Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls.

OBJECTIVE: Menopausal transition has been known to be associated with the loss of muscle mass. However, muscle health in women with premature menopause, that is, premature ovarian insufficiency (POI), remains unclear. We aimed to investigate and compare muscle mass parameters and the prevalence of low muscle mass between patients with spontaneous POI and healthy controls. METHODS: In this cross-sectional study, 59 women with spontaneous POI and 57 premenopausal controls with normal ovarian function were enrolled at the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) from June 17, 2020, to August 20, 2021. Muscle mass parameters were measured by dual-energy x-ray absorptiometry, and low muscle mass was diagnosed using the Asian Working Group for Sarcopenia criteria. In addition, participants provided their sociodemographic data, menstrual and reproductive history, lifestyle factors, and medical history. Multivariate linear regression analysis was conducted. RESULTS: Muscle mass parameters, including appendicular skeletal muscle mass (ASM), ASM/height2, ASM/weight, ASM/body mass index, total skeletal muscle mass (TSM), and TSM/weight, were significantly lower in women with POI as compared with healthy controls (ASM: 14.62 ± 2.08 vs 15.97 ± 1.78, P < 0.001; ASM/height2: 5.71 ± 0.64 vs 6.15 ± 0.62, P < 0.001; ASM/weight: 0.27 [0.25, 0.28] vs 0.28 [0.27, 0.29], P = 0.002; ASM/BMI: 0.68 ± 0.07 vs 0.73 ± 0.06, P = 0.001; TSM: 33.85 ± 4.08 vs 36.43 ± 3.56, P < 0.001; TSM/weight: 0.63 [0.59, 0.65] vs 0.64 [0.61, 0.67], P = 0.02). The prevalence of low muscle mass in POI patients was significantly higher than that in controls (32.20% vs 8.77%, χ2 = 9.70, P = 0.002). Furthermore, multivariate linear regression analyses demonstrated that POI status was an independent risk factor for ASM (ß = -1.13; 95% CI, -1.62 to -0.65), ASM/height2 (-0.35, -0.47 to -0.22), ASM/weight (-0.01, -0.02 to -0.009), ASM/BMI (-0.05, -0.07 to -0.02), TSM (-2.16, -3.14 to -1.17), and TSM/weight (-0.03, -0.04 to -0.02). CONCLUSIONS: Women with POI exhibit significant loss of muscle mass as compared with healthy controls. Early diagnosis and long-term health management in POI patients are important.

Impact of premature natural menopause on body composition and physical function in elderly women: A Korean frailty and aging cohort study.

ABSTRACT: Induced premature menopause accelerates the rate of body composition changes (decrease in skeletal muscle mass and increase in fat mass) and deteriorating physical function. However, few studies have focused on the impact of premature natural menopause. This study aimed to investigate the impact of age at natural menopause (ANM) on body composition and physical function in elderly women.Using data from the Korean Frailty and Aging Cohort Study, 765 community-dwelling elderly women aged 70 to 85 years who experienced natural menopause were recruited in this study. Body composition was measured using dual-energy X-ray absorptiometry. Physical function was evaluated by grip strength, the timed up and go test (TUG), and the short physical performance battery (SPPB). Participants were categorized into 4 groups according to their ANM: <40 (premature natural menopause, PNM), 40 to 44 (early natural menopause, ENM), 45 to 54 (normal menopause, NM), and ≥55 (late menopause, LM) years.There were no significant differences in the body composition parameters, such as the appendicular skeletal muscle mass index (PNM: 5.90 ±â€Š0.90 vs ENM: 5.91 ±â€Š0.70 vs NM: 5.85 ±â€Š0.73 vs LM: 5.90 ±â€Š0.75, kg/m2, P = .75) and trunk fat mass index (PNM: 19.4 ±â€Š3.9 vs ENM: 19.9 ±â€Š4.4 vs NM: 19.9 ±â€Š3.9 vs LM: 20.0 ±â€Š3.8, %, P = .87) between the groups. In the physical function evaluation, there was no significant difference between the groups in grip strength (PNM: 19.8 ±â€Š0.6 vs ENM: 20.3 ±â€Š0.4 vs NM: 20.6 ±â€Š0.2 vs LM: 20.6 ±â€Š0.4, kg, P = .53). However, in the TUG (PNM: 11.8 ±â€Š0.4 vs ENM: 10.3 ±â€Š0.3 vs NM: 10.6 ±â€Š0.1 vs LM: 10.2 ±â€Š0.3, seconds, P < .01) and SPPB (PNM: 10.0 ±â€Š0.2 vs ENM: 10.5 ±â€Š0.2 vs NM: 10.6 ±â€Š0.1 vs LM: 10.8 ±â€Š0.2, points, P < .05), the PNM group showed significantly lower values than the other groups did. There was no difference in physical function between the groups except the PNM.Premature natural menopause did not affect the body composition in elderly women but was associated with physical function deterioration. Therefore, more attention should be paid to the prevention of the physical function deterioration caused by premature natural menopause in elderly women.

Assessment of premature menopause on the sexual function and quality of life in women.

INTRODUCTION: Premature Ovarian Insufficiency (POI) is characterized by ending menstruation in women under 40 years of age. It has a significant effect on women's sexuality and mental health and quality of life. This study aimed to evaluate the sexual function and quality of life of premature menopausal women. METHODS: This study was a case-control study on 132 people (66 women with a diagnosis of POF and 66 women of reproductive age with normal ovarian function) who were matched in terms of the age, presenting to Women's Clinic in Jahrom in 2019. The WHOQOL-BREF questionnaire and the Female Sexual Function Index (FSFI) questionnaire were used to collect data. p < .05 was considered statistically significant. RESULTS: The mean score of sexual function in premature menopausal women was 21.35 ± 4.82 and in non-menopausal women was 25.4 ± 6.61 (OR = 0.11, 95% CI = 0.04-0.28). All areas of sexual function; desires disorder (OR = 0.21 95% CI = 0.07-0.56), Arousal disorder(OR = 0.28, 95% CI = 0.08-0.93), orgasm disorder (OR = 0.36 95% CI = 0.16-0.80), lubrication disorder (OR = 0.21 95% CI= 0.05-0.78), satisfaction disorder (OR = 0.11, 95% CI = 0.04-0.28) and quality of life domains: physical health (OR = 0.4 95%CI = 0.06-0.3), mental health (OR = 0.28 95% CI = 0.06-0.1), environmental health (OR = 0.22 95%CI = 0.04-0.6) and social health (OR = 0.28 95%CI = 0.01-0.2) saw a decrease in the premature menopausal women group compared to the control group. CONCLUSION: The results demonstrated that premature menopausal women are found to be weaker than the control group in all areas of sexual function and quality of life. Among the areas of sexual function, such as libido, arousal, satisfaction, and pain have the most impact on quality of life. Therefore, based on the results from improving sexual function, this issue can improve the quality of life.

Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women.

