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Objective: This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women., Methods: The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders., Results: The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) ( p  = 0.002 and p  < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol ( p  = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) ( p  = 0.024, p  = 0.003 and p  < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C ( p  = 0.024)., Conclusions: In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.

The clinical effects of testosterone in women have expanded from the field of androgen excess to consideration of testosterone action and the consequences of depletion and replacement. This article is not a comprehensive review of the vast and increasing literature in this field. Rather, it summarizes some of what is known of testosterone in women that the author elected to highlight in a plenary lecture and is hopefully informative, but not to be considered conclusive.

This review was conducted to explore the association between endogenous testosterone blood concentrations and cognitive performance among community dwelling postmenopausal women. We searched Ovid MEDLINE, EMBASE, PsycINFO and Web of Science databases for observational studies with at least 100 postmenopausal participants. The results were categorized by study design, reporting of total or free testosterone and risk of bias assessments, narratively. Ten of the 26 articles retrieved for full-text review met the inclusion criteria, six provided cross-sectional data, seven provided longitudinal data and one provided case-control data. Cognitive performance tests differed between studies. Eight studies measured testosterone by immunoassay, one by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and one did not specify their methodology. Eleven different cognitive domains were tested by 37 different instruments. Irrespective of the study design, the findings were inconsistent and inconclusive. Both positive and inverse associations were reported for each of global cognition and immediate and delayed verbal recall. The majority of studies reported no association between total or free testosterone and cognitive performance. Although this review did not demonstrate an association between testosterone and cognitive performance in postmenopausal women, the findings should be considered inconclusive due to the imprecision of testosterone measurement and the methodological heterogeneity of the included studies.

Premature ovarian insufficiency (POI) results in both estrogen and testosterone insufficiency. Whether testosterone therapy may be of benefit for women with POI is uncertain. Presently, the only evidence-based indication for testosterone therapy for women is for the treatment of postmenopausal women with low sexual desire with associated personal distress. Consistent with this, available evidence does not support the prescription of testosterone to prevent cardiometabolic disease, bone loss, sarcopenia, or cognitive decline or to improve well-being and low mood in postmenopausal women. Data pertaining to the treatment of women with POI with testosterone are limited. This article reviews androgen physiology in premenopausal women and the impact of POI on circulating androgen concentrations, summarizes findings from observational studies and clinical trials of testosterone therapy in premenopausal women and women with POI, and concludes with recommendations regarding testosterone use in women with POI.

The physiological, clinical and therapeutic aspects of testosterone in women's health are still a matter of controversy and debate. Quality evidence data of clinical trials favors the use of transdermal testosterone in postmenopausal women with female sexual dysfunction causing distress. Doses of testosterone should approximate physiological testosterone levels found in premenopausal women, avoiding supraphysiological concentrations that expose women to adverse events. Short-term treatment periods have been shown to be effective and safe in postmenopausal women with hypoactive sexual desire disorder/dysfunction. However, long-term safety of testosterone use must be determined.

Objective: The aim of this review was to summarize the literature regarding the potential role of testosterone therapy for women., Methods: The author conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2013) for English-language studies that included the following search terms: 'testosterone' or 'androgen' combined with 'women', 'therapy' or 'treatment'., Results: Randomized, placebo-controlled trials have consistently shown that transdermal testosterone therapy improves sexual desire, arousal, orgasm frequency and satisfaction in premenopausal and postmenopausal women presenting with sexual desire/arousal problems. No adverse metabolic effects have been observed in these studies. In postmenopausal women, testosterone therapy has also been associated with favorable effects on body composition, bone, cardiovascular function and cognitive performance., Conclusions: Although androgens have many varied roles, the focus of testosterone therapy for women has been on improving sexual desire. Not only do testosterone effects on sexuality extend beyond libido, but testosterone has other key physiological actions. Issues that urgently need to be addressed include approval of a testosterone formulation that delivers a female dose such that physicians refrain from prescribing compounded testosterone or modifying doses of testosterone formulated for men and regulation of prescription of compounded androgens for women.

Objective: To evaluate the efficacy and safety of a transdermal testosterone patch (TTP, 300 microg/day) in naturally menopausal women with hypoactive sexual desire disorder (HSDD)., Methods: A total of 272 naturally menopausal women, predominantly not using hormone therapy, were randomized in this 6-month, placebo-controlled, double-blind, multicenter study to receive twice weekly either TTP or an identical placebo. Efficacy endpoints measured were the 4-week frequency of satisfying sexual episodes (SSE) using the Sexual Activity Log, the sexual desire domain of the Profile of Female Sexual Function and distress by the Personal Distress Scale. Safety was assessed by adverse events, laboratory parameters and hormone levels., Results: The TTP group demonstrated significant improvements in SSE (p = 0.0089) as well as in sexual desire (p = 0.0007) and reduced personal distress (p = 0.0024) versus placebo at 6 months (intent-to-treat analysis, n = 247). The results were significant for all three endpoints in the subgroup (n = 199) not using hormone therapy. Similar numbers of women treated with placebo and TTP discontinued (n = 39, 27.5% vs. n = 26, 20%), reported adverse events (including application site reactions) (n = 101, 71.1% vs. n = 81, 62.3%) and withdrew due to adverse events (n = 20, 14.1% vs. n = 9, 6.9%). No clinically relevant changes were noted in laboratory parameters. Serum free and total testosterone levels increased from baseline in the TTP group (geometric means 5.65 pg/ml and 67.8 ng/dl, respectively, at week 24) within the physiological range; no changes were seen in estradiol and sex hormone binding globulin levels., Conclusions: TTP was effective in treating HSDD and improving sexual function in this study of naturally menopausal women with and without concurrent hormone therapy.

