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Background: Although clinicians often measure the serum concentration of androgens in premenopausal women presenting with sexual dysfunction, with some women given testosterone or dehydroepiandrosterone as treatment if their concentrations are low, whether androgens are determinants of sexual function in women of reproductive age is uncertain. We aimed to clarify the associations between androgens and sexual function in a community-based sample of non-health-care-seeking women., Methods: This is a substudy of the Grollo-Ruzzene cross-sectional study, which recruited women aged 18-39 years from eastern states in Australia (QLD, NSW, VIC). After providing consent, women completed an online survey that included the Profile of Female Secual Function (PFSF) questionnaire, and those who were who were not pregnant, breastfeeding, or using systemic steroids were asked to provide a blood sample. At sampling, women were asked the dates of their last menstrual bleed. Serum androgens was measured by liquid chromatography and tandem mass spectrometry and sex hormone binding globulin (SHBG) by immunoassay. Associations between androgens and domains of sexual function, assessed by the PFSF, were examined in participants with regular menstrual cycles. After univariable linear regression (model 1), age, BMI, stage of menstrual cycle, and smoking status were added to the model (model 2), and then parity, partner status, and psychotropic medication use (model 3)., Findings: Of 6986 women who completed the online survey (surveys completed between Nov 11, 2016, and July 21, 2017), 3698 were eligible and 761 (20·6%) provided blood samples by Sept 30, 2017. Of those who provided a blood sample, 588 (77·3%) had regular menstrual cycles and were included in the analysis. Adjusting for age, BMI, cycle stage, smoking, parity, partner status, and psychoactive medication, sexual desire was positively associated with serum dehydroepiandrosterone (β-coefficient 3·39, 95% CI 0·65 to 6·03) and androstenedione (4·81, 0·16 to 9·12), and negatively with SHBG (-5.74, -9.54 to -1·90), each model explaining less than 4% of the variation in desire. Testosterone (6·00, 1·29 to 10·94) and androstenedione (6·05, 0·70 to 11·51) were significantly associated with orgasm, with the final models explaining less than 1% of the variation in orgasm. Significant associations were found between androstenedione (7·32, 0·93 to 13·08) and dehydroepiandrosterone (4·44, 0·86 to 7·95) and pleasure, and between testosterone and sexual self-image 5·87 (1·27 to 10·61), with inclusion of parity, partners status, and psychotropic drug use increasing the proportion of variation explained by each model to approximately 10%. There were no statistically significant associations between 11-oxygenated steroids and any PFSF domain, or between arousal or responsiveness and any hormone. No associations were seen between 11-oxygenated steroids and any sexual domain, or between arousal or responsiveness and any hormone., Interpretation: Associations between androgens and sexual function in premenopausal women are small, and their measurement offers no diagnostic use in this context. Further research to determine whether 11-ketoandrostenedione or 11-ketotestosterone are of clinical significance is warranted., Funding: The Grollo-Ruzzene Foundation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Context: An important element of the diagnosis of polycystic ovary syndrome is hyperandrogenism., Objective: To determine the distribution of modified Ferriman-Gallwey (mF-G) scores, as a measure of facial and body hair growth, and associations between the mF-G scores and serum androgen concentrations, including 11-oxygenated androgens., Design: Cross-sectional study of non-health-care-seeking women, aged 18 to 39 years, recruited from the eastern states of Australia from November 2016 to July 2017., Participants and Measurements: Participants provided an mF-G self-assessment that corresponded to their appearance when not using treatment for excess hair. Androgens were measured in 710 women by liquid chromatography and tandem mass spectrometry., Results: The distribution of the mF-G scores was right-skewed. The median (range) mF-G score of all participants (73.1% Caucasian) was 5 (0-36). The mF-G scores were negatively associated with age (rs = 0.124; P < 0.0001) and positively associated with body mass index (BMI) (rs = 0.073; P < 0.0001). Only androstenedione remained significantly associated with mF-G scores when controlling for age and BMI. Cluster analysis identified 2 groups with mF-G score of < 10 and ≥ 10. Repeating the cluster analysis using the combined vector of mF-G score and androstenedione returned a similar cluster structure, and again separated the 2 groups at a mF-G score < 10 versus ≥ 10., Conclusions: A self-assessed mF-G score ≥ 10 is indicative of excess body hair. Androstenedione, as well as testosterone, should be measured when hyperandrogenism is being evaluated. The lack of association between mF-G scores and the 11-oxygenated androgens highlights the need for a better understanding of these steroids., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Whether serum androgen levels can identify women with "androgen insufficiency" or "androgen excess" is unresolved; thus, what constitutes "normal" remains uncertain. We sought to determine whether androgens, including 11-oxygenated C19 steroids, vary with age, menstrual cycle, or body mass index (BMI), during the reproductive years., Design and Setting: Cross-sectional study recruited from eastern Australian states., Participants: A total of 588 women, aged 18 to 39 years, who were not pregnant, lactating, or using systemic hormone therapy, with regular menstrual cycles and no previous diagnosis of polycystic ovarian syndrome., Main Outcome Measures: Sex steroids measured using liquid chromatography-tandem mass spectrometry., Results: Testosterone and androstenedione concentrations were significantly higher during the menstrual cycle mid- and luteal phases than in the early follicular phase, with median values across the cycle of 0.34 nmol/L (range, 0.04 to 1.01) and 1.97 nmol/L (range, 0.53 to 7.89), respectively. No cyclical variations were found in dehydroepiandrosterone (DHEA; 4.91 nmol/L; range, 0.08 to 23.51), 11-ketoandrostenedione (11KA; 7.99 nmol/L; range, 0.07 to 31.67), or 11-ketotestosterone (11KT; 1.27 nmol/L; range, 0.03 to 7.61). Overweight women had lower median testosterone (P < 0.05), DHEA (P < 0.05), and 11KA (P < 0.01) levels than normal-weight women. All C19 steroids were significantly lower (P < 0.01) in those aged 35 to 39 years than in those aged 18 to 25 years. The median 11KA/androstenedione (4.3:1) and 11KT/testosterone (3.9:1) ratios did not change with age, after adjustment for BMI and cycle stage., Conclusions: We have demonstrated that 11KA and 11KT are stable across the menstrual cycle and make major quantitative contributions to the circulating androgen pool. All C19 androgens declined with age before menopause; hence, age-specific reference ranges are required for the interpretation of androgen levels in premenopausal women., (Copyright © 2019 Endocrine Society.)

This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women's Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynecologists., (Copyright © 2019 The Author(s), Published by the 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.

Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect on reproductive outcome. The rationale for asking this question lies in the existing scientific evidence derived from basic research and animal studies regarding the action of androgens during folliculogenesis, showing that their main effect in follicular development is defined during the earlier developmental stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because the short administration and the high dose of testosterone is not in line with the ovarian actions of androgens and the presence of androgen receptors during follicular development.

Objective: The objective of this consensus document is to broaden the perspective on clinical management of genitourinary syndrome of menopause to include androgens., Methods: A modified Delphi method was used to reach consensus among the 14 international panelists representing multiple disciplines and societies., Results: Menopause-related genitourinary symptoms affect over 50% of midlife and older women. These symptoms have a marked impact on sexual functioning, daily activities, emotional well-being, body image, and interpersonal relations. Tissues in the genitourinary system are both androgen and estrogen-dependent. The clitoris, vestibule, including minor and major vestibular glands, urethra, anterior vaginal wall, periurethral tissue, and pelvic floor are androgen-responsive. Historically, treatment of postmenopausal genitourinary symptoms involved both androgens and estrogens. This subsequently gave rise to predominantly estrogen-based therapies. More recently, double-blind, placebo-controlled clinical trials have demonstrated that local vaginal dehydroepiandrosterone improves symptoms in postmenopausal women, including moderate to severe dyspareunia. Limited data suggest that systemic testosterone treatment may improve vaginal epithelial health and blood flow. Open-label studies that have used high doses of intravaginal testosterone in the presence of aromatase inhibitor therapy for breast cancer have resulted in supraphysiological serum testosterone levels, and have been reported to lower vaginal pH, improve the vaginal maturation index, and reduce dyspareunia., Conclusions: Vaginal dehydroepiandrosterone, hypothesized to enhance local production of both androgen and estrogen, is effective for the management of dyspareunia in menopause. Vaginal testosterone offers potential as a treatment for genitourinary syndrome of menopause, but more studies are needed.

There is significant interest in the use of androgen therapy for postmenopausal women. This review provides background on endogenous androgens in women, describes factors that affect circulating androgen concentrations, and examines the relationship between low levels of androgens and sexual problems. Possible effects of androgens in postmenopausal women beyond sexual function also are discussed. Clinical trials of androgen therapy for the treatment of hypoactive sexual desire disorder are reviewed, with a discussion of potential risks. A practical approach to using androgens to treat low sexual desire with associated distress is presented, accompanied by an illustrative case.

