycle but there is no correlation between anxiety scores and FKBP5 mRNA.
Hirokazu Uemura, Toshiyuki Yasui, Yuka Miyatani, Masayo Yamada, Mineyoshi Hiyoshi, Kokichi Arisawa and Minoru Irahara : Circulating osteoprotegerin is associated with age and systolic blood pressure, but not with lipid profile or fasting glucose, in postmenopausal women., Menopause, Vol.15, No.1, 180-184, 2008.
(Summary)
OBJECTIVE: Osteoprotegerin (OPG), an inhibitor of osteoclastogenesis and osteoclast activation, has been reported to be linked to vascular biology. The aim of this study was to clarify the relationships between circulating OPG and the risk factors for vascular disorders in postmenopausal women. DESIGN: Eighty Japanese postmenopausal women were enrolled in this cross-sectional study. Clinical parameters (age, number of years since menopause, body mass index, systolic and diastolic blood pressure); serum concentrations of OPG, creatinine, calcium, and phosphorus; serum lipid profile; plasma glucose; and bone mineral density of the L2-4 vertebral bodies were determined for each woman. RESULTS: In rank-order correlation analysis, serum OPG concentrations had significant positive correlations with age (r = 0.29, P = 0.03), systolic blood pressure (r = 0.45, P < 0.01), diastolic blood pressure (r = 0.34, P < 0.01), and serum creatinine (r = 0.29, P = 0.04). Serum OPG concentration also had a marginally significant negative correlation with bone mineral density of the L2-4 vertebral bodies (r = -0.25, P = 0.06). However, serum OPG did not correlate with body mass index, serum lipid profile, or plasma glucose. The correlation of serum OPG with systolic blood pressure persisted after adjustment for both age and serum creatinine. CONCLUSIONS: These results suggest that increased circulating OPG in postmenopausal women is closely related to higher systolic blood pressure, which could cause atherosclerosis.
(Keyword)
Age Factors / Atherosclerosis / Blood Glucose / Blood Pressure / Body Mass Index / Bone Density / Calcium / Creatinine / Cross-Sectional Studies / Female / Humans / Japan / Lipids / Middle Aged / Osteoprotegerin / Phosphorus / Postmenopause / Risk Factors
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Murakami, Fumi Shimizu, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Decreased expression of kisspeptin mediates acute immune/inflammatory stress-induced suppression of gonadotropin secretion in female rat., Journal of Endocrinological Investigation, Vol.31, No.7, 656-659, 2008.
(Summary)
Kisspeptin and its corresponding receptor, the G protein-coupled receptor 54, play an important role in reproductive systems. It has been suggested that reproductive disorders in metabolically disrupted animals are caused by the alteration of hypothalamic KiSS-1 systems. Immune/inflammatory challenge is also known to disrupt reproductive function. However, the effects of immune/inflammatory challenge on KiSS-1 systems have not been investigated. In this study, we showed that lipopolysaccharide (LPS) injection decreased hypothalamic KiSS-1 mRNA expression as well as plasma LH levels in ovariectomized rats. Indomethacin completely blocked the suppressive effects of LPS on LH secretion and KiSS-1 mRNA level. Furthermore, we showed that i.v. injection of kisspeptin increased plasma LH levels in LPS-administrated rats to the same degree as in saline-injected rats. These results suggest that KiSS-1 systems are sensitive to immune/inflammatory challenge conditions and transmit these signals into the central reproductive system.
Toshiyuki Yasui, Hirokazu Uemura, Minoru Irahara, Makoto Arai, Noriko Kojimahara, Ryugo Okabe, Ishii Yasutomo, Shin-ichi Tashiro and Hiroshi Sato : Differences in sensitivity to cold in Japanese men and postmenopausal women aged > or =50 years., Gender Medicine, Vol.4, No.4, 359-366, 2007.
(Summary)
Sensitivity to cold is associated with several factors, such as aging, sex, and body composition. However, no previous studies have examined the differences in sensitivity to cold in men and women or the association of hormonal levels with sensitivity to cold. The aim of the present study was to clarify both the change in sensitivity to cold with aging and the difference in sensitivity to cold between men and women. Associations were also examined between circulating hormonal concentrations and the changes with aging and differences in sensitivity. This population-based cohort study enrolled healthy Japanese men and women aged > or = 50 years. A standardized 210-item health questionnaire was used to obtain information on symptoms of sensitivity to cold. Serum concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin (SHBG) were measured. Of the 154 men and 180 women enrolled in this study, more women than men had sensitivity to cold. Whereas the percentage of men who had sensitivity to cold significantly increased with aging (P < 0.05), the percentage of women who had sensitivity to cold was already high (23.7%) at 50 to 60 years of age and did not change with aging. In men, advancing age and low body mass index (BMI) were significantly associated with sensitivity to cold (P < 0.05); however, age and BMI in women were not similarly associated. In addition, the effect of sex after adjustment for age was significant (P < 0.05), and there was also a numeric but nonsignificant effect of sex after adjustment for BMI. In men, low serum levels of the gonadal hormone FSH were significantly associated with sensitivity to cold in logistic analysis, but this association was nonsignificant after multivariate analysis. Serum concentrations of gonadal hormones and SHBG in women were not associated with sensitivity to col. The association of age with sensitivity to cold was different in men and women; the association of BMI with sensitivity to cold might be different in men and women. In addition, these changes in sensitivity to cold were not associated with circulating hormonal concentrations.
(Keyword)
Age Factors / Aged / Aged, 80 and over / Aging / Asian Continental Ancestry Group / Body Mass Index / Cohort Studies / Cold Temperature / Female / Gonadal Steroid Hormones / Gonadotropins, Pituitary / Health Surveys / Humans / Male / Middle Aged / Sex Factors / Sex Hormone-Binding Globulin / Thermosensing
Fumi Shimizu, Toshiya Matsuzaki, Takeshi Iwasa, Masahiro Minakuchi, Akira Kuwahara, Toshiyuki Yasui and Minoru Irahara : Estradiol suppresses NMU mRNA expression during sexual maturation in the female rat pituitary., International Journal of Developmental Neuroscience, Vol.26, No.3-4, 381-384, 2007.
(Summary)
Neuromedin U (NMU) suppresses food intake and gonadotropin secretion. However, the developmental transition of NMU expression in the pituitary gland and the regulation of NMU expression are unclear. The objective of this study was to examine the transition of the expression of NMU mRNA in the pituitary glands of female rats from the juvenile period to the mature period of development. Furthermore, factors such as estradiol, insulin, leptin, and inhibin A, whose expressions change throughout puberty and which affect gonadotropin secretion in pituitary cell culture, were examined. In the pituitary gland, the expression of NMU mRNA was significantly lower in 8-week-old rats than in 4- and 6-week-old rats. In the pituitary cell culture, the expressions of NMU mRNA in the estradiol- and insulin-treated groups were significantly lower than in the control group. These results suggest that the expression of NMU mRNA in the female rat pituitary is reduced as the rats develop from the pubertal to the mature period. Additionally, the reduction of NMU expression in the pituitary may be related to the increases in serum estradiol and insulin levels that occur during the pubertal period, which may negate NMU suppression of gonadotropin secretion.
Toshiyuki Yasui, Junko Tomita, Yuka Miyatani, Masayo Yamada, Hirokazu Uemura, Minoru Irahara, Makoto Arai, Noriko Kojimahara, Ryugo Okabe, Yasutomo Ishii, Shin-ichi Tashiro and Hiroshi Sato : Associations of adiponectin with sex hormone-binding globulin levels in aging male and female populations., Clinica Chimica Acta, Vol.386, No.1-2, 69-75, 2007.
(Summary)
Changes with aging in serum gonadal hormones, sex hormone-binding globulin (SHBG) and adiponectin, which are involved in insulin resistance and metabolic syndrome, are different in men and women. We examined the relationships of serum adiponectin concentrations with serum concentrations of hormones and SHBG in men and women. One hundred fifty-four men and 180 women aged from 50 to 85 years were included in the cross-sectional study. Serum concentrations of testosterone, estradiol, dehydroepiandrosterone-sulfate, SHBG and adiponectin were measured in men and women. Serum adiponectin concentration showed a significant positive correlation with serum SHBG concentration in men and women (r=0.404, p<0.0001 and r=0.348, p<0.0001, respectively). Multiple regression analysis also showed that SHBG was the significant predictor for adiponectin in men and women. Serum adiponectin concentration in men showed a significant positive correlation with total testosterone concentration, but that in women was not significantly correlated with total testosterone concentration. Both adiponectin and SHBG concentrations in men (r=-0.222, p=0.0051 and r=-0.334, p<0.0001, respectively) and women (r=-0.281, p=0.0014 and r=-0.251, p=0.0048, respectively) showed significant negative correlations with the homeostasis model assessment (HOMA) index. Correlations between adiponectin and SHBG were significantly positive in both men and women, and both adiponectin and SHBG might be involved in insulin resistance in both sexes.
(Keyword)
Adiponectin / Aged / Aged, 80 and over / Aging / Body Mass Index / Female / homeostasis / Humans / insulin resistance / Male / Metabolic Syndrome X / Middle Aged / Models, Biological / Regression Analysis / Risk Assessment / Sex Factors / Sex Hormone-Binding Globulin / Testosterone
Toshiyuki Yasui, Masahiko Maegawa, Junko Tomita, Yuka Miyatani, Masayo Yamada, Hirokazu Uemura, Shu-ichi Ueno, Shusuke Numata, Tetsuro Ohmori, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Shuichi Takeda and Minoru Irahara : Association of serum cytokine concentrations with psychological symptoms in midlife women., Journal of Reproductive Immunology, Vol.75, No.1, 56-62, 2007.
(Summary)
The purpose of the present study was to clarify the association of serum cytokine concentrations, determined using a multiplexed cytokine assay, with psychological symptoms in midlife women. Fifty-three peri- and post-menopausal women with and without psychological symptoms in Greene's climacteric scale were enrolled in this study. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Serum interleukin (IL)-6 concentration in women with psychological symptoms (2.71+/-047 pg/ml) was significantly (p=0.009) higher than that in women without psychological symptoms (0.98+/-0.18 pg/ml). Serum IL-8 concentration in women with psychological symptoms (33.4+/-8.17 pg/ml) was also significantly (p=0.022) higher than that in women without psychological symptoms (7.87+/-1.64 pg/ml). In addition, serum IL-10 concentration in women with psychological symptoms (0.74+/-0.26 pg/ml) was significantly (p=0.048) higher than that in women without psychological symptoms (0.07+/-0.04 pg/ml). Tumor necrosis factor (TNF)-alpha in serum was detected only in women with psychological symptoms. Serum IL-2 concentration in women with psychological symptoms tended (p=0.066) to be higher than that in women without psychological symptoms. No significant differences were found between levels of other cytokines in women with and without psychological symptoms. Psychological stress manifested as climacteric symptoms in midlife women may be associated with increases in serum concentrations of IL-6, IL-8, IL-10, and TNF-alpha.
Takeshi Iwasa, Toshiya Matsuzaki, Masahiro Minakuchi, Naoko Tanaka, Fumi Shimizu, Yohko Hirata, Akira Kuwahara, Toshiyuki Yasui, Masahiko Maegawa and Minoru Irahara : Diagnostic performance of serum total testosterone for Japanese patients with polycystic ovary syndrome., Endocrine Journal, Vol.54, No.2, 233-238, 2007.
