TRANSDERMAL TESTOSTERONE ADMINISTRATION IN WOMEN WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME WASTING - A PILOT-STUDY

Although human immunodeficiency virus (HIV) disease is increasing rapi dly among women, no prior studies have investigated gender-based thera peutic strategies for the treatment of acquired immunodeficiency syndr ome (AIDS) and its complications in this population. Markedly decrease d serum androgen levels have been demonstrated in women with AIDS and may be a contributing factor to the wasting syndrome in this populatio n. To assess the effects of androgen replacement therapy in women with AIDS wasting, we conducted a randomized, placebo-controlled, pilot st udy of transdermal testosterone administration. The primary aim of the study was to determine efficacy in terms of the change in serum testo sterone levels, safety parameters and tolerability. A secondary aim of the study was to investigate testosterone effects on weight, body com position, quality of life, and functional indexes. Fifty-three ambulat ory women with the AIDS wasting syndrome defined as weight less than 9 0% of ideal body weight or weight loss of more than 10% of the preilln ess maximum, free of new opportunistic infection within 6 weeks of stu dy initiation, and with screening serum levels of free testosterone le ss than the mean of the normal reference range (<3 pg/mL) were enrolle d in the study. Subjects were age 37 +/- 1 yr old (mean +/- SEM), weig hed 92 +/- 2% of ideal body weight, and had lost 17 +/- 1% of their ma ximum weight. CD4 count was 324 +/- 36 cells/mm(3), and viral burden w as 102,382 +/- 28,580 copies. Subjects were randomized into three trea tment groups, in which two placebo patches (PP), one active/one placeb o patch (AP group), or two active patches (AA group) were applied twic e weekly to the abdomen for 12 weeks. The expected nominal delivery ra tes of testosterone were 150 and 300 mu g/day, respectively, for the A P and AA groups. Forty-five subjects completed the study (PP group, n = 13; AP group, n = 14; AA group, n = 18). Two additional subjects fro m the PP group and two from the AP group were included in the intent t o treat analysis. Serum free testosterone levels increased significant ly from 1.2 +/- 0.2 to 5.9 +/- 0.8 pg/mL (AP) and from 1.9 +/- 0.4 to 12.4 +/- 1.6 pg/mL (AA.) in response to testosterone administration (P < 0.0001 for comparison of AA vs. PP and AP vs. PP; normal range, 1.3 -6.8 pg/mL). Testosterone administration was generally well tolerated locally and systemically, with no adverse trends in hirsutism scores, lipid profiles, or liver function tests. Weight increased significantl y in the AP group (1.9 +/- 0.7 kg) us. the PP group (0.6 +/- 0.8 kg; P = 0.043), but did not increase significantly in the AA group (0.9 +/- 0.4 kg; P = 0.263 us. PP, by mixed effects model assessing the intera ction of time and treatment on all available data, one-tailed test). I mproved social functioning (P = 0.024, by one-tailed test) and a trend toward improved pain score (P = 0.059) were observed in the AP us, th e PP-treated patients (RAND 36-Item Health Survey questionnaire). Five of six previously amenorrheic patients in the AP group had spontaneou s resumption of menses compared to only one of four amenorrheic patien ts in the AA group (P = 0.045 for comparison of actual number of perio ds during the study). This study is the first investigation of testost erone administration in women with AIDS wasting. We demonstrate a nove l method to augment testosterone levels in such patients that is safe and well tolerated during short term administration. At the lower of t he two doses administered in this study, testosterone therapy was asso ciated with positive trends in weight gain and quality of life. Higher , more supraphysiological, dosing was not associated with positive tre nds in weight or overall well-being. These data suggest that testoster one administration may improve the status of women with AIDS wasting. Further studies are needed to assess the effects of testosterone on we ight in HIV-infected women and to define the optimal therapeutic windo w for testosterone administration in this population.