Introduction: Androgens have been implicated as important for female sexual function and dysfunction., Aim: To review the role of androgens in the physiology and pathophysiology of female sexual functioning and the evidence for efficacy of androgen therapy for female sexual dysfunction (FSD)., Methods: We searched the literature using online databases for studies pertaining to androgens and female sexual function. Major reviews were included and their findings were summarized to avoid replicating their content., Main Outcome Measures: Quality of data published in the literature and recommendations were based on the GRADES system., Results: The literature supports an important role for androgens in female sexual function. There is no blood androgen level below which women can be classified as having androgen deficiency. Clinical trials have consistently demonstrated that transdermal testosterone (T) therapy improves sexual function and sexual satisfaction in women who have been assessed as having hypoactive sexual desire disorder. The use of T therapy is limited by the lack of approved formulations for women and long-term safety data. Most studies do not support the use of systemic dehydroepiandrosterone therapy for the treatment of FSD in women with normally functioning adrenals or adrenal insufficiency. Studies evaluating the efficacy and safety of vaginal testosterone and dehydroepiandrosterone for the treatment of vulvovaginal atrophy are ongoing., Conclusion: Available data support an important role of androgens in female sexual function and dysfunction and efficacy of transdermal T therapy for the treatment of some women with FSD. Approved T formulations for women are generally unavailable. In consequence, the prescribing of T mostly involves off-label use of T products formulated for men and individually compounded T formulations. Long-term studies to determine the safety of T therapy for women and possible benefits beyond that of sexual function are greatly needed., (Copyright © 2016. Published by Elsevier Inc.)

Testosterone is an essential hormone for women, with physiological actions mediated directly or via aromatisation to oestradiol throughout the body. Despite the crucial role of testosterone and the high circulating concentrations of this hormone relative to oestradiol in women, studies of its action and the effects of testosterone deficiency and replacement in women are scarce. The primary indication for the prescription of testosterone for women is loss of sexual desire, which causes affected women substantial concern. That no formulation has been approved for this purpose has not impeded the widespread use of testosterone by women--either off-label or as compounded therapy. Observational studies indicate that testosterone has favourable cardiovascular effects measured by surrogate outcomes; however, associations between endogenous testosterone and the risk of cardiovascular disease and total mortality, particularly in older women, are yet to be established. Adverse cardiovascular effects have not been seen in studies of transdermal testosterone therapy in women. Clinical trials suggest that exogenous testosterone enhances cognitive performance and improves musculoskeletal health in postmenopausal women. Unmet needs include the availability of approved testosterone formulations for women and studies to elucidate the contribution of testosterone to cardiovascular, cognitive, and musculoskeletal health and the risk of cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To update practice guidelines for the therapeutic use of androgens in women., Participants: A Task Force appointed by the Endocrine Society, American Congress of Obestricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), European Society of Endocrinology (ESE), and International Menopause Society (IMS) consisting of six experts, a methodologist, and a medical writer., Evidence: The Task Force commissioned two systematic reviews of published data and considered several other existing meta-analyses and trials. The GRADE methodology was used; the strength of a recommendation is indicated by a number "1" (strong recommendation, we recommend) or "2" (weak recommendation, we suggest)., Consensus Process: Multiple e-mail communications and conference calls determined consensus. Committees of the Endocrine Society, ASRM, ACOG, ESE, and IMS reviewed and commented on the drafts of the guidelines., Conclusions: We continue to recommend against making a diagnosis of androgen deficiency syndrome in healthy women because there is a lack of a well-defined syndrome, and data correlating androgen levels with specific signs or symptoms are unavailable. We recommend against the general use of T for the following indications: infertility; sexual dysfunction other than hypoactive sexual desire disorder; cognitive, cardiovascular, metabolic, or bone health; or general well-being. We recommend against the routine use of dehydroepiandrosterone due to limited data concerning its effectiveness and safety in normal women or those with adrenal insufficiency. We recommend against the routine prescription of T or dehydroepiandrosterone for the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, surgical menopause, pharmacological glucocorticoid administration, or other conditions associated with low androgen levels because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk. Evidence supports the short-term efficacy and safety of high physiological doses of T treatment of postmenopausal women with sexual dysfunction due to hypoactive sexual desire disorder. Importantly, endogenous T levels did not predict response to therapy. At present, physiological T preparations for use in women are not available in many countries including the United States, and long-term safety data are lacking. We recommend that any woman receiving T therapy be monitored for signs and symptoms of androgen excess. We outline areas for future research. Ongoing improvement in androgen assays will allow a redefinition of normal ranges across the lifespan; this may help to clarify the impact of varying concentrations of plasma androgens on the biology, physiology, and psychology in women and lead to indications for therapeutic interventions.

Testosterone is physiologically important for women. Serum testosterone levels decline with age, with the most precipitous fall being prior to menopause. There is no level of testosterone which defines a woman as being testosterone deficient. However, there is substantial high quality evidence to support the use of testosterone for the treatment of hypoactive sexual desire disorder in postmenopausal women. Although preliminary data suggests testosterone has favorable effects on bone and muscle mass, cognitive function and the cardiovascular system, further research regarding its therapeutic effects in these domains is warranted. As no testosterone product has been approved for women there is extensive off-label prescribing of testosterone products for women as well as the prescription of compounded therapy. This raises serious safety concerns and together with the evidence for the negative impact of FSD on quality of life, highlights the need for an approved testosterone formulation for women. This article is part of a Special Issue entitled 'Menopause'., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.)

Clinical Scenario: Andrea, a 53-year-old postmenopausal woman, is concerned about her loss of desire for sexual activity. Her last menstrual period occurred 2 years ago, and she has experienced minimal vasomotor symptoms. She has a loving relationship with her husband, to whom she has been married for 5 years and with whom she has previously enjoyed sexual intimacy, often initiating it. She is disturbed by the fact that not only has she no sexual desire but also that she has become unresponsive to her husband's sexual advances. The problem predates menopause by 1 to 2 years. She has recently heard that testosterone may be a treatment for this and wants to know what options are available.

Objective: The relationships between endogenous sex hormone levels and cardiovascular disease risk in women are contentious. Our aim was to systematically investigate the relationships between sex steroids and lipid levels in postmenopausal women, taking into account other potential risk factors., Methods: This is a cross-sectional study of 624 naturally and surgically postmenopausal women not using any systemic hormones or lipid-lowering therapy, with a mean (SD) age of 53.9 (5.8) years, who were recruited in the United States, Canada, Australia, UK, and Sweden between July 2004 and February 2005. The relationships between total testosterone, dihydrotestosterone, estrone, estradiol, sex hormone-binding globulin (SHBG), the homeostasis model assessment for insulin resistance (HOMA-IR), and each lipid variable were explored using multivariable linear regression., Results: None of the sex steroids measured made an independent contribution to the multivariable models for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, or triglycerides (TG). The best model for total cholesterol included race and age, and that for LDL cholesterol included race and blood pressure, with each model only explaining 4.8% and 3.3% of the variation in each lipid, respectively. About 7.7% of the variation in non-HDL cholesterol was explained by HOMA-IR, race, and SHBG. HOMA-IR, SHBG, age, and surgical menopause explained 22.8% of the variation in HDL cholesterol, whereas HOMA-IR, SHBG, race, and surgical menopause explained 25.4% of the variation in TG., Conclusions: Endogenous estrogen and androgen levels are not independent predictors of lipid levels in postmenopausal women. HOMA-IR and SHBG each make independent contributions to HDL cholesterol and TG. These factors make little contribution to total and LDL cholesterol.

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 (r(2) = 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., (© 2011 Blackwell Publishing Ltd.)

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.)

In women, sexual function, hormones and aging are inextricably related. Sexual activity in women involves interest and motivation, the ability to become aroused and achieve orgasm, the pleasure of the experience and subsequent personal satisfaction. Androgens, as endogenous hormones or given as a therapy, potentially influence female sexual function, with research into the effects of exogenous androgens in women mostly devoted to effects on sexual desire. Some studies have been conducted to delineate the effects of testosterone on arousal, however arousal determined by laboratory measures does not always correlate with subjective reporting of a sensation of arousal. Overall large randomised controlled trials of exogenous testosterone show benefits over placebo on sexual desire, arousal, orgasm, pleasure and satisfaction. The aspects of consideration of androgen therapy for women that continue to stimulate debate in this therapeutic area include whether female sexual dysfunction is a condition that merits pharmacotherapy, how effective is such treatment and whether testosterone therapy is safe., (Copyright © 2010. Published by Elsevier Inc.)

The available clinical evidence supports efficacy of testosterone therapy for the treatment of postmenopausal women with hypoactive sexual desire disorder (HSDD) who have undergone a comprehensive clinical evaluation. Although few preparations designed to deliver an appropriate dose of testosterone for women are available, use of testosterone by women for the management of HSDD is widespread. Issues that continue to simulate debate in this therapeutic area include whether HSDD is a condition that merits pharmacotherapy, how effective is such treatment and whether testosterone therapy is safe. Hence the question, should women receive androgen replacement therapy, and if so, how?

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.

Background: The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown., Methods: We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes., Results: At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 microg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 microg per day, P<0.001; 150 microg per day, P=0.04) and decreases in distress (300 microg per day, P<0.001; 150 microg per day, P=0.04). The rate of androgenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization., Conclusions: In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. (ClinicalTrials.gov number, NCT00131495.), (Copyright 2008 Massachusetts Medical Society.)

Hypopituitarism is a rare disorder, but its prevalence has increased as a result of an increase in secondary causes of hypopituitarism such as traumatic brain injury and cranial irradiation. Estrogen with or without progestogen (progestin) treatment is conventional therapy in women with hypopituitarism. Recent data demonstrate that women with hypopituitarism may experience marked androgen deficiency as a consequence of secondary loss of function of the adrenal cortex and/or ovaries. This deficiency is not always considered and therefore androgen therapy is not routinely prescribed. Recent clinical trials indicate that testosterone supplementation in physiological doses for androgen-deficient women with hypopituitarism may improve psychological well-being and sexual function, and increase bone mineral density and lean body mass. Dehydroepiandrosterone (DHEA; prasterone) supplementation may be an option for women with hypopituitarism who have secondary adrenal insufficiency and low levels of DHEA and DHEA sulfate. While short-term treatment with testosterone or DHEA appears to be safe, long-term safety data are lacking. Androgenic adverse effects limit the acceptability of treatment for some women. Further studies to establish the efficacy and safety of androgen treatment for long-term intervention in a larger group of hypopituitary androgen-deficient women are needed.

