Comparative pharmacokinetics of three doses of percutaneous dihydrotestosterone gel in healthy elderly men--a clinical research center study

Abstract

Twenty-five men, 60-80 yr old, participated in a pharmacokinetic study to compare three doses (16, 32, and 64 mg/day, n = 8 or 9 in each group) of 5alpha-dihydrotestosterone (DHT) gel (0.7% hydroalcoholic gel with 2.3 g gel delivering 16 mg DHT) applied daily over one upper arm (16 mg); both arms and shoulders (32 mg); and bilateral arms, shoulders, and upper abdomen (64 mg), respectively. Multiple blood samples for the pharmacokinetic profile for DHT and testosterone (T) were drawn over a 24-h period before application, after first application, and after 14 days of daily application of DHT gel. Additional blood samples for DHT, T, and estradiol were obtained 24 h after application on days 3, 5, 7, and 11 and after discontinuation of DHT gel for 3, 5, 7, and 14 days (days 17, 19, 21, and 28 after first instituting treatment). No skin irritation was observed in any of the subjects. Before treatment, mean serum DHT and T levels were not different among the three dose groups. The serum DHT levels increased gradually after gel application on the first day, reaching a plateau between 12-18 h. During the 14 days of daily application of DHT gel, the mean baseline DHT levels reached steady state by day 2 or 3 and were elevated considerably above baseline. Mean serum DHT levels varied between 8-11, 12-17, and 14-24 nmol/L in the 16-, 32-, and 64-mg groups, respectively. The area under curve (AUC) of serum DHT levels over 24 h on day 14 were 6.0-, 6.9-, and 16.1-fold above pretreatment levels for the three doses. Concomitant with the increase in serum DHT levels, the AUC produced by endogenous serum T levels decreased to 75, 56, and 36% of baseline after 14 days of 16, 32, and 64 mg/day DHT gel. Similar patterns of decreases in AUC of serum estradiol levels were found. The calculated mean total androgen levels (T + DHT) rose with DHT gel application in all groups (P < 0.0001) on both days 1 and 14. We conclude that the three doses of DHT gel tested might provide adequate androgen replacement in hypogonadal men at the low, middle, and high physiological androgen (T + DHT) range.