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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., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Objective: The contribution of testosterone to depression in older women is uncertain. This review was conducted to investigate the association between endogenous testosterone blood concentrations and depression in postmenopausal women., Methods: We searched Ovid MEDLINE, EMBASE, PsycINFO, and Web of Science databases for observational studies with at least 100 community-dwelling participants. The results were categorised by study design, and the reporting of total, bioavailable and free testosterone findings is narrative., Results: The search strategy retrieved 28 articles for full-text review, of which eight met the criteria for inclusion; these described 6 cross-sectional and 2 longitudinal studies. Testosterone was measured by immunoassay in all of the included studies. No association was seen between total testosterone or free testosterone and depression in either the cross-sectional or the longitudinal studies. A significant association between bioavailable testosterone and incident depressive symptoms was limited to women at least 21 years postmenopause in one study. Most of the cross-sectional studies were not representative of national populations and lacked random selection., Conclusions: This systematic review does not support an association between testosterone and depression in postmenopausal women. However, as the included studies had substantial methodological limitations, studies of community-based samples, employing validated instruments for depression and precise measurement of blood testosterone, are needed to address this knowledge gap., Competing Interests: Declaration of competing interest SRD reports unrelated support that includes grants from the NHMRC Australia, personal fees for educational activities from Besins Healthcare, Abbott Chile, and BioFemme, personal Advisory Board/consultancy fees from Theramex, Abbott Laboratories, Astellas, Mayne Pharmaceuticals, Roche Diagnostics, Lawley Pharmaceuticals and Que. Oncology and has received institutional grant funding from Que. Oncology and Ovoca research. The other authors declare they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Context: There is a lack of understanding of what is normal in terms of sex steroid levels in older women., Objective: To determine whether sex steroid levels vary with age in and establish reference ranges for women >70 years of age., Design and Setting: Cross-sectional, community-based study., Participants: Included 6392 women ≥70 years of age., Main Outcome Measures: Sex steroids measured by liquid chromatography-tandem mass spectrometry. A reference group, to establish sex steroid age-specific reference ranges, excluded women using systemic or topical sex steroid, antiandrogen or glucocorticoid therapy, or an antiglycemic agent., Results: The reference group of 5326 women had a mean age of 75.1 (±4.2) years, range of 70 to 94.7 years. Median values (range) were 181.2 pmol/L (3.7 to 5768.9) for estrone (E1), 0.38 nmol/L (0.035 to 8.56) for testosterone (T), 2.60 nmol/L (0.07 to 46.85) for dehydroepiandrosterone (DHEA), and 41.6 nmol/L (2.4 to 176.6) for SHBG. Estradiol and DHT were below method sensitivity in 66.1% and 72.7% of the samples, respectively. Compared with women aged 70 to 74 years, women aged ≥85 years had higher median levels of E1 (11.7%, P = 0.01), T (11.3%, P = 0.02), and SHBG (22.7%, P < 0.001) and lower DHEA (30% less, P < 0.001). Women with overweight and obesity had higher E1 (P < 0.001) and T (P < 0.03) and lower SHBG (P < 0.001) than did women with normal body mass index. Smokers had 17.2% higher median T levels (P = 0.005)., Conclusion: From the age of 70 years, T and E1 increase with age, despite a steady decline in DHEA. Whether E1 and T are biomarkers for longevity or contribute to healthy aging merits investigation., (Copyright © 2019 Endocrine Society.)

Background: The benefits and risks of testosterone treatment for women with diminished sexual wellbeing remain controversial. We did a systematic review and meta-analysis to assess potential benefits and risks of testosterone for women., Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for blinded, randomised controlled trials of testosterone treatment of at least 12 weeks' duration completed between Jan 1, 1990, and Dec 10, 2018. We also searched drug registration applications to the European Medicine Agency and the US Food and Drug Administration to identify any unpublished data. Primary outcomes were the effects of testosterone on sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42018104073., Findings: Our search strategy retrieved 46 reports of 36 randomised controlled trials comprising 8480 participants. Our meta-analysis showed that, compared with placebo or a comparator (eg, oestrogen, with or without progestogen), testosterone significantly increased sexual function, including satisfactory sexual event frequency (mean difference 0·85, 95% CI 0·52 to 1·18), sexual desire (standardised mean difference 0·36, 95% CI 0·22 to 0·50), pleasure (mean difference 6·86, 95% CI 5·19 to 8·52), arousal (standardised mean difference 0·28, 95% CI 0·21 to 0·35), orgasm (standardised mean difference 0·25, 95% CI 0·18 to 0·32), responsiveness (standardised mean difference 0·28, 95% CI 0·21 to 0·35), and self-image (mean difference 5·64, 95% CI 4·03 to 7·26), and reduced sexual concerns (mean difference 8·99, 95% CI 6·90 to 11·08) and distress (standardised mean difference -0·27, 95% CI -0·36 to -0·17) in postmenopausal women. A significant rise in the amount of LDL-cholesterol, and reductions in the amounts of total cholesterol, HDL-cholesterol, and triglycerides, were seen with testosterone administered orally, but not when administered non-orally (eg, by transdermal patch or cream). An overall increase in weight was recorded with testosterone treatment. No effects of testosterone were reported for body composition, musculoskeletal variables, or cognitive measures, although the number of women who contributed data for these outcomes was small. Testosterone was associated with a significantly greater likelihood of reporting acne and hair growth, but no serious adverse events were recorded., Interpretation: Testosterone is effective for postmenopausal women with low sexual desire causing distress, with administration via non-oral routes (eg, transdermal application) preferred because of a neutral lipid profile. The effects of testosterone on individual wellbeing and musculoskeletal and cognitive health, as well as long-term safety, warrant further investigation., Funding: Australian National Health and Medical Research Council., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Testosterone therapy for women is in widespread use, primarily in the form of compounded preparations and off-label use of formulations for men. The benefits and risks of such therapy remain uncertain. This review will identify and evaluate studies that have examined the effects of testosterone therapy for women on a range of outcomes including sexual function, cardiovascular events, metabolic parameters, musculoskeletal health, wellbeing, cancer events, androgenic effects and withdrawal rates., Methods: Studies meeting our pre-determined inclusion criteria will be identified through searches in Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science. Assessing a range of outcomes, we will assess the risk-of-bias of relevant studies and draw conclusions about the strength of evidence for benefits and risks of testosterone therapy for each outcome., Discussion: This comprehensive systematic review with meta-analysis will provide the foundation for the development of evidence-based clinical practice guidelines that will address benefits and risks of testosterone therapy, when treatment might be appropriate or inappropriate, areas of clinical uncertainty and the basis for assessment and monitoring of patients., Systematic Review Registration: PROSPERO registration number: CRD42018104073.

Context: Intravaginal testosterone (IVT) is a potential treatment of vulvovaginal atrophy (VVA) associated with aromatase inhibitor (AI) use., Objective: To investigate the effects of IVT on sexual satisfaction, vaginal symptoms, and urinary incontinence (UI) associated with AI use., Design: Double-blind, randomized, placebo-controlled trial., Setting: Academic clinical research center., Participants: Postmenopausal women taking an AI with VVA symptoms., Intervention: IVT cream (300 μg per dose) or identical placebo, self-administered daily for 2 weeks and then thrice weekly for 24 weeks., Main Outcomes and Measures: The primary outcome was the change in the sexual satisfaction score on the Female Sexual Function Index (FSFI). Secondary outcomes included vaginal symptoms and responses to the Profile of Female Sexual Function, the Female Sexual Distress Scale-Revised (FSDS-R), and the Questionnaire for UI Diagnosis. Serum sex steroids were measured., Results: A total of 44 women were randomly assigned and 37 provided evaluable data, (mean age 56.4 years, SD 8.8 years). At 26 weeks, the mean between-group difference in the baseline-adjusted change in FSFI satisfaction scores was significantly greater for the IVT group than the placebo group (mean difference 0.73 units; 95% CI, 0.02 to 1.43; P = 0.043). IVT cream resulted in significant improvements, compared with placebo, in FSDS-R scores (P = 0.02), sexual concerns (P < 0.001), sexual responsiveness (P < 0.001), vaginal dryness (P = 0.009), and dyspareunia (P = 0.014). Serum sex steroid levels did not change. Few women had UI symptoms, with no treatment effect., Conclusion: IVT significantly improved sexual satisfaction and reduced dyspareunia in postmenopausal women on AI therapy. The low reporting of UI among women on AI therapy merits further investigation.