(Summary)
It is reported that the incidence of clinical and biochemical hyperandrogenism may be lower in Japanese patients with PCOS. Hyperandrogenism is included as a referential but not as an essential factor in the diagnostic criteria of the Japanese Society of Obstetrics and Gynecology (JSOG 1993). However, some patients with the typical clinical features of PCOS are not diagnosed with PCOS using JSOG 1993 criteria because they do not have a high LH level, which is defined as essential for diagnosis. In this study, we compared total testosterone (T) levels between Japanese patients with PCOS diagnosed using the JSOG 1993 criteria and normal menstrual women (controls). Fifty controls and 46 patients with PCOS were enrolled in this study. Furthermore, we evaluated the sensitivity and specificity of each cut-off value of T. The mean T level of patients with PCOS was significantly higher than that of the control (86 +/- 48 vs 68 +/- 46, P<0.01), and the prevalence rates of hyperandrogenism (T >114 ng/dL; defined as the mean +2SD of the control) were 10.2% in patients with PCOS and 4% in controls. The area under the ROC curve of T was 0.72, and there was no decision threshold to diagnose PCOS by T alone with both high sensitivity and high specificity. If the threshold is set as 110 ng/dL in order to gain high specificity, 94% of women whose serum level passed the threshold will be patients with PCOS. Although T should not be used as an independent essential factor of Japanese PCOS, it might be useful as a complementary factor in order to diagnose patients who have typical clinical features of PCOS but does not fulfill the JSOG 1993 criteria for PCOS.
(Keyword)
Asian Continental Ancestry Group / Chemiluminescent Measurements / Female / Humans / Hyperandrogenism / Immunoassay / Polycystic Ovary Syndrome / Prevalence / ROC Curve / Sensitivity and Specificity / Testosterone
Takashi Kaji, Toshiyuki Yasui, Masanori Suto, Ryuji Mitani, Mikio Morine, Hirokazu Uemura, Kazuhisa Maeda and Minoru Irahara : Effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women., Bone, Vol.40, No.4, 1088-1094, 2007.
(Summary)
The aims of our study were to evaluate the changes in bone turnover markers during pregnancy and puerperium as a longitudinal study and to elucidate the effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women. The study population comprised 27 Japanese pregnant women aged 23-40 years. All women were recruited for the longitudinal study from the outpatients clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. Concentrations of serum bone-specific alkaline phosphatase (BAP), urinary cross-linked type I collagen N-telopeptides (NTx), serum NTx and urinary C-terminal telopeptide of type I collagen (CTx) were measured at 10, 26, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum. In addition, we recruited 15 pregnant women (aged 25-35 years) who were treated by bed rest before 30 weeks of pregnancy for threatened premature delivery and compared bone turnover markers in these women with those in 22 normal pregnant women (aged 22-39 years). Concentrations of serum BAP, serum NTx, urinary NTx and urinary CTx were measured at 30 and 34 weeks of pregnancy and at 4 days and 1 month postpartum. In the longitudinal study, serum BAP concentration at 1 month postpartum was significantly higher than that at any stage of pregnancy and that at 4 days postpartum. Urinary concentration of NTx increased gradually during pregnancy and showed a peak at 36 weeks of pregnancy, followed by a decrease in the postpartum period. Serum NTx concentration and urinary CTx concentration showed the same patterns of change as that of urinary NTx concentration. In the comparison study, urinary concentrations of NTx and CTx at 30 and 34 weeks of pregnancy in women with bed rest were significantly (p<0.0001 and p<0.001, respectively) higher than those in normal pregnant women. Serum NTx concentration at 34 weeks of pregnancy in women with bed rest was also significantly (p=0.0029) higher than that in normal pregnant women. Serum BAP concentration at 34 weeks of pregnancy in women with bed rest was significantly (p=0.0038) higher than that in normal pregnant women, and these high levels were maintained during puerperium. Serum BAP concentration at 34 weeks of pregnancy was significantly correlated with duration of bed rest (r=0.767, p=0.0041). Immobilization due to bed rest during pregnancy is associated with increases in bone turnover markers in pregnant and postpartum women. Concentrations of bone resorption markers increased rapidly at the start of bed rest, while the concentration of a bone formation marker gradually increased toward puerperium.
(Keyword)
Adult / Alkaline Phosphatase / Bed Rest / Biological Markers / Bone Remodeling / Calcium / Case-Control Studies / Collagen Type I / Female / Humans / Longitudinal Studies / Peptides / Postpartum Period / Pregnancy / Pregnancy Complications / Prospective Studies
Takeshi Iwasa, Toshiya Matsuzaki, Machiko Kiyokawa, Fumi Shimizu, Masahiro Minakuchi, Akira Kuwahara, Masahiko Maegawa, Toshiyuki Yasui and Minoru Irahara : The type 2 corticotrophin-releasing hormone receptor mediates orexin A-induced luteinising hormone suppression in ovariectomised rats., Journal of Neuroendocrinology, Vol.19, No.9, 732-738, 2007.
(Summary)
Orexins are thought to be regulatory factors of the arousal and sleep patterns. They also affect immune, feeding, autonomic and neuroendocrine systems. We have previously shown that intracerebroventricular (i.c.v.) injection of orexin decreases pulsatile luteinising hormone (LH) secretion in ovariectomised (OVX) rats. However, the details of this mechanism have not been fully examined. Intracerebroventricular injection of orexin A also stimulates corticotrophin-releasing hormone (CRH) systems, which have been implicated in the stress-induced suppression of reproductive function. In the present study, we investigated the role of CRH systems in orexin-induced LH suppression. OVX rats were implanted with i.c.v. and intravenous (i.v.) cannulae. After i.c.v. injection of orexin and/or CRH receptor antagonists, blood samples were collected through the i.v. cannula at 6-min intervals for 120 min for LH measurement. Intracerebroventricular injection of orexin A or B (3 nmol/2.5 microl) suppressed pulsatile LH secretion. Coadministration of orexin A and alpha-helical corticotrophic-releasing factor (CRF), a nonselective CRH receptor antagonist (13 nmol/2.5 microl), or astressin(2)B, a selective type2 (CRH-R2) CRH receptor antagonist (28 nmol/2.5 microl), partly restored pulsatile LH secretion. Orexin B-induced LH suppression was not restored by alpha-helical CRF. In addition, i.c.v. injection of orexin A increased CRH and urocortin II (UcnII), but not Ucn mRNA levels, in the hypothalamus. These findings suggest that CRH-R2 mediates orexin A-induced LH suppression and it is possible that CRH and UcnII in the hypothalamus are involved in this pathway.
The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.
Toshiyuki Yasui, Hirokazu Uemura, J Tomita, Y Miyatani, M Yamada, M Miura and Minoru Irahara : Association of serum undercarboxylated osteocalcin with serum estradiol in pre-, peri- and early post-menopausal women., Journal of Endocrinological Investigation, Vol.29, No.10, 913-918, 2006.
(Summary)
We investigated changes in serum concentration of undercarboxylated osteocalcin (ucOC), which is a sensitive marker of vitamin K status, and association of ucOC concentration with estradiol concentration in pre-, peri- and early post-menopausal women. The study population consisted of 193 pre-, peri- and post-menopausal Japanese women aged 39-66 yr. Serum ucOC concentration was measured to assess vitamin K status; serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as bone formation markers; and urine concentration of N-telopeptide was measured as a bone resorption marker. Serum estradiol and estrone concentrations were measured by a highly sensitive radioimmunoassay. Bone mineral density (BMD) was measured at the lumbar spine. Serum concentration of ucOC in peri-menopausal women was significantly (p=0.0005) higher than that in pre-menopausal women, while serum OC concentration in post-menopausal women for whom 1 yr had passed since menopause was significantly (p=0.0003, p=0.024, respectively) higher than the concentrations in pre-menopausal and peri-menopausal women. Serum ucOC concentration showed a significant negative correlation with estradiol concentration (r=-0.372, p<0.0001) and a significant positive correlation with serum FSH concentration (r=0.324, p<0.0001). Serum OC concentration was positively correlated with serum FSH concentration (r=0.317, p<0.001). The results showed that the change in ucOC concentration during the menopausal transition is different from that in OC concentration. In addition, serum ucOC concentration is closely associated not only with FSH concentration but also estradiol concentration.
(Keyword)
Adult / Aged / Aging / Alkaline Phosphatase / Bone Density / Collagen Type I / Cross-Sectional Studies / Estradiol / Female / Follicle Stimulating Hormone / Humans / Lumbar Vertebrae / Middle Aged / Osteocalcin / Peptides / Perimenopause / Postmenopause / Premenopause / Vitamin K
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17185901
We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period. The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured. Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p<0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p<0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different. The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.
Toshiyuki Yasui, Hirokazu Uemura, Junko Tomita, Yuka Miyatani, Masayo Yamada, Akira Kuwahara, Toshiya Matsuzaki, Masahiko Maegawa, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Shuichi Takeda and Minoru Irahara : Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women., The Journal of Clinical Endocrinology and Metabolism, Vol.91, No.12, 4805-4808, 2006.
(Summary)
The purpose of this study was to identify serum cytokine concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes. Serum concentrations of 17 cytokines were simultaneously measured using a multiplexed human cytokine assay in 129 premenopausal, perimenopausal, and postmenopausal women and 50 bilateral oophorectomized women. Serum IL-8 concentrations in midlife women and bilateral oophorectomized women with severe hot flashes were significantly higher than the concentrations in women without hot flashes and women with mild and moderate hot flashes. Serum macrophage inflammatory protein-1beta concentration in women with severe hot flashes was significantly higher than those in women without hot flashes and women with mild and moderate hot flashes. Serum IL-8 concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes were significantly higher than those in women without hot flashes. IL-8 may be associated with peripheral vasodilation in women with hot flashes.
Toshiyuki Yasui, Yuka Miyatani, Junko Tomita, Masayo Yamada, Hirokazu Uemura, Masakazu Miura and Minoru Irahara : Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women., Gynecological Endocrinology, Vol.22, No.8, 455-459, 2006.
(Summary)
We examined the serum level of undercarboxylated osteocalcin (uc OC), which is a sensitive marker of vitamin K status, and levels of bone turnover markers in early postmenopausal women receiving vitamin K2 treatment with or without vitamin D3. Thirty-four postmenopausal women with a mean age of 53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia and osteoporosis) were treated with vitamin K2 or with a combination of vitamin K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2 plus 0.75 microg 1alpha-hydroxyvitamin D3. Serum levels of uc OC, intact osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2 years after the start of treatment. Serum uc OC levels in women treated with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with vitamin K2 did not show significant changes, while those in women who received the combined treatment decreased significantly (p < 0.05). On the other hand, urinary DPD level in women treated with vitamin K2 did not change, while that in women who received the combined treatment tended to decrease (p < 0.1). Serum uc OC levels in early postmenopausal women who received vitamin K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2 and vitamin D3 may be effective for sustaining BMD in early postmenopausal women whose bone turnovers are highly activated.
(Keyword)
Alkaline Phosphatase / Amino Acids / Bone Density / Bone Density Conservation Agents / Bone Diseases, Metabolic / Cholecalciferol / Drug Therapy, Combination / Female / Humans / Middle Aged / Osteocalcin / Osteoporosis, Postmenopausal / Postmenopause / Vitamin K 2
Toshiyuki Yasui, Hirokazu Uemura, Junko Tomita, Yuka Umino, Masayo Yamada, Akira Kuwahara, Toshiya Matsuzaki, Masahiko Maegawa, Masakazu Miura and Minoru Irahara : Different effects of oral conjugated equine estrogens and transdermal estrogen on undercarboxylated osteocalcin concentration in postmenopausal women., Menopause, Vol.13, No.4, 651-659, 2006.
