A number of studies have demonstrated the efficacy, safety, and reversibility of male hormonal contraception. To date, male hormonal contraceptive regimens have relied on various combinations of testosterone (T) or its esters (injections, patches, or pellets) and progestins (injectable, oral, or implants in 2 delivery forms). A single method of administration combining a testosterone and a progestin could improve acceptability and compliance among men. Nesterone (NES) is a nonandrogenic progestin used for male contraception. In a pilot study conducted in healthy men, use of T and NES transdermal gels for 20 days suppressed spermatogenesis and provided effective gonadotropin suppression with no significant adverse events.
The aim of this randomized, double-blind, comparator clinical trial was to evaluate the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. A total of 99 healthy male volunteers (aged 18–50 years) were enrolled in 2 academic health centers. Participants were randomized to receive 1 of 3 transdermal gels applied daily (group 1 [n = 32]: T gel 10 g + NES 0 mg/placebo gel; group 2 [n = 33]: T gel 10 g + NES gel 8 mg; or group 3 [n = 34]: T gel 10 g + NES gel 12 mg). The primary study outcome variable was estimation of the percentage of men in each treatment group whose sperm concentrations were suppressed to 1 million/mL or less by 20 to 24 weeks of treatment.
A total of 56 subjects who adhered to the protocol and completed at least 20 weeks of treatment were included in the primary efficacy analyses. The data showed that the percentage of men whose sperm concentration was suppressed to 1 million/mL or less at 20 to 24 weeks was significantly higher in T+NES 8 (89%, P < 0.0001) and T+NES 12 (88%, P = 0.0002) groups compared with the T+NES 0 group (23%). In all groups, both median serum total and free T concentrations were maintained within the adult male physiological range during the treatment period. No serious adverse effects were noted. More than one third of the subjects discontinued treatment during the study, mostly for personal reasons, not adverse effects.
These findings show that a single transdermal gel preparation combining NES+T is effective when administered daily for suppression of gonadotropins and spermatogenesis and has potential for use as a male hormone contraceptive.
Department of Medicine (N.I., R.S.S., C.W.), Division of Endocrinology, Harbor–University of California, Los Angeles, Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA; Department of Medicine (M.Y.R., J.K.A., S.T.P., W.J.B.), University of Washington, Seattle, WA; Health Decisions (C.D.), Durham, NC; Center for Biomedical Research (R.S.-W., N.K.), Population Council, New York, NY; and Contraception and Reproductive Health Branch (D.L.B.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD