Systematic review and meta-analysis «Islam RM, Bell RJ, Green S, ym. Safety and efficac...»1 on the safety and efficacy of the use of testosterone treatment in women comprises evidence from 46 articles from 36 RCTs with a total of 8480 participants. 43 studies included postmenopausal women, 2 studies premenopausal, and 1 study both pre- and postmenopausal women. Oral testosterone treatment was assessed in 15 studies, testosterone patch in 13, 2 studies were done on testosterone cream, 2 on gel, 1 on spray, 1 on sublingual, 1 on intramuscular, and 1 on subcutaneous testosterone implants. Data specifically on sexual function were available from 15 studies on postmenopausal women (n=3766), and 3 studies on premenopausal women (n=226). Main outcomes of interest include effects on sexual function (sexual events, scores for sexual function, desire, arousal, orgasm, pleasure, concerns, responsiveness, self-image distress). Safety was assessed by reviewing effects on cardiovascular and musculoskeletal health and cognition.13/46 studies assessed specifically women with low sexual function. Longest follow-up was available for up to 2 years (2 studies), whereas other follow-up times varied between 1 year (3 studies), 24 to 26 weeks (14 studies), or less.
Treatment with testosterone compared with placebo or a comparator significantly increased the number of satisfying sexual events (mean difference 0.85, 95% CI 0.52 to 1.18) (Table «Postmenopausal testosterone therapy in treatment of sexual dysfunction....»1). Oral testosterone compared to comparator (9 studies, 637 participants) had unfavorable effects on blood lipids, which was not seen with transdermal administration (10 studies, 1774 participants). Breast density (n=345 postmenopausal women) or endometrial thickness (n=843 postmenopausal women) did not change with testosterone treatment. Treatment with testosterone (at doses intended to approximate physiological levels in premenopausal women) compared to a comparator was associated increase acne (risk ratio 1.46, 95%CI 1.11 to 1.92; 11 studies, 3264 participants), hair growth (risk ratio 1.69, 95%CI 1.33 to 2.14; 11 studies, n=4178 participants), but no alopecia, clitoromegaly, voice change, or serious adverse events (e.g. acute myocardial infarction, stroke, deep vein thrombosis, or cardiovascular death).
| * Prediction intervals indicated that treatment with testosterone may however not be beneficial in future individual studies. | |
| Treatment with testosterone compared with comparator (placebo or menopausal hormone therapy) | |
|---|---|
| Number of sexually satisfying events | Mean difference 0.85 (0.52-1.18) [I2 58%]* |
| Sexual desire | Standardized mean difference 0.36, 95%CI 0.22 to 0.50 [I2 69%]* |
| Arousal | Standardized mean difference 0.28, 95%CI 0.21 to 0.35 |
| Orgasm | Standardized mean difference 0.25, 95%CI 0.18 to 0.32 |
| Pleasure | Standardized mean difference 6.86, 95%CI 5.19 to 8.52 |
| Responsiveness | Standardized mean difference 0.28, 95%CI 0.21 to 0.35 |
| Self-image | Mean difference 5.64, 95%CI 4.03 to 7.26 |
| Reduced concern | Mean difference 8.99, 95%CI 6.90 to 11.08 |
| Reduced sexual distress | Standardized mean difference -0.27, 95%CI -0.36 to -0.17 |
Comment: The quality of evidence is downgraded due to limited effect size and relatively short duration of follow-up. The data also present with attrition bias. Data are scarce or lacking on younger than postmenopausal women.
General comment: Data on the safety of testosterone use in women are derived from trials up to 2 years. Data on the use of testosterone for HSDD in perimenopausal women and women with premature ovarian insufficiency are needed. Low-dose transdermal testosterone products designed specifically for use by women are available in very few countries and the use by women of products designed for men is off-label.
A Cochrane review «Scheffers CS, Armstrong S, Cantineau AE, ym. Dehyd...»2 assessed the effectiveness and safety of dehydroepiandrostendione (DHEA) in menopausal women. A total of 28 randomized controlled trials with a total of 1273 participants were included in the review. 24 trials investigated DHEA versus control (placebo or no treatment) and 14 provided data on quality of life or wellbeing. Over 95% of the study populations were postmenopausal women aged 36 to 80 years. In more than 80% of the trials DHEA was administered orally with the daily doses varying between 10 mg and 1600 mg. Primary outcomes of interest were changes in quality of life and general wellbeing as assessed with different questionnaires, and adverse effects. Sexual function was assessed as a secondary outcome and data for this were available from 8 studies. Treatment with DHEA did not improve quality of life compared to placebo (standardized mean difference [SMD] 0.16, 95%CI -0.03 to 0.34; 8 studies, 287, I2 0%), whereas androgenic side effects (mainly acne) occurred in 15% of the women on DHEA versus <3% of women on placebo (OR 3.77, 95% CI 1.36 to 10.40, 5 studies, 376 women, I2 10%. Treatment with DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women, I2 0%). This improvement, however, was deemed minimal.
Comment: The quality of data in the reviewed studies was low or moderate with several risks of bias.