(Summary)
Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status, and triglyceride (TG) has been shown to be the main transporter of vitamin K. In the present study, we examined the difference between ucOC concentrations in postmenopausal women receiving hormone therapy (HT) with oral conjugated equine estrogens (CEE) and transdermal estradiol (TE2). We also examined the associations of ucOC concentration with estradiol concentration and TG. Ninety-two postmenopausal women were recruited for this study. Serum concentrations of ucOC, intact osteocalcin, estradiol, and TG were measured before and after 12 months of HT. Forty-six women received oral administration of 0.625 mg of CEE and 2.5 mg of medroxyprogesterone acetate daily, and 46 women received transdermal administration of 50 mug of 17beta-estradiol twice weekly and 2.5 mg of medroxyprogesterone acetate daily. The ucOC concentration in women during HT with oral CEE was significantly (P < 0.01) lower than that in women during HT with TE2. Serum estradiol concentrations during HT with CEE showed a significant inverse correlation with ucOC concentrations and the ratio of ucOC/OC during HT (P < 0.05 and P < 0.01, respectively). In addition, the serum ucOC concentration in women with an increased percentage of change in TG was significantly (P < 0.01) lower than that in women with a decreased percentage of change in TG during HT with oral CEE. The effect of HT with TE2 on ucOC concentration in women is weaker than the effect of HT with oral CEE. Suppression of ucOC concentration in postmenopausal women during HT with oral CEE might be associated with the effect of vitamin K through increased TG induced by oral CEE.
Toshiyuki Yasui, Hirokazu Uemura, Yuka Umino, Masayo Yamada, Akira Kuwahara, Toshiya Matsuzaki, Masahiko Maegawa, Hiroyuki Furumoto, Masakazu Miura and Minoru Irahara : Undercarboxylated osteocalcin concentration in postmenopausal women receiving hormone therapy daily and on alternate days., Menopause, Vol.13, No.2, 314-322, 2006.
(Summary)
Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status. The authors examined the difference in serum ucOC concentrations in postmenopausal women receiving hormone therapy (HT) daily and on alternate days, and assessed the association between ucOC and triglyceride concentrations, which are related to the transport of vitamin K. Seventy-three postmenopausal women were recruited for this study. Thirty-seven women received 0.625 mg of conjugated equine estrogens (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) daily, and 36 women received 0.625 mg of CEE and 2.5 mg of MPA on alternate days. The concentrations of serum ucOC, bone turnover markers, lipid profiles, and hormones were measured before and after 12 months of HT. The ucOC concentration in women taking HT daily was significantly (P < 0.01) lower than that in women taking HT on alternate days. Serum ucOC concentrations during HT showed a significant (P < 0.01) inverse correlation with estradiol concentrations during HT. Serum estradiol concentrations during HT showed a significant (P < 0.01) positive correlation with triglyceride concentrations during HT. Furthermore, ucOC concentrations during HT showed a significant (P < 0.05) inverse correlation with triglyceride concentrations in women receiving HT. The effect of HT on alternate days on ucOC concentration was weaker than the effect of HT daily. In addition, ucOC concentration after 12 months of HT daily might be decreased due to the conversion of ucOC to carboxylated OC by the effect of vitamin K through increased triglyceride levels induced by oral CEE.
Takeshi Iwasa, Toshiya Matsuzaki, Naoko Tanaka, Masahiro Minakuchi, Fumi Shimizu, Rie Ogata, Machiko Kiyokawa, Masahiko Maegawa, Toshiyuki Yasui, Akira Kuwahara and Minoru Irahara : Comparison and problems of measured values of LH, FSH, and PRL among measurement systems., Endocrine Journal, Vol.53, No.1, 101-109, 2006.
(Summary)
Several measurement systems are used for LH, FSH, and PRL in Japan, but the comparison of the measured values is difficult in some cases. In this study, we compared the measured values of 3 types of measurement systems widely used in Japan, SPAC-S, ARCHITECT, and Centaur, in females with a normal menstrual cycle and with various ovulatory disorders. Variant LH was discriminated by the criterion, SPAC-S LH/ARCHITECT LH ratio <0.5. Excluding the variant LH, the correlation of the measured LH values among the measurement systems was high, 0.94-0.99, and the value measured by ARCHITECT LH and Centaur LH was slightly higher than that measured by SPAC-S LH. As for FSH, the correlation was also high, 0.94-1.00, and the value measured by ARCHITECT FSH and Centaur FSH was slightly lower than that measured by SPAC-S FSH. The important judgment criterion of polycystic ovary syndrome (PCOS), a high level of LH relative to FSH, has been set to 1.0 or higher LH/FSH using SPAC-S. When the regression line of the LH/FSH ratio among the measurement systems was investigated, it can be said that 1.25 or higher by ARCHITECT and 1.40 or higher by Centaur are appropriate for the judgment criteria of a high level of LH relative to FSH. As for PRL, the correlation was high, 0.96-0.99, but the value showed large differences among the systems. For the diagnosis of hyperprolactinemia, the higher limit of the normal range may be 15 ng/mL for SPAC-S, 30 ng/mL for ARCHITECT, and 24 ng/mL for Centaur.
Hirokazu Uemura, Toshiyuki Yasui, Y Umino, M Yamada, Akira Kuwahara, Toshiya Matsuzaki, M Maegawa and Minoru Irahara : Regulatory factors on parathyroid hormone-related peptide production by primary culture of lactating rat mammary gland., Hormone and Metabolic Research, Vol.37, No.8, 463-467, 2005.
(Summary)
Parathyroid hormone-related protein (PTHrP) is a major cause of humoral hypercalcemia of malignancy, but has also been widely found in fetal and adult non-neoplastic tissues. Lactating mammary gland has been shown to produce large amounts of PTHrP, and high levels of PTHrP have been measured in milk. We have examined the influences of several substances on the secretion of two different forms of PTHrP by primary cultures of mammary cells isolated from lactating rats to examine the regulatory mechanisms of PTHrP production by mammary cells. Primary cultures of mammary cells seeded at a density of 10(5) cells per 35 mm culture dish were grown on collagen gels. First, after cells were left 24 hours for attachment and incubated in 2 % FCS containing medium with for 12 hours, PTHrP (1 - 87) secretions were measured in conditioned medium with hormone supplementation for 1, 24 and 48 hours. Progesterone (10(-7) - 10(-5) mol/l) significantly suppressed PTHrP (1 - 87) secretion in a dose-dependent manner (p < 0.01), while 17beta-estradiol had no influence on PTHrP (1 - 87) secretion. Prolactin, a known stimulator of PTHrP expression in vivo, had no effect in this in vitro model. Second, PTHrP (1 - 34) secretion levels from confluent lactating mammary cells for 24 hours were evaluated. The same results were obtained in the case of PTHrP (1 - 87) secretion from non-confluent cells. Furthermore, dexamethasone (10(-6) mol/l) significantly suppressed PTHrP (1 - 34) secretion (p < 0.01). These results suggest that PTHrP production from the lactating mammary gland is suppressed by progesterone as well as dexamethasone. Progesterone dramatically falls after delivery, thus possibly accelerating PTHrP production by lactating mammary glands and resulting in considerable amounts of PTHrP secreted into the milk.
Hirokazu Uemura, M Kamada, M Maegawa, Y Ohmoto, K Murata, Akira Kuwahara, Toshiya Matsuzaki, Toshiyuki Yasui, T Takeji and Minoru Irahara : Effect of hormone replacement therapy on the production of bone-resorbing cytokines by peripheral blood cells in postmenopausal women., Hormone and Metabolic Research, Vol.37, No.4, 226-230, 2005.
(Summary)
We studied the effects of hormone replacement therapy (HRT) with estrogen on postmenopausal changes in the production of bone-resorbing cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta were significantly higher in women in their 40s and 50s and in postmenopausal women than in women in their teens, 20s and 30s, while the levels of TNFalpha did not show any changes related to age. Both levels in HRT-treated women were significantly lower than those in untreated women at almost every postmenopausal stage. In a prospective study, HRT induced significant declines in both levels. These results show that estrogen decreases the accelerated production of IL-1beta and reduces the production of TNFalpha in postmenopausal women at each postmenopausal stage, even in late-postmenopausal women.
Toshiyuki Yasui, Yuka Umino, Masaya Takikawa, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Masahiko Maegawa, Hiroyuki Furumoto, Masakazu Miura and Minoru Irahara : Effects of postmenopausal hormone therapy every day and every other day on lipid levels according to difference in body mass index, Menopause, Vol.12, No.2, 223-231, 2005.
(Summary)
The objective of this study was to determine the effects of postmenopausal estrogen and progestogen therapy (EPT) every day and every other day on lipid levels, particularly triglyceride (TG) levels, according to difference in body mass index (BMI). Ninety-nine postmenopausal women (mean age, 53.9 +/- 5.6 years; mean BMI, 22.8 +/- 2.8 kg/m) were randomly treated with EPT every other day or every day for 1 year. Fifty women received oral administration of 0.625 mg of conjugated equine estrogen (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) every other day, and 49 women received oral administration of 0.625 mg of CEE and 2.5 mg of MPA every day. Blood samples were collected at baseline and after 1 year of therapy for measurement of fasting TG, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and apolipoproteins. Data from 88 of the 99 postmenopausal women were used for analysis. In women whose BMI was 25 kg/m or higher, TG levels during EPT every day increased by 26.8%, while TG levels during EPT every other day decreased by 12.3%. There was a significant (P < 0.05) difference between percentage changes in TG during EPT every day and every other day. In women whose BMI was less than 25 kg/m, TG levels during EPT every day increased by 21.7%, while during EPT every other day TG levels did not change. The mean levels of estradiol during EPT every day in women whose BMI was less than 25 kg/m and in women whose BMI was 25 kg/m or higher were 28.5 and 38.7 pg/mL, respectively, the difference between these levels was significant (P < 0.01). On the other hand, there was no significant difference between levels of estradiol during EPT every other day in these two BMI groups. Triglyceride levels during EPT every day with conventional doses of CEE and MPA increased more in overweight and obese postmenopausal women in association with increased estrogen levels.
Toshiyuki Yasui, Hirokazu Uemura, Yuka Umino, Masaya Takikawa, Seiichiro Saito, Akira Kuwahara, Toshiya Matsuzaki, Masahiko Maegawa, Hiroyuki Furumoto, Masakazu Miura and Minoru Irahara : Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women, Maturitas, Vol.50, No.1, 19-29, 2005.
(Summary)
The objective of this study was to determine the relationships of serum estrogen levels after hormone replacement therapy (HRT) every other day and every day with body mass index (BMI) in postmenopausal and bilaterally ovariectomized women. Eighty-six postmenopausal and 51 bilaterally ovariectomized women who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly treated with HRT every other day or every day. Seventy-four patients received oral administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) every other day, and 63 patients received oral administration of 0.625 mg CEE and 2.5 mg MPA every day as conventional HRT. Eighty-four postmenopausal and 50 bilaterally ovariectomized women completed this study. Serum estradiol levels after HRT every day in postmenopausal and bilaterally ovariectomized women were significantly (P <0.05 and <0.01, respectively) correlated with BMI, while those after HRT every other day were not correlated with BMI. The differences between estradiol levels after 12 months of treatment and initial estradiol levels were also significantly (P <0.01) correlated with BMI in both postmenopausal and bilaterally ovariectomized women who received HRT every day but not in women who received HRT every other day. Serum estrone level after HRT every day and the difference between estrone level after 12 months of treatment and initial estrone level were significantly (P <0.05 and <0.01, respectively) correlated with BMI only in bilaterally ovariectomized women. Serum estradiol levels after HRT every day increase more in overweight women than in non-overweight postmenopausal and bilaterally ovariectomized women. The results of the present study regarding the relationship between serum estradiol levels after HRT and BMI should be useful for selecting dosages of drugs to be used in HRT.