The investigation of female sexual dysfunction (FSD) is an evolving area in which definitions and models for female sexual functioning are being continually reviewed and revised. The lack of consensus amongst experts in the field and regulating authorities regarding appropriate inclusion and exclusion criteria for FSD trials, and main outcome measures appropriate for the evaluation of drug interventions has somewhat hampered progression in this area. Nonetheless, there is evidence from randomized controlled trials that androgen therapy improves the quality of the sexual experience for postmenopausal women with low libido, and preliminary data that this may also apply to premenopausal women.

Objective: Whether endogenous androgen levels contribute to the cardiovascular disease (CVD) risk profile in women is controversial. The purpose of this study was to investigate systematically the relationships between serum levels of endogenous androgens and sex hormone-binding globulin (SHBG) and biochemical CVD risk profile, taking other known risk factors into account., Design: This community-based cross-sectional study included 587 non-healthcare-seeking-women, aged 18 to 75 years, who were randomly recruited from the community via the electoral roll from April 2002 to August 2003. Participants were euthyroid; had no usage of exogenous steroids; had no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and did not have hyperprolactinemia or polycystic ovarian syndrome. The relationships between total testosterone, SHBG, free testosterone, dehydroepiandrosterone sulfate, and androstenedione and high-sensitivity C-reactive protein (CRP) and lipids were explored using linear regression with natural logarithm (ln) -or square root-transformed data as indicated. Issues of nonlinearity and interaction were addressed by the inclusion of extra regression terms where appropriate. We determined the change in the proportion of variation for each marker of the CVD risk profile explained by the addition of each hormone term to the models, having adjusted for age, body mass index, smoking, alcohol, and exercise., Results: Menopausal status did not influence the statistical models for high-sensitivity CRP and high-density lipoprotein cholesterol, but for both low-density lipoprotein cholesterol and triglycerides, the proportion of variation explained by the models was substantially less in postmenopausal than in premenopausal women. Almost all of the highly statistically significant findings were related to the addition of the SHBG terms to the models. The changes in r2 values were highly statistically significant for the addition of the SHBG terms to the models for ln CRP and ln high-density lipoprotein for both pre- and postmenopausal women (P <= 0.01 and < 0.001, respectively) and for ln triglycerides in postmenopausal (P < 0.001) and premenopausal women (P < 0.01)., Conclusions: Endogenous testosterone and the adrenal preandrogens per se are not significant independent determinants of circulating high-sensitivity CRP or lipoprotein lipids. Our analyses provide further support for the independent predictive value of low SHBG levels for CVD risk profile and an independent contribution of the menopausal transition to the determination of low-density lipoprotein cholesterol and triglycerides.

To date there is no clinical indication for the use of testosterone in women and long-term safety data is lacking. This minireview examines androgen therapy in women. Issues relating to research into sexual function and androgens in women are discussed. Androgen physiology is described and studies examining endogenous androgens in women cited. A Cochrane review found that adding testosterone to a hormone therapy regimen has beneficial effects on sexual function in postmenopausal women and subsequent studies have supported the role of testosterone in sexual function and well-being. However studies on safety and efficacy of testosterone beyond 24 weeks are lacking.

Objective: To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause., Design: A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 microg/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24)., Results: A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels < or = 160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels < or = 160 nmol/L, mean change of 2.1 +/- 0.28 versus 0.5 +/- 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 +/- 0.26 versus 0.5 +/- 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated., Conclusions: Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder.

Objective: We investigated whether there is a relationship between androgens levels and well-being in pre- and postmenopausal women., Design: We randomly recruited 1423 women aged 18 to 75 years from the community via the electoral roll. Each provided a morning blood sample and completed the Psychological General Well Being Index questionnaire on the same day. Women were excluded if they took medication for any psychiatric illness, had abnormal thyroid function, or had documented polycystic ovarian syndrome. Analysis was by linear regression for well-being, including demographic and lifestyle variables as well as serum levels of androgens., Results: We included 1224 women in the analysis. Being partnered was positively associated with well-being in premenopausal women. In postmenopausal women, well-being was positively related to age and exercising, whereas smoking, obesity, and postmenopausal hormone therapy use were each negatively associated with well-being. None of the measured androgens (total and free testosterone, dehydroepiandrosterone sulfate, and androstenedione) made an independent contribution to well-being in postmenopausal women (n = 603). However, for premenopausal women (n = 621), levels of dehydroepiandrosterone sulfate were independently and positively associated with the domain score for vitality., Conclusions: Our findings do not support an important independent role for androgens as determinants of well-being in postmenopausal women. That dehydroepiandrosterone sulfate alone is associated with greater vitality in premenopausal women is of interest but requires further evaluation as an a priori hypothesis in another study.