BACKGROUND: Premature menopause is an independent risk factor for cardiovascular disease in women, but mechanisms underlying this association remain unclear. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic cells with leukemogenic mutations without detectable malignancy, is associated with accelerated atherosclerosis. Whether premature menopause is associated with CHIP is unknown. METHODS: We included postmenopausal women from the UK Biobank (n=11 495) aged 40 to 70 years with whole exome sequences and from the Women's Health Initiative (n=8111) aged 50 to 79 years with whole genome sequences. Premature menopause was defined as natural or surgical menopause occurring before age 40 years. Co-primary outcomes were the presence of any CHIP and CHIP with variant allele frequency >0.1. Logistic regression tested the association of premature menopause with CHIP, adjusted for age, race, the first 10 principal components of ancestry, smoking, diabetes, and hormone therapy use. Secondary analyses considered natural versus surgical premature menopause and gene-specific CHIP subtypes. Multivariable-adjusted Cox models tested the association between CHIP and incident coronary artery disease. RESULTS: The sample included 19 606 women, including 418 (2.1%) with natural premature menopause and 887 (4.5%) with surgical premature menopause. Across cohorts, CHIP prevalence in postmenopausal women with versus without a history of premature menopause was 8.8% versus 5.5% (P<0.001), respectively. After multivariable adjustment, premature menopause was independently associated with CHIP (all CHIP: odds ratio, 1.36 [95% 1.10-1.68]; P=0.004; CHIP with variant allele frequency >0.1: odds ratio, 1.40 [95% CI, 1.10-1.79]; P=0.007). Associations were larger for natural premature menopause (all CHIP: odds ratio, 1.73 [95% CI, 1.23-2.44]; P=0.001; CHIP with variant allele frequency >0.1: odds ratio, 1.91 [95% CI, 1.30-2.80]; P<0.001) but smaller and nonsignificant for surgical premature menopause. In gene-specific analyses, only DNMT3A CHIP was significantly associated with premature menopause. Among postmenopausal middle-aged women, CHIP was independently associated with incident coronary artery disease (hazard ratio associated with all CHIP: 1.36 [95% CI, 1.07-1.73]; P=0.012; hazard ratio associated with CHIP with variant allele frequency >0.1: 1.48 [95% CI, 1.13-1.94]; P=0.005). CONCLUSIONS: Premature menopause, especially natural premature menopause, is independently associated with CHIP among postmenopausal women. Natural premature menopause may serve as a risk signal for predilection to develop CHIP and CHIP-associated cardiovascular disease.

Menopausal age and left ventricular remodeling by cardiac magnetic resonance imaging among 14,550 women.

The present study included 14,550 postmenopausal female participants in the UK Biobank who completed cardiac magnetic resonance imaging. Earlier age at menopause was significantly and independently associated with smaller left ventricular end-diastolic volume and smaller stroke volume, a pattern suggesting acceleration of previously described age-related left ventricular remodeling. These findings may have implications for understanding mechanisms of heart failure, specifically heart failure with preserved ejection fraction, among women with early menopause.

Ovarian Rejuvenation Through Platelet-Rich Autologous Plasma (PRP)-a Chance to Have a Baby Without Donor Eggs, Improving the Life Quality of Women Suffering from Early Menopause Without Synthetic Hormonal Treatment.

Due to the fact that modern American and European women postpone childbirth until later in life, they are more likely to face the problem of ovarian insufficiency by the time they are ready to have children. So, the ability to restore the ovarian function safely is crucially important. Our study involved 38 women 31-45 years of age with low ovarian reserves and at least two unsuccessful attempts to receive their oocytes through IVF. The blood from the patients was collected into two BD vacutainers for PRP preparation. The platelet concentration in the PRP was 1 × 106 µl. PRP injections into the ovaries were performed by a gynecologist with a special 25G needle, 20 cm in length, as an ultrasound-guided procedure or a laparoscopic-assisted approach. After PRP treatment, women were tested with several criteria for 12 months. We saw a significant improvement in hormone levels; six healthy babies were born, ten pregnancies were achieved, and four out of the ten were from natural conception. The PRP injections into the ovaries are safe, productive, and a natural treatment that may help women with premature ovarian insufficiency to give birth to their own child. The difference and novelty with our method of ovarian rejuvenation is in obtaining a higher platelet concentration (about 1 × 106 µl), which allows us to achieve long-lasting results, within 12 months, after a single procedure. Additionally, for the first time, we proposed and successfully performed a laparoscopically assisted technique for administering PRP into the ovary.

Effects of Hormone Replacement Therapy on Bone Mass After Allogeneic Hematopoietic Stem Cell Transplantation.