(Keyword)
Serum estrogen level / Hormone replacement therapy / Ovariectomized women
Toshiyuki Yasui, Hirokazu Uemura, Yuka Umino, Masaya Takikawa, Akira Kuwahara, Seiichiro Saito, Toshiya Matsuzaki, Masahiko Maegawa, Hiroyuki Furumoto, Masakazu Miura and Minoru Irahara : Serum estradiol concentration as measured by HPLC-RIA and bone mineral density in postmenopausal women during hormone replacement therapy, Hormone Research, Vol.61, No.3, 117-125, 2004.
(Summary)
To determine the relationship between the serum estradiol concentration and bone mineral density (BMD) of the lumbar spine in postmenopausal women treated with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) every other day and every day. Eighty-four postmenopausal women were randomly treated with hormone replacement therapy (HRT) every other day and every day. Forty-seven women received oral administration of 0.625 mg CEE and 2.5 mg MPA every other day, and 37 women received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. BMD of the lumbar spine at 12 months and serum concentrations of estradiol and estrone at 6 and 12 months after treatment were examined. The estradiol concentration in subjects treated every other day showed a significant (p < 0.001) positive correlation with the percentage change in lumbar BMD, while that in subjects treated every day was not correlated with the percentage change in BMD. The differences between serum estradiol concentrations after 12 months of treatment and initial serum estradiol values in women treated every other day and every day also showed a significant (p < 0.01 and 0.05, respectively) positive correlation with percentage changes in BMD. In women treated every other day, body mass index (BMI) in the subjects in whom BMD did not increase was significantly (p < 0.01) lower than that in the subjects in whom BMD did increase. The serum estradiol concentration in women treated every other day has a strong positive correlation with the percentage change in lumbar BMD, but a higher estradiol concentration may be needed for women in whom BMD did not increase with HRT every other day after due consideration of individual characteristics such as BMI.
Hirokazu Uemura, Toshiyuki Yasui, Yuka Umino, Hirobumi Niki, Masaya Takikawa, Seiichiro Saito, Hiroyuki Furumoto and Minoru Irahara : Circulating osteoprotegerin in women during GnRH-agonist treatment and their relationships with mineral components and biomarkers of bone turnover, Bone, Vol.33, No.5, 860-866, 2003.
(Summary)
A novel cytokine termed osteoprotegerin (OPG) that is also called osteoclastogenesis-inhibitory factor, which inhibits osteoclast maturation and activity, was recently isolated. In order to determine the influence of estrogen deficiency on the levels of circulating OPG in women, we studied the changes in the levels of circulating OPG in 10 Japanese women ages 25-49 (mean +/- SD, 34.0 +/- 6.9) years with endometriosis receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We further analyzed whether the levels of circulating OPG have relations with the levels of the biomarkers of bone turnover or those of circulating mineral components in these patients during GnRH-a treatment. The patients were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. In all patients, the concentrations of serum estradiol decreased after 6 months of GnRH-a treatment. The bone mineral density of the lumber spines in these patients significantly (P < 0.01) decreased (percentage change: mean +/- SD, -5.4 +/- 2.1%), while circulating OPG levels significantly (P < 0.01) increased after 6 months of treatment. The values of circulating OPG had significant correlations with those of urinary pyridinoline (r = 0.59, P < 0.01), urinary deoxypylridinoline (Dpd) (r = 0.46, P < 0.05), and serum alkaline phosphatase (r = 0.66, P < 0.01) but not with those of serum carboxy-terminal propeptide of type I procollagen during GnRH-a treatment. The values of circulating OPG also correlated significantly with those of serum calcium (Ca) and phosphorus (P) (r = 0.65 and 0.72, P < 0.01). Further analyses revealed that the percentage change in the value of circulating OPG had a significant correlation with that of urinary Dpd (r = 0.84, P < 0.01). These results suggest that circulating OPG levels rise against the increase in osteoblastic bone resorption and circulating Ca levels in the case of estrogen deficiency, possibly as a compensatory mechanism serving to limit circulating Ca levels and bone density.
(Keyword)
Adult / Bone Density / Bone Remodeling / Endometriosis / Female / Glycoproteins / Gonadotropin-Releasing Hormone / Humans / Leuprolide / Middle Aged / Osteoprotegerin / Receptors, Cytoplasmic and Nuclear / Receptors, Tumor Necrosis Factor / Statistics, Nonparametric
Toshiyuki Yasui, Hirokazu Uemura, Masaya Takikawa and Minoru Irahara : Hormone replacement therapy in postmenopausal women., The Journal of Medical Investigation : JMI, Vol.50, No.3-4, 136-145, 2003.
(Summary)
Hormone replacement therapy (HRT) is effective for relieving vasomotor symptoms such as hot flash and vaginal atrophy and for preventing bone loss in postmenopausal and bilaterally ovariectomized women. However, compliance with HRT was reported to be low despite the benefits of HRT. In addition, results of several recent large-scale randomized clinical trials have demonstrated that protection from cardiovascular disease is not an indication for treatment with estrogen and progestin in postmenopausal women. Recent studies have demonstrated that low-dose HRT is safe and effective for prevention of postmenopausal bone loss. Low-dose HRT has also been shown to be effective for reducing the number and severity of hot flashes, improving vaginal atrophy, and inducing favorable changes in lipids, lipoproteins and hemostatic factors. Moreover, low-dose regimens of CEE (conjugated equine estrogen) and MPA (medroxyprogesterone acetate) result in higher rates of amenorrhea and endometrial protection compared with the conventional dose of HRT. Low-dose HRT may improve the compliance rate and may be more effective than conventional-dose HRT for reducing the risk of breast cancer. On the other hand, it has been shown that transdermal estrogen treatment reduces the incidence and severity of hot flashes and that long-term treatment with transdermally administered estrogen is effective for protection against osteoporosis. Transdermal administration of estrogen is recommended in postmenopausal women with hypertriglycemia because this treatment has little effect on lipid metabolism. The serum estradiol level was reported to be closely related to estrogenic effects on various tissues. An HRT regimen should be based on the needs of each patient. Serum estradiol levels in women should be maintained at appropriate levels for benefits and not be excessively high in order to prevent side effects. Selection of the most appropriate regimen of HRT (dose, route of administration and schedule) for the needs of the individual are important factors to increase the rate of continuation with HRT.
Toshiyuki Yasui, Toshiya Matsuzaki, Kenjiro Ushigoe, Akira Kuwahara, Masahiko Maegawa, Hiroyuki Furumoto, Toshihiro Aono and Minoru Irahara : Stimulatory Effect of the Herbal Medicine Keishi-bukuryo-gan on a Cytokine-induced Neutrophil Chemoattractant,in Rat Ovarian Cell Culture, American Journal of Reproductive Immunology, Vol.50, No.1, 90-97, 2003.
(Summary)
We investigated the effects of Keishi-bukuryo-gan, a Japanese herbal medicine, and its crude ingredients in relation to the production of cytokine-induced neutrophil chemoattractant (CINC/gro), interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha), which are known to stimulate the secretion of CINC/gro in the ovulatory process, and the effects of Keishi-bukuryo-gan with those of Toki-shakuyaku-san, which has been shown to have an effect on the ovary. We cultured whole ovarian dispersates from immature (3-week-old) female rats with Keishi-bukuryo-gan, Toki-shakuyaku-san and crude ingredients of Keishi-bukuryo-gan. The contents of CINC/gro, IL-1beta and TNFalpha in the cultured media were determined by enzyme-linked immunosorbent assay (ELISA). Keishi-bukuryo-gan stimulated the secretion of CINC/gro in a dose-dependent manner, and the secretion of CINC/gro into the culture medium increased significantly at concentrations of Keishi-bukuryo-gan of 10 and 100 microg/mL (P < 0.001). The stimulatory effect of Keishi-bukuryo-gan on the production of CINC/gro is significantly (P < 0.001) stronger than that of Toki-shakuyaku-san at the same concentrations of 100 microg/mL. In addition, Keishi-bukuryo-gan stimulated the secretion of IL-1beta in a dose-dependent manner, while it did not stimulate the secretion of TNFalpha even at a concentration of 100 microg/mL. Moutan Cortex, Paeoniae Radix and Persicae Semen, which are crude ingredients of Keishi-bukuryo-gan, enhanced the secretion of CINC/gro significantly (P < 0.01) in cultured whole ovarian dispersates. These results show that Keishi-bukuryo-gan can stimulate the secretion of CINC/gro as well as the production of IL-1beta and that this stimulatory effect of Keishi-bukuryo-gan was significantly stronger than that of Toki-shakuyaku-san in immature rat ovarian cell culture.
Toshiyuki Yasui, Toshiya Matsuzaki, Rie Ogata, Machiko Kiyokawa, Kenjiro Ushigoe, Hirokazu Uemura, Akira Kuwahara, Hiroshi Ikawa, Masahiko Maegawa, Hiroyuki Furumoto, Toshihiro Aono and Minoru Irahara : The herbal medicine Unkei-to stimulates the secretion of a cytokine-induced neutrophil chemoattractant, CINC/gro, in the rat ovarian cell culture, American Journal of Reproductive Immunology, Vol.49, No.1, 14-20, 2003.
(Summary)
We investigated the ovulation-inducing effects of Unkei-to, a Japanese herbal medicine, in relation to the production of sex steroid hormones (17beta-estradiol and progesterone), cytokine-induced neutrophil chemoattractant (CINC/gro), interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in the rat ovarian cell culture. Unkei-to at a concentration of 100 microg/mL significantly stimulated the secretions of 17beta-estradiol and progesterone (P < 0.01) in cultured whole ovarian dispersates. Unkei-to also enhanced the secretion of CINC/gro in a dose-dependent manner, and the secretions of CINC/gro increased significantly at concentrations of 10 and 100 microg/mL (P < 0.01). These stimulatory effects of Unkei-to on steroidgenesis and CINC/gro production are very similar to those of another Japanese herbal medicine, Toki-Shakuyaku-san. In addition, Unkei-to significantly (P < 0.01) enhanced the secretions of both IL-1beta and TNF-alpha, which are known to stimulate the secretion of CINC/gro in the ovulatory process, at concentrations of 10 and 100 microg/mL. The stimulatory effect of Unkei-to at a concentration of 100 microg/mL on IL-1beta/was significantly (P < 0.01) lower than that of Toki-Shakuyaku-san, while the stimulatory effects of these two herbal medicines at a concentration of 100 microg/mL on TNF-alpha were similar. These results show that Unkei-to can stimulate ovarian steroidgenesis and the ovulatory process by inducing the secretion of CINC/gro with IL-1beta and TNF-alpha in vitro. Unkei-to has stimulatory effects on both steroidgenesis and the ovulatory process in the ovary as well as a stimulatory effect on the hypothalamus-pituitary axis, and it may be useful for treating patients with ovulatory disorders.
Masayo Yamada, Toshiya Matsuzaki, Takeshi Iwasa, Fumi Shimizu, Naoko Tanaka, Rie Ogawa, Machiko Kiyokawa, Toshiyuki Yasui, Minoru Irahara and Toshihiro Aono : Serum Leptin Levels in Women throughout Life;Relationship to Body Mass Index and Serum Estradiol Levels, Japanese Journal of Reproductive Endocrinology, Vol.8, 55-60, 2003.
(Keyword)
Leptin / Estradiol / Body mass index
150.
Hirokazu Uemura, Toshiyuki Yasui, Machiko Kiyokawa, Akira Kuwahara, Hiroshi Ikawa, Toshiya Matsuzaki, Masahiko Maegawa, Hiroyuki Furumoto and Minoru Irahara : Serum osteoprotegerin/osteoclastogenesis-Inhibitory factor during pregnancy and lactation and their relationships with calcium regulating hormones and bone turnover markers, The Journal of Endocrinology, Vol.174, No.2, 353-359, 2002.
(Summary)
Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.
Mitsuhiro Kimura, Minoru Irahara, Toshiyuki Yasui, Seiichiro Saito, Michiko Tezuka, Shuji Yamano, Masaharu Kamada and Toshihiro Aono : The Obesity in Bilateral Ovariectomized Rats is Related to a Decrease in the Expression of Leptin Receptors in the Brain, Biochemical and Biophysical Research Communications, Vol.290, No.4, 1349-1353, 2002.
(Summary)
We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly (P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly (P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly (P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 beta-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight.
(Keyword)
leptin receptor / long form / short form / estrogen
Michiko Tezuka, Minoru Irahara, Koji Ogura, Machiko Kiyokawa, Takao Tamura, Toshiya Matsuzaki, Toshiyuki Yasui and Toshihiro Aono : Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells, European Journal of Endocrinology, Vol.146, No.2, 261-266, 2002.
Minoru Irahara, Hirokazu Uemura, Toshiyuki Yasui, Hiromi Kinoshita, Masayo Yamada, Michiko Tezuka, Machiko Kiyokawa, Masaharu Kamada and Toshihiro Aono : Efficacy of every-other-day administration of conjugated equine estrogen and medroxyprogesterone acetate on gonadotropin-releasing hormone agonists treatment in women with endometriosis, Gynecologic and Obstetric Investigation, Vol.52, No.4, 217-222, 2001.
(Summary)
We performed a randomized controlled study to determine the efficacy of add-backed therapy by every-other-day administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) on GnRH agonists (GnRH-a) treatment in Japanese women with symptomatic endometriosis. At the end of treatment, serum estrone and estradiol levels in the add-back group (n = 11) were significantly higher than those in the control group (n = 10). The assessment of Beecham classification by bimanual examination, serum CA-125 levels, and the frequency of genital bleeding revealed no significant differences between the two groups. The add-back group showed reduced Kupperman indices relative to those of the control group, and could prevent the loss of bone density. These findings led to a conclusion that GnRH-a therapy added back by every-other-day administration of 0.625 mg CEE and 2.5 mg MPA was a safe and effective treatment for Japanese women with endometriosis.
Keizo Deguchi, Masaharu Kamada, Minoru Irahara, Masahiko Maegawa, Satoshi Yamamoto, Yasukazu Ohmoto, Kaoru Murata, Toshiyuki Yasui, Shuji Yamano and Toshihiro Aono : Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy, Menopause, Vol.8, No.4, 266-273, 2001.
(Summary)
An appropriate defense against infective agents or malignant cells is attributed to the exquisitely balanced T helper 1 type (cellular) and T helper 2 type (humoral) immune reactions. We investigated the effect of hormone replacement therapy (HRT) on postmenopausal changes in the production of interferon (IFN)-gamma and interleukin (IL)-10, a type 1 and a type 2 cytokine, respectively. Both cytokines were measured by ELISA in the supernatant of lipopolysaccharide-stimulated whole blood cells from 72 untreated and 44 HRT-treated women. Thirteen women were examined before and during HRT. The production of IFN-gamma in women in their 40s and in postmenopausal women was significantly higher compared with that of younger women. However, IFN-gamma fell to the lowest level in the late postmenopausal stage, whereas the production of IL-10 increased gradually with age and in parallel with the postmenopausal period. Thus, in women in the mid-and late postmenopausal period, excessive production of type 2 cytokine (IL-10) compared with type 1 cytokine (IFN-gamma) occurred. The IFN-gamma levels of women on HRT were significantly lower than those of untreated women in the early and mid-postmenopausal stages, and IL-10 levels of women on HRT were significantly lower than those of untreated women in the mid-and late postmenopausal stages. HRT induced a significant decrease in the production of IL-10 and tended to lower the level of IFN-gamma. Production of IL-10 is augmented in postmenopausal women. HRT probably prevents postmenopausal women from an aberration of the immune system by improving the balance of type 1 and type 2 immune reactions.
Koji Ogura, Minoru Irahara, Machiko Kiyokawa, Michiko Tezuka, Toshiya Matsuzaki, Toshiyuki Yasui, Masaharu Kamada and Toshihiro Aono : Effects of leptin on secretion of LH and FSH from primary cultured female rat pituitary cells, European Journal of Endocrinology, Vol.144, No.6, 653-658, 2001.
(Summary)
Leptin, which is the product of the obese gene, is believed to play important roles in pubertal development and reproductive function in females. In a study using adult male rats, it was found that leptin stimulated secretion of gonadotropin from the pituitary in a dose-related manner. However, there has been no such study in female rats. To investigate the effects of leptin on the production of LH and FSH from the pituitary in female rats, using primary cultured pituitary cells. In this study, we determined body weight, serum leptin concentration and serum estradiol (E(2)) concentration in female Wistar rats at 3, 5, 6, 7, 9 and 11 weeks of age, and cultured pituitary cells from 6-week-old female Wistar rats with leptin (0--10(-7) mol/l) and GnRH (0 or 10(-8) mol/l). Then basal and GnRH-stimulated extra- and intracellular LH and FSH were assayed by RIA. Serum leptin concentration increased with increases in body weight and E(2) concentration. The pubertal serum leptin concentration was about 10(-10) mol/l. At a lower or moderate concentration, leptin produced dose-related increases in both basal and GnRH-stimulated extra- and intracellular LH and FSH in pituitary cells. At a concentration of 10 mol/l, leptin significantly (P<0.05) stimulated both basal and GnRH-stimulated extra- and intracellular LH and FSH. However, at greater concentrations, these effects diminished. These results indicated that leptin induced pituitary cells to produce and secrete both LH and FSH, with or without GnRH. The concentration of leptin that induced the greatest production of gonadotropins by pituitary cells was 10(-10) mol/l, which was the same as the physiological pubertal concentration. Leptin may be involved in the onset of puberty. It is also conceivable that leptin may be a cause of ovulatory failure, not only in weight loss but also in weight gain.
Minoru Irahara, Takao Tamura, Toshiya Matsuzaki, Seiichiro Saito, Toshiyuki Yasui, Shuji Yamano, Masaharu Kamada and Toshihiro Aono : Orexin-A Suppresses the Pulsatile Secretion of Luteinizing Hormone via β-Endorphin, Biochemical and Biophysical Research Communications, Vol.281, No.1, 232-236, 2001.
(Summary)
Orexins, the novel hypothalamic neuropeptides that stimulate feeding behavior, have been shown to suppress the pulsatile secretion of LH in ovariectomized rats. However, the mechanism of this action is still not clear. We examined the effect of naloxone, a specific opioid antagonist, on the suppression of the pulsatile secretion of LH by orexins to determine whether beta-endorphin is involved in this suppressive effect. We administered orexins intracerebroventricularly and injected naloxone intravenously in ovariectomized rats, and we measured the serum LH concentration to analyze the pulsatile secretion. Administration of orexin-A significantly reduced the mean LH concentration and the pulse frequency, but coadministration of naloxone significantly restored the mean LH concentration and the pulse frequency. Administration of orexin-B also significantly reduced the mean LH concentration and the pulse frequency, and coadministration of naloxone did not restore them. These results indicate that orexin-A, but not orexin-B, suppresses GnRH secretion via beta-endorphin.
Masaharu Kamada, Minoru Irahara, Masahiko Maegawa, Yasukazu Ohmoto, Takashi Takeji, Toshiyuki Yasui and Toshihiro Aono : Postmenopausal changes in serum cytokine levels and hormone replacement therapy, American Journal of Obstetrics and Gynecology, Vol.184, No.3, 309-314, 2001.
(Summary)
Our purpose was to investigate the effect of hormone replacement therapy on the postmenopausal changes in serum cytokine levels. Fifteen cytokines were measured by an enzyme-linked immunosorbent assay in 97 untreated and hormone replacement-treated women. Thirteen women were examined before and during hormone replacement therapy. Serum concentrations of macrophage colony-stimulating factor were significantly (P < .05) lower during the early postmenopausal period (< or = 10 years) than the values in premenopause and the elevated levels in the late postmenopausal period (< or = 30 years). A significant increase in tumor necrosis factor alpha and a decline in transforming growth factor beta1 were found in late postmenopausal women. Serum levels of macrophage colony-stimulating factor in women receiving hormone replacement therapy were significantly higher than those in untreated postmenopausal women. Furthermore, hormone replacement therapy induced a significant (P < .01) increase in serum levels of macrophage colony-stimulating factor, whereas serum levels of other cytokines were not affected. It is well documented that macrophage colony-stimulating factor lowers serum cholesterol concentrations and prevents atherosclerosis. Inducing the production of macrophage colony-stimulating factor is a possible additional mechanism of hormone replacement therapy in mediating the antiatherogenic effect.
Masaharu Kamada, Minoru Irahara, Masahiko Maegawa, Toshiyuki Yasui, Shuji Yamano, Masayo Yamada, Mitiko Tezuka, Yuka Kasai, Keiichi Deguchi, Yasukazu Ohmoto and Toshihiro Aono : B cell subsets in postmenopausal women and the effect of hormone replacement therapy, Maturitas, Vol.37, No.3, 173-180, 2001.
(Summary)
In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5+ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5+) and conventional CD5- B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1alpha were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. In late postmenopausal women (> or = 30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.
Hiromi Kinoshita, Toshiyuki Yasui, Kenjiro Ushigoe, Minoru Irahara, Minoru Tanaka, Kunio Nakashima and Toshihiro Aono : Expression of Ovarian Prolactin Receptor in Relation to Hormonal Changes during Induction of Ovulation in the Rat, Gynecologic and Obstetric Investigation, Vol.52, No.2, 132-138, 2001.