Objectives: To evaluate the relationship between serum testosterone (T), preandrogens and sex hormone binding globulin (SHBG), and the knee structure in middle-aged women without knee pain., Methods: One hundred and thirty-nine healthy women without knee pain, aged 40 to 67 years, underwent magnetic resonance imaging of their dominant knee to measure tibial and patella cartilage volumes and defects, respective bone area and volume, and bone marrow lesions. The serum level of T, preandrogens, and SHBG were analyzed using linear regression to determine whether associations existed between these hormones and knee structure., Results: Free T and total T showed no association with cartilage volume or bone structures in the knee. SHBG showed a statistically positive association with patella bone volume after adjusting for confounders (P = 0.02)., Conclusion: Our study suggests there are no associations between serum levels of T or the preandrogens and knee structure in women. The observed positive association between SHBG and patella bone volume may reflect a favorable effect of estrogen exposure on patella bone volume.

There is increasing awareness of the significant and varied actions of endogenous androgens in women, and acknowledgement that women might experience symptoms secondary to androgen deficiency. There is also substantial evidence that prudent testosterone replacement is effective in relieving both the physical and psychological symptoms of androgen insufficiency in clinically affected women. However, our understanding of the actions of testosterone in women is incomplete, with no consensus as to what constitutes either biochemical or clinical testosterone deficiency. The focus of the limited research into testosterone replacement has been on sexuality, primarily sexual desire. However, the influence of testosterone on mood and well being also requires further exploration.

The gender difference in cardiovascular disease has been partly attributed to higher androgenic hormone levels. Although testosterone in women may not affect lipids, it remains unknown whether it negates favorable estrogenic effects on endothelial function. We have investigated the effects of testosterone implant therapy on arterial reactivity encompassing endothelial-dependent and -independent vasodilation in women using hormone replacement therapy (HRT). B-mode ultrasound measurements of resting brachial artery diameter, following reactive hyperemia [endothelium-dependent flow- mediated dilation (FMD)] and following glyceryl trinitrate (GTN) (endothelium-independent dilation), were recorded in 33 postmenopausal women stabilized on HRT (>6 months), at baseline, and 6 weeks after a testosterone implant (50 mg), with 15 postmenopausal nonusers of HRT serving as controls. In the brachial artery, baseline resting diameter was similar (0.40 +/- 0.01 vs. 0.41 +/- 0.01 cm, P = 0.5). In the treated group, testosterone levels increased (0.99 +/- 0.08 to 4.99 +/- 0.3 nmol/L, P < 0.001), associated with a mean 42% increase in FMD (6.4% +/- 0.7 to 9.1% +/- 1.1, P = 0.03). The control group did not change (8.1% +/- 1.4 to 5.6% +/- 1.0, P = 0.4). ANOVA of repeated measures (P = 0.04) and mean change (P = 0.02) in FMD both demonstrated significantly greater improvement with testosterone compared with controls. GTN induced vasodilation increased with testosterone treatment (14.9% +/- 0.9 to 17.8% +/- 1.2, P = 0.03). Our preliminary data indicate that parenteral testosterone therapy improves both endothelial-dependent (flow-mediated) and endothelium-independent (GTN-mediated) brachial artery vasodilation in postmenopausal women using long-term estrogen therapy. The mechanisms underlying these potentially beneficial cardiovascular effects require further investigation.

Objective: The cardioprotective effects of postmenopausal estrogen replacement therapy are mediated by several mechanisms, including favorable effects on lipids and lipoproteins. The extent to which the latter reflects modification of body fat distribution by sex steroids is not known. Hence, we investigated the relationships between changes in lipids and measures of body composition in postmenopausal women who were administered estrogen therapy with and without testosterone., Design: We randomized 33 postmenopausal women to treatment with either estradiol 50 mg (E) alone or estradiol 50 mg plus testosterone 50 mg implants (E&T) administered every 3 months for 2 years in conjunction with cyclic oral progestins for women with an intact uterus., Results: Both therapies were associated with sustained reductions in total cholesterol and low-density lipoprotein (LDL) cholesterol. In women who received E but not E&T, hip (p < 0.001) and abdominal circumferences (p < 0.05) and fat mass:fat-free mass (FM:FFM) ratio over the abdomen (p < 0.05) declined. E&T but not E resulted in increased FFM (p < 0.001) and a reduced FM:FFM ratio (p < 0.05). For E but not E&T, the decrease in LDL cholesterol was significantly related to changes in total and compartmental body fat and to change in the FM:FFM ratio (p < 0.05)., Conclusion: Estrogen replacement has effects on body fat distribution in postmenopausal women that are associated with improved lipid parameters. Addition ofparenteral testosterone does not negate the favorable effects of estrogen on LDL cholesterol levels but may attenuate the reduction in centralized body fat achieved with E implants.

