Pharmacokinetics of a novel testosterone matrix transdermal system in healthy, premenopausal women and women infected with the human immunodeficiencyvirus

The clinical consequences of androgen deficiency in human immunodeficiency virus (HIV)-infected women remain underappreciated. The pharmacokinetics of transdermally administered testosterone in premenopausal women and HN-infe cted women have not been studied. In this study we compared the pharmacokin etics of a novel testosterone matrix transdermal system (TMTDS) in healthy premenopausal women and women infected with HIV. Eight menstruating HIV-inf ected women, 18-50 yr of age, who had been receiving stable antiretroviral therapy, including a protease inhibitor, for at least 12 weeks and nine hea lthy, menstruating women of comparable age were enrolled. After baseline sa mpling during a 24-h control period in the early follicular phase (days 1-6 ), two TMTDS patches were applied with an expected delivery rate of 300 mu g testosterone daily over an application period of 3-4 days. After 72 h, th e patches were removed, a second set of two patches was applied, and blood samples were drawn over 96 h. Baseline serum total and free testosterone levels were lower in HIV-infecte d women than in healthy women. A diurnal rhythm of testosterone secretion, with higher levels in the morning and lower levels in the late afternoon, w as apparent in both groups of women. Free testosterone levels were in the m idnormal range at baseline in healthy women and increased above the upper l imit of normal during TMTDS application. In HIV-infected women, free testos terone levels were in the low normal range at baseline and rose into the up per normal range during patch application. Serum total testosterone levels increased into the midnormal range in HIV-infected women and into the upper normal range in healthy women during patch application. The mean increment s in free and total testosterone levels were significantly lower in HIV-inf ected women than in healthy women. Testosterone bioavailability, expressed as the mean +/- SEM baseline-subtracted area under the total testosterone c urve, was significantly greater in healthy women than in HIV-infected women [3323 +/- 566 ng/dl.h (115 +/- 20 nmol/L.h) vs. 1506 +/- 316 ng/dL.h (52 /- 11 nmol/L h); P = 0.016]. Assuming a daily testosterone delivery rate of 300 mu g/day, the apparent plasma clearance was significantly higher ih HI V-infected women than in healthy women (2531 +/- 469 vs. 1127 +/- 217 L/day l P = 0.022), respectively. There was no significant change from baseline i n serum LH, sex hormone-binding globulin, and estradiol levels in either gr oup. Serum FSH levels showed a greater decrease from baseline in healthy wo men. A regimen of two testosterone patches applied twice a week. can maintain se rum total and free testosterone levels in the mid- to upper normal range, r espectively, in HIV-infected women with low testosterone levels. During TMT DS application, the increments in serum total and free testosterone levels are lower in HIV-infected women than in healthy women, presumably due to in creased plasma clearance or decreased absorption. Further studies are neede d to assess the effects of physiological androgen replacement in HIV-infect ed women.