(Summary)
We examined the relationships between the expression of the short and long forms of the prolactin (PRL) receptor (PRLR) mRNA in the ovary and changes in the levels of serum hormones such as sex steroid hormones and PRL during induction of ovulation in the rat. The expression of both forms of PRLR mRNA in the ovary was examined by Northern blot analysis in immature female rats treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Ovarian tissues and blood samples were obtained before treatment, 24 and 48 h after PMSG injection and 4, 6, 8, 12, 24 and 48 h after hCG treatment. Serum levels of 17beta-estradiol, progesterone and PRL were determined by radioimmunoassay. Serum levels of 17beta-estradiol rapidly increased to a maximal level 48 h after PMSG injection and then rapidly declined until 4 h after hCG injection. Serum levels of progesterone gradually increased after PMSG treatment, markedly increased to 114.2 nmol/l 8 h after hCG treatment and remained high until 48 h after hCG treatment. The serum level of PRL peaked at 66.2 microg/l (p < 0.01) 48 h after PMSG injection, and a temporary decrease after hCG treatment was followed by a continuously high level from 8 to 48 h. The expression of the long form of PRLR mRNA increased significantly (p < 0.01) to 688% of the control level after PMSG treatment, while that of the short form increased to only 184% of the control level. The expression of the long form of PRLR-mRNA rapidly declined until 6 h and then gradually increased until 48 h after hCG treatment. On the other hand, the expression of the short form of PRLR mRNA decreased to a nadir 12 h after hCG injection and then increased significantly (p < 0.01) to 142% of the control level. Our results showed that the changes in the short and long forms of PRLR mRNA differed in a time-specific manner and that these two forms are involved in different functions in the rat ovary during induction of ovulation. It is thought that the long form of PRLR mRNA is involved in folliculogenesis, while the short form of PRLR mRNA may play an important role in the formation and maintenance of the corpus luteum in the rat ovulatory cycle.
(Keyword)
Prolactin / Prolactin receptor / Overy / Induction of ovulation
Masaharu Kamada, Minoru Irahara, Masahiko Maegawa, Yasukazu Ohmoto, Kaoru Murata, Toshiyuki Yasui, Shuji Yamano and Toshihiro Aono : Transient Increase in the Levels of T-Helper 1 Cytokines in Postmenopausal Women and the Effects of Hormone Replacement Therapy, Gynecologic and Obstetric Investigation, Vol.52, No.2, 82-88, 2001.
(Summary)
The aim of this study was to determine, at least in part, T-cell function in postmenopausal women and the effects of hormone replacement therapy (HRT). Levels of T-helper 1 (Th1) cytokines (IL-2 and IFN-gamma) and T-helper 2 (Th2) cytokines (IL-4 and IL-10) produced by phytohemagglutinin-stimulated whole blood cells from 72 untreated and 44 HRT-treated women were measured by ELISA. Thirteen of the 44 HRT-treated women were examined before and during HRT. The production of IL-2 increased gradually with advance of the postmenopausal period. The levels of IL-2 in women in the early (< or =10 years) and mid (>10 and <30 years) postmenopausal stages were significantly higher than those in women in their second, third and fourth decades. The level in women in the late (> or =30 years) postmenopausal stage, however, was significantly lower than those in women in the early and mid postmenopausal stages. The level of IFN-gamma was highest in women in the mid postmenopausal stage. On the other hand, the levels of Th2 cytokines did not change with age or after menopause until the mid postmenopausal period but were significantly lower in women in the late postmenopausal stage. IFN-gamma levels in women on HRT were significantly lower than those in untreated postmenopausal women at all postmenopausal stages. HRT induced a significant decrease in the production of IL-2 and IL-4. In conclusion, production of Th1 cytokines is augmented in women after menopause. HRT prevents this increase, thereby improving the aberration of Th1/Th2 balance that is implicated in an inadequate immune response and pathological conditions.
Toshiyuki Yasui, Hirokazu Uemura, Michiko Tezuka, Masayo Yamada, Minoru Irahara, Masakazu Miura and Toshihiro Aono : Biological Effects of Hormone Replacement Therapy in Relation to Serum Estradiol Levels, Hormone Research, Vol.56, No.1-2, 38-44, 2001.
(Summary)
Tissues in various parts of the body have different sensitivities to estradiol. However, it is very difficult to measure the serum estradiol levels precisely in women receiving oral conjugated equine estrogen, which is a mixture of estrogens. In the present study, we precisely measured the serum levels of estradiol in postmenopausal women undergoing hormone replacement therapy (HRT), and we clarified the relationships between serum estradiol levels and the effects of HRT on the Kupperman index, bone mineral density (BMD), serum gonadotropin, lipid metabolism and unscheduled bleeding as the clinical endpoints. Sixty-eight postmenopausal or bilaterally ovariectomized women, aged 30-64 years, who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly assigned to two groups: one group of 34 patients who received oral administration of 0.625 mg conjugated equine estrogen (CEE, Premarin, Wyeth) and 2.5 mg medroxyprogesterone acetate (MPA, Provera, Upjohn) every other day, and another group of 34 patients who received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. All subjects were re-classified into three groups according to the serum estradiol level after 12 months of treatment: (1) low estradiol group (<15 pg/ml, n = 25); (2) middle estradiol group (> or =15 and <25 pg/ml, n = 27), and (3) high estradiol group (> or =25 pg/ml, n = 16). We examined the relationships between serum estradiol level and the effects of estradiol on the Kupperman index, BMD, serum gonadotropin levels, lipid profile and unscheduled bleeding in these three groups. RESULTS obtained by using our newly developed high-performance liquid chromatography (HPLC)-radioimmunoassay (RIA) system clearly showed that the effects on each tissue in postmenopausal women receiving oral CEE and MPA is closely related to estradiol level. The effects of HRT on BMD, serum gonadotropin levels and lipid profile were shown to be clearly dependent on the serum estradiol levels, while the effect of HRT on the Kupperman index was independent of the serum estradiol level. Furthermore, it was also found that a very low concentration of estradiol (<15 pg/ml) was sufficient to suppress the serum LH and FSH levels and to relieve vasomotor symptoms, and that the minimum concentration of estradiol required to increase BMD was 15 pg/ml. On the other hand, the level of estradiol required to reduce total cholesterol, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo B) was found to be more than 25 pg/ml, while the level required to increase high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) was at least 15 pg/ml. The incidence of unscheduled bleeding was also lower in the low estradiol group than in the other estradiol level groups. These results suggest that the different clinical endpoints have different response thresholds and thus reflect tissue sensitivity to estradiol levels achieved by HRT.
Minoru Irahara, Toshiyuki Yasui, Michiko Tezuka, Kenjiro Ushigoe, Shuji Yamano, Masahiko Kamada and Toshihiro Aono : Evidence that Toki-shakuyaku-san and its Ingredients Enhance the Secretion of a Cytokine-Induced Neutrophil Chemoattractant (CINC/gro) in the Ovulatory Process, Methods and Findings in Experimental and Clinical Pharmacology, Vol.22, No.10, 725-730, 2000.
(Summary)
We investigated the effects of Toki-shakuyaku-san and its crude ingredients in relation to the secretion of a cytokine-induced neutrophil chemoattractant, CINC/gro, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) in the ovulatory process. Toki-shakuyaku-san significantly (p < 0.01) stimulated the secretion of 17 beta-estradiol but did not stimulate the secretion of progesterone in cultured whole ovarian dispersates. Toki-shakuyaku-san enhanced the secretion of CINC/gro in a dose-dependent manner and the production of CINC/gro at concentrations of 10 and 100 micrograms/ml of Toki-shakuyaku-san increased significantly (p < 0.01). Toki-shakuyaku-san also enhanced secretions of both IL-1 beta and TNF alpha, which are known to stimulate the secretion of CINC/gro in the ovulatory process. The production of TNF alpha increased significantly (p < 0.05) with 10 and 100 micrograms/ml of Toki-shakuyaku-san. Atractylodis Lanceae Rhizoma, Cnidii Rhizoma, Angelicae Radix, Paeoniae Radix and Alismatis Rhizoma, which are crude ingredients of Toki-shakuyaku-san, significantly (p < 0.01) enhanced the secretion of CINC/gro at concentrations of 100 micrograms/ml. The results of this study show that Toki-shakuyaku-san can stimulate the secretion of 17 beta-estradiol and stimulate the ovulatory process by stimulating the production of CINC/gro, IL-1 beta and TNF alpha in vitro. As a treatment for ovulatory disorders, Toki-shakuyaku-san may have stimulatory effects on both steroidogenesis and the ovulatory process.
Masaharu Kamada, Minoru Irahara, Masahiko Maegawa, Toshiyuki Yasui, Takashi Takeji, Masayo Yamada, Mitiko Tezuka, Yuka Kasai and Toshihiro Aono : Effect of hormone replacement therapy on post-menopausal changes of lymphocytes and T cell subests, Journal of Endocrinological Investigation, Vol.23, No.6, 376-382, 2000.
(Summary)
Immunosenescence is associated with the occurrence of lethal diseases, such as infection and malignancy. Since endocrinosenescence occurs simultaneously with immunosenescence, we determined whether or not lymphocytes and T cell subsets were altered in post-menopausal women. The ability of hormone replacement therapy (HRT) to reverse or modify the aberrations of the cell populations observed in elderly women was also examined. Thirty-nine untreated post-menopausal women and 39 women on HRT were studied. The proportions of lymphocytes and T cell subsets (helper, cytotoxic and immature T cells, and naive and memory/activated T cells) were determined by two color flow cytometry. Thirteen women were examined before and during HRT. At late post-menopause (> or = 30 years post-menopausal period), the proportion of peripheral blood lymphocytes showed a tendency to decline (p=0.06) compared with that at early (< or = 10 years) post-menopause. Significant (p<0.05) decrease in naive T cells and an increase in memory/activated T cells occurred at late post-menopause compared to those at early post-menopause. The percentage of lymphocytes in women on HRT was significantly (p<0.05) higher than that in untreated women at late post-menopausal stage. Furthermore, in a prospective study, HRT induced a significant (p<0.02) increase in the percentage of lymphocytes but showed no effect on the aberrations of naive and memory/activated T cells. HRT prevents the decline in the lymphocytes observed in post-menopausal women. However, HRT appears not to influence the observed alteration in T cell subsets.
(Keyword)
Menopause / immunosenescence / naive T cell / memory T cell / estrogen deficiency / aging
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Hirokazu Uemura, Minoru Irahara, Naoto Yoneda, Toshiyuki Yasui, Kaori Genjida, Ken-ichi Miyamoto, Toshihiro Aono and Eiji Takeda : Close correlation between estrogen treatment and renal phosphate reabsorption capacity, The Journal of Clinical Endocrinology and Metabolism, Vol.85, No.3, 1215-1219, 2000.
(Summary)
To determine the influence of estrogen on the activity of renal proximal tubular reabsorption of inorganic phosphate (Pi) in women, we examined the changes of the renal threshold phosphate concentration (also denoted as TmP/GFR), as well as the changes in the concentrations of mineral components in the circulation in two groups of women--one receiving hormone replacement therapy (HRT) and one receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We also examined the changes in the concentrations of serum PTH in the GnRH-a group. The patients in the HRT group were continuously treated with 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate per day. The patients in the GnRH-a group were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. The values of TmP/GFR decreased in all of the patients who received HRT. The mean percentage change in TmP/GFR was -14.5% (range, -24.3% to -9.6%). In contrast, in all of the patients treated with GnRH-a, the values of TmP/GFR increased after 6 months of treatment (the mean percentage change was 28.5%; range, 18.2-78.3%) and returned to the preadministration level at 12 weeks after stopping therapy. In these patients, both the values of TmP/GFR and the concentrations of serum Pi correlated significantly with circulating estradiol levels (r = -0.767, P < 0.01 and r = -0.797, P < 0.01, respectively), but the concentrations of serum corrected calcium did not correlate. Moreover, in the same patients, the levels of serum intact PTH decreased significantly (P < 0.05) after 6 months of treatment, but at 12 weeks after stopping therapy the trends of these levels varied among individual patients. These results suggest that estrogen could act directly to suppress sodium-dependent Pi reabsorption in the renal proximal tubules.
Toshiyuki Yasui, T Murakami, Toshio Maeda and T Oka : Involvement of gonadal steroid hormone disturbance in altered prolactin receptor gene expression in the liver of diabetic mice, The Journal of Endocrinology, Vol.161, No.1, 33-40, 1999.
