Effect of early menopause on cognition and brain morphology in an Urban Indian Cohort.

BACKGROUND: Evidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population. METHODS: We aimed to examine the effect of early menopause (≤45 years) on cognitive performance and brain morphology among older dementia-free females of the TLSA cohort using a multiple linear regression analysis. RESULTS: In a sample of 528 women, 144 (27%) had early menopause. The linear regression analysis showed that women with early menopause performed poorly in cognition and had lesser total gray matter volume [ß = -11973.94, p = 0.033], left middle frontal [ß = -353.14, p = 0.033], and left superior frontal [ß = -460.97, p < 0.026] volume. CONCLUSION: Dementia-free women with early menopause had poorer cognition, lower total gray matter, and frontal lobe. More research is needed to explore the link between earlier menopause and cognitive decline and develop ways to address it. HIGHLIGHTS: Evidence on the effect of early menopause on brain morphology is inconsistent and scant in low and middle-income countries, such as India. In a cohort of dementia-free individuals in urban Bangalore, we observed that participants with early menopause had significantly lower cognitive performance and lower total gray matter and frontal lobe volume. We recommend increasing awareness of this fact among the medical community and the general public. There is an urgent need to explore the underlying biological mechanism and to discover effective interventions to mitigate the effect.

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.

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.

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.

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.

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:

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.

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.

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.

Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact on reproduction remain poorly defined. METHODS: The menopausal status of 2930 survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20 years]) who were aged > 18 years at the time of the current study (median age, 35 years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as the cessation of menses ≥6 months in duration occurring 5 years after diagnosis and before age 40 that was not due to pregnancy, surgery, or medications. Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years [range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3) compared with siblings. Independent risk factors included exposure to a procarbazine dose ≥4000 mg/m2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT ≥ 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (rate ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95% CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood cancer are at risk of NSPM associated with lower rates of live birth in their 30s. Those at risk should consider fertility preservation if they anticipate delaying childbearing. Cancer 2018;124:1044-52. © 2018 American Cancer Society.

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.

Early menarche, nulliparity and the risk for premature and early natural menopause.

STUDY QUESTION: Are parity and the timing of menarche associated with premature and early natural menopause? SUMMARY ANSWER: Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women. WHAT IS KNOWN ALREADY: Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power. STUDY DESIGN, SIZE, DURATION: This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). PARTICIPANTS/MATERIALS, SETTING, METHODS: Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation. MAIN RESULTS AND THE ROLE OF CHANCE: The median age at FMP was 50 years (interquartile range 48-53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53-2.12) and early menopause (1.31, 1.19-1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84-2.77) and early menopause (1.32, 1.09-1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04-7.87) and 2-fold increased risk of early menopause (2.16, 1.48-3.15) compared with women who had menarche at ≥12 years and two or more children. LIMITATIONS, REASONS FOR CAUTION: Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause. STUDY FUNDING/COMPETING INTEREST(S): InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.

Management of sexuality, intimacy, and menopause symptoms in patients with ovarian cancer.

Issues of sexuality, intimacy, and early menopause significantly impact the quality of life of patients following the diagnosis and treatment of ovarian cancer. These are undertreated problems. Successful treatment requires the provider's awareness of the problem, ability to identify it, and willingness to treat it. Unfortunately many providers do not address these issues in the pretreatment or perioperative period. Furthermore, patients do not often alert their providers to their symptoms. While systemic hormone therapy may improve many of the issues, they are not appropriate for all patients given their action on estrogen receptors. However, other nonhormonal treatments exist including selective serotonin reuptake inhibitors, antiepileptics, natural remedies, and pelvic floor physical therapy. In addition psychological care and the involvement of the partner can be helpful in managing the sexual health concerns of these patients. At the time of diagnosis or at initial consultation, women should be informed of the potential physiologic, hormonal, and psychosocial effects of ovarian cancer on sexuality and that there is a multimodal approach to dealing with symptoms.

Bone mineral density and fractures after surgical menopause: systematic review and meta-analysis.

BACKGROUND: Oophorectomy is recommended for women at increased risk for ovarian cancer. When performed at premenopausal age oophorectomy induces acute surgical menopause, with unwanted consequences. OBJECTIVE: To investigate bone mineral density (BMD) and fracture prevalence after surgical menopause. SEARCH STRATEGY: A literature search of PubMed, EMBASE and Cochrane library was performed with no date restriction. Date of last search was March 1st, 2016. SELECTION CRITERIA: Primary studies reporting on BMD, T-scores or fracture prevalence in women with surgical menopause and age-matched control groups. DATA COLLECTION AND ANALYSIS: Data were extracted on BMD (g/cm2 ), T-scores and fracture prevalence in women with surgical menopause and control groups. Quality was assessed by an adaptation of the Downs and Black checklist. Random effects models were used to meta-analyse results of studies reporting on BMD or fracture rates. MAIN RESULTS: Seventeen studies were included, comprising 43 386 women with surgical menopause. Ten studies provided sufficient data for meta-analysis. BMD after surgical menopause was significantly lower than in premenopausal age-matched women [mean difference lumbar spine, -0.15 g/cm2 (95% CI, -0.19 to -0.11 g/cm2 ); femoral neck, -0.17 g/cm2 (95% CI, -0.23 to -0.11 g/cm2 )] but not lower than in women with natural menopause [lumbar spine, -0.02 g/cm2 (95% CI, -0.04 to 0.00 g/cm2 ); femoral neck, 0.04 g/cm2 (95% CI, -0.09 to 0.16 g/cm2 )]. Hip fracture rate was not higher after surgical menopause compared with natural menopause [hazard ratio: 0.85 (95% CI, 0.70 to 1.04)]. AUTHOR'S CONCLUSIONS: No evident effect of surgical menopause was observed on BMD and fracture prevalence compared with natural menopause. However, available studies are prone to bias and need to be interpreted with caution. TWEETABLE ABSTRACT: Bone health after menopause: no evidence for additional effect of surgical menopause on BMD and fractures.

