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Objective: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain‐predicted age difference (brain‐PAD). Design: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. Patients: Community‐dwelling older women (aged 70+ years). Measurements: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex‐hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1‐weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. Results: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain‐PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p =.04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain‐PAD cross‐sectionally, nor were any of the examined sex hormones or SHBG associated with brain‐PAD longitudinally. Conclusion: No strong evidence of an association between circulating sex hormones and brain‐PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted. [ABSTRACT FROM AUTHOR]

Objective: To explore the associations between endogenous testosterone blood concentrations and muscle mass, strength and performance in community dwelling women. Design, Patients and Measurements: Online databases, including Ovid MEDLINE, EMBASE and Web of Science, were searched for observational studies, with at least 100 female participants, reporting associations between endogenous testosterone blood concentrations and muscle mass, strength and performance. The findings were synthesized in a narrative review. Heterogeneity in study design and analysis precluded a meta‐analysis. Results: Of the 36 articles retrieved for full‐text review, 10 met the inclusion criteria. Eight studies were cross‐sectional, 1 longitudinal and 1 provided both cross‐sectional and longitudinal data. Testosterone was measured by liquid chromatography‐tandem mass spectrometry in two studies and by immunoassay in 8. An association between total testosterone and muscle mass, strength or performance in women was not found. The studies of calculated free or bioavailable testosterone and lean muscle mass reported a positive association, but no association was reported for muscle strength or performance. Each included study was limited by a high risk of bias in at least one assessed domain. Conclusions: This review does not support an association between testosterone and muscle mass, strength or performance in women. This, together with the reported associations between free or bioavailable testosterone and muscle mass should be interpreted cautiously due to the predominant use of immunoassay and the inaccuracy of calculated variables. Additionally, biological significance of nonprotein bound testosterone has not been established. Further studies examining the relationship between precisely measured testosterone and muscle mass and function in women are required. [ABSTRACT FROM AUTHOR]

Objective: To document associations between anti‐Müllerian hormone (AMH) and circulating androgens in nonhealthcare‐seeking premenopausal women. Design: Community‐based, cross‐sectional study. Setting: Eastern states of Australia. Participants: Women aged 18–39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal. Measurements: AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11‐oxygenated C19 steroids, measured by liquid chromatography–tandem mass spectrometry. Results: Data were available for 794 women, median age of 33 years (range: 18–39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho =.29, p <.001) androstenedione (rho =.39, p <.001) and DHEA (rho =.10, p =.005) but not 11‐ketoandrostenedione or 11‐ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (β coefficient: 20.90, 95% confidence interval [CI]: 13.79–28.03; p <.001) and androstenedione (β coefficient: 5.90, 95% CI: 3.76–8.03; p <.001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21–1.90] vs. 0.36 nmol/L [range: 0.13–0.87]; p =.001) in women with self‐reported polycystic ovary syndrome. Conclusions: The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of two anti‐Mullerian (AMH) assays over a range of concentrations, in samples collected from young women. Design: A cross‐sectional method‐comparison study of 168 non‐healthcare‐seeking women. Participants: Included women were aged 18–39 years, not recently pregnant, breast feeding or using systemic hormones. Measurements: Serum AMH levels were analysed with the Beckman Coulter Access 2 assay from fresh samples and the Ansh picoAMH assay using samples stored at −80°C, in a parallel setting. Comparisons between the two assays were examined using Bland‐Altman plots. Results: Participants had a mean ± SD age of 32.6 ± 5.4 years and body mass index of 28.1 ± 7.9 kg/m2, and 60.1% were parous. Although the assay results were highly correlated (Spearman correlation.982, P <.001), the relationship between the assays was nonlinear. Serum AMH values below 4 pmol/L were lower with the picoAMH assay compared with the Access AMH assay (mean difference in this range was −0.49 pmol/L), but for samples with a mean value above 10 pmol/L, the picoAMH assay consistently measured higher than the Access AMH assay (mean difference in this range was +8.2 pmol/L). As AMH concentrations increased the absolute discrepancy between the assays also increased. Conclusions: This study demonstrates that despite the high correlation between two commercially available AMH assays, the assays performed in a discordant manner at high and low concentrations. Hence, the results of these assays are not interchangeable, highlighting the need to establish specific reference limits for individual assays to guide clinical decision‐making and the challenge of establishing future universal cut‐offs for the application of AMH levels in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Sex steroid levels in women vary with increasing age from the age of 70 years (70+). Whether this reflects change within individuals with age or a survival advantage is not known. This study aimed to determine the stability of circulating sex steroids and SHBG over time in individual women aged 70+. Design: A prospective cohort study. Participants: 400 women, aged 70+ not using any sex steroid, anti‐androgen/oestrogen or glucocorticoid therapy. Main outcome measurements: Sex steroid concentrations, measured by liquid chromatography‐tandem mass spectrometry and sex hormone‐binding globulin (SHBG) by immunoassay, in paired blood samples drawn 3 years apart and analysed together. Results: 400 women, median (IQR) age 78.0 (8.6) years, were included in the analysis. Mean testosterone concentrations were statistically significantly higher in follow‐up samples compared with baseline. The change was modest (mean change 31 pmol/L, 95% confidence interval (CI) 2.4–59.8; p =.034), and an increase was not observed in all women. There was a statistically significant decline in mean body mass index (mean change −0.4 kg/m2, 95% CI 0.6 to −0.3; p <.001) and a significant increase in the mean serum SHBG concentration (mean change 4.0 nmol/L, 95% CI 2.7–5.4; p <.001). The change observed in testosterone was not explained by the observed change in SHBG. There was no significant change in the mean oestrone or dehydroepiandrosterone concentration. Conclusions: Testosterone concentrations in women aged 70+ were more likely to increase than decrease. Whether increasing testosterone concentrations in older women confer a survival advantage needs investigation. [ABSTRACT FROM AUTHOR]

Summary: Background: We investigated whether metformin prevents tamoxifen‐induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: This was a single‐centre, randomized, double‐blind, placebo‐controlled, parallel group trial. Postmenopausal women with hormone receptor‐positive breast cancer taking tamoxifen were randomly allocated to metformin 850 mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA‐IR). Results: A total of 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43‐72) years, with 5(0.5‐28) years postmenopause, and had taken tamoxifen for 28.9 (0‐367.4) weeks. The baseline ET was 2.9 mm (1.4‐21.9) for the placebo group (n = 52) and 2.5 mm (1.3‐14.8) for the metformin group (n = 50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4‐7.8) vs 3.0 (1.2‐11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4 mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline‐adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA‐IR (P < 0.001). Conclusions: Metformin appears to inhibit tamoxifen‐induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to examine the effects of testosterone on verbal learning and memory in postmenopausal women. Design Randomized, placebo-controlled trial in which participants were randomized (1:1) to transdermal testosterone gel 300 mcg/day, or identical placebo, for 26 weeks. Patients Ninety-two postmenopausal women aged 55-65 years, on no systemic sex hormone therapy. Measurements The primary outcome was the score for the International Shopping List Task ( ISLT) of CogState. Secondary outcomes included other CogState domains, the Psychological General Well-Being Index ( PGWB) and safety variables. Results Eighty-nine women, median age 60 years, were included in the primary analysis. Testosterone treatment resulted in statistically significantly better performance for the ISLT (improved verbal learning and memory) compared with placebo, adjusted for age and baseline score (mean difference 1·57; 95% CI 0·13, 3·01) P = 0·03). There were no significant differences for other CogState domains or the PGWB scores. At 26 weeks, the median total testosterone was 1·7 n m (interquartile range ( IQR) 1·1, 2·4) in the testosterone group and 0·4 n m ( IQR 0·3, 0·5) in the placebo group. Conclusions The small but statistically significant effect of testosterone treatment on verbal learning and memory in postmenopausal women provides the basis for further clinical trials. [ABSTRACT FROM AUTHOR]

Objective Sex hormone-binding globulin (SHBG) is a robust predictor of insulin resistance. Whether this is independent of circulating sex steroid levels remains uncertain. The aim of this study was to investigate the determinants of SHBG in postmenopausal women and whether the relationship between SHBG and insulin resistance is independent of oestrogen and androgen levels. Design A cross-sectional study of naturally and surgically menopausal women. Participants Seven hundred and sixty three postmenopausal women not using any systemic hormone therapy, mean age 54·4 ± 5·8 years, recruited in the US, Canada, Australia, UK and Sweden between July 2004 and February 2005. Measurements Relationships between log-transformed (ln) SHBG and ln homoeostasis model assessment for insulin resistance (HOMA-IR) were explored, taking into account age, body mass index (BMI), blood pressure (BP) and circulating oestradiol, oestrone, testosterone and dihydrotestosterone. Results Taking into account age, race, years since menopause, menopause type, BMI, BP, prior postmenopausal hormone use and the sex steroids measured, 34·4% of the variation in SHBG could be explained by the model that included negative contributions by HOMA-IR, BMI and diastolic BP, and a positive contribution by total testosterone ( P < 0·001). None of the sex steroids made independent contributions to HOMA-IR, which was best explained by the model that included BMI, SHBG, systolic BP and surgical menopause, with each variable being positively related to HOMA-IR ( r2 = 0·3152, P = 0·03). Conclusions The relationship between SHBG and HOMA-IR, as an estimate of insulin resistance, is not explained by endogenous oestrogen and androgen levels and is, at least in part, independent of BMI in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to evaluate whether subclinical thyroid disease is associated with impaired health-related quality of life and a more adverse cardiovascular disease risk profile. Design A community-based cross-sectional study. Setting and participants A total of 1423 non-healthcare-seeking women, aged 18–75 years were randomly recruited from the community via the electoral roll from April 2002 to August 2003. Main outcome measures These were the scores for the Short-Form 36 (SF-36), the Psychological General Well-being Index (PGWI), thyroid hormone levels, serum lipids and high sensitivity C-reactive protein (hsCRP). Subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCHyper) were defined as serum TSH > 4·0 mIU/l and < 0·5 mIU/l, respectively, with a normal free thyroxine (free T4) level. Results Evaluable data were available for all participants. 10·7% of all women had an abnormal TSH value. The prevalence of a low TSH level by age group ranged from 1·2% to 6·4%, whereas the prevalence of an elevated TSH level ranged from 2·8% to 9·2% and increased with age ( P = 0·002). There were no significant differences between women with SCH or SCHyper and age-matched controls for the total PGWI score or the Mental and Physical Component Scores of the SF-36. Women with SCH were no different from controls for serum lipids or hsCRP. Using linear regression, SCH vs. euthyroidism did not make an independent contribution to variation in either total cholesterol or triglycerides, with or without adjustment for age ± age2 ± BMI. Conclusions Our data indicate that subclinical thyroid disease in women in the community is not associated with lower well-being or impaired health-related quality of life and SCH is not associated with increased serum markers of CVD risk. [ABSTRACT FROM AUTHOR]