(Summary)
The levels of mRNA for long and three short forms of prolactin receptor (PRLR) were examined in the livers of normal (db+/db-) and insulin-resistant diabetic (db+/db+) mice to assess the role of gonadal steroid hormones in the regulation of PRLR gene expression in diabetes mellitus. In females, plasma levels of testosterone in diabetic mice were higher, and those of 17beta-estradiol were lower when compared with levels in normal mice. By contrast, diabetic male mice had lower plasma levels of testosterone than normal males and showed no significant difference in the low circulating level of 17beta-estradiol compared with normal males. The short 3 form of PRLR (PRLR3) mRNA was the most abundant in the liver of both normal and diabetic mice. In addition, the level of PRLR3 mRNA in normal females was 8-fold higher than in normal males. The level of PRLR3 mRNA in diabetic females was approximately a quarter lower than in normal females, whereas the level of PRLR3 mRNA in diabetic males was approximately 2-fold higher than in normal males. During postnatal development, the level of PRLR3 mRNA increased during puberty in normal females, while the level in diabetic females decreased to a nadir at 7 weeks of age followed by a progressive rise. On the other hand, the levels of PRLR3 mRNA in both normal and diabetic males decreased gradually during 5 to 14 weeks of age. Testosterone treatment of diabetic males and females resulted in a 49.1 and 49.8% decrease of PRLR3 mRNA respectively. 17beta-Estradiol treatment slightly (18%) increased levels of PRLR3 mRNA in diabetic males. These results suggest that the hepatic level of PRLR mRNA is regulated by the inhibitory effect of testosterone and the stimulatory effect of estrogen in both normal and diabetic mice.
Toshiyuki Yasui, M Yamada, H Kinoshita, Hirokazu Uemura, N Yoneda, Minoru Irahara, Toshihiro Aono, S Unahara, Y Mito, F Kuritoto and K Hata : Combination of automatic HPLC-RIA method for determination of estrone and estradiol in serum, Journal of Clinical Laboratory Analysis, Vol.13, No.6, 266-272, 1999.
(Summary)
We developed a highly sensitive assay for estrone and 17 beta-estradiol in serum. Estrone and 17 beta-estradiol, obtained by solid-phase extraction using a Sep pak tC18 cartridge, were purified by high-performance liquid chromatography (HPLC). Quantitation of estrone and 17 beta-estradiol were carried out by radioimmunoassay. Not insignificantly, this automatic system of extraction and HPLC succeeded in analyzing 80 samples a week. Intra-assay coefficients of variation (CV) for estrone and 17 beta-estradiol ranged from 19.5 to 28.7%, and from 8.5 to 13.7%, respectively. The minimum detectable dose for estrone and 17 beta-estradiol were 1.04 pg/ml and 0.64 pg/ml, respectively. The serum levels of 17 beta-estradiol using our method strongly correlated with those by Gas chromatography mass spectrometry (GC-MS). The serum levels of estrone and 17 beta-estradiol in 154 peri- and postmenopausal women were estimated to be between 15 and 27 pg/ml and between 3.5 and 24.0 pg/ml, respectively, while the serum level of 17 beta-estradiol in postmenopausal women, in particular, was estimated to be from 3.5 to 6.3 pg/ml. For postmenopausal women who suffered from vasomotor symptoms, the mean levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with daily 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) were 135.0 and 21.3 pg/ml at 12 months, respectively. On the other hand, levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with CEE and MPA every other day, were 73.4 and 15.3 pg/ml, respectively. These highly sensitive assays for estrone and 17 beta-estradiol are useful in measuring low levels of estrogen in postmenopausal women, and monitoring estrogen levels in women receiving CEE as hormone replacement therapy.
Hirokazu Uemura, Toshiyuki Yasui, N Yoneda, Minoru Irahara and T Aono : Measurement of N- and C-terminal-region fragments of parathyroid hormone-related peptide in milk from lactating women and investigation of the relationship of their concentrations to calcium in milk., The Journal of Endocrinology, Vol.153, No.3, 445-451, 1997.
(Summary)
Parathyroid hormone-related peptide (PTHrP) is found in very high concentrations in the milk of various mammals. However, little is known about its physiological role in this fluid. To obtain detailed profiles of PTHrP in milk, we measured the concentrations of PTHrP in human milk by two different region-specific assays, PTHrP(1-87) (N-PTHrP) and PTHrP(109-141) (C-PTHrP). We also examined the correlations between PTHrP and Ca concentrations in milk as well as the correlations between PTHrP and secreted milk volume. The levels of N-PTHrP and C-PTHrP were relatively low after delivery and gradually increased to 13.87 +/- 2.40 nmol/l (mean +/- S.E.M.) and 56.39 +/- 11.31 nmol/l respectively on the 10th day postpartum. N-PTHrP concentration remained steady until the 6th month postpartum when weaning starts, at which point it decreased slightly. C-PTHrP levels changed in a similar way to N-PTHrP levels but were 2- to 5-fold higher. Milk Ca concentration, and content, correlated with C-PTHrP concentration, and content (r = 0.422 and r = 0.769 respectively; P < 0.0001) but not with N-PTHrP. N-PTHrP concentration in the milk samples on the 4th day postpartum correlated with the volume of milk secreted during the 24 h before the samples were taken (r = 0.524, P < 0.01), but C-PTHrP concentration did not. These results suggest that PTHrP in human milk may play some role in the maintenance of lactation through the N-terminal region and in promoting Ca transfer into milk via the C-terminal region.
Toshiyuki Yasui, Hirokazu Uemura, Minoru Irahara and Toshihiro Aono : Effects of transforming growth factor-β on the production of parathyroid hormone-related peptide in a human ovarian cancer cell line in vitro, Journal of Obstetrics and Gynaecology Research, Vol.23, No.3, 231-238, 1997.
176.
Toshiyuki Yasui, Hirokazu Uemura, N Yoneda, Minoru Irahara, T Aono, S Sunahara and K Hata : [Assessment of serum estrogen levels by RIA with HPLC during hormone replacement therapy]., Acta Obstetrica et Gynaecologica Japonica, Vol.47, No.7, 655-661, 1995.
(Summary)
We studied the serum estradiol and estrone levels in 146 peri and postmenopausal women, and in 38 women who had complained of various climacteric disturbance symptoms during daily hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) 0.625 mg and medroxyprogesterone acetate (MPA) 2.5 mg. Serum estradiol and estrone were measured before treatment, and at 6 months, and after one year of the HRT therapy by HPLC-radioimmunoassay. In 146 peri and postmenopausal women, the serum level of estradiol was from 3 to 6pg/ml. The serum level of estradiol in 38 women after HRT significantly increased (p < 0.01) from 3.34 to 23.6 pg/ml at 6 months, and 21.5 pg/ml at 12 months. The serum level of estrone significantly increased (p < 0.01) from 26.6pg/ml to 156.7pg/ml at 6 months, and 137.2pg/ml at 12 month. These results are very useful for deciding on the doses of hormones and the expected serum estradiol level in HRT for Japanese women.
Toshiyuki Yasui, Naoto Yoneda, Hirokazu Uemura, Hiroyuki Kaji, Akira Kuwahara, Yuji Yokoyama, Seiichiro Saito, Keiji Shitsukawa, Keiichiro Azuma, Minoru Irahara and Toshihiro Aono : The effect of continuous combined regimen of estrogen progestin on the postmenopausal woman, The Journal of the Japan Menopause Society, Vol.2, No.1, 130-138, 1994.
Toshiyuki Yasui, Minoru Irahara, Masaharu Kamada and Toshihiro Aono : Inhibitory effect of Sho-saiko-to on the growth of gynecological cancer cell lines by autocrine mechanism of transforming growth factor-β, Journal of Traditional Medicinen, Vol.11, No.3, 161-167, 1994.
(Keyword)
Sho-saiko-to / gynecological cancer / TGF-β / MTT / assay
183.
Toshikazu Miyake, Minoru Irahara, Keiji Shitukawa, Toshiyuki Yasui and Toshihiro Aono : Interaction of Activin A and Gonadal Steroids on FSH Secretion from Primary Cultured Rat Anterior Pituitary Cells, Biochemical and Biophysical Research Communications, Vol.194, No.1, 413-419, 1993.
184.
Masaki Q Fujita, Toshiyuki Yasui, Bunzo Sato, Naomi Uchida, Kiyohisa Uchida, Osamu Shiratori, Kenichi Takeda and Keishi Matsumoto : Maintenance of Androgen-,Glucocorticoid-or Estrogen-responsive Growth in Shionogi Carcinoma 115 Subline Subline Sustained in Castrated Mice with High Dose of Estrogen for 30 Generations(3 Years), Gann : Japanese Journal of Cancer Research, Vol.83, No.9, 995-1001, 1992.
Hiroshi Yamanishi, Norio Nonomura, Akira Tanaka, Toshiyuki Yasui, Yasuko Nishizawa, Keishi Matsumoto and Bunzo Sato : Roles of Transforming Growth Factor β in Inhibition of Androgen-induced Growth of Shionogi Carcinoma Cellsin Serum-Free Medium, Cancer Research, Vol.50, No.19, 6179-6183, 1990.
186.
Toshiyuki Yasui, Minoru Irahara, K Shisukawa, K Azuma and Toshihiro Aono : The mechanism of the effect of combination treatment with clomiphene and bromocriptine in patients with normoprolactinemic anovulation, Journal of Endocrinological Investigation, Vol.13, No.7, 549-554, 1990.
Akira Tanaka, Jian Lu, Norio Yamanishi, Toshiyuki Yasui, Masataka Maeyama, Yasuko Nishizawa, Keishi Matsumoto and Bunzo Sato : Effects of Androgen,Fibroblast Growth Factors or Other Various Growth Factors on Growth of Shinogi Carcinoma Cells in a Protein-Free Medium, Anticancer Research, Vol.10, 1637-1642, 1990.
Toshiyuki Yasui, 松浦 幸恵, 河北 貴子 and 吉田 加奈子 : 女性のQOL向上のためのホルモン療法, Japanese Journal of Medicine and Pharmaceutical Science, Vol.77, No.10, 1367-1374, Oct. 2020.
Toshiyuki Yasui and 遠藤 逸朗 : 産婦人科処方のすべて, Clinical Gynecology and Obstetrics, Vol.74, No.4, 132-138, Apr. 2020.
16.
Toshiyuki Yasui, Yukie Matsuura, Takako Kawakita and Kanako Yoshida : OC・LEPの有害事象, Japanese Journal of Medicine and Pharmaceutical Science, Vol.77, No.10, 1367-1374, 2020.
高松 潔, 加藤 育民, 小川 真里子, Toshiyuki Yasui and 林 邦彦 : 日本におけるホルモン補充療法データベース構築のための基礎調査, The Journal of Japan Society for Menopause and Women's Health, Vol.26, No.2, 275-278, 2019.
H Okano, T Higuchi, T Kurabayashi, K Makita, H Mizunuma, Y Mochizuki, S Obayashi, Toshiyuki Yasui and K Takamatsu : Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health 2017 guidelines for hormone replacement therapy, The Journal of Obstetrics and Gynaecology Research, Vol.44, No.8, 1355-1368, Jun. 2018.
(Summary)
Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.
