BACKGROUND: Women who undergo bilateral oophorectomy before menopause experience a 50% drop in serum testosterone because of a lack of ovarian androgen production. Many of these women report decreased sexual desire and activity, and pleasure not improved with estrogen therapy. Previous studies of testosterone therapy have used supraphysiologic doses and were not double blinded.
POPULATION STUDIED: The investigators enrolled 75 healthy women aged 31 to 56 years from 9 clinical sites in the United States. The method of patient recruitment was not specified. Approximately two thirds of the patients were married, and two thirds were white. All had undergone bilateral salpingo-oophorectomy and hysterectomy a mean of 4.7 years ago. Other inclusion criteria were treatment with at least 0.625 mg conjugated equine estrogen daily for 2 months, history of a stable monogamous heterosexual relationship for 1 year, and a composite sexual function score (Brief Index of Sexual Functioning for Women) less than the mean value for normal women. Persons taking steroids, selective serotonin reuptake inhibitors, or tricyclic antidepressants were excluded.
STUDY DESIGN AND VALIDITY: This was a double-blind placebo-controlled crossover study occurring over 40 consecutive weeks. It consisted of a 4-week baseline period followed by 3 12-week treatment periods. Using identical-appearing experimental patches, patients received in random order placebo, testosterone 150 mg per day, and testosterone 300 mg per day transdermally for 12 weeks each. The Brief Index of Sexual Functioning for Women was used to determine a composite sexual function score at baseline and again after each treatment period. Intention-to-treat data analysis was performed for the 65 women who completed this index at least once during treatment. Mood was assessed at similar intervals using the Psychological General Well-Being Index. A telephone-based diary was used to assess the self-reported frequency of sexual thoughts, desires, and activities. Standard laboratory tests and validated measures of hirsutism and acne were used to determine safety and tolerability. The crossover design did not include a washout period. However, analysis-of-variance models were appropriately used to rule out significant effects of treatment period, sequence, and carryover. Previously validated measurement tools were used extensively. Overall, the placebo response in this study was strong. This suggests the presence of confounding factors that could limit study usefulness. The possibilities discussed included a stimulus effect of a visible patch and a potential limitation of the crossover design, whereby patients alter their patterns of sexual activity early in the study and then maintain the new patterns throughout.
OUTCOMES MEASURED: The primary outcomes addressed were the composite sexual function score and the self-reported frequency of sexual thoughts, desires, and activities.
RESULTS: The composite sexual function score was low at baseline (52%±27% of the mean value for healthy women). Sexual function as measured by this score significantly improved with testosterone 300 mg per day (increased to 81%±37% of the mean vs 72%±38% for placebo, P=.05). The effect of testosterone 150 mg per day was not significantly different from that of placebo. Composite telephone-based diary scores did not increase significantly. Compliance with telephone reporting of sexual activity was poor and resulted in the withdrawal of 6 patients. Notable secondary outcomes were improved mood, according to the Psychological General Well-Being Index composite score (P=.04), and lack of clinically significant changes in serum lipids, hematocrit, liver function tests, and objective measures of acne and hirsutism. This study was too small to detect adverse effects on mortality.
Transdermal testosterone at 300 mg per day, when administered together with oral estrogen, provides some benefit for women who are sexually impaired following oophorectomy. The safety and efficacy of long-term treatment need to be established before widespread use. This study does not address treatment of impaired sexual function in postmenopausal women who have not had surgery. However, the results are suggestive of benefit over that of estrogen therapy in any woman lacking ovarian androgen production. Further research should answer this question as well.