CONTEXT AND OBJECTIVES: This study aimed to assess the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in young women who underwent allogeneic hematopoietic stem cell transplantation (HSCT). PARTICIPANTS AND METHODS: This retrospective cohort included 234 female patients with premature ovarian insufficiency (POI) who underwent allogeneic HSCT between April 2009 and April 2016 at Seoul St. Mary's Hospital in Seoul, Korea. Inclusion criteria included adult patients who were age 40 years or younger at the time of transplantation and were followed for at least 3 years after HSCT. RESULTS: At the first and second years after HRT, there was a significant increase in the BMD of the lumbar spine of the HRT group (n = 170) compared to that of the non-HRT group (n = 64) (P = .033 and P = .047, respectively). The BMD of the lumbar spine significantly increased from baseline by 4.16 ±â€…4.39% and 5.42 ±â€…5.86% after 1 and 2 years of HRT, respectively (P = .037 and P = .021). The BMD of the femoral neck and total hip also showed a significant percentage increase from baseline after 2 years of HRT. These changes were significant even in the presence of graft-versus-host disease or steroid exposure. For HRT that was initiated within 12 months after HSCT, the increase in BMD in the lumbar spine was greatest after 2 years of HRT. CONCLUSIONS: These results support that early and active hormonal therapy might be beneficial for BMD in female HSCT recipients with POI.

The role of oxidative stress on subclinical atherosclerosis in premature ovarian insufficiency and relationship with carotid intima-media thickness.

Objective: We aimed to investigate the relationship between oxidative stress (OS) and subclinical atherosclerosis in patients with premature ovarian insufficiency (POI), by analyzing the dynamic thiol/disulfide homeostasis (TDH) parameters as an OS marker and carotid intima-media thickness (CIMT).Materials and methods: A total of 69 women, 34 with POI and 35 healthy controls were included in this prospective cross-sectional study. TDH parameters (plasma native thiol, total thiol, disulfide, disulfide/native thiol, native thiol/total thiol, and disulfide/total thiol ratios) and CIMT were measured and compared between the two groups.Results: In primary ovarian insufficiency group, native thiol (p=.009) and total thiol (p=.010) levels were significantly decreased, and CIMT values were significantly increased (p= <.001). CIMT values were negatively correlated with native thiol (r=-0.553, p=.001) and total thiol levels (r=-0.565, p=.001); and positively correlated with age (r = 0.457, p=.007), BMI (r = 0.408, p=.017), and total cholesterol (r = 0.605, p<.001) in POI group.Conclusions: Decreased native thiol and total thiol levels demonstrate the defective anti-oxidant mechanism in POI. Negative correlation between native thiol, total thiol levels, and CIMT means the presence of abnormal anti-oxidant mechanisms may play a role in the development of subclinical atherosclerosis in patients with POI. This is a novel report on the mechanism of subclinical atherosclerosis in women with POI, which needs to be supported with further studies evaluating the pathophysiology of OS.

Demographic, clinical and hormonal characteristics of patients with premature ovarian insufficiency and those of early menopause: data from two tertiary premature ovarian insufficiency centers in Greece.

The aim of the study was to compare demographic, hormonal and clinical parameters in patients with premature ovarian insufficiency (POI) and women with early menopause in Greece. One hundred thirty-nine women of Greek origin, aged 14-45 years, referring for oligomenorrhea and having elevated FSH concentrations were divided into three groups regarding the age of menstrual disturbances onset [POI1:

Hormone Replacement Therapy Prescription after Premature Surgical Menopause.

STUDY OBJECTIVE: To assess hormone replacement therapy (HRT) prescription pattern in patients undergoing premature surgical menopause on the basis of surgical indication. DESIGN: Retrospective cohort study. SETTING: Academic tertiary care center. PATIENTS: Surgically menopausal patients aged ≤45 years who underwent a minimally invasive hysterectomy with salpingo-oophorectomy. INTERVENTIONS: HRT prescription in the 6-week postoperative period. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients met inclusion criteria. Of these, 52% (n = 33) were prescribed HRT in the 6-week postoperative period. Indications for surgical menopause included pelvic pain or endometriosis (31.7%), gynecologic malignancy (20.6%), BRCA gene mutation (17.4%), breast cancer (9.5%), Lynch syndrome (4.8%), and other (15.8%). In total, 80% of patients with pelvic pain, 25% with gynecologic malignancies, 45% with BRCA gene mutations, 33.3% with breast cancer, and 66.6% with Lynch syndrome used HRT postoperatively. In patients who used HRT postoperatively, 76% were offered preoperative HRT counseling. This is in contrast with those patients who did not use HRT postoperatively, of whom only 33% were offered HRT counseling (p <.001). Perioperative complications were not predictive of HRT use postoperatively. In patients who did not use HRT postoperatively, 13.3% used alternative nonhormonal therapy. CONCLUSION: In patients who underwent premature surgical menopause, 52% used HRT postoperatively. Patients with pelvic pain and Lynch syndrome were more likely to use HRT, whereas those with gynecologic or breast malignancies and BRCA gene mutations were less likely to use HRT. Preoperative HRT counseling was associated with postoperative HRT use.

