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.

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.

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).

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.

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).

Guideline for Gynecological Practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition.

Nine years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 4th Revised Edition was published in 2020. The 2020 Guidelines includes 4 additional clinical questions (CQ), which brings the total to 99 CQ (12 on infectious disease, 29 on oncology and benign tumors, 29 on endocrinology and infertility and 29 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Annual report of the Women's Health Care Committee, Japan Society of Obstetrics and Gynecology, 2020.

Our committee was founded in 2010 with the goal of improving women's health. This academic year, we focused on five activities: cooperation between the departments of pediatric surgery and 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 health-care 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 2020;72(6):697-707).

The Diverse Efficacy of Food-Derived Proanthocyanidins for Middle-Aged and Elderly Women.

Middle-aged and elderly women are affected by various symptoms and diseases induced by estrogen deficiency. Proanthocyanidins, widely present in many kinds of fruits and berries, have many beneficial effects, such as antioxidative, anti-inflammatory, and antimicrobial activities. We researched the effects of proanthocyanidins for middle-aged and elderly women, finding that it has been revealed in many clinical trials and cohort studies that proanthocyanidins contribute to the prevention of cardiovascular disease, hypertension, obesity, cancer, osteoporosis, and urinary tract infection, as well as the improvement of menopausal symptoms, renal function, and skin damage. Thus, proanthocyanidins can be considered one of the potent representatives of complementary alternative therapy.

Daily Coffee and Green Tea Consumption Is Inversely Associated with Body Mass Index, Body Fat Percentage, and Cardio-Ankle Vascular Index in Middle-Aged Japanese Women: A Cross-Sectional Study.

This study aimed to investigate the links between coffee (CF)/green tea (GT) consumption and body composition/cardiovascular parameters in middle-aged Japanese women. We conducted a cross-sectional study of 232 Japanese women aged 40-65 years who had been referred to the menopause clinic of Tokyo Medical and Dental University Hospital between November 2007 and August 2017. Body composition, cardiovascular parameters, and CF/GT consumption frequency were evaluated on their initial visits, using a body composition analyzer, vascular screening system, and brief-type self-administered diet history questionnaire, respectively. We investigated the associations between variables using multivariate logistic regression. After adjustment for age, menopausal status, and other factors, daily CF consumption was inversely associated with high body mass index (BMI) (adjusted odds ratio, 0.14; 95% confidence interval, 0.14-0.96) and body fat percentage (BF%) (0.33; 0.14-0.82), and daily GT consumption with high BF% (0.36; 0.14-0.96). Daily CF + GT consumption was also inversely associated with high BMI (0.15; 0.05-0.50) and BF% (0.30; 0.12-0.74). In pre- and perimenopausal women, daily CF + GT consumption was inversely associated with high cardio-ankle vascular index (CAVI) (0.05; 0.003-0.743). In conclusion, daily CF/GT consumption was inversely associated with high BMI, BF%, and CAVI in middle-aged Japanese women.

Management manual for cancer treatment-induced bone loss (CTIBL): position statement of the JSBMR.

Androgen deprivation therapy and aromatase inhibitors are known to cause a decrease in bone mineral density and an increase in fractures. Patients receiving these treatments have been shown to have a fracture risk equal to or greater than that of patients with osteoporosis with prevalent fractures. This manual was created to prevent fractures in patients with cancer treatment-induced bone loss with high fracture risks who cannot be treated under the current Japanese guideline for the prevention and treatment of osteoporosis. This manual recommends drug treatment for patients with BMD - 2.0 ≤ T score < - 1.5 with the family history of hip fracture or 15% or more 10-year probability of major osteoporotic fractures by FRAX®; or in patients with BMD T score < - 2.0. It is important to verify whether the use of this manual can reduce fractures and improve the quality of life of patients with cancer treatment-induced bone loss by prospective studies.

Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study.

This study aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension. We conducted a randomized, double-blind, placebo-controlled study on 6 men and 24 women aged 40-64 years old. The participants were randomized to receive tablets containing either low-dose (200 mg/day) or high-dose (400 mg/day) GSPE, or placebo, for 12 weeks. Systolic and diastolic blood pressures (SBP and DBP, respectively), brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured before and after 4, 8, and 12 weeks of treatment. The mean SBP in the high-dose group significantly decreased by 13 mmHg after 12 weeks (P = 0.028), although FMD did not change. In an ad hoc analysis of non-smoking participants (n = 21), the mean SBP, DBP, stiffness parameter ß, distensibility, incremental elastic modulus (Einc), and pulse wave velocity (PWV) also significantly improved in the high-dose group after 12 weeks. Changes in Einc and PWV from baseline to 12 weeks were significantly greater in the high-dose group than in the placebo group (Einc, P = 0.023; PWV, P = 0.03). GSPE consumption could help maintain vascular elasticity and normal blood pressure in this population.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2017 edition.

