A pilot study of an investigational testosterone transdermal patch system in young women with spontaneous premature ovarian failure

Context: Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women. Objective: The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone. Design: This was an open-label study (2-month baseline period followed by 2- month treatment period). Patients: Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded. Intervention: Four consecutive 28-d cycles of transdermal estradiol (E-2; 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 mu g/d) was applied twice weekly to the abdomen. Main Outcome Measures: Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied. Results: The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9-9.9) mu g/ml; 26.0 (17.2-34.6) pmol/liter (with E-2), and 6.9 (4.9-8.8) mu g/ml; 23.9 (17.2-30.5) pmol/liter (with E-2 and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 mu g/ml (23.5 pmol/liter), although the mean values are slightly above this. Conclusions: The addition of TTP to cyclic E-2/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress.