Low-dose isoflavone aglycone alleviates psychological symptoms of menopause in Japanese women: a randomized, double-blind, placebo-controlled study.

PURPOSE: Many studies have demonstrated the effectiveness of isoflavones on menopausal symptoms; however, these mostly used high dosages. Because high-dose isoflavone may result in endometrial hyperplasia, we investigated whether low-dose isoflavone aglycone alleviates menopausal symptoms similarly to high dosages. METHODS: We conducted a randomized, double-blind, placebo-controlled study in 90 healthy women aged 40-60 years who had at least one menopausal symptom on the Menopausal Symptom Scale (MSS). The participants were randomized to receive active tablets containing ultralow-dose (12.5 mg/day; n = 30) or low-dose (25 mg/day; n = 30) isoflavone aglycone, or placebo (n = 30) tablets, for 8 weeks. Their menopausal symptoms were evaluated using MSS, Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) before, and 4 and 8 weeks after treatment. RESULTS: Eighty-seven women (97 %) completed the 8-week treatment. In the low-dose group, significant improvement was observed from baseline, in the following parameters: (1) HADS-depression subscale score, (2) AIS score, (3) MSS-somatic symptom score after 4 and 8 weeks of treatment, and (4) MSS-vasomotor symptom score after 8 weeks of treatment. The changes in scores on HADS-depression subscale and AIS from baseline to 8 weeks were significantly higher in the low-dose group than in the placebo group. CONCLUSIONS: Low-dose (25 mg/day) isoflavone aglycone significantly alleviated symptoms of depression and insomnia in Japanese middle-aged women. Clinical Trial Registration UMIN-CTR UMIN000011876.

Tomato juice intake increases resting energy expenditure and improves hypertriglyceridemia in middle-aged women: an open-label, single-arm study.

BACKGROUND: Tomato-based food products have health-promoting and disease-preventing effects. Some tomato juice ingredients may have health benefits for middle-aged women, including women with menopausal symptoms and cardiovascular diseases. We investigated the net effect of tomato juice intake on several health parameters in women in this age group. METHODS: An open-label, single-arm study was conducted, involving 95 women (40-60-years-old) who had at least one menopausal symptom. The participants refrained from foods and drinks rich in tomato and tomato-based products for 2 weeks prior to the study and during the 8 weeks of tomato juice consumption. After the run-in period, the women were asked to consume 200 mL of unsalted tomato juice, twice daily for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Symptom Scale (MSS), Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) before the study, and at 4 and 8 weeks after study commencement. At the same times, body composition; blood pressure; heart rate; resting energy expenditures (REEs); and serum levels of triglyceride (TG), cholesterol, glucose, and hemoglobin A1c were measured. RESULTS: Ninety-three women (98%) completed the study. The following parameters showed significant changes, compared with baseline, at study weeks 4 and 8 (mean ± standard deviation at baseline, week 4, and week 8): (1) the MSS score improved (9.9 ± 5.2, 8.5 ± 5.0, 8.3 ± 5.0; P < 0.0001, repeated measures analysis of variance(ANOVA)), (2) the HADS-anxiety subscale score improved (5.3 ± 2.7, 4.8 ± 2.4, 4.9 ± 2.9; P = 0.041, Friedman test), (3) heart rate increased (62.6 ± 9.4 bpm, 64.4 ± 8.6 bpm, 63.8 ± 8.2 bpm; P = 0.028, Friedman test), (4) REE increased (1980 ± 368 kcal/day, 2108 ± 440 kcal/day, 2149 ± 470 kcal/day; P = 0.0030, repeated measures ANOVA), (5) serum TG level decreased in the subgroup of women (n = 22) who had high TG (150 mg/dL or higher) at baseline (237.8 ± 88.9 mg/dL, 166.7 ± 86.1 mg/dL, 170.9 ± 109.7 mg/dL; P = 0.0002, Friedman test). CONCLUSIONS: Tomato juice intake alleviated menopausal symptoms, including anxiety, increased REEs and heart rate, and lowered high baseline serum TG levels in middle-aged women. TRIAL REGISTRATION: UMIN-CTR UMIN000011877 .

