OBJECTIVE: The steady-state pharmacokinetics of two doses of a transdermal testosterone cream (TTC) was investigated after daily application for 21 days. METHODS: This was a two-way cross-over study conducted for 6 weeks. Seven healthy postmenopausal women (mean age, 59.3 y) were randomly allocated to 5 or 10 mg of TTC applied daily to the upper arm. Serum total testosterone (TT), free testosterone (fT), sex hormone-binding globulin, and metabolite concentrations were measured. Baseline-corrected and uncorrected serum TT and fT pharmacokinetic parameters (AUC0-24, Cavg, Cmax, and Tmax) were calculated using a standard model-independent approach. RESULTS: After the single-dose application of 5 mg of TTC on day 22, the median uncorrected TT Cavg was found to be 0.54 ng/mL (range, 0.43-1.31), and the median uncorrected fT Cavg was found to be 4.14 pg/mL (range, 2.41-9.72). Doubling of the dose only resulted in a 30 increase in baseline-corrected TT Cavg (0.52 vs 0.69 ng/mL for 5 and 10 mg, respectively) and a 31 increase in baseline-corrected fT Cavg (4.75 vs 6.24 pg/mL for 5 and 10 mg, respectively). Neither dose resulted in any meaningful variation in dihydrotestosterone, estrone, estradiol, or sex hormone-binding globulin across the postdose sampling period. CONCLUSIONS: The 5-mg TTC dose restores TT and fT levels to levels above and within the reference range, respectively, for premenopausal women.