Six years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the third revised edition was published in 2017. The 2017 Guidelines includes 10 additional clinical questions (CQ), which brings the total to 95 CQ (12 on infectious disease, 28 on oncology and benign tumors, 27 on endocrinology and infertility and 28 on healthcare for women). Currently a consensus has been reached on the Guidelines and therefore the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding recommendation level (A, B, C) is indicated.

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.

[Pharmacokinetics of selective estrogen receptor modulators(SERMs).]

Selective estrogen receptor modulators(SERMs), or estrogen receptor agonists/antagonists(ERAAs), are a class of compounds that function as estrogen receptor(ER)agonists or antagonists tissue-dependently. Two types of SERMs are currently used in Japan to treat osteoporosis, raloxifene(RLX:Evista)and bazedoxifene(BZA:Viviant). This article describes the pharmacokinetics of these two drugs.

Dkk-3 induces apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer cells.

OBJECTIVE: Dkk-3 is a Wnt signaling inhibitor that is frequently inactivated in human cancers. Dkk-3 possesses an antiproliferative activity and induces apoptosis in tumor cells, suggesting that it functions as a tumor suppressor. In this study, we investigated the molecular function of Dkk-3 in human ovarian cancer cells. METHODS: We assessed the levels of Dkk-3 protein expression in human mucinous and clear cell ovarian cancer cells, and compared cell viabilities between cell lines that expressed Dkk-3 and those that did not, as well as between cells that expressed Dkk-3 and those whose expression of Dkk-3 was reduced by small interfering RNA. We also evaluated the characteristic fragmentation of DNA to detect apoptosis in Dkk-3-deficient cells. To further investigate the molecular mechanisms of apoptosis, we assessed the expression of molecules involved in apoptosis signaling pathways in Dkk-3-deficient cells. RESULTS: The expression of the Dkk-3 protein was observed in most of the ovarian cancer cell lines tested. Dkk-3-deficient cells showed faster growth than Dkk-3-replete cells. The characteristic fragmentation of DNA was not observed in Dkk-3-deficient cells, which showed decreased levels of expression in caspase-3, activated caspase-9, Bax, p53, activated caspase-8, and Fas/CD95, as well as an increase in Bcl-2 expression. CONCLUSIONS: Although Dkk-3 expression was observed in most of human ovarian cancer cell lines, Dkk-3 has a tumor-suppressive function and a proapoptotic effect, inducing apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer MCAS cells.

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 oral estradiol and levonorgestrel on cardiovascular risk markers in postmenopausal women.

PURPOSE: This study aimed at investigating changes in postmenopausal women's cardiovascular risk markers induced by hormone therapy regimens of low (1.0 mg) or ultra-low (0.5 mg) doses of micronized estradiol (mE(2)) and levonorgestrel (LNG). METHODS: Three randomized placebo-controlled trials were reanalyzed with regard to changes in cardiovascular risk markers, such as serum lipids, lipoproteins, and coagulation parameters. Trial 1 (n = 210) was an 8-week study comparing the effects of 1.0 or 0.5 mg of unopposed mE(2) on menopausal symptoms. Trial 2 (n = 194) was a 24-week study comparing the effects of 1.0 mg of mE(2) combined with 10, 20, or 40 µg of LNG on endometrial safety. Trial 3 (n = 195) was a 52-week study comparing the effects of 1.0 or 0.5 mg mE(2) + 40 µg LNG on bone metabolism. RESULTS: 1.0 mg of unopposed mE(2) reduced low-density lipoprotein cholesterol (LDL-C) after as little as 8 weeks. 1.0 mg mE(2) for 24 weeks lowered the serum levels of total cholesterol (TC) and LDL-C, whereas the addition of LNG caused decreases in the levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in a dose-dependent fashion. 1.0 or 0.5 mg mE(2) + 40 µg LNG for 52 weeks also lowered the levels of TC, HDL-C, LDL-C, and TG. Both regimens slightly lowered antithrombin and Protein C activities within normal limits. CONCLUSIONS: Hormone therapy using 1.0 or 0.5 mg of mE(2) and LNG lowers the serum levels of TC, HDL-C, LDL-C, and TG without significantly affecting coagulation/fibrinolysis parameters.

[Bone and calcium metabolism in menopause transition].

Menopause, or estrogen deficiency, predispose women towards fragility fractures resulting from impaired bone strength, as the composite consequence of : (1) increased bone resorption caused by proliferation and activation of osteoclasts ; (2) dissociation of coupling bone formation with resorption ; (3) deterioration of bone quality ; (4) decreased calcium absorption from intestines and resorption from renal tubules. The current explanation of each phenomenon is described in this article, although the exact mechanisms have not been unanimously defined.