Menstruation-Related Symptoms and Associated Factors among Female University Students in Vietnam

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.


Differences in Changes in Game Usage Time and Game Use-Related Factors Depending on Parity in a Prospective Study of Pregnant Women in Japan

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.


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

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.


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


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


Game Usage in Pregnant Women at Early Gestation in Japan


Ultrasonographic changes in quadriceps femoris thickness in women with normal pregnancy and women on bed rest for threatened preterm labor.

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.


Associations of psychological status in the early postpartum period with resumption of menstruation and degree of menstruation-related symptoms

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.


Associations of psychological status in the early postpartum period with resumption of menstruation and degree of menstruation-related symptoms.


Complaints of reduced cognitive functioning during perimenopause: A cross-sectional analysis of the Japan Nurses' Health Study

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.


わが国の更年期障害治療における漢方薬使用の現状 --- 日本産科婦人科学会女性ヘルスケア委員会全国調査より

産婦人科漢方研究のあゆみ

産婦人科漢方研究のあゆみ


Differences in Menstruation-Related Symptoms of University Students Depending on their Living Status in Japan

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.


Comparison of Menstruation-Related Symptoms Before and During Menstruation of University Students in Japan, a Year after the COVID-19 Pandemic


Differences in Male Climacteric Symptoms by Aging Males Symptoms Scale and Coping Strategies with Aging among Rotating Night Shift Workers


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


Development and Psychometric Testing of the Mental Health Scale for Childrearing Fathers


Hypertensive disorders of pregnancy increase risk of future menopausal hot flashes in Japanese women: results from the Japan Nurses' Health Study.

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.


Correlations of Androstenediol with Reproductive Hormones and Cortisol According to Stages during the Menopausal Transition in Japanese Women. J

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.

The Journal of Steroid Biochemistry and Molecular Biology


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


Relationship between maternal mental status and social supports during pregnancy and until one month after childbirth in a local city

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.

The Journal of Medical Investigation : JMI


Validity of self-reported diagnoses of gynaecological and breast cancers in a prospective cohort study: the Japan Nurses' Health Study

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.


Associations between sensitivity to cold, menstruation-related symptoms and handgrip strength in female university students in Japan


Daily intake of Lactobacillus gasseri CP2305 ameliorates psychological premenstrual symptoms in young women: A randomized, double-blinded, placebo-controlled study


Management skills required for nursing middle managers in the next generation in perinatal medical care


Differences in Male Climacteric Symptoms and Lifestyle Depending on the Duration of Working among Rotating Night Shift Workers


Usefulness of measurement of proximal phalanx length by using ultrasonography in newborn infants.

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.


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


Relationships of Handgrip Strength with Menstruation-Related Symptoms in Female University Students in Japan


Change in appetite and food craving during menstrual cycle in young students

International Journal of Nutrition and Metabolism


Modified diabetes oral health assessment tool (M-DiOHAT©) for nurses and their association with efficacy beliefs and outcome expectancies in patients with diabetes

JNI : The Journal of Nursing Investigation


Menopausal Symptoms in Japanese Nurses: Differences between Smokers and Non-Smokers


Differences in Physical and Psychological Condition, Sleeping Status and Menstruation-Related Symptoms before and after Smartphones Use in Young Female Students in Japan


Prevalence and factors related to hot flashes and night sweats in postpartum women in Japan

International Journal of Nursing and Midwifery


Differences in male climacteric symptoms with aging among rotating night shift workers

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.


Seasonal variation of serum 25(OH)vitamin D levels in maternal and umbilical cord blood in Japanese women

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.

The Journal of Medical Investigation : JMI


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


Association between FSH, E1, and E2 levels in urine and serum in premenopausal and postmenopausal women


Variation of urinary follicle-stimulating hormone level after menopause: From the results of Japan Nurses' Health Study

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.


The effects of androgens on metabolic functions and their underlying mechanisms in females of reproductive age


The association of urinary estrogen levels with urinary isoflavone levels: Difference between premenopausal women and postmenopausal women

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.


Differences in menopausal symptoms and coping strategies according to personality in Japanese nurses.

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.


Uterine leiomyomata: aretrospective study of correlations with hypertension and diabetes mellitus from the Japan Nurses' Health Study.

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.


Association of Low Back and Pelvic Pain with Mental Health Condition during Pregnancy and Postpartum


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


Differences in strategies for coping with menopausal symptoms in full-time workers and part-time workers in Japan

International Journal of Nursing and Midwifery


産婦人科医による骨粗鬆症診療の現状:第二報

産婦人科医による骨粗鬆症診療の現状:第二報


Association of Low Back and Pelvic Pain at the Second Trimester with that at the Third Trimester and Puerperium in Japanese Pregnant Women


Circulating dehydroepiandrosterone-sulphate decreases even with a slight change in oestradiol.

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.


Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol.

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.


Expression of cytokine-induced neutrophil chemoattractant suppresses tumor necrosis factor alpha expression and thereby prevents the follicles from undergoing atresia and apoptosis.

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.


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


Evaluation of effects of various drugs on platelet functions using phorbol 12-myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells

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.


Changes of liver enzymes and triglyceride during the menopausal transition in Japanese women.

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.


The sensitivity of adipose tissue visfatin mRNA expression to lipopolysaccharide-induced endotoxemia is increased by ovariectomy in female rats.

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.


High androgenicity and unfavorable cardiovascular risk profiles in non-obese women around menopausal transition.

Andrology & Gynecology: Current Research


Differences in coping with menopausal symptoms in nurses and general workers in Japan.

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.


Factors related with low back pain and pelvic pain at the early stage of pregnancy in Japanese women.