Objective: To evaluate the clinical usefulness for the measurement of testosterone (T) values in the "low" female range with a direct radioimmunoassay (RIA) for total T by comparing total T values measured by this assay with values determined by conventional RIA after organic solvent extraction/column chromatography., Design: Cross-sectional study., Setting: Victoria, Australia., Patient(s): Two hundred fifty-nine healthy women, aged 18-75 years, recruited from the community., Intervention(s): Fasting serum samples were obtained and stored at -80 degrees C., Main Outcome Measure(s): Total T measurement. Total T was measured by the direct RIA method using antibody-coated tubes and iodine-labeled T tracer. For comparison, total T levels were also measured using the conventional RIA method after organic solvent (ethyl acetate:hexane [3:2]) extraction and celite column partition chromatography before RIA., Result(s): The mean T level by direct RIA was 0.76 nmol/L (median, 0.70; SD, 0.54; minimum, 0.10; maximum, 3.2). The mean difference between the two measurements (direct RIA - conventional RIA) was -0.28 (SD, 0.3). The direct RIA value was 63% (95% confidence interval, 26%-155%) of the conventional RIA estimate. For the classification of values at the lower end of the range, there was very good agreement beyond chance (kappa = 0.68-0.74) for values in approximately the lowest 10th-40th percentiles., Conclusion(s): The direct RIA is a clinically useful assay for the study of the issue of "low" T within the female population.

Androgens have important physiological effects in women. Postmenopausal androgen replacement, most commonly as testosterone therapy, is becoming increasingly widespread. This is despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety data. With respect to the breast specifically, there is the potential for exogenous testosterone to exert either androgenic or indirect estrogenic actions, with the latter potentially increasing breast cancer risk. In experimental studies, androgens exhibit growth-inhibitory and apoptotic effects in some, but not all, breast cancer cell lines. Differing effects between cell lines appear to be due primarily to variations in concentrations of specific coregulatory proteins at the receptor level. In rodent breast cancer models, androgen action is antiproliferative and proapoptotic, and is mediated via the androgen receptor, despite the potential for testosterone and dehydroepiandrosterone to be aromatized to estrogen. The results from studies in rhesus monkeys suggest that testosterone may serve as a natural endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium. Epidemiological studies have significant methodological limitations and provide inconclusive results. The strongest data for exogenous testosterone therapy comes from primate studies. Based on such simulations, inclusion of testosterone in postmenopausal estrogen-progestin regimens has the potential to ameliorate the stimulating effects of combined estrogen-progestin on the breast. Research addressing this is warranted; however, the number of women that would be required for an adequately powered randomized controlled trial renders such a study unlikely.

Objective: Circulating testosterone in women declines during the late reproductive years such that otherwise healthy women in their 40s have approximately half the testosterone level as women in their 20s. Despite this, research showing the benefits of androgen replacement has been limited to the postmenopausal years. In view of the known premenopausal physiological decline in testosterone, we have evaluated the efficacy of transdermal testosterone therapy on mood, well-being, and sexual function in eugonadal, premenopausal women presenting with low libido., Design: Premenopausal women with low libido participated in a randomized, placebo-controlled, crossover, efficacy study of testosterone cream (10 mg/day) with two double-blind, 12-week, treatment periods separated by a single-blind, 4-week, washout period., Results: Thirty-four women completed the study per protocol, with 31 women (mean age 39.7 +/- 4.2 years; serum testosterone 1.07 + 0.50 nmol/L) providing complete data. Testosterone therapy resulted in statistically significant improvements in the composite scores of the Psychological General Well-Being Index [+12.9 (95% CI, +4.6 to +21.2), P = 0.003] and the Sabbatsberg Sexual Self-Rating Scale [+15.7 (95% CI, +6.5 to +25.0), P = 0.001] compared with placebo. A mean decrease in the Beck Depression Inventory score approached significance [-2.8 (95% CI, -5.7 to +0.1), P = 0.06]. Mean total testosterone levels during treatment were at the high end of the normal range, and estradiol was unchanged. No adverse effects were reported., Conclusions: Testosterone therapy improves well-being, mood, and sexual function in premenopausal women with low libido and low testosterone. As a substantial number of women experience diminished sexual interest and well-being during their late reproductive years, further research is warranted to evaluate the benefits and safety of longer-term intervention.

