Supplementation with cassis polyphenol has no effect on menopausal symptoms in healthy middle-aged women: A randomized, double-blind, parallel-group, placebo-controlled trial.

Hormonal changes during the menopause transition may lead to vasomotor symptoms, including hot flashes (HFs) and neuropsychiatric symptoms such as anxiety and irritability. We hypothesized that the effects of cassis polyphenol (CaP) to improve microcirculation and vasorelaxation may alleviate menopausal symptoms. We performed a randomized, double-blind, parallel-group, placebo-controlled trial involving 59 healthy women (mean [standard deviation] age, 51.3 [4.3] years; body mass index, 20.8 [2.6] kg/m2). Participants experiencing subjective menopausal symptoms consumed CaP tablets (400 mg/d, CaP group) or placebo tablets (placebo group) for 4 weeks. Participants were evaluated using questionnaires at baseline, during the 4-week intervention period, and during a 2-week postinterventional observation period. The primary objective was to evaluate the effects of supplementation with CaP on HFs in healthy Japanese women with menopausal symptoms. Additional assessments included the modified Kupperman menopausal index, World Health Organization-5 Well-Being Index, World Health Organization quality-of-life 26-item index, State-Trait Anxiety Inventory (anxiety and trait components), and Oguri-Shirakawa-Azumi sleep inventory (middle-aged and elderly versions). During the 4-week intervention period, no significant between-group differences were detected in the HF frequency, HF score, sweating frequency, menopausal symptoms, quality of life, anxiety, or sleep. During the 2-week postintervention observational period, the HF score and sweating frequency were significantly decreased in the CaP group compared with the placebo group. These findings suggest that twice daily intake of CaP for 4 weeks does not alleviate menopause symptoms, but the improvement observed in the CaP intake group during the postintervention period warrants confirmation through further large-scale studies.

Effect of shift work on excessive daytime sleepiness in female nurses: results from the Japan nurses' health study.

We investigated the relationship between shift work and excessive daytime sleepiness (EDS) among participants in the Japan Nurses' Health Study (JNHS). Responses of 9,728 female nurses to the 6th follow-up questionnaire were cross-sectionally analyzed. EDS was defined as an Epworth Sleepiness Scale score ≥11. EDS-associated factors were evaluated using Poisson regression analysis after adjustment for multiple confounders. Of the participants (mean age, 52.2 ± 8.0 yr), 28.7% were engaged in shift work, and the overall prevalence of EDS was 24.6%. EDS-associated factors were investigated separately in women aged <40 yr (n=250), 40-59 yr (n=7,467), and ≥60 yr (n=2,011). Current engagement in shift work (prevalence ratio: 1.92 [95% confidence interval: 1.20-3.06], compared with no experience of shift work) and obesity (2.08 [1.11-3.88] for BMI ≥30 and 1.39 [1.02-1.90] for BMI of 25.0-30.0, compared with BMI of 18.5-25.0) showed an independent association with EDS in women aged ≥60 yr. The effect of shift work on EDS in female nurses differed by age, as shift work and obesity contributed to EDS only in older participants. Shift work should be assigned after full consideration of age, sleep, and health status to minimize medical errors.

The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis.

INTRODUCTION: Although synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30-50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months. MATERIALS AND METHODS: The Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method. RESULTS: Bisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients. CONCLUSION: The 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

Effect of Flavanol-Rich Cacao Extract on the Profile of Mood State in Healthy Middle-Aged Japanese Women: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

To investigate the effects of flavanol-rich cacao extract on healthy middle-aged women's fatigue and mood conditions, we conducted a randomized, double-blind, placebo-controlled study in women aged 40-60 years who had reported fatigue and had shown high levels of a serum oxidative stress marker. We randomized the participants (n = 60) into equal groups receiving either a beverage containing cacao flavanols (240 mg/200 mL/day) or a placebo for 8 weeks. Before and after the 8-week treatment, we determined the participants' Chalder fatigue scale (CFS) scores, various mood states, autonomic nervous system (ANS) activity levels, and their ANS balance. The results demonstrated that among the mood states, the indicators of negative mood (e.g., depression, fatigue, and anger) and the total mood disturbance score were significantly lower in the cacao group compared to the placebo group after the treatment (p < 0.05). The change in the index of positive mood (i.e., vigor) from baseline to 8 weeks was significantly higher in the cacao group versus the placebo group (p < 0.05). There were no significant between-group differences in the changes in the CFS score or ANS activity level. The consumption of flavanol-rich cacao extract both suppressed negative moods and promoted positive moods in healthy middle-aged women. These results suggest that cacao flavanols may be a useful food material that can improve variable mood conditions in middle-aged women and support their active lives.

Gender Differences in Premenstrual Syndrome and Premenstrual Dysphoric Disorder Diagnosis and Treatment among Japanese Obstetricians and Gynecologists: A Cross-Sectional Study.

Premenstrual symptoms are characterized by unpleasant psychophysical symptoms that appear during the luteal phase before menstruation and interfere with a woman's quality of life. Premenstrual syndrome (PMS) is a pathological condition with premenstrual symptoms, of which premenstrual dysphoric disorder (PMDD) is a particularly severe psychological symptom. This study aimed to examine the gender differences in the diagnosis and treatment of PMS and PMDD among obstetricians and gynecologists (OB/GYNs) in Japan. Data were obtained from the survey conducted by the Japanese Society of Obstetrics and Gynecology. We used data from 1,257 of the 1,265 OB/GYNs who are engaged in PMS/PMDD practice and reported their gender. Multivariate regression analysis adjusted for propensity scores was performed. Female OB/GYNs were more frequently engaged in treating patients with PMS/PMDD than males [odds ratio (OR) 1.74; 95% confidence interval (CI) 1.36-2.21]. With regard to the diagnostic methods, more female OB/GYNs selected the two-cycle symptom diary than males (OR 2.88; 95% CI 1.80-4.60). Regarding treatment, fewer female OB/GYNs selected selective serotonin reuptake inhibitors as their first-line drug (OR 0.39; 95% CI 0.17-0.89). Gender differences were found in the selection of PMS/PMDD diagnosis and treatment methods among Japanese OB/GYNs.

Women's Health Care Committee, Japan Society of Obstetrics and Gynecology: Annual report-2023.

The Women's Health Care Committee was established in 2010 with the goal of improving women's health. In the current academic year, there are six subcommittees focusing on conducting the following surveys: (1) the current status of pregnancy-associated breast cancer in Japan; (2) surgery for disorders of sex development; (3) diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder; (4) obstetrics and gynecology-based treatment for patients with eating disorders in Japan; (5) multi-drug-resistant bacterial infections in the field of obstetrics and gynecology; and (6) changing the methodology of the treatment of dysmenorrhea and continuing medical education. The activities of each subcommittee are described below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2023;75(6):662-86).

Efficacy and safety of lemborexant in midlife women with insomnia disorder.

OBJECTIVE: Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a subgroup of midlife women (age, 40-58 y) from Study E2006-G000-303 (Study 303; SUNRISE-2). METHODS: This was a randomized, double-blind, placebo (PBO)-controlled (first 6 mo) study of adults with insomnia disorder ( N = 949). During treatment period 1 (TP1), participants received PBO or LEM 5 mg (LEM5) or 10 mg (LEM10). During TP2 (second 6 mo), LEM participants continued their assigned dose; PBO participants were rerandomized to LEM5 or LEM10. Assessments included patient-reported sleep- and fatigue-related measures and treatment-emergent adverse events. RESULTS: The midlife female subgroup comprised 280 of 949 participants (TP1: PBO, n = 90 of 318 [28.3%]; LEM5, n = 82 of 316 [25.9%]; LEM10, n = 108 of 315 [34.3%]). At 6 months, median changes from baseline in subjective sleep-onset latency (in minutes) were -17.9, -20.7, and - 30.4 for PBO, LEM5, and LEM10 (vs PBO: LEM5, P = not significant; LEM10, P = 0.0310). At 6 months, mean changes from baseline in subjective wake after sleep onset (in minutes) were -37.0 (59.6), -50.1 (74.5), and -54.5 (65.4) for PBO, LEM5, and LEM10 (vs PBO: LEM5 and LEM10, P = not significant), with benefits sustained through 12 months. Greater decreases from baseline (improvement) in Insomnia Severity Index total score and Fatigue Severity Scale total score were seen with LEM versus PBO at 6 months; benefits continued through 12 months. Most treatment-emergent adverse events were mild to moderate in severity. CONCLUSIONS: Consistent with the total population, subjective sleep parameters improved, and improvement was sustained over time in midlife women. LEM was well tolerated, suggesting that LEM may be a potential treatment option for midlife women with insomnia.

Current status and problems in the diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder from the perspective of obstetricians and gynecologists in Japan.

AIM: To investigate the current status and problems in the diagnosis and treatment of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) from the perspective of obstetricians and gynecologists (OB/GYNs) in Japan, the Japanese Society of Obstetrics and Gynecology (JSOG) conducted a national-wide survey. METHODS: An email survey was sent to all JSOG members (16 732) and a web-based survey was conducted using a Google form between September and November 2021. The current status and problems in PMS/PMDD diagnosis and treatment were surveyed in this cross-sectional study. RESULTS: In total, 1312 respondents (7.8% of all JSOG members) completed the questionnaire. In terms of diagnoses and treatment, OB/GYN was preferred over psychiatrist for PMS (91.4% vs. 45%); however, no differences were noted for PMDD (76.1% vs. 73.7%). A total of 1267 (96.6%) respondents engaged in routine PMS/PMDD treatment. Regarding the general diagnosis procedure, 84.4% respondents answered "only a vague medical interview," 8.4% kept a two-cycle symptom diary, and 10.3% used a screening questionnaire. The most commonly used medication was oral contraceptive pills (OCPs) (98.1%), followed by the Kampo, traditional Japanese herbal medicines, Kamishoyosan (73.6%). Concerning first-line drugs for treatment, OCPs were the most common (76.8%), followed by Kampo medicine (19.5%); selective serotonin reuptake inhibitors (SSRIs) were less frequently used (2.6%). Regarding first-line drugs among OCPs, 65.1% respondents reported drospirenone-ethinylestradriol use. CONCLUSIONS: This study indicates that only a few OB/GYNs practicing PMS/PMDD in Japan use a prospective diary, which is an essential diagnostic criterion for PMS/PMDD. Regarding treatment, SSRIs were used less frequently.

Investigation of exacerbating factors for postpartum hair loss: a questionnaire-based cross-sectional study.

Background: Although postpartum hair loss is believed to be common, there is little reliable information. Objective: We sought to examine the factors that were associated with postpartum hair loss and to elucidate factors correlated with its pathogenesis. Methods: We carried out a questionnaire-based cross-sectional study. The study participants were women who delivered at 2 facilities and filled the questionnaire 10-18 months after delivery. The survey questionnaire included baseline characteristics, pregnancy details, delivery, childcare, and extent of postpartum hair loss. We divided participants into 2 groups according to the absence or presence of postpartum hair loss and performed logistic regression analyses. Results: A total of 331 (21.0%) responses were analyzed; among these 304 (91.8%) women had postpartum hair loss. The average time for the start, peak, and end of hair loss was 2.9, 5.1, and 8.1 months, respectively. Women with hair loss had an earlier time of delivery, a lower birth weight, a higher preterm labor rate, and longer-term breastfeeding. Logistical regression analyses revealed that longer-term breastfeeding and preterm labor were independent predictors of postpartum hair loss. The adjusted odds ratio for postpartum hair loss in women who ended breastfeeding 6-12 months postpartum versus those who ended it after 12 months or more was 5.96 (95% confidence interval [CI] [1.68, 21.09]) and 6.37 (95% CI [1.95, 20.76]) compared with those who stopped breastfeeding within 6 months postpartum. Limitations: Finer details such as pregnancy complications and delivery information may not be accurate since all results are based on questionnaire responses. There may be a sampling bias because women who suffer from postpartum hair loss may tend to participate more frequently. Conclusion: Over 90% of women experienced postpartum hair loss. Our data show that long-term breastfeeding and preterm labor correlate with postpartum hair loss.

