(009) Testosterone Management in Women with Hypoactive Sexual Desire Disorder Who Have Reduced 5α-Reductase Activity: A Unique Population

Abstract

Abstract Introduction According to the Global Consensus Position Statement on the Use of Testosterone Therapy for Women, testosterone can significantly improve desire in menopausal women with hypoactive sexual desire disorder. Based on safety and efficacy of different formulations, the recommended treatment is 1/10th of a man’s dose, using a government approved topical testosterone gel or solution, or AndroFeme which is approved for use in menopausal women in Australia. There are, however, a subset of women without significant improvement in desire with this dose who experience improvement using higher doses of testosterone. These women have low or lower tertile dihydrotestosterone blood test values despite their total testosterone being above normal range or even in the upper tertile. The enzyme 5α-reductase converts testosterone to the more active form, dihydrotestosterone, that has a higher affinity for the androgen receptor than testosterone. 5α-reductase activity varies in different individuals. It is postulated that there are menopausal women with HSDD who have reduced 5α- reductase activity and therefore require a higher dose of testosterone from the gel or solution, or need a different testosterone formulation to realize clinical benefit. This subset of women do not appear to experience the usual adverse side effects of elevated testosterone (acne, thinning scalp hair, facial hair, aggressive behavior), in part because of low levels of dihydrotestosterone. Objectives This study examines the efficacy and safety of higher doses of testosterone using products government approved for men. Methods This is a retrospective chart review of menopausal women who were provided menopause management at our clinic focusing on women for whom 1/10th of a man’s dose of gel or solution did not provide symptom relief. Options included increasing the dose of gel or solution, or administration of an alternative delivery system of FDA approved (for men) testosterone including insertion of one or two 75 mg testosterone pellets (Testopel) or weekly intramuscular injection of testosterone cypionate (100 mg/ml – 0.1 ml or 10 mg). Results A total of 11 women (mean age 58 +/− 6 years) failed the usual 1/10th dose of topical testosterone gel for treatment of HSDD. Using testosterone pellet therapy, with 1-2 pellets implanted every 4-6 months, 6 patients had excellent desire as well as energy and self-confidence; 4 patients had excellent clinical response to weekly IM testosterone administration; 1 had improved symptoms by increasing the gel to 1 tube/4 days. While these treatments resulted in systemic levels of total testosterone outside the normal range for women (100 – 200 ng/dl), dihydrotestosterone values remained low or in the lower tertile (mean value 36 +/− 8 ng/dl; normal range 30 – 80 ng/dl). In general, side effects to be expected with higher doses of testosterone were not experienced despite elevated testosterone values. No patient complained of side effects consistent with excess testosterone other than mild facial hair. Conclusions In some women with reduced 5α-reductase activity, higher testosterone levels result in improved quality of life without expected negative side effects from higher physiologic levels of testosterone. Disclosure No.