The role of androgen treatment in women remains controversial. The proposed "Female Androgen Insufficiency Syndrome" (Fertility and Sterility, April 2002) describes a number of non-specific symptoms including unexplained fatigue, decreased well being/dysphoric mood and/or blunted motivation and diminished sexual function. An estimated 40% of women experience sexual dysfunction, highlighting the need for ongoing research into this field in order to fully define the possible contribution of androgen insufficiency. The increasing availability of products, such as dehydroepiandrosterone (DHEA) supplements also points to the need for controlled studies to assess the safety of these and other preparations. Measurement of androgens in women requires sensitive assays with the ability to detect low levels and a narrow range with precision. Normal ranges of androgens for women of reproductive and post-reproductive age remain poorly defined. Debate exists as per importance of measurement of free versus total testosterone, with the "free androgen index" offering an alternative method of assessment of testosterone availability. Testosterone treatment is being developed for women in the form of transdermal patches, gels or cream, with percutaneous implants in common usage in some countries. Recent research has highlighted alternative means of administration, such as oral inhalation or buccal lozenge. DHEA is widely available in some countries. Research to date has demonstrated improvements in libido and sexual function, mood and well being. Evidence points to other potential benefits of androgen treatment, including preservation of bone mass, a possible protective role in breast cancer and beneficial effects on cognition. Adverse effects of androgen treatment in women are dose-dependent and include virilisation, mood disturbance and acne. These are uncommon if appropriate doses are administered and highlight the need for treatment to be closely monitored clinically and biochemically. Beneficial effects of testosterone treatment in post-menopausal women with lowered androgen levels have been well documented, and preliminary evidence suggests a role for treatment in pre-menopausal women with symptoms and lowered testosterone levels.

The concept of a female androgen insufficiency syndrome, although not new, remains somewhat controversial. Androgens are quantitatively the predominant sex steroid in women, circulating in the micromolar and nanomolar concentration range, compared with picomolar levels of oestrogens. The most significant biologically active androgen is testosterone (T), which circulates bound tightly to sex-hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG-bound fraction is the bioavailable moiety. Hence, clinically useful T measurements require data on total concentrations as well as SHBG level. Testosterone insufficiency occurs in a number of circumstances, including hypopituitarism, premature ovarian failure, adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (causing elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen insufficiency include loss of libido, diminished well-being, fatigue and blunted motivation and have been reported to respond well to T replacement, generally without significant side-effects.

To date, no formal definition of female androgen insufficiency (FAI) based on strong epidemiological data exists. However the proposed key symptoms of FAI, being reduced libido, diminished well-being, and lowered mood, have been reported to respond well to testosterone replacement, generally without significant adverse effects. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of estrogens. Androgens have important physiological roles in women, acting both as precursors for estrogen biosynthesis and directly via the androgen receptor. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone binding globulin and loosely to albumin. Circulating androgen levels decline in the years preceding menopause. This may be attributed to the gradual reduction in adrenal androgen production with age and to the loss of cyclical ovarian androgen production in the late reproductive years. Those who experience surgical menopause, have adrenal insufficiency or pituitary insufficiency, or those who experience premature ovarian failure, also have reduced androgen production. Androgen replacement therapy in the form of either dehydroepiandrosterone or testosterone is becoming increasingly widespread for the treatment of FAI. Evidence exists for the benefits of such therapy in relieving both the physical and psychological symptoms thought to be due to FAI in clinically affected women. However, clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety remain lacking.

The concept of an androgen deficiency syndrome in women is a relatively old one, although it has gained substantially increased attention in recent years. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of oestrogen. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG bound fraction is the bioavailable moiety. Hence interpretable testosterone measurements require data on total concentrations as well as the SHBG level. Testosterone deficiency occurs in a number of situations such as hypopituitarism, primary ovarian and adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (due to the elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen deficiency include lethargy, tiredness and loss of sex drive and interest, and have responded well to androgen replacement, generally without significant side-effects., (Copyright 2002 Elsevier Science Ltd.)

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]

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]