Body weight and body fat are negatively associated with severe dyspareunia in postmenopausal women.

AIM: This cross-sectional study aimed to investigate the factors associated with dyspareunia in pre-, peri-, and postmenopausal Japanese women participating in the health and nutrition education program at a menopause clinic. METHODS: First-visit records of 1702 pre-, peri-, and postmenopausal Japanese women (aged 40-79 years) were analyzed. The relationship between severe dyspareunia and background characteristics was examined by multivariate logistic regression analysis. RESULTS: The average age of the participants was 53.0 ± 6.3 years. The percentage of women who suffered from severe dyspareunia in the pre-, peri-, postmenopausal, and the hormone therapy receiving groups were 7.1%, 10.5%, 14.6%, and 7.8%, respectively. In the postmenopausal group, the percentage of women affected by severe dyspareunia was the highest between 2 and 5 years after menopause (18.8%), presumably owing to the gradual postmenopausal decline in the number of sexually active women. In sexually active postmenopausal women, body weight, body mass index (BMI), and body fat percentage (BF%) differed significantly among those who had severe dyspareunia (N = 119) and those who did not (N = 334). BMI and BF% were negatively associated with severe dyspareunia, even after adjustment for age and years since menopause (adjusted odds ratio [95% confidence interval]: BMI, 0.894 [0.825-0.964], p = 0.003; BF%, 0.947 [0.909-0.985], p = 0.006). CONCLUSIONS: BMI and BF% were negatively associated with dyspareunia in sexually active postmenopausal women. In addition to aging, the loss of body weight and fat could negatively impact intercourse in sexually active postmenopausal women.

Women's Health Care Committee, Japan Society of Obstetrics and Gynecology: Annual report-2022.

The Women's Health Care Committee was instituted in 2010 with the goal of improving women's health. In the current academic year, there are 6 subcommittees focusing on conducting the following surveys: (1) Current status of pregnancy-associated breast cancer in Japan; (2) Surgery for disorders of sex development; (3) Diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder; (4) Obstetrics and gynecology-based treatment for patients with eating disorders in Japan; (5) Multi-drug-resistant bacterial infections in the field of obstetrics and gynecology; and (6) Changing methodology of treatment of dysmenorrhea and continuing medical education. The activities of each subcommittee are detailed below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2022;74(6): XXX-XXX).

Fractures within 2 years of an obstetric hospitalization: analysis of nationwide administrative data in Japan.

INTRODUCTION: Pregnancy- and lactation-associated osteoporosis (PLO) is a condition in which young women develop fractures during pregnancy or breastfeeding. Though PLO is a severely debilitating disease, its pathophysiology and epidemiology have not been clarified and its treatment has not been established. We aimed to identify the incidence and factors associated with fractures occurring within 2 years following an obstetric hospitalization. MATERIALS AND METHODS: We extracted data on fractures occurring within 2 years of an obstetric hospitalization from the Japanese Diagnosis Procedure Combination database. We analyzed the implementation of bone mineral density and bone metabolism marker tests, prescription status, and factors associated with fractures occurring within 2 years of an obstetric hospitalization. RESULTS: Among 837,347 patients with a history of obstetric hospitalization from 2010 to 2014, 379 patients had a history of hospitalization due to a fracture occurring within 2 years (4.5/10,000 pregnancies). Among the patients with fractures occurring within 2 years of an obstetric hospitalization, 6.7% underwent bone mineral quantification or a bone metabolism marker test, and 7.5% were prescribed a lactation inhibitor or osteoporosis treatment. Factors associated with fractures occurring within 2 years following an obstetric hospitalization identified included Cushing syndrome, Charlson Comorbidity Index score ≥ 1, age ≥ 40 years old at pregnancy, smoking history, and steroid administration. CONCLUSION: We investigated fracture cases occurring within 2 years of an obstetrics hospitalization. This finding may be useful in selecting preventative measures for patients at risk of fractures within 2 years after obstetric hospitalization, including PLO.

The Inverse Correlation of Isoflavone Dietary Intake and Headache in Peri- and Post-Menopausal Women.

This study investigated the relationship between headache and dietary consumption of a variety of nutrients in middle-aged women. This cross-sectional analysis used first-visit records of 405 women aged 40-59 years. The frequency of headaches was assessed using the Menopausal Health-Related Quality of Life Questionnaire. Of the 43 major nutrient intakes surveyed using the brief-type self-administered diet history questionnaire, those that were not shared between women with and without frequent headaches were selected. Multiple logistic regression analysis was used to identify nutrients independently associated with frequent headaches. After adjusting for background factors related to frequent headache (vasomotor, insomnia, anxiety, and depression symptoms), the estimated dietary intake of isoflavones (daidzein + genistein) (mg/1000 kcal/day) was negatively associated with frequent headaches (adjusted odds, 0.974; 95% confidence interval, 0.950-0.999). Moreover, the estimated isoflavone intake was not significantly associated with headache frequency in the premenopausal group, whereas it significantly correlated with that in the peri- and post-menopausal groups. Headache in peri- and post-menopausal women was inversely correlated with the dietary intake of isoflavones. Diets rich in isoflavones may improve headaches in middle-aged women.

Sleep apnea in postmenopausal women is associated with joint pain severity and fatigability: a cross-sectional study.

OBJECTIVE: This study aimed to investigate the relationships between sleep apnea parameters and various symptoms in postmenopausal women who had treatment-resistant sleep disorders. METHODS: The respiratory disturbance index (RDI), the number of times apnea-hypopnea occurred in an hour, and transcutaneous oxygen saturation (SpO2) were monitored during one night of sleep using a portable monitoring device in 51 postmenopausal women who did not have an improved subjective sleep quality with the use of hypnotics. Physical and psychological health statuses and subjective sleep disturbance were evaluated using validated questionnaires, including the Epworth Sleepiness Scale, the Cornell Medical Index, and the Questionnaire for Assessment of Climacteric Syndrome in Japanese Women. The associations between RDI, nadir SpO2 and various symptoms, as well as cardiovascular parameters, such as blood pressure, serum lipid profile, and glucose tolerance, were analyzed separately. RESULTS: Among the 51 study participants, seven (13.7%) were diagnosed with obstructive sleep apnea. After adjustment for age, body mass index, and the background factors related to RDI and nadir SpO2, the association remained significant between a higher RDI and joint pain (Questionnaire for Assessment of Climacteric Syndrome in Japanese Women) (standardized partial regression coefficient [ß] = 0.423, P  = 0.016), and between lower nadir SpO2 and fatigability (Cornell Medical Index) (ß = -0.472, P  = 0.007). CONCLUSIONS: Detailed examination of sleep-disordered breathing is warranted in women with severe joint pain and fatigability.

Annual report of the Women's Healthcare Committee, Japan Society of Obstetrics and Gynecology, 2021.