Subgrouping of Japanese middle-aged women attending a menopause clinic using physical and psychological symptom profiles: a cross-sectional study.

BACKGROUND: Women in the menopausal transition and the postmenopausal period are affected with vasomotor symptoms, urogenital atrophy, sexual dysfunction, somatic symptoms, cognitive difficulty, sleep disturbance, and psychological problems. It is important to gain a better understanding of the complexity and diversity of climacteric disturbance in order to optimize treatments for individual patients. The aim of this study was to identify subgroups of Japanese perimenopausal and postmenopausal women attending a menopause clinic based on their physical and psychological symptom profiles. METHODS: We administered the Menopausal Health-Related Quality of Life questionnaire to 491 Japanese women aged 40-64 years who had enrolled in the Systematic Health and Nutrition Education Program at the Menopause Clinic of the Tokyo Medical and Dental University Hospital between 2005 and 2012. We performed a principal component analysis followed by a hierarchical cluster analysis of the responses to 9 physical and 12 psychological items on the questionnaire. RESULTS: The first analysis extracted 3 principal components that defined the variance of physical and psychological symptom profiles: depression, somatic, and vasomotor/sleep. A subsequent cluster analysis was performed based on the 3 principal components to generate 4 clusters, CL8 (N = 162; 33.0%), CL6 (N = 111; 22.6%), CL5 (N = 102; 20.8%), and CL4 (N = 116; 23.6%). CL8 included women who only had mild-to-moderate musculoskeletal pains and tiredness. All women in CL6, CL5, and CL4 described their musculoskeletal pains and tiredness as moderate to severe. The women in CL5 also had moderate-to-severe vasomotor symptoms, while the women in CL4 also suffered from moderate-to-severe psychological symptoms, such as depression, anxiety, and insomnia. CONCLUSIONS: Distinct subgroups of Japanese perimenopausal and postmenopausal women were identified based on their symptom profiles. Menopausal symptoms were shown to accumulate in this population in the order of musculoskeletal pains and tiredness, vasomotor symptoms, and psychological symptoms.

Associations among depression, anxiety and somatic symptoms in peri- and postmenopausal women.

AIM: The aim of this study was to investigate the associations among depression, anxiety and physical symptoms in peri- and postmenopausal women in a clinical setting. MATERIAL AND METHODS: Two hundred and thirty-seven peri- and postmenopausal women enrolled in the Systematic Health and Nutrition Education Program at the Menopause Clinic of the Tokyo Medical and Dental University Hospital. Their responses to the Menopausal Health-Related Quality of Life (MHR-QOL) and Hospital Anxiety and Depression Scale (HADS) questionnaires were subjected to a cross-sectional analysis. The study focused on the relationship between the scores for HADS depression (HADS-D) and anxiety (HADS-A) subscales and those for somatic (nausea, dizziness, numbness, muscle and joint pains, tiredness, headaches), urinary (frequent urination), and vasomotor symptoms (hot flashes, night sweats) in the MHR-QOL questionnaire. RESULTS: The correlations among the scores for the six somatic symptoms and HADS-D and HADS-A were stronger than those for urinary or vasomotor symptoms. Multiple logistic regression analysis revealed that the score for headaches and that for HADS-A were significantly associated with severe depression after adjustment (odds ratio (OR) [95% confidence interval (CI)]: 1.49 [1.06-2.10] and 1.58 [1.37-1.83], respectively), whereas the scores for nausea and numbness, as well as HADS-D, were significantly associated with severe anxiety (OR [95% CI]: 1.65 [1.15-2.39], 1.39 [1.05-1.84], and 1.36 [1.23-1.50], respectively). CONCLUSION: Headaches were associated with depression, whereas nausea and numbness were associated with anxiety in peri- and postmenopausal women. The assessment of underlying mood disorders is required for the management of middle-aged women presenting with these somatic symptoms.

Effects of three Kampo formulae: Tokishakuyakusan (TJ-23), Kamishoyosan (TJ-24), and Keishibukuryogan (TJ-25) on Japanese peri- and postmenopausal women with sleep disturbances.

PURPOSE: To assess the effects of Kampo, a traditional Japanese adaptation of Chinese herbal medicine, on peri- and postmenopausal women with sleep disturbances. METHODS: Among the records of 1,523 peri- and postmenopausal women who are enrolled in the Health and Nutrition Education Program at the Tokyo Medical and Dental University, Menopause Clinic, during 1995-2009, about 151 women suffering from moderate to severe sleep disturbances were retrospectively analyzed. These women had received only health/nutrition education (control; n = 77) or received treatment with one of the three major Kampo formulae: Tokishakuyakusan (TJ-23; n = 42), Kamishoyosan (TJ-24; n = 16), or Keishibukuryogan (TJ-25; n = 16) according to their "Sho" or symptom patterns. Subjective sleep parameters, menopausal symptoms, health-related quality of life, body composition, blood pressure, and pulse rate were compared before and after the intervention. RESULTS: The TJ-25 group had significantly higher body weight, body mass index, body fat, lean body mass, resting energy expenditure, and relatively high blood pressure and heart rate at baseline than the other groups. After ~5-month follow up, TJ-23 reduced the sleep disruption frequency, increased lean body mass, and decreased diastolic pressure. TJ-24 alleviated subjective sleep disturbances; improved difficulties in initiating sleep, disrupted sleep, and non-restorative sleep; and relieved headache/dizziness. TJ-25 improved subjective sleep disturbances, alleviated perspiration, and reduced systolic/diastolic pressure and heart rate. CONCLUSIONS: Each of the Kampo formulae effectively alleviated sleep disturbances in Japanese peri- and postmenopausal women. Middle-aged female patients having sleeping disorder could successfully be treated using Kampo medicines.

Higher intake of cryptoxanthin is related to low body mass index and body fat in Japanese middle-aged women.

OBJECTIVES: The prevalence of cardiovascular diseases increases with age, especially in postmenopausal women. In this study, we investigated the dietary patterns associated with body mass and body fat in Japanese middle-aged women. STUDY DESIGN: Cross-sectional. MAIN OUTCOME MEASURES: This study used baseline data collected in a previous study in 88 women aged 40-60 years. Participants were assessed for age, menopausal status, lifestyle factors, body composition, and dietary habits using a brief-type self-administered diet history questionnaire, which provides information on the amounts of nearly 100 nutritional factors consumed during the previous month. Classifying body mass index (BMI) as low (≤22kg/m2) or high (>22kg/m2) and percentage body fat as low (≤25%) or high (>25%), we sought to identify the nutritional factors associated with BMI and percentage body fat. RESULTS: Consumption differences between high/low BMI and high/low body fat percentage groups were not significant for any nutritional factors except cryptoxanthin. Multiple logistic regression analysis adjusting for age, menopausal status, working, exercise, and smoking revealed that higher cryptoxanthin intake was associated with low BMI (adjusted odds ratio, 1.22 per 100µg/day increase of cryptoxanthin intake; 95% confidence interval, 1.01-1.52) and low body fat percentage (adjusted odds ratio, 1.36 per 100µg/day increase of cryptoxanthin intake; 95% confidence interval, 1.13-1.70). CONCLUSIONS: Higher intake of cryptoxanthin was shown to be related to low body mass and body fat in Japanese middle-aged women.

Depressive symptoms are associated with oxidative stress in middle-aged women: a cross-sectional study.

BACKGROUND: Oxidative stress is known to be a factor in various diseases. In this study, we investigated whether physical and psychological symptoms of menopause, cardiovascular parameters, body composition, and lifestyle factors are associated with oxidative stress in middle-aged women. METHODS: This cross-sectional study used baseline data collected in a previous study that examined the effects of a dietary supplement on a variety of health parameters in 95 women aged 40 to 60 years. Participants had been assessed for age, menopausal status, body composition, cardiovascular parameters, physical and psychological symptoms of menopause, and lifestyle factors. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) level, an oxidative stress marker, had also been measured. Dichotomizing 8-OHdG levels as low (≤25 ng/mg creatinine) and high (>25 ng/mg creatinine), we sought to identify the health parameters that are associated with high 8-OHdG level. RESULTS: Women with a high 8-OHdG level had lower body weight, lower body mass index, lower body fat mass, higher body temperature, scored higher for both anxiety and depression on the Hospital Anxiety and Depression Scale (HADS), and consumed more alcohol. Multiple logistic regression analysis revealed that the HADS-depression subscale (HADS-D) score was the sole independent contributor to high 8-OHdG level (adjusted odds ratio, 1.23 per point increase in HADS-D score; 95 % confidence interval, 1.06-1.45). CONCLUSION: Depressive symptom score was shown to be independently associated with high 8-OHdG level in middle-aged women, suggesting a link between mood disorder and oxidative stress. TRIAL REGISTRATION: UMIN-CTR UMIN000009353.

Prevalence and predictors of storage lower urinary tract symptoms in perimenopausal and postmenopausal women attending a menopause clinic.

OBJECTIVE: This study was undertaken to evaluate the prevalence and predictors of storage lower urinary tract symptoms (LUTS) in perimenopausal and postmenopausal women attending a menopause clinic. METHODS: The records of 351 women aged 40 to 76 years who enrolled in a health and nutrition education program at a menopause clinic were analyzed cross-sectionally. The prevalence of frequency, nocturia, urge incontinence, and stress incontinence was estimated based on women's responses to the Menopausal Health-Related Quality of Life Questionnaire. Effects of background characteristics, including age, menopause status, vaginal dryness, body composition, cardiovascular parameters, physical fitness, and psychological symptoms, on storage LUTS were assessed using multivariate logistic regression analysis. RESULTS: Frequency, nocturia, urge incontinence, and stress incontinence were reported by 45.9%, 10.8%, 11.4%, and 32.8% of women, respectively. Multiple logistic regression analysis revealed independent associations between storage LUTS and the following predictors after adjustment: frequency was associated with nonrestorative sleep score (odds ratio, 1.63; 95% CI, 1.35-1.95); nocturia was associated with nonrestorative sleep score (odds ratio, 2.26; 95% CI, 1.57-3.25) and waist-to-hip ratio (odds ratio, 1.12; 95% CI, 1.05-1.18); urge incontinence was associated with reaction time (odds ratio, 1.10; 95% CI, 1.01-1.19); and stress incontinence was associated with body fat (odds ratio, 1.06; 95% CI, 1.03-1.09). CONCLUSIONS: Storage LUTS are highly prevalent in perimenopausal and postmenopausal women attending a menopause clinic. Nonrestorative sleep score is associated with frequency and nocturia; body fat and visceral fat accumulation are associated with nocturia and stress incontinence; and delayed reaction time is associated with urge incontinence. Careful evaluation of nonrestorative sleep, body fat and visceral fat accumulation, or delayed reaction time might reveal undisclosed storage LUTS in this population.

Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: This study aims to assess the effects of proanthocyanidin-a class of polyphenol antioxidants extracted from grape seeds-on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women. METHODS: We conducted a randomized, double-blind, placebo-controlled study in 96 women aged 40 to 60 years who had at least one menopausal symptom. The study participants were randomized to receive grape seed extract tablets containing either low-dose (100 mg/d) or high-dose (200 mg/d) proanthocyanidin, or placebo, for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Health-Related Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, and Athens Insomnia Scale before and after 4 and 8 weeks of treatment. Body composition and cardiovascular parameters were also measured. RESULTS: A total of 91 women (95%) completed the study. Background characteristics, including age, menopause status, subjective symptom scores, body composition, and cardiovascular parameters, were similar among the groups. The following significant changes were observed during the course of the study: (1) physical symptom score, hot flash score, and (2) Athens Insomnia Scale score decreased in the high-dose group after 8 weeks of treatment; (3) Hospital Anxiety and Depression Scale Anxiety score and (4) systolic and diastolic blood pressure decreased in the low-dose and high-dose groups after 4 weeks; and, (5) lastly, muscle mass increased in the low-dose and high-dose groups after 8 weeks of treatment. CONCLUSIONS: Grape seed proanthocyanidin extract is effective in improving the physical and psychological symptoms of menopause while increasing muscle mass and reducing blood pressure in middle-aged women.

Effects of the kampo formula tokishakuyakusan on headaches and concomitant depression in middle-aged women.

Objectives. To identify the correlates of headaches in middle-aged women and investigate the effects of Tokishakuyakusan (TJ-23), a formula of traditional Japanese herbal therapy Kampo, on headache and concomitant depression. Methods. We examined cross-sectionally the baseline records of 345 women aged 40-59 years who visited our menopause clinic. Among them, 37 women with headaches were treated with either hormone therapy (HT) or TJ-23; the data of these women were retrospectively analyzed to compare the effects of the treatment. Results. The women were classified into 4 groups on the basis of their headache frequency, and no significant intergroup differences were noted in the physical or lifestyle factors, except age. Multiple logistic regression analysis revealed that the significant contributors to the women's headaches were their age (adjusted OR 0.92 (95% CI 0.88-0.97)) and their depressive symptoms (adjusted OR 1.73 (95% CI 1.39-2.16)). Compared to women treated with HT, women treated with TJ-23 reported relief from headaches (65% versus 29%) and concomitant depression (60% versus 24%) more frequently. Improvement in the scores of headaches and depression correlated significantly with TJ-23 treatment. Conclusions. Headache in middle-aged women is significantly associated with depression; TJ-23 could be effective for treating both of these symptoms.

Associations between anxiety, depression and insomnia in peri- and post-menopausal women.

OBJECTIVES: To determine the correlation between somatic and psychological symptoms and insomnia and the contribution of depression and anxiety to insomnia in a sample of peri- and post-menopausal women in a clinical setting. STUDY DESIGN: The responses of 237 peri- and post-menopausal women enrolled in the Systematic Health and Nutrition Education Program (SHNEP) at the Menopause Clinic of the Tokyo Medical and Dental University Hospital between November 2007 and December 2010 to the Menopausal Health-Related Quality of Life (MHR-QOL) and Hospital Anxiety and Depression Scale (HADS) questionnaires were subjected to Spearman's rank correlation and logistic regression analyses. RESULTS: The analysis revealed that (1) insomnia is highly prevalent, (2) the symptoms of difficulty in initiating sleep (DIS) and experiencing non-restorative sleep (NRS) are more strongly correlated with psychological than somatic symptoms, and (3) DIS is strongly associated with anxiety while NRS is strongly associated with depression in the population studied. CONCLUSIONS: Insomnia is highly prevalent among peri- and post-menopausal female patients in a clinical setting and more closely associated with psychological than somatic symptoms. DIS is strongly correlated with anxiety while NRS is strongly correlated with depression.

Effects of the Kampo medication keishibukuryogan on blood pressure in perimenopausal and postmenopausal women.