Introduction It is a commonly held belief that combined oral contraceptive ( COC) pills containing an androgenic progestin may be less likely to impair sexual function than COCs containing an anti-androgenic progestin. Aim The study aims to compare the effects of a COC containing a progestin with an anti-androgenic profile (estradiol valerate [ E2V]/dienogest [ DNG]) to that of one with an androgenic progestin (ethinyl estradiol [ EE]/levonorgestrel [ LNG]) on sexual function in women with COC-associated sexual dysfunction. Methods In this multicenter, randomized, double-blind, noninferiority study, women with COC-associated female sexual dysfunction ( FSD) were randomized to E2V/DNG or EE/LNG for six cycles. The primary outcome was the change in the sum of Female Sexual Function Index ( FSFI) desire and arousal component scores between baseline and cycle 6. Secondary outcome measures included changes to the FSFI domains, the Female Sexual Distress Scale ( FSDS-R), Vaginal Health Assessment, the Atrophy Symptom Questionnaire, and the Psychological General Well Being Index over six treatment cycles. Main Outcome Measure The main outcome is the change in the sum of FSFI desire and arousal component scores between baseline and cycle 6. Results Of 276 women screened, 213 received treatment and 191 completed the study. The mean increase in the sum of FSFI desire and arousal component scores was 5.90 (standard deviation [ SD] 5.45) for E2V/DNG and 5.79 ( SD 6.17) for EE/LNG (change from baseline P < 0.0001, both groups). Both treatments showed equal efficacy and were associated with improvements in all domains of the FSFI, with no between-group differences. Both COCs reduced the distress associated with FSD, as indicated by reduced FSDS-R scores. Conclusion In women with COC-associated FSD, switching to either E2V/DNG or EE/LNG was associated with equivalent improvements in symptoms, challenging the perception that COCs containing anti-androgenic progestins have a detrimental effect on sexual function relative to those containing androgenic progestins. D avis SR , B itzer J , G iraldi A , P alacios S , P arke S , S errani M , M ellinger U , and N appi RE . Change to either a nonandrogenic or androgenic progestin-containing oral contraceptive preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction. J S ex M ed 2013;10:3069-3079. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen–progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. Objective: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. Design: Literature review. Setting: The Jean Hailes Foundation, Research Unit. Main Outcome Measures: Mammary epithelial proliferation, apoptosis and breast cancer. Results: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. Conclusion: Available data indicate the inclusion of testosterone in estrogen–progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting. [Copyright &y& Elsevier]

Objective: To review causes of female androgen insufficiency (FAI) other than menopause. Design: A review of the available literature in this field. Result(s): Androgen levels decline with increasing age during the reproductive years in healthy women and vary little or not at all across menopause, with controversy as to whether levels change in the postmenopausal years. Thus the premenopausal decline in androgens potentially is the most common cause of female androgen insufficiency (FAI), whereas natural menopause in itself is not a cause of androgen deficiency. Pathophysiological causes of FAI can be divided into those that affect ovarian androgen production, those that affect adrenal androgen production, and combined deficiency states. Surgical menopause is characterized by an abrupt onset of symptoms, in contrast to a more insidious onset of relatively nonspecific symptoms in women who have FAI due to aging. Conclusion(s): The decline in testosterone with normal aging before menopause may well be the most common cause of FAI, although many women do not present with symptoms and most are not diagnosed until they have reached menopause. [ABSTRACT FROM AUTHOR]

Objective: To review causes of female androgen insufficiency (FAI) other than menopause.Design: A review of the available literature in this field.Result(s): Androgen levels decline with increasing age during the reproductive years in healthy women and vary little or not at all across menopause, with controversy as to whether levels change in the postmenopausal years. Thus the premenopausal decline in androgens potentially is the most common cause of female androgen insufficiency (FAI), whereas natural menopause in itself is not a cause of androgen deficiency. Pathophysiological causes of FAI can be divided into those that affect ovarian androgen production, those that affect adrenal androgen production, and combined deficiency states. Surgical menopause is characterized by an abrupt onset of symptoms, in contrast to a more insidious onset of relatively nonspecific symptoms in women who have FAI due to aging.Conclusion(s): The decline in testosterone with normal aging before menopause may well be the most common cause of FAI, although many women do not present with symptoms and most are not diagnosed until they have reached menopause. [Copyright &y& Elsevier]

Androgen deficiency in women is a valid diagnosis in premenopausal, as well as in postmenopausal women, under certain conditions. This diagnosis is hampered by a lack of precise definitions and sensitive assays for testosterone. Precise normal ranges for control populations are lacking, and thus many studies have used pharmacological instead of physiological levels of testosterone in treatment protocols. Despite these shortcomings, and a shortage of controlled studies, there is ample evidence that testosterone treatment has helped many women with signs and symptoms of deficiency. [ABSTRACT FROM AUTHOR]

Sexual health is an important component of overall health and well-being. Multiple factors clearly influence an individual's sexuality; however, there is a general trend in Western societies to blame psychosocial factors for diminished sexuality in women. Sex steroid hormones are important determinants of sexual function in women and men, and there is increasing agreement that androgens play a key role in female sexuality. Androgen levels in women decline substantially during the reproductive years, with little change subsequent to spontaneous menopause. The most common complaint of women experiencing androgen deficiency is loss of sexual desire, and several studies have now shown improvements in a number of parameters of sexuality in postmenopausal women treated with exogenous testosterone. [ABSTRACT FROM AUTHOR]

Se presenta una reseña del artículo "The relationship between endogenous androgens and body fat distribution in early and late postmenopausal women" de Yuankui Cao, Shaofen Zhang, Shien Zou y Xian Xia, el cual apareció en la revista "PLoS ONE", volumen 8, 2013.