International Journal of Nursing and Midwifery


Assessment of pelvic shape by a newly developed posture analyzer in young women in Japan.

Journal of Women's Health, Issues & Care


Characteristic Autonomic Nervous Activity of Institutionalized Elders with Dementia


Arterial stiffness is increased in young women with endometriosis.

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.


The advancement of the onset of vaginal opening in female rats subjected to chronic testosterone treatment occurs independently of hypothalamic Kiss1 and RFRP expression.

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.


The effects of LPS-induced endotoxemia on the expression of adiponectin and its receptors in female rats.

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.


Sensitive Test for Screening for Autonomic Neuropathy of Type 2 Diabetes

Information : an International Interdisciplinary Journal


Measuring quality of sleep and autonomic nervous function in healthy Japanese women


High adiponectin level in late postmenopausal women with normal renal function.

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.


Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women.

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.


Difference in the Ratio of High-Molecular Weight (HMW) to Total Adiponectin and HMW Adiponectin in Late Postmenopausal Women.

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.

Journal of Endocrinological Investigation


Associations of estrogen and testosterone with insulin resistance in pre- and postmenopausal women with and without hormone therapy.

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.

International Journal of Endocrinology and Metabolism


Changes before and after improvement of subjective sleep state of a man diagnosed with pre-diabetes and sleep disorder


Developmental changes in the responsiveness of hypothalamic ER alpha mRNA levels to food deprivation.

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.


Differences in knowledge of and attitudes regarding complementary and alternative medicine among health care profession students in Japan

Takata T, Kuramoto M, Imamura M, Kishida S, Yasui T

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.

医療系大学生の補完代替医療 (CAM) に関する認識と学科間の相違について実態を明らかにすることを目的とし，医学科，看護学・助産学，放射線科，検査科，栄養学，歯学科，口腔保健学，薬学の学部学生 2120 名を対象に，無記名の構成的質問紙票によるアンケート調査を行い，属性および 17 種類の CAM について 7 項目を質問した．医療系大学生の CAM に対する認識は，CAM の種類や学科によって差がみられることが明らかになった．看護・助産学学生は，CAM に対して肯定的で積極的な傾向が認められた．マッサージ，アロマテラピー，ヨガ，整体，精神療法への「興味関心」と「有効性」は他学科の学生より有意に高かった (p < 0.05)．看護・助産学学生の興味関心が高いこれらの CAM は，高価な物品等を必要とせず，臨床ですぐに実践できる手技・手法であり，看護ケアに有用であることが示唆された．

Japanese Journal of Complementary and Alternative Medicine


Prepubertal exposure to glucocorticoid delays puberty independent of the hypothalamic Kiss1-GnRH system in female rats.

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.

International Journal of Developmental Neuroscience


Association of circulating adiponectin with testosterone in women during the menopausal transition.

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.


更年期障害 (特集 ホルモン補充療法の最新知識 : リスク・ベネフィットを今,どう考えるか)


Changes in insulin sensitivity during GnRH agonist treatment in premenopausal women with leiomyoma.

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.


単胎妊婦と双胎妊婦におけるカルシウム代謝ならびにビタミンDの動態の比較 (第22回婦人科骨粗鬆症研究会) -- (WORKSHOP 若年女性における骨の管理)

オステオポローシスジャパン : 日本骨粗鬆症学会雑誌

オステオポローシスジャパン : 日本骨粗鬆症学会雑誌


Roscovitine in combination with calcium ionophore induces oocyte activation through reduction of M-phase promoting factor activity in mice.

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.


Fasting reduces the kiss1 mRNA levels in the caudal hypothalamus of gonadally intact adult female rats.

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.


Effect of immune stress on body weight regulation is altered by ovariectomy in female rats.

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.


Induction of circulating monocyte chemoattractant protein-1 in women with gonadotropin-releasing hormone agonist.

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.


Changes in responsiveness of appetite, leptin and hypothalamic IL-1β and TNF-α to lipopolysaccharide in developing rats.

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.


Differences in bone metabolism between singleton pregnancy and twin pregnancy.

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.


The role of blood in early endometrial-peritoneal interactions in a syngeneic mouse model of endometriosis


Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies.

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.

The Journal of Medical Investigation : JMI


Effects of Japanese traditional medicines on circulating cytokine levels in women with hot flashes.

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.


Gneder differences in attitudes regarding complementary and alternative medicine among health care profession students in Japan

Japanese Journal of Complementary and Alternative Medicine


Neonatal LPS injection alters the body weight regulation systems of rats under non-stress and immune stress conditions.

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.

International Journal of Developmental Neuroscience


Association of N-terminal pro B-type natriuretic peptide and sex hormone-binding globulin in non-obese peri- and postmenopausal women.

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.


Effects of intrauterine undernutrition on hypothalamic Kiss1 expression and the timing of puberty in female rats.

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.


Hypothalamic Ghrelin suppresses pulsatile secretion of luteinizing hormone via beta-endorphin in ovariectomized rats.

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.


Interleukin-7 is associated with monocyte chemoattractant protein-1 and soluble E-selectin levels in peripheral blood of newly post-menopausal women.

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.


Reproducibility of luteinizing hormone hypersecretion in different phases of the menstrual cycle in polycystic ovary syndrome.

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.

The Journal of Obstetrics and Gynaecology Research


Effects of oral and transdermal estrogen therapies on circulating cytokines and chemokines in postmenopausal women with hysterectomy.

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.


Neonatal lipopolysaccharide exposure attenuates the homotypic stress-induced suppression of LH secretion in adulthood in male rat.

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.


Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitor and Japanese traditional medicine.

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.


Raloxifene reduces circulating levels of interleukin-7 and monocyte chemoattractant protein-1 in postmenopausal women.

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.