Objectives: Intravaginal testosterone has emerged as a potential treatment for vulvovaginal atrophy (VVA) in women, in general, and women taking an aromatase inhibitor (AI). A systematic review of the literature was undertaken to determine whether available clinical trial data support efficacy and safety of intravaginal testosterone for the treatment of VVA., Methods: Scopus, MEDLINE, EMBASE, and the Cochrane Library databases were systematically searched on July 26, 2017, for human studies published in English of clinical trials of intravaginal testosterone., Results: Six separate clinical trials were identified that ranged in size from 10 to 80 participants, with either single dose, or durations of 4 to 12 weeks. Only one study incorporated a double-blind design. Three studies were of women taking an AI.Taken together, the studies suggest that intravaginal testosterone may lower vaginal pH, increase the proportion of vaginal lactobacilli, and possibly improve the vaginal maturation index. The lack of a placebo treatment in four studies, and failure to adjust for baseline differences, resulted in uncertainty of the effect on sexual function. Safety remains uncertain because of the small number of women exposed, short study durations, and inconsistent and incomplete outcome reporting for sex steroid levels., Conclusion: Adequately powered double-blind, placebo-controlled clinical trials of intravaginal testosterone therapy are needed to establish both efficacy and safety.

Objective: The steady-state pharmacokinetics of two doses of a transdermal testosterone cream (TTC) was investigated after daily application for 21 days., Methods: This was a two-way cross-over study conducted for 6 weeks. Seven healthy postmenopausal women (mean age, 59.3 y) were randomly allocated to 5 or 10 mg of TTC applied daily to the upper arm. Serum total testosterone (TT), free testosterone (fT), sex hormone-binding globulin, and metabolite concentrations were measured. Baseline-corrected and uncorrected serum TT and fT pharmacokinetic parameters (AUC0-24, C avg, Cmax, and Tmax) were calculated using a standard model-independent approach., Results: After the single-dose application of 5 mg of TTC on day 22, the median uncorrected TT C avg was found to be 0.54 ng/mL (range, 0.43-1.31), and the median uncorrected fT C avg was found to be 4.14 pg/mL (range, 2.41-9.72). Doubling of the dose only resulted in a 30% increase in baseline-corrected TT C avg (0.52 vs 0.69 ng/mL for 5 and 10 mg, respectively) and a 31% increase in baseline-corrected fT C avg (4.75 vs 6.24 pg/mL for 5 and 10 mg, respectively). Neither dose resulted in any meaningful variation in dihydrotestosterone, estrone, estradiol, or sex hormone-binding globulin across the postdose sampling period., Conclusions: The 5-mg TTC dose restores TT and fT levels to levels above and within the reference range, respectively, for premenopausal women.

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 nm (interquartile range (IQR) 1·1, 2·4) in the testosterone group and 0·4 nm (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., (© 2014 John Wiley & Sons Ltd.)

Objective: This study aims to investigate the effects of testosterone on cognitive performance during functional magnetic resonance imaging (fMRI) in healthy estrogen-treated postmenopausal women., Methods: This was an open-label study in which postmenopausal women on nonoral estrogen therapy were treated with transdermal testosterone for 26 weeks. Women performed tests of verbal fluency (number of words) and mental rotation (reaction time and accuracy) during pretreatment and posttreatment fMRI. Blood oxygen level-dependent (BOLD) signal intensity was measured during fMRI tasks., Results: Nine women with a mean (SD) age of 55.4 (3.8) years completed the study. Twenty-six weeks of testosterone therapy was associated with significant decreases in BOLD intensity during the mental rotation task in the right superior parietal, left inferior parietal, and left precuneus regions, and during the verbal fluency task in the left inferior frontal gyrus, left lingual gyrus, and medial frontal gyrus (all P < 0.05), with no change in task performance, accuracy, or speed., Conclusions: Testosterone therapy is associated with reduced BOLD signal activation in key anatomical areas during fMRI verbal fluency and visuospatial tasks in healthy estrogen-treated postmenopausal women. Our interpretation is that testosterone therapy facilitates preservation of cognitive function with less neuronal recruitment.

Introduction: Female sexual dysfunction is a side effect of selective serotonin reuptake inhibitor (SSRI)/serotonin noradrenalin reuptake inhibitor (SNRI) therapy., Aims: The aim of this study is to investigate the efficacy of transdermal testosterone (TT) as a treatment for SSRI/SNRI-emergent loss of libido., Methods: This was a double-blind, randomized, placebo-controlled study. Forty-four women, aged 35-55 years, on a stable dose of SSRI or SNRI with treatment-emergent loss of libido were randomly allocated to treatment with a TT patch delivering 300 mcg of testosterone/day or an identical placebo patch (Pl) for 12 weeks., Main Outcome Measures: The primary outcome measure was the change in the Sabbatsberg Sexual Self-rating Scale (SSS) total score over 12 weeks. The 4-week frequency of Satisfactory Sexual Events (SSEs) and the Female Sexual Distress Scale-Revised (FSDS-R) were also measured., Results: At baseline, there were no differences between the treatment groups. At week 12, the change in the SSS score did not differ between the two groups. The increase in the 4-week frequency of SSEs was significantly greater for the TT group than for the Pl group (an increase of 2.3 events vs. 0.1, P = 0.02). The between-group difference in the change in the FSDS-R score approached statistical significance (P = 0.06). The mean total serum testosterone level at 12 weeks in the TT group was 2.1 nmol/L. No women withdrew because of androgenic adverse events., Conclusions: TT therapy resulted in a significant increase in the number of SSEs compared with Pl therapy in women with SSRI/SNRI-emergent loss of libido. The lack of improvement in the SSS total score may reflect lack of sensitivity of this instrument for the measurement of change in sexual function. This provides the first evidence that TT therapy may be a treatment option for women with SSRI/SNRI-emergent loss of libido who need to remain on their antidepressant therapy., (© 2014 International Society for Sexual Medicine.)

Objective: To explore the effects of testosterone on cognitive performance in healthy postmenopausal women., Study Design: Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47-60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison., Main Outcome Measures: Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks., Results: There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group (p<0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p<0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p<0.02)., Conclusion: Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Although the efficacy of testosterone for the treatment of hypoactive sexual desire disorder is well established, the effect of testosterone therapy on breast cancer risk remains uncertain., Aim: The incidence of invasive breast cancer among past and current testosterone users., Methods: Retrospective cohort study of 631 women ever treated with testosterone between January 1989 and December 2007 in a clinical endocrinology practice., Main Outcome Measure: The incidence of invasive breast cancer since first exposure, and the standardized incidence rate ratio (IRR) calculated using Australian age-specific incidence rates for 2005., Results: The mean age of the women at first exposure to testosterone therapy was 49.1 +/- 8.2 years, median treatment duration, 1.3 years, and mean follow-up of 6.7 +/- 4.6 years, providing 4,015 woman-years of follow-up. Twelve cases of invasive breast cancer occurred among 599 women breast cancer-free before treatment, giving an age adjusted IRR of 1.35 (95% confidence interval 0.76-2.38). There was no evidence of an independent effect of duration of exposure on breast cancer risk., Conclusion: In this study, testosterone use was not associated with a significant increase in breast cancer risk.

Objective: To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy, estrogen-treated postmenopausal women., Design: Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks, with a serum total testosterone less than 1.2 nmol/L participated in a single-center, double-blind, randomized, placebo-controlled study. All participants received transdermal testosterone, 400 muL of a 0.5% testosterone gel, daily and were randomized to receive either letrozole 2.5 mg/day or an identical placebo tablet. The main outcome measure was cognition, evaluated using a comprehensive battery of standardized neuropsychological tests, at baseline and week 16., Results: Thirty women in each group completed the study. Free testosterone increased from baseline in both groups, with no difference between groups. Free testosterone levels achieved were below the 90th centile for young women in 80% of the participants at week 16. Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study. No clinically significant effects of testosterone treatment were seen for attention and working memory, psychomotor speed, or executive function. Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy, all of which were unaffected by the aromatase inhibitor., Conclusions: We did not observe any effects of aromatase inhibition on cognition in healthy, estrogen-treated postmenopausal women treated with testosterone. This may be due to insufficient study power or a true lack of effect. However, our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large randomized, controlled trials.

Objective: The extent to which aromatization of testosterone (T) to estradiol is required for the observed effects of testosterone therapy on sexual function and well-being are not known. Therefore, the authors investigated the effects of aromatase enzyme inhibition on sexual function, well-being, and mood in estrogen- and T-replete postmenopausal women in a double-blind, randomized, placebo-controlled study., Design: Postmenopausal women using transdermal estrogen therapy for at least 8 weeks and reporting low sexual satisfaction (score <42 for the Sabbatsberg Sexual Self-rating Scale [SSS]) with a total T value of less than 1.2 nmol/L were treated with 400 muL of a 0.5% T gel (total dose 2 mg) and were randomly assigned to receive treatment with either 2.5 mg/day of letrozole or an identical placebo tablet. Women were assessed at baseline (week -2) and at 0, 4, 8, and 16 weeks. Sexual function was assessed with the SSS, well-being was assessed with the Psychological General Well-being Index, and mood was assessed with the Beck Depression Inventory at 0 and 16 weeks. Eighty-one women were screened, 76 were randomly assigned to a treatment group, and 30 in each group completed the study. Because this was a mechanistic study, only the 60 women who completed the study per protocol were included in the final analysis., Results: Total T and calculated free T increased from baseline in both groups, with no difference between groups. At 16 weeks, estradiol, sex hormone-binding globulin, fasting lipids, lipoprotein(a), and C-reactive protein did not differ from baseline or between groups. Significant increases in total Sabbatsberg Sexual Self-rating Scale scores, total Psychological General Well-being Index scores, and a reduction in Beck Depression Inventory scores from baseline to 16 weeks was seen for both treatment groups, with no effect of treatment allocation. No adverse treatment effects were reported., Conclusions: Increases in total and free T in the physiologic range in postmenopausal women were associated with improved sexual satisfaction, well-being, and mood. In this study, aromatase inhibition did not influence any of these outcomes. Short-term transdermal T therapy did not modify fasting lipids, lipoprotein(a), or C-reactive protein.

Context: It has been proposed that low sexual desire and sexual dysfunction are associated with low blood testosterone levels in women. However, evidence to support this is lacking., Objective: To determine whether women with low self-reported sexual desire and sexual satisfaction are more likely to have low serum androgen levels than women without self-reported low sexual desire and sexual satisfaction., Design, Setting, and Participants: A community-based, cross-sectional study of 1423 women aged 18 to 75 years, who were randomly recruited via the electoral roll in Victoria, Australia, from April 2002 to August 2003. Women were excluded from the analysis if they took psychiatric medication, had abnormal thyroid function, documented polycystic ovarian syndrome, or were younger than 45 years and using oral contraception., Main Outcome Measures: Domain scores of the Profile of Female Sexual Function (PFSF) and serum levels of total and free testosterone, androstenedione, and dehydroepiandrosterone sulfate., Results: A total of 1021 individuals were included in the final analysis. No clinically significant relationships between having a low score for any PFSF domain and having a low serum total or free testosterone or androstenedione level was demonstrated. A low domain score for sexual responsiveness for women aged 45 years or older was associated with higher odds of having a serum dehydroepiandrosterone sulfate level below the 10th percentile for this age group (odds ratio [OR], 3.90; 95% confidence interval [CI], 1.54-9.81; P = .004). For women aged 18 to 44 years, having a low domain score for sexual desire (OR, 3.86; 95% CI, 1.27-11.67; P = .02), sexual arousal (OR, 6.39; 95% CI, 2.30-17.73; P<.001), and sexual responsiveness (OR, 6.59; 95% CI, 2.37-18.34; P<.001) was associated with having a dehydroepiandrosterone sulfate level below the 10th percentile., Conclusions: No single androgen level is predictive of low female sexual function, and the majority of women with low dehydroepiandrosterone sulfate levels did not have low sexual function.

