Topical Testosterone for Menopausal Symptoms

Is topical testosterone safe and effective for sexual function and vaginal symptoms in menopausal and postmenopausal women?

Topical testosterone can be used to manage sexual function and vaginal symptoms associated with menopause. (Strength of Recommendation: B, systematic review and meta-analysis.) Combined with estrogen replacement therapy, topical testosterone increases the number of satisfying sexual episodes compared with placebo.

A 2017 systematic review and meta-analysis (N = 3,035) analyzed results from seven randomized controlled trials (RCTs) studying the effects of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder.¹ The primary outcome was the number of satisfying sexual episodes. In five studies, the testosterone group had significantly more satisfying sexual episodes than the placebo group. There was no difference in outcomes between women taking estrogen with or without progestin as hormone replacement therapy combined with transdermal testosterone and women using transdermal testosterone alone. In the pooled data, significantly more acne was noted in the testosterone group, but there were no differences in facial hair, voice deepening, alopecia, or lipid or metabolic profiles. Also, there were no differences in total or severe adverse effects.

A 2010 RCT (N = 75) evaluated the effectiveness of 12 weeks of 0.625-mcg vaginal estrogen cream with or without 1 mg of testosterone on urogenital atrophy and sexual dysfunction in postmenopausal women.² The study included several outcome measures. One was a urogenital score that assessed subjective vaginal dryness, dyspareunia, and urinary symptoms. Another was the McCoy Female Sexuality Questionnaire, which evaluated satisfaction with sexual activities and fantasies, orgasm, intensity of desire, self-classification of sex life, and frequency of arousal. The Vaginal Health Index also was used to assess vaginal moisture, elasticity, pH, and epithelial integrity.

After 12 weeks, mean sexuality scores improved by 42.4% in the estrogen-only group and by 147.3% in the estrogen plus testosterone group compared with 18.6% in the control group (P < .01). Urogenital scores improved by 58.7% with estrogen alone and by 62.3% with estrogen plus testosterone compared with scores in the control group. Vaginal Health Index scores also improved in the treatment groups. There were no significant differences in adverse effects. Limitations included small sample size and short study duration.

A 2011 open-label extension study (N = 967) of two similar double-blind RCTs (ie, Intimate SM13 and SM24) evaluated the long-term tolerability and safety of adding transdermal testosterone to estrogen hormone replacement therapy in surgically postmenopausal women with hypoactive sexual desire disorder.⁵ The initial studies both compared a 300-mcg testosterone transdermal patch with placebo over 6 months.^3,4 The primary outcome was frequency of satisfying sexual episodes. Additional outcomes included sexual desire, personal distress, serum testosterone level, and results of various tests (eg, serum chemistry, hematology tests, lipid profile, carbohydrate metabolism, kidney and liver function tests, coagulation parameters). In the double-blind studies, the frequency of satisfying sexual episodes improved significantly in the transdermal testosterone groups compared with the placebo groups.

The extension study followed patients for 4 years.⁵ All patients received 300 mcg of transdermal testosterone, were assessed for adverse effects, and underwent laboratory testing, physical examination, and mammography. No deaths were reported. The rate of serious adverse effects (eg, increased blood pressure, stroke, palpitations, angina) was 3.2% in year 1 and 1.8% in year 4. The most common adverse effect was application site reaction, followed by mild androgenic effects. There were no increases in the frequency or severity of these effects over time. No clinically meaningful increase in lipid levels or changes in metabolic profiles were found, and the rate of invasive breast cancer was similar to age-adjusted estimates.