In women who have undergone bilateral oophorectomy, serum levels of testosterone decline within days of surgery, and in some women, this fall is accompanied by a loss of sexual desire and coital frequency. Intrinsa delivers a constant low dose of testosterone, with daily levels compatible with those seen in premenopausal women.
The efficacy of Intrinsa has been studied in two double-blind, placebo-controlled phase III trials, INTIMATE SM11 and INTIMATE SM22 (Investigation of Natural Testosterone In Menopausal women Also Taking Estrogen in Surgically Menopausal women). Both trials were conducted in oophorectomised and hysterectomised women (SM1 n=562, SM2 n=533), aged 20 to 70 years with HSDD, on concomitant oestrogen (oral or transdermal).
In both trials, patients were randomised to receive either Intrinsa or placebo, twice weekly, for 24 weeks. The primary endpoint was the change from baseline in the four-week frequency of total satisfying sexual episodes during weeks 21 through to 24, measured by the Sexual Activity Log (SAL). The SAL was completed for eight weeks before, and during the 24 weeks of the study. It addressed patient physical health status, partner availability, and the frequency of sexual activity during the preceding seven days.
Secondary endpoints included other aspects of sexual function, assessed using questionnaires, such as sexual desire score and the frequency of satisfying sexual activity, and distress associated with low sexual desire. Blood samples were also collected at baseline and after 24 weeks of treatment to determine hormone levels.
At 24 weeks, results from SM1 showed a significant increase from baseline in the frequency of total satisfying sexual activity of 2.1 episodes per four weeks in the testosterone group, compared with an increase of 0.98 episodes per four weeks in the placebo group. The testosterone group also experienced significant improvements in sexual desire and a decrease in distress at 24 weeks. The decrease in personal distress was also observed at week four and at all subsequent time points throughout the study. Adverse effects, including androgenic effects, occurred with similar frequency in the placebo and testosterone-treated groups. Approximately 30 per cent of women experienced application site reactions; most were described as mild.
At 24 weeks, results from SM2 showed that total satisfying sexual activity increased significantly in the testosetrone group compared with placebo. Patients receiving testosterone had a mean increase of 1.56 satisfying episodes per four weeks (corresponding to a 51 per cent increase over the baseline mean) compared with a mean increase of 0.73 for the placebo group.
The overall incidence of adverse effects and withdrawals were similar between the placebo and treatment groups. The most common adverse effects were application site reactions, upper respiratory infection, facial hair and headache. The overall incidence of androgenic adverse effects was higher in the testosterone group (19.5 per cent) compared with placebo (11.3 per cent); most were reported to be mild.
1. Simon J, Braunstein G, Nachtigall L et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab, 2005: 90(9); 5226-33.
2. Buster JE, Kingsberg SA, Aguirre O et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol 2005:105 (5); 944-52.
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