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]

Context 11 β -Hydroxyandrostenedione (11OHA4), 11 β -hydroxytestosterone (11OHT), and their respective peripheral derivatives, 11-ketoandrostenedione (11KA4) and 11-ketotesosterone (11KT), have been implicated in androgen-related physiopathology. Little is known of these steroids in postmenopausal women or whether exogenous testosterone therapy influences their levels. Objective The impact of exogenous testosterone on serum levels of 11-oxygenated steroids was determined in healthy postmenopausal women. Participants and Methods Levels of 19-carbon (C19) steroids were measured by liquid chromatography–tandem mass spectrometry in serum obtained at baseline and at 12 and 26 weeks from 73 healthy postmenopausal women, aged 55 to 65 years, who participated in a randomized, double-blind, placebo-controlled clinical trial assessing the effects of transdermal testosterone on cognitive performance. Results Of the 11-oxygenated androgens, 11OHA4 was the most abundant (median, 6.46 nmol/L; range, 1.51 to 23.82 nmol/L), with concentrations several fold greater than its precursor androstenedione (median, 1.38 nmol/L; range, 0.52 to 2.92 nmol/L). Baseline median (range) testosterone and 11KT levels were similar [0.56 (0.23 to 1.48) nmol/L; 0.85 (0.25 to 2.86) nmol/L, respectively). 11OHT was closely correlated with 11KT (Spearman rank correlation coefficient, 0.79; P < 0.001) and 11OHA4 correlated with 11KA4 (Spearman rank correlation coefficient, 0.73; P < 0.001). Testosterone therapy resulted in an increase in serum testosterone level, whereas all 11-oxygenated androgens remained unchanged throughout the 26 weeks of treatment. Conclusion After menopause, the adrenal production of 11-oxygenated derivatives of androstenedione and testosterone contributes importantly to the total circulating androgen pool. Exogenous testosterone does not influence the circulating levels 11-oxygenated C19 steroids. [ABSTRACT FROM AUTHOR]

• Low levels of testosterone and oestrone are associated with depressive symptoms in older women. • While statistically significant, the contribution of sex hormones to the likelihood of depression was small in the present study. • The use of sex hormones for the treatment of depression in older women is discouraged. We investigated whether low sex hormone concentrations are associated with depression in older women. This was a cross-sectional study of Australian women, aged at least 70 years, not taking medications modulating sex hormone levels. Associations between hormones, measured by liquid chromatography-tandem mass spectrometry, and depression were examined by logistic regression adjusted for potential confounders. The primary outcome was a Center for Epidemiologic Studies Depression score >10, designated as 'depression', with an expanded definition that included anti-depressant use as a secondary outcome. For the 5535 participants in the analysis, median age 74.0 years (interquartile range 71.7–77.7), depression prevalence was 5.8 % (95 % CI 5.2–6.4 %). In the adjusted models, a statistically significantly greater likelihood of depression was seen for women with testosterone and oestrone blood concentrations in quartile 1 compared with quartiles 2–4 (odds ratio 1.33, 95 % CI 1.04 to 1.70, p = 0.022; and 1.37, 95 % CI 1.06 to 1.78, p = 0.017, respectively). For the expanded definition, the odds ratios for the lowest testosterone and oestrone quartile compared with other quartiles were 1.47 (95 % CI 1.24 to 1.75, p < 0.001) and 1.31 (95 % CI 1.09 to 1.58, p < 0.001), respectively. A significant association for low DHEA was seen only for the expanded definition of depression (1.36, 95 % CI 1.13 to 1.64, p = 0.001). Receiver operating characteristic curves showed that the contribution of each sex hormone to the likelihood of depression was small. Amongst older women not taking medications that influence sex hormone concentrations, low testosterone and oestrone levels are associated with a greater likelihood of depression, but the effects are small. International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and clinicaltrials.gov (NCT01038583). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented commenting on a cohort study conducted by Davis and colleagues determining whether exogenous testosterone exposure influences breast cancer.