An accumulating body of data indicates that many women experience a cluster of symptoms that are responsive to testosterone treatment and may be due to androgen deficiency. Characteristically, affected women complain of low libido, persistent fatigue, and diminished well-being and are found to have low circulating bioavailable testosterone. Whether the apparent therapeutic effects of testosterone are mediated via the androgen receptor or as a consequence of metabolism to estrogen is not known. Despite the lack of understanding of the mechanism(s) by which testosterone may enhance libido, the prescription of testosterone to women in a variety of formulations is becoming increasingly popular. This article provides an overview of the rationale for testosterone therapy in women, offers a broad definition of androgen deficiency in women based on the clinical experience of the author, and outlines the currently available options and potential risks of testosterone replacement in women.

Many women, both before and after menopause, may have symptoms of androgen deficiency: unexplained fatigue, lack of well-being and diminished libido. If plasma levels of bioavailable testosterone are low, these symptoms will mostly be relieved by judicious administration of testosterone. The addition of testosterone to postmenopausal hormone replacement regimens is becoming more widespread, and other potential uses include prevention and treatment of bone loss, treatment of spontaneous or iatrogenic androgen deficiency in premenopausal women, and, possibly, management of the premenstrual syndrome.

Androgens have significant and varied actions in women and there is now acknowledgment that women may experience symptoms secondary to androgen deficiency. There is also substantial evidence that prudent androgen replacement can be effective in relieving both the physical and psychological symptoms of androgen insufficiency, and is indicated for clinically affected women. Testosterone replacement for women is now available in a variety of formulations. It appears to be safe, with the caveat that doses are restricted to the 'therapeutic' window for androgen replacement in women, such that the beneficial effects on wellbeing and quality of life are achieved without incurring undesirable virilizing side effects. The predominant symptom of women with androgen deficiency is loss of sexual desire. This is not limited to women experiencing a surgical menopause but may also be a feature of women who have either undergone premature or natural menopause. There is increasing interest in other uses of androgen replacement in women that include premenopausal iatrogenic androgen deficiency states, glucocorticosteroid-induced bone loss, management of wasting syndromes and possibly premenopausal bone loss, premenopausal loss of libido and the treatment of the premenstrual syndrome.

Androgens have an important physiological role in women. Not only are they the precursor hormones for oestrogen production in the ovaries and extragonadal tissues, but they also appear to act directly, via androgen receptors, throughout the body. Androgen levels decline with increasing age in women, who may experience a variety of physical symptoms secondary to androgen depletion, as well as physiological changes that affect their quality of life. In this chapter, the changes in androgens as women age are reviewed, and the rationale for physiological androgen, specifically testosterone replacement, in women is addressed.

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.

Serum androgen levels decline with age in women, a decline already demonstrable prior to menopause. Oestrogen administration is associated with a decrease in bioavailable testosterone. Testosterone administration can lead to increases in a number of parameters of sexuality, probably by direct neural effects. Androgens also have anabolic effects on bone, and do not adversely affect lipids, especially when given parenterally.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Background The loss of estrogen at menopause and the gradual decline in testosterone with age are associated with urogenital atrophy and, as a result, urogenital tract symptoms, including lower urinary tract symptoms and dyspareunia. These symptoms will persist unless treated. Objective To review the prevalence of urogenital tract symptoms and sexual health problems associated with menopause and the role in the use of hormone therapy for the treatment of symptomatic women, with a specific focus on what has been learned since the first publication of the Women's Health Initiative (WHI) estrogen and estrogen + progestin studies. Conclusion Studies support the use of local estrogen therapy, but not systemic estrogen therapy, for the treatment of urge urinary incontinence, overactive bladder and to reduce the number of urinary tract infections. The current evidence does not favor a beneficial effect on stress urinary incontinence. Local estrogen therapy is effective for the treatment of dyspareunia caused by vulvovaginal atrophy. Preliminary studies suggest a potential role for both intravaginal dehydroepiandrosterone and testosterone in the treatment of dyspareunia secondary to vulvovaginal atrophy, however, confirmatory studies are required before either therapy can be recommended. Post WHI, there is a need for medical practitioners to proactively raise the topic of urogynecological and sexual health in order to discuss the most suitable treatment option. [ABSTRACT FROM AUTHOR]

This article presents a study which aims to determine whether low serum testosterone level is associated with low sexual desire in women living in Victoria, Australia. A serum dehydroepiandrosterone sulfate (DHEA) level below the aged-adjusted 10th percentile is a better marker for low sexual desire and function, but the majority of women with a low DHEA level do not have sexual dysfunction. There is no evidence to support measurement of serum testosterone in women with low sexual desire or function. The practice of prescribing exogenous testosterone for women with low sexual desire or function requires further study and should not be routine.