(Keyword)
Estrogen Replacement Therapy / Gynecology / Humans / Menopause / Obstetrics / Practice Guidelines as Topic / Societies, Medical
Toshiyuki Yasui : Strategy using OC/LEP or HRT for women aged 40 years, The Journal of Japan Society for Menopause and Women's Health, Vol.23, No.2, 352-357, Apr. 2016.
Toshiyuki Yasui : 女性医学におけるHRTの位置付け, 日本産科婦人科学会雑誌, Vol.65, No.5, 1293-1304, May 2013.
71.
Toshiyuki Yasui : Management of bone health in women during the menopausal transition, The Journal of Japan Society for Menopause and Women's Health, Vol.20, No.3, 469-476, Apr. 2013.
Toshiyuki Yasui : Health Care for Women Medical Treatment for Menopausal Symptoms : Indication and Limitation, Acta Obstetrica et Gynaecologica Japonica, Vol.64, No.9, 367-372, Jun. 2012.
Toshiyuki Yasui : Factors associated with age at menopause in Japanese women, The Journal of Japan Society for Menopause and Women's Health, Vol.20, No.1, 161-165, Apr. 2012.
Toshiyuki Yasui : Estrogen and Cytokine during the menopausal transition, The Journal of Japan Society for Menopause and Women's Health, Vol.20, No.1, 78-85, Apr. 2012.
Sumika Matsui, Toshiyuki Yasui, Takashi Kaji, 山本 哲史, Hirokazu Uemura and Minoru Irahara : NT-proBNP in perimenopausal women, The Journal of Japan Society for Menopause and Women's Health, Vol.19, No.1, 37-41, Apr. 2011.
Toshiyuki Yasui : Medical Treatment for Total Health Care in Women, The Journal of Japan Society for Menopause and Women's Health, Vol.19, No.1, 120-126, Apr. 2011.
Toshiyuki Yasui and 松井 寿美佳，山本 哲史 : Examination for hormone replacement therapy in postmenopausal women, Journal of Medical Technology, Vol.55, No.3, 293-297, Mar. 2011.
Toshiyuki Yasui and Minoru Irahara : Herbal medicine in women with infertility, Obstetrical and Gynecological Therapy, Vol.86, No.5, 960-967, May 2003.
(Keyword)
不妊症 / 漢方薬 / エビデンス
111.
Toshiyuki Yasui and Minoru Irahara : Improvement of long-term comliance with hormone replacement therapy by modulating dose and route of administration, The Journal of the Japan Menopause Society, Vol.11, No.1, 125-132, Apr. 2003.
Minoru Irahara, Toshiyuki Yasui and Hirokazu Uemura : 【ホルモン補充療法】HRTの副作用, Popular Medicine, Vol.219, 69-73, May 2001.
116.
Toshiyuki Yasui, Minoru Irahara and Toshihiro Aono : Chinese herbal medicine in gynecology, Obstetrical and Gynecological Therapy, Vol.82, No.3, 284-292, Mar. 2001.
Toshiyuki Yasui and Toshihiro Aono : Hormone replacement therapy for postmenopausal women with climacteric symptoms, Obstetrical and Gynecological Therapy, Vol.77, No.1, 78-81, Jul. 1998.
Yukie Matsuura, HoangNam Tran and Toshiyuki Yasui : Exploring Menstrual Symptom Changes in Freshwomen Students: A Prospective Cohort Study, International Conference for Public Health, Environment, and Education for Sustainable Development Goals and Lifelong Learning, 135, Bangkok, Sep. 2023.
(Keyword)
menstrual-related symptoms / female university students / three months and nine months after admission / prospective cohort study / lifestyle
2.
Sachi Kishida, Yumi Kuwamura, Toshiyuki Yasui, M Tuji, Issei Imoto and Minoru Irahara : Characteristics of Japanese Pregnant Women Who Had Hereditary Counseling About Noninvasive Prenatal Genetic Testing (NIPT) In Tokushima, 2nd Technological Competency as Caring in the Health Sciences 2018, 80, Aug. 2018.
S Matsui, Toshiyuki Yasui, K Kasai, K Yoshida, T Kato, H Uemura and M Irahara : Dehydroepiandrosterone sulfate level decreases even with a slight change in estradiol in women., The 8th Congress of the International Society for Gender Medicine, Sendai, Sep. 2017.
5.
K Hayashi, Toshiyuki Yasui, JS Lee, Y Ideno, T Kubota and H. Mizunuma : Reduced cognitive functioning during peri-menopausal period, The 6th Scientific Meeting of the Asia Pacific menopause Federation, Singapore, Apr. 2017.
6.
Toshiyuki Yasui and H. Moyo Hayashi K Kurabayashi T Lee JS Kubota T Mizunuma Ri : Pregnancy induced hypertension as a risk factor in the occurrence of hot flashes among perimenopausal women. 15th World Congress on Menopause, Prague (Czech Republic), Sep. 2016.
7.
Yuko Uemura, Toshiyuki Yasui, Mari Haku and Hirokazu Uemura : Changes in low back pain during first trimester and second trimester in Japanese pregnant women, 19th East Asian Forum Of Nursing Scholars, Chiba, Mar. 2016.
8.
Tomoko Ishibashiri, Yuko Tanaka, Mikiyo Wakamatsu, Miyuki Yukura, Keiko Takebayashi, Mari Haku, Toshiyuki Yasui and kentyo Matsuura : Survey on Provision of Information to Guardians About Uterine Cancer Screening and Cervical Cancer Prevention, The ICM Asia Pacific Regional Conference 2015, 339, Yokohama, Jul. 2015.
9.
NAKAYAMA Soichiro, Takashi Kaji, Toshiyuki Yasui, HICHIJO Atsuko, TAKAHASHI Yohei and Minoru Irahara : Serum 25(OH)D3 concentrations and season-specific correlates in Japanese pregnancy women., IFFS/JSRM International Meeting,2015, Yokohama, Apr. 2015.
10.
Takashi Kaji, Toshiyuki Yasui, HICHIJO Atsuko, TAKAHASHI Yohei, NAKAYAMA Soichiro, Hirokazu Uemura, Kazuhisa Maeda and Minoru Irahara : Effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women., IFFS/JSRM International Meeting,2015, Yokohama, Apr. 2015.
11.
Sumika Matsui, Toshiyuki Yasui, Kaoru Keyama, Takeshi Katou, Hirokazu Uemura and Minoru Irahara : Ultra-low-dose estradiol improves arterial stiffness in postmenopausal women., IFFS/JSRM International Meeting,2015, Yokohama, Apr. 2015.
12.
MAEGAWA Masahiko, TANI Anna, YAMAMOTO Satoshi, KUNIMI Kotaro, Takeshi Katou, Sumika Matsui, Kaoru Keyama, Hirokazu Uemura, Toshiyuki Yasui, KAMADA Masaharu, MITANI Ryuji, MIYATANI Yuka and Minoru Irahara : Arterial stiffness is increased in young women with endometriosis., IFFS/JSRM International Meeting 2015, Yokohama, Apr. 2015.
13.
Yuko Yasuhara, Rozzano De Castro Locsin, Tetsuya Tanioka and Toshiyuki Yasui : Objective Determination of Sleep Conditions of Women with Ischemic Heart Disease (IHD) Post- elective Percutaneous Coronary Intervention (Using Actigraphy), AMERICAN ACADEMY OF NURSING 2014 TRANSFORMING HEALTH, DRIVING POLICY CONFERENCE, Washington,DC, Oct. 2014.
14.
Toshiyuki Yasui : The 5th Scientific Meeting of the Asia Pacific Menopause Federation "Current status of HRT in Japan", Tokyo, Oct. 2013.
15.
Toshiyuki Yasui : Testosterone in Women, 6th JAPAN-ASEAN Conference on Men's Health & Aging, Kamakura, Jul. 2011.
16.
Toshiyuki Yasui, Hirokazu Uemura, Y Miyatani, M Yamada, N Tsuchiya, M Yuzurihara, S Takeda and Minoru Irahara : Interleukin-8 and hot flushes in pre-, peri- and postmenopausal women and bilateral oophorectomized women., The 3rd Scientific Meeting of the Asian Pacific Menopause Federation (APMF), Taipei, Mar. 2007.
17.
Hirokazu Uemura, Toshiyuki Yasui, Y Miyatani, M Yamada, Mineyoshi Hiyoshi, Hideo Takeda, Kokichi Arisawa and Minoru Irahara : Relationships between circulating osteoprotegerin and the risk factors of vascular disorders in postmenopausal women., The 3rd Scientific Meeting of the Asian Pacific Menopause Federation (APMF), Taipei, Mar. 2007.
18.
Yuka Kasai, Anna Tani, Ayako Nakajima, Dan Kinoshita, hirokazu Uemura, Masahiko Maegawa, Toshiyuki Yasui, Masaharu Kamada and Minoru Irahara : Pro-Inflammatory Cytokine Changes in Postmenopausal Women Treated with Hormone Replacement Therapy, IX International Congress of Reproductive Immunology, Vol.52, No.Supplement 1, 57, Kanagawa, Oct. 2004.
19.
Akira Kuwahara, Yu Tanaka, Yukari Tsutsumi, Kenji Hinokio, Toshiya Matsuzaki, Masahiko Maegawa, Toshiyuki Yasui, Shuji Yamano and Minoru Irahara : Clinical outcomes of "true" unexplainedinfertility after laparoscopy, The 4th Conference of the Pacific Rim Society for Fertility and Sterility, Okinawa, Mar. 2004.
20.
R Ogata, Toshiyuki Yasui, Hirokazu Uemura, Machiko Kiyokawa, Masakazu Miura, Toshihiro Aono and Minoru Irahara : Serum estradiol level that is required to achieve a sufficient increase in bone mineral density during hormone replacement therapy, 9th International Menopause Society World Congress on the Menopause, Berlin, Jun. 2002.
21.
Minoru Irahara, Masaharu Kamada, Hirokazu Uemura, Toshiyuki Yasui, Machiko Kiyokawa, Akira Kuwahara, Hiroshi Ikawa, Toshiya Matsuzaki and Toshihiro Aono : Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy, 9th International Menopause Society World Congress on the Menopause, Berlin, Jun. 2002.
22.
Hirokazu Uemura, Toshiyuki Yasui, Machiko Kiyokawa, Akira Kuwahara, Hiroshi Ikawa, Toshiya Matsuzaki, Toshihiro Aono and Minoru Irahara : Changes in the levels of circulating osteoprotegerin in case of estrogen deficiency, 9th International Menopause Society World Congress on the Menopause, Berlin, Jun. 2002.
Toshiyuki Yasui : Risk factors and comorbidity for endometriosis: analysis of the Japan Nurses' Health Study baseline survey. The 7th conference of gynecological hormone dependent diseases, May 2016.
57.
Toshiyuki Yasui : 高脂肪食が卵の人工的活性化に及ぼす影響 第57回日本卵子学会, May 2016.
Real World Evidence for Health Care in Japanese Women (Project/Area Number: 18H04069 )
Study of timing regulation in the network among the pituitary, the ovary and the adrenal gland in women during the menopausal transition (Project/Area Number: 16K11143 )
Role of androgen for metabolism in women during the menopausal transition (Project/Area Number: 25462596 )
Intervention study to the parent who is the consultation action influence factor of the adolescent girls - Does the HPV vaccine spread advance by approaching a parent? - (Project/Area Number: 23593297 )
Effects of endocrinological and immunological factors on metabolism in women during the menopausal transition (Project/Area Number: 22591857 )
Crosstalk from energy regulating system to female reproductive system (Project/Area Number: 14571566 )