The cardiovascular risk profile of middle age women previously diagnosed with premature ovarian insufficiency: A case-control study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. METHODS AND FINDINGS: We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8-9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0-98.0) versus 80.7 (IQR: 75.1-86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85-0.93) versus 0.79 (IQR: 0.75-0.83), p < 0.01), systolic blood pressure (124 (IQR 112-135) versus 120 (IQR109-131), p < 0.04) and diastolic blood pressure (81 (IQR: 76-89) versus 78 (IQR: 71-86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1-9.4) versus 7.9 (IQR: 7.1-8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 µm (500-615) versus 684 µm (618-737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7-10.6) versus 6.0% (IQR: 3.9-9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. CONCLUSIONS: Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02616510.

Trajectory analysis of sleep maintenance problems in midlife women before and after surgical menopause: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Investigate temporal patterns of sleep maintenance problems in women who became surgically menopausal (hysterectomy with bilateral oophorectomy) before their final menstrual period and examine whether presurgery trajectories of sleep maintenance problems are related to problems staying asleep postsurgery. METHODS: Longitudinal analysis of sleep self-reports collected every 1 to 2 years from 1996 to 2013 from 176 surgically menopausal women in the Study of Women's Health Across the Nation, a seven-site community-based, multiethnic/multiracial, cohort study. Median follow-up was 15.3 years (4.2 years presurgery, 10.2 years postsurgery). Group-based trajectory modeling was used to identify patterns of problems staying asleep, and the presurgery trajectories were used to predict similar postsurgery sleep problems. RESULTS: Four trajectory patterns of sleep maintenance problems were identified: low (33.5% of women), moderate (33.0%), increasing during presurgery (19.9%), and high (13.6%). One-fifth of women reported a presurgery increase in these problems. Postsurgically, problems staying asleep remained associated with similar levels of presurgical problems, even after adjusting for postsurgical early morning awakening, frequent vasomotor symptoms, and bodily pain score (ßlow = -1.716, ßmoderate = -1.144, ßincreasing = -0.957, ßhigh = -1.021; all P values <0.01). CONCLUSIONS: Sleep maintenance problems were relatively stable across time postsurgery. These data are remarkably consistent with our trajectory results across the natural menopause, suggesting that presurgical assessment of sleep concerns could help guide women's expectations postsurgically. Although reassuring that sleep complaints do not worsen postsurgically for most surgically menopausal women, referral to a sleep specialist should be considered if sleep symptoms persist or worsen after surgery.

Does Type of Menopause Affect the Sex Lives of Women?

BACKGROUND The aim of this study was to investigate factors affecting the sex lives of middle-aged women, and whether surgical menopause affects sexual function differently from natural menopause, by comparing effects on sexual performance of women with similar demographic features. MATERIAL AND METHODS The study included 151 women with surgical menopause (SM), 357 women with natural menopause (NM), and 186 perimenopausal women (PM). The women were asked to complete a 6-question survey of sexual performance parameters. The relationship between the demographic and clinical features and hormone levels of the groups and sexual function parameters were evaluated. We also compared these parameters between the 3 study groups, and paired comparisons were made between the SM group and the NM group. RESULTS Demographic features, serum DHEA-S, total testosterone, and FSH levels were found to have statistically significant effects on sexual performance of women (p<0.05). The sexual function scores for the frequency of sexual desire, coitus, and orgasm were significantly higher in the PM group, whereas vaginal lubrication scores were lower compared to the NM and SM group (p<0.05). In paired comparison of NM and SM, the scores for the frequency of coitus, orgasm, and vaginal lubrication were significantly higher in the SM group, while sexual desire frequency scores were higher in the NM group (p<0.05). CONCLUSIONS Our study approached to this topic in an extended manner and found significant relationships between several demographic-clinical and hormonal factors. SM was found to not affect female sexual performance, except for sexual desire, more than NM.

