Kling, Juliana M.

Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. Testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD). However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause. In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms “HSDD,” “DHEA in women,” “testosterone in women,” and “androgens in women,” and reviewed most references from all relevant articles. Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known. A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of postmenopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45 ± 2.49 yr of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE; n = 109), transdermal 17β-estradiol (t-E2; n = 107), or placebo ( n = 146). Androstenedione, testosterone, 17β-estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum before (baseline) and 48 mo after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE, t-E2, and placebo on these hormone levels at 48 mo, adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 mo within treatment groups. As expected, at 48 mo of treatment, hormone levels differed between women in the two active treatment groups compared with placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups compared with placebo. Associations among testosterone, 17β-estradiol, FSH, and LH differed between the o-CEE group compared with t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and interhormonal associations in recently menopausal women. These interactions provide the basis for future studies investigating the impact of hormonal modulation of aging, including cognitive decline in women.

The Clinical Update series is intended to help busy providers stay up to date with important and potentially practice changing articles that have been published on topics pertinent to the care of women. The rates of obesity and the resultant morbidities are rising worldwide, making it a high-priority health issue for the medical community. Moreover, the pathophysiology and management of obesity and visceral fat accumulation in women has important nuances, distinct from those in men. It is important to consider the effect of unique female-specific influences such as reproductive stage and pregnancy. Therefore, we have chosen to review six high-impact recent studies relating to obesity and its management in women. These include guidelines for management of obesity in pregnancy, risk of nonmelanoma skin cancer in overweight/obese women, the association of vascular fat and decline in physical function in midlife women, the predictors for weight gain in premenopausal women with early-stage breast cancer, dietary patterns and obesity in postmenopausal women, and finally, normal weight obesity and mortality risk in postmenopausal women.

Abstract Introduction Sexual dysfunction is a common problem in women and the nature of its association with alcohol use remains unclear. Aim To explore the association between alcohol use and female sexual dysfunction (FSD). Methods Associations between self-reported drinking and sexual function were evaluated in 2,253 women presenting for consultation to a women’s health specialty clinic. A short version of the Alcohol Use Disorders Identification Test (AUDIT-C) was used to evaluate alcohol use. Women with an AUDIT-C ≥3 were considered at risk for hazardous drinking. Multivariable regression, controlling for depression, anxiety, and abuse (childhood and recent), was used to assess the association between alcohol consumption and FSD (defined as a Female Sexual Function Index [FSFI] ≤26.55 and Female Sexual Distress Scale [FSDS] ≥11) in sexually active women. Main Outcome Measure The main study outcome measure was the presence of FSD as defined by a score ≤26.55 on the FSFI and ≥11 on the FSDS. Results 57% of the 1,649 sexually active women were classified as having FSD; 80% reported any alcohol use and 38% reported drinking patterns with the potential to be hazardous. The women at risk for hazardous drinking had significantly higher FSFI domain scores indicating better sexual function (P ≤ .001). However, in multivariable analyses, there was no significant difference in the rates of FSD across alcohol use categories in women. Conclusion In women presenting for consultation to a women’s health specialty clinic, an association between alcohol use and FSFI scores was seen, in which greater risk of hazardous drinking was associated with better sexual function scores. However, when sexual distress was included to define sexual dysfunction, those with FSD were not at higher risk of hazardous drinking. Given the complex nature of FSD, additional study is needed to further clarify these relationships.

The risks and benefits of menopausal hormonal therapy (HT) have been evaluated extensively over the past three decades. While the efficacy of HT for management of menopausal symptoms, including vasomotor symptoms and vaginal dryness is well established, its relationship to cardiovascular outcomes is complex. The timing hypothesis, which posits that the cardiovascular effects of HT depend on the timing of initiation of HT in relation to menopause, has helped shape our understanding of the cardiovascular outcomes related to HT. Based on results from female monkey studies, the timing hypothesis provides a framework to explain discrepancies in results between multiple observation studies and the Women's Health Initiative (WHI) hormone therapy trials. The WHI trials closed early in 2002 in part because of increased cardiovascular events seen in women on treatment. Subanalysis of the WHI results by age group, and more recent randomized control studies, including the Kronos Early Estrogen and Prevention Study (KEEPS) and Early Versus Late Intervention Trial (ELITE), demonstrate that the risk of adverse cardiovascular events for HT are low for women <60 years of age or within 10 year from menopause. Although current data does not support using HT for primary prevention of cardiovascular disease, it does suggest that HT can be safely used to treat symptoms in appropriately selected women close to menopause.