Our committee was founded in 2010 with the goal of improving women's health. This academic year we focused on the following five activities for the second consecutive year: cooperation between the department of pediatric surgery and the department of obstetrics and gynecology for the treatment of persistent cloaca and Mayer-Rokitansky-Küster-Hauser syndrome in Japan; assessment of the educational training of women's healthcare advisers; increasing screening for breast and cervical cancer; conducting the Nationwide Survey of Prescribing Practices for the Treatment of Menopausal Symptoms; and preventing osteoporosis in survivors of gynecologic cancer. The activities of each subcommittee are detailed below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2021;73(6):684-699).

Vasomotor symptoms, sleep problems, and depressive symptoms in community-dwelling Japanese women.

AIM: To assess prevalence and characteristics of vasomotor symptoms in community-dwelling Japanese women. METHODS: These were cross-sectional analyses using data from the National Institute for Longevity Sciences-Longitudinal Study of Aging. The main outcome measures were prevalence and severity of hot flashes and sweating. Associations between hot flashes/sweating (slight, moderate, or severe vs none) and sleep problems were explored using logistic regression, with and without adjustment for age, daily physical activity, and number of urinations/night. Associations between hot flashes/sweating and sleep problems, depressive symptoms, and dietary variables were explored in logistic regression models or general linear models. RESULTS: A total of 1152 women between 40 and 91 years of age were enrolled. Hot flashes were reported by 24.5% of participants; with prevalence and severity highest in those 50-54 years or 2-5 years postmenopause. Sleep problems were reported 15 percentage points more frequently by women who reported hot flashes than by those without hot flashes. Adjusted odds ratios [95% CI] for difficulty in falling asleep and difficulty in sleeping through were 2.09 [1.565-2.796] and 2.07 [1.549-2.763]), respectively. Also, hot flashes were associated with higher risk of depressive symptoms (adjusted odds ratio [95% CI]: 2.99 [2.07-4.32]) and lower life satisfaction, self-esteem, and self-rated health status. A similar pattern was observed in women with and without sweating. No associations were found between hot flashes and dietary factors. CONCLUSIONS: Clear associations were found between hot flashes and sleeping problems, even after adjusting for potential confounding factors. Women who reported hot flashes also reported worse mental and physical health than those who did not report hot flashes.

Independent association of palpitation with vasomotor symptoms and anxiety in middle-aged women.

OBJECTIVE: Palpitation, or the sensation of rapid or irregular heartbeats, is common in menopausal women; however, the precise underlying mechanisms are unknown. We aimed to investigate factors associated with palpitation in middle-aged women. METHODS: Medical records of 394 women aged 40 to 59 years (108 premenopausal, 85 perimenopausal, and 201 postmenopausal) were analyzed cross-sectionally. Palpitation severity was estimated based on responses to the Menopausal Symptom Scale. Effects of background characteristics, including age, menopausal status, body composition, cardiovascular parameters, basal metabolism, physical fitness, lifestyle factors, vasomotor, and psychological symptoms on palpitation were assessed using multivariate logistic regression analysis. The association between autonomic nervous system activity and palpitation was also analyzed in 198 participants. RESULTS: Prevalence of palpitation by severity was as follows: none, 26.4%; mild, 32.7%; moderate, 29.4%; severe, 11.4%. In univariate analyses, the more severely the women were affected by palpitation, 1) the higher their systolic blood pressure, 2) the less exercise they performed, 3) the lower they scored in the sit-and-reach test, 4) the higher their vasomotor symptoms score in the Menopausal Health Related-Quality of Life questionnaire, and 5) the higher their Hospital Anxiety and Depression Scale. Multiple logistic regression analysis revealed that moderate to severe palpitation was independently associated with the vasomotor symptom score (adjusted odds ratio [95% confidence interval]: 1.18 [1.07-1.31]) and Hospital Anxiety and Depression Scale anxiety subscale score (1.19 [1.12-1.27]). CONCLUSIONS: Rapid or irregular heartbeats are highly prevalent in middle-aged women. It is not associated with age, menopausal status, heart rate, arrhythmia, autonomic nervous system activity, caffeine, or alcohol consumption, but with vasomotor symptoms and anxiety.