Cost-utility, cost-effectiveness, and budget impact of Internet-based cognitive behavioral therapy for breast cancer survivors with treatment-induced menopausal symptoms.

PURPOSE: Internet-based cognitive behavioral therapy (iCBT), with and without therapist support, is effective in reducing treatment-induced menopausal symptoms and perceived impact of hot flushes and night sweats (HF/NS) in breast cancer survivors. The aim of the current study was to evaluate the cost-utility, cost-effectiveness, and budget impact of both iCBT formats compared to a waiting list control group from the Dutch healthcare perspective. METHODS: A Markov model was constructed with a 5-year time horizon. Costs and health outcomes were measured alongside a randomized controlled clinical trial and included quality-adjusted life years (QALYs), overall levels of menopausal symptoms, and perceived impact of HF/NS. Uncertainty was examined using probabilistic and deterministic sensitivity analyses, together with a scenario analysis incorporating a different perspective. RESULTS: iCBT was slightly more expensive than the waiting list control, but also more effective, resulting in incremental cost-utility ratios of €23,331/QALY and €11,277/QALY for the guided and self-managed formats, respectively. A significant reduction in overall levels of menopausal symptoms or perceived impact of HF/NS resulted in incremental costs between €1460 and €1525 for the guided and €500-€753 for the self-managed format. The estimated annual budget impact for the Netherlands was €192,990 for the guided and €74,592 for the self-managed format. CONCLUSION: Based on the current trial data, the results indicate that both guided and self-managed iCBT are cost-effective with a willingness-to-pay threshold of well below €30,000/QALY. Additionally, self-managed iCBT is the most cost-effective strategy and has a lower impact on healthcare budgets.

Identifying and addressing osteoporosis knowledge gaps in women with premature ovarian insufficiency and early menopause: A mixed-methods study.

OBJECTIVE: Osteoporosis associated with premature ovarian insufficiency (POI) and early menopause (EM) is a major concern for women. We aimed to (a) identify information and knowledge gaps and behaviours regarding bone health in women with POI/EM and (b) co-design an osteoporosis fact sheet. DESIGN: Mixed-methods study: survey of women and online resource appraisals to develop and refine, using semi-structured interviews, an osteoporosis fact sheet. PATIENTS: Women with POI/EM (menopause before ages 40 and 45 years respectively). MEASUREMENTS: Demographics, comorbidities, information needs, calcium intake, exercise, osteoporosis knowledge (OKAT), beliefs and self-efficacy, DISCERN appraisal (validated scales). ANALYSIS: descriptive statistics, logistic regression and thematic analysis of interviews. RESULTS: Median age of survey respondents (n = 316) was 54(IQR47-63) years, median age of menopause was 40(IQR38-43) years, and osteoporosis diagnosis was reported in 19%. Most reported inadequate dietary calcium intake (99%) and exercise (65%). Median OKAT score 8 [IQR6-10]/19 indicated knowledge gaps regarding risk factors and treatment options. Adjusting for age and education, OKAT predicted calcium intake (OR 1.126 [CI 1.035-1.225]; P = 0.006) and screening (OR 1.186 [CI 1.077-1.305]; P = 0.001); beliefs predicted screening (OR 1.027 [CI 1.004-1.050]; P = 0.019); and self-efficacy predicted calcium intake (OR1.040 (CI 1.013-1.069); P = 0.003] and exercise (OR 1.117 [CI 1.077-1.160]; P < 0.001). Current online resources have deficiencies. Five themes identified from two interview rounds (n = 10/ round) were as follows: content, emotional response, design, perceived usefulness and clinical considerations. The final fact sheet was considered acceptable and useful in addressing knowledge gaps, promoting information-seeking, impacting behaviours and facilitating healthcare discussions. CONCLUSION: A co-designed fact sheet is acceptable and addresses identified osteoporosis knowledge gaps in women with POI/EM.

Association between age at menopause and fracture risk: a systematic review and meta-analysis.

PURPOSE: Early menopause (EM, age at menopause < 45 years) and premature ovarian insufficiency (POI, age at menopause < 40 years) are associated with an increased risk of osteoporosis. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The primary aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and fracture risk. The secondary aim was to evaluate this effect concerning the site of fractures. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 January 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for quantifying heterogeneity. RESULTS: Eighteen studies were included in the qualitative and quantitative analysis (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36, 95% CI 1.11-1.66, p < 0.002, I² 81.5%). Women with POI did not display any difference in fracture risk compared either with women with age at menopause > 40 (OR 1.23, 95% CI 0.72-2.09, p = 0.436, I² 62.5%) or >45 years (OR 0.54, 95% CI 0.22-1.29, p = 0.17, I2 0%). No difference was evident when a separate analysis was performed for vertebral, non-vertebral and hip fractures. CONCLUSIONS: This is the first meta-analysis showing that EM is associated with increased fracture risk compared with normal age at menopause, without any distinct effect on the site of the fracture.

Managing vulvovaginal atrophy after breast cancer.

Cancer treatment may result in loss of ovarian function through surgical removal of the ovaries, chemotherapy or radiation. While menopausal symptoms, such as hot flushes, night sweats, sleep disturbance, memory concerns and mood issues can be extremely bothersome to some women going through menopause naturally, women who undergo an induced menopause usually experience more sudden and severe symptoms. Pain and vaginal dryness can occur whether a woman has a sexual partner or not. In women with breast cancer, the aetiology of impaired sexual functioning, and lowered sexual desire, is often multifactorial, and may be related to physical and/or psychological reasons. Pain and vaginal dryness in women without a history of breast cancer can usually be safely treated with vaginal estrogens, in the form of a cream, pessary or ring, and simple lubricants or vaginal moisturisers. Safe usage of vaginal estrogen replacement therapy in breast cancer patients has not been studied within randomised clinical trials of long duration; the guidelines below reflect a clinical consensus.

Physical activity is not related to risk of early menopause in a large prospective study.

STUDY QUESTION: Is physical activity associated with incident early menopause? SUMMARY ANSWER: Physical activity is not associated with incident early menopause. WHAT IS KNOWN ALREADY: Lifestyle factors such as physical activity may influence menopause timing, but results from prior research are inconsistent. STUDY DESIGN, SIZE, DURATION: We evaluated the association between physical activity and the occurrence of early natural menopause in a prospective cohort study, the Nurses' Health Study II. Women were followed prospectively from 1989 to 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analysis included 107 275 women who were premenopausal at baseline. Menopause status was self-reported biennially. Time per week participating in specific activities was reported approximately every 4 years and used to calculate metabolic task hours per week (MET h/week). We used Cox proportional hazards model to evaluate the association between physical activity and incidence of natural menopause before age 45 years while controlling for potential confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: There were 2 786 study members who experienced menopause before the age of 45. After adjustment for age, smoking and other factors, we observed no association between adulthood physical activity and early menopause. For example, compared to women reporting <3 MET h/week, the hazard ratio for women in the highest category (≥42 MET h/week) of cumulatively-averaged total physical activity was 0.89 (95% confidence interval: 0.76-1.04; P-trend: 0.26). Neither moderate nor strenuous activity in adolescence and young adulthood were related to risk. The relation of physical activity and early menopause did not vary across strata of body mass index or smoking status. LIMITATIONS, REASONS FOR CAUTION: Physical activity and menopausal status were self-reported, but repeated assessment of physical activity and prospective report of menopause status likely reduce the potential for non-differential misclassification. While the majority of our study participants were white, it is unlikely that the physiological relation of activity and early menopause varies by ethnicity. WIDER IMPLICATIONS OF THE FINDINGS: Findings from our large prospective study do not support an important association between physical activity and early menopause. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by UM1CA176726 and R01HD078517 from the National Institutes of Health, Department of Health and Human Services. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.