OBJECTIVE: To examine the effects of keishibukuryogan (TJ-25)-a medicine of the Kampo tradition (the Japanese adaptation of Chinese herbal medicine)-on middle-aged women with high blood pressure. METHODS: The records of 77 peri- and postmenopausal women with high-normal blood pressure or hypertension were analyzed retrospectively. The women had participated in the Systematic Health and Nutrition Education Program at the Tokyo Medical and Dental University in Tokyo, Japan, and had received education only (controls; n = 47) or education and treatment with TJ-25 (n = 30). RESULTS: The baseline characteristics of the 2 groups were comparable. After approximately 6 months, women in the TJ-25 group showed significant reductions in their systolic blood pressure (from 148.4mm Hg to 134.8mm Hg), diastolic blood pressure (from 89.7 mm Hg to 83.7 mm Hg), pulse rate (from 79.5 beats/min to 73.5 beats/min), and resting energy expenditure (from 1552 kcal/day to 1373 kcal/day). Several menopausal symptoms including perspiration, difficulty in initiating sleep, nonrestorative sleep, and headaches/dizziness were also improved. In addition, women in the TJ-25 group had increased health-related quality of life scores in the domains of physical health and life satisfaction. CONCLUSION: TJ-25 alleviates menopausal symptoms and concurrently lowers the blood pressure of middle-aged women with high blood pressure.

Relationship between estrogen, vasomotor symptoms, and heart rate variability in climacteric women.

The present study investigated resting cardiac autonomic function in Japanese climacteric women using heart rate variability (HRV) power spectral analysis to evaluate the relationship between HRV indices and estrogen, as well as the ability of each HRV index to predict vasomotor symptoms. Forty-five peri- and postmenopausal women completed a questionnaire about the presence of vasomotor symptoms (hot flashes, sweating). To analyze the relationship between HRV and hot flashes or sweating, we classified subjects into groups based on symptoms and combinations of symptoms: no hot flashes (H1), hot flashes (H2), non-sweating (S1), sweating (S2), neither hot flashes nor sweating (V1), either hot flashes or sweating (V2), and both hot flashes and sweating (V3). Values for total power and the low-frequency component of HRV were significantly lower in the H2 group than in H1 (p < 0.05); values for total power and the high-frequency and low-frequency components of HRV were significantly lower in group S2 than S1 (p < 0.05); and values for total power and the high-frequency and low-frequency component of HRV were significantly lower in groups V2 and V3 compared to V1 (p < 0.05). Clinical diagnosis of climacterium relies upon subjective complaints of patients. Our findings suggest that HRV indices may help to evaluate vasomotor symptoms.

Body fat and blood lipids in postmenopausal women are related to resting autonomic nervous system activity.

The present study investigated the activity of the autonomic nervous system (ANS), a major influence in normal physiological function, and its association with unfavorable postmenopausal states in body composition, lipid and/or glucose metabolism, or cardiovascular profiles. Body composition, blood pressure, and blood profiles of lipid and glucose of 175 postmenopausal women were measured. Resting ANS activity was assessed by heart rate variability (HRV) power spectral analysis. To scrutinize the influence of ANS activity levels on postmenopausal obesity-related factors, we divided the subjects into a low group ( < 220 ms(2)) and a high group ( > 220 ms(2)), based on the total power of HRV. Low-frequency (P < 0.01) and high-frequency power (P < 0.01) were both significantly lower in the low group. No significant difference was found in age, age at menopause, or years after menopause between the two groups. In contrast, body mass index (P < 0.05), percentages of body fat (P < 0.01), and systolic (P < 0.01) and diastolic (P < 0.01) blood pressure were significantly greater in the low group. As to blood lipid profiles, triglycerides (P < 0.05), total cholesterol (P < 0.05), and low-density lipoprotein cholesterol (P < 0.05) were significantly higher in the low group. Our findings indicate that reduced sympatho-vagal activity is associated with higher postmenopausal body fat content, blood pressure, and blood lipid concentrations. This study further implies that such autonomic depression could be a crucial risk factor in undermining the health and, ultimately, the quality of life, of postmenopausal women.