Background. The paucity of pharmacokinetic data on androgen formulations in women has hindered clinical trials of testosterone supplementation in women.

Objective. To determine the time course and profile of serum testosterone concentrations during treatment with different doses of testosterone gel in postmenopausal women, and assess whether estrogen treatment affects pharmacokinetics of testosterone gel

Methods. Postmenopausal women with total testosterone< 33 ng/dL, after baseline 24-hour sampling, were treated with 4.4, 8.8, or 13.2 mg testosterone gel daily for 7 days each in random order with a seven-day washout period between doses. We studied 13 women who had not received estrogen therapy (group I), and 13 who had received stable estrogen therapy for three months (group II). Total and free testosterone concentrations were measured for 48 h on the seventh day of each dose administration.

Results. Twenty-six women were randomized; of these, 24 were evaluable, 13 in group I and 11 in group II. The average (Cav) serum total and free testosterone concentrations increased with increasing testosterone dose and were highly correlated with the dose (dose effect P < 0.00001), but were not affected by estrogen therapy (P = 0.43). In both groups, 4.4 mg dose increased Cav total and free testosterone concentrations into mid- to high normal range, while 8.8 and 13.2 mg doses raised total (Cav 22.3, 51.6, 80.3, and 92.0 ng/dL in group I and 22.7, 59.8, 82.0, 114.3 ng/dL in group II at 0, 4.4, 8.8, and 13. 2 mg doses) and free testosterone (5.9, 8.4, 11.5,12.8 pg/mL in group I and 5.0,7.6,11.1,10.8 in group II, respectively at the various doses) above the physiologic range. The area-under-the-curve, Cmax, Cmin, and Cav for total and free testosterone were dose-related and significantly higher during administration of the 13.2 mg dose than 0 or 4.4 mg dose; estrogen therapy had no significant effect on these measures. Serum estradiol, LH, FSH, and SHBG levels did not change significantly at any dose. Testosterone gel was well tolerated.

Conclusions. Administration of testosterone gel to postmenopausal women raised total and free testosterone concentrations in proportion to the administered dose without affecting estradiol levels; 4.4 mg dose raised testosterone levels into the mid- to high-normal range. Prior estrogen therapy had no significant effect on testosterone pharmacokinetics over this short duration.