Sexual Health and Quality of Life Assessment among Ovarian Cancer Patients during Chemotherapy.

BACKGROUND: During the last decades many successful efforts have been made in order to increase life expectancy in ovarian cancer (OC) patients. However, just a few studies have investigated the impact of OC on quality of life (QoL) and sexual function in OC cases during treatment. OBJECTIVE: The aim of this study was to evaluate the QoL and sexual function of OC patients during chemotherapy (CT). PATIENTS AND METHODS: Forty-nine subjects were enrolled and filled in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires. The results were evaluated globally and consequently stratified into several groups: single surgery versus multiple surgeries, age ≤48 years versus >48 years, and first-line CT versus multiple lines of CT. RESULTS: Menopause-related symptoms, body image and attitude toward the disease were significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006, respectively). Sexual outcomes resulted in better scores in younger patients in all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28 items: p = 0.022). Scores concerning body image, attitude toward the disease and CT-associated symptoms resulted worse in patients after the first surgery (p = 0.017, p = 0.002 and p = 0.012, respectively). CONCLUSION: Our study confirms that OC has a detrimental impact on QoL and intimacy, particularly in younger patients, during the first course of CT and after the first cytoreductive surgery.

Early menopause: A hazard to a woman's health.

Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadotropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoimmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI.

Natural menopause among women below 50 years in India: A population-based study.

BACKGROUND & OBJECTIVES: The age at which menopause naturally occurs may reflect nutritional and environmental circumstances as well as genetic factors. In this study we examined natural menopause as a marker of women's health at the population level in India and in some major States. METHODS: Data from the Indian District Level Household Survey (DLHS) carried out during 2007-2008 covering 643,944 ever-married women aged 15-49 yr were used; women of older ages were not included in this survey. Since not all women in this age group had achieved natural menopause at the time of survey, Cox proportional hazard regression models were employed to obtain the median age of women reporting a natural menopause, excluding those who underwent hysterectomy. Hazard ratios (HRs) were estimated for key socio-economic and reproductive variables that could potentially affect the age at natural menopause <40 yr. RESULTS: Overall, menopause prior to age 40 was reported by approximately 1.5 per cent of women. In the national data set, significant associations with age at natural menopause were identified with marriage breakdown or widowhood, poverty, Muslim religious affiliation, 'scheduled caste' status, not having received schooling, rural residence, having never used contraceptive pills, not been sterilized or had an abortion, low parity and residence in the western region. Within data from five selected States examined separately, the strength of these associations varied. INTERPRETATION & CONCLUSIONS: Associations of natural menopause with sociocultural, family planning and demographic variables were noted. Most importantly, there was an association with poverty that would require further investigation as to causality. The proportion of women experiencing early menopause may represent a useful overall indicator of women's health. The data are reassuring with regard to possible late effects of sterilization on ovarian function.

Postmenopausal hormone therapy and cognition.

This article is part of a Special Issue "Estradiol and cognition". Prior to the publication of findings from the Women's Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the 'critical window hypothesis', which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as lower global cognition or diabetes. Lastly, we point towards implications for future research and clinical treatments.

Ovarian function in female survivors after multimodal Ewing sarcoma therapy.

BACKGROUND: With advances in cancer care, more young women with Ewing sarcoma (ES) survive after treatment. Thus, we sought to analyze the ovarian function in prepubertal, pubertal and postpubertal females and young women receiving multimodal therapy for ES, and to identify patients at risk of infertility on whom fertility preservation would be indicated. PROCEDURES: Twenty-seven female survivors of ES were included in this retrospective multiinstitutional study. Patients were classified into four groups according to the treatment received: chemotherapy (CHT) without pelvic radiation (pRT), chemotherapy and pRT, CHT and autologous hematopoietic cell stem rescue (aHSCT) without pRT, and CHT + pRT + aHSCT. The ovarian function and fertility outcomes were analyzed. RESULTS: At a median follow-up of 5.7 years from diagnosis, and at median age at follow-up of 16.3 years, 67% of the survivors had premature ovarian insufficiency, including all patients receiving pelvic RT and 87.5% of patients who underwent aHSCT, independent of chemoprotection. Thirty-seven percent of patients had a clinical syndrome of premature menopause. The relative risk (RR) of premature ovarian insufficiency of a survivor was 3.9 (p 0.03) for pRT, and 2.4 (p 0.07) for aHSCT. On multivariate analysis, radiation therapy was a significant predictor of higher risk of premature ovarian insufficiency over chemotherapy alone. CONCLUSIONS: A large proportion of women receiving multimodal therapy for ES develop premature ovarian insufficiency. Patients and guardians should be informed about the reproductive potential and strategies for preservation of ovarian function should be considered individually. Pediatr Blood Cancer 2015;62:341-345. © 2014 Wiley Periodicals, Inc.