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Progestin-androgen combination regimens for male contraception.


 Testosterone enanthate (TE) administration is associated with a failure rate (3.4/100 person-years) considerably lower than that of other currently available reversible male contraceptive methods. However, acceptability of this regimen is limited by the need for weekly injections, the lack of complete azoospermia, and the decrease in high-density lipoprotein (HDL)-cholesterol. Under investigation is the concurrent administration of a progestin that can act synergistically with TE in the suppression of gonadotropins. Because of the additive effects, the dose of each steroid can be decreased, minimizing androgen-related side effects. Third-generation progestins and hybrid progestins seem to offer the most potential for such an approach. In particular, the combination of cyproterone acetate (CPA) and TE has been found to result in a rapid, profound suppression of spermatogenesis, without side effects, through its ability to block both the follicle-stimulating hormone and androgen effects at the testis level. The anti-androgenic action of CPA is based on its ability to competitively inhibit the binding of testosterone and dehydrotestosterone to androgen receptors. The block of intratesticular testosterone effect by CPA is presumed to cause a decrease in cell-adhesion molecule concentrations and contribute to the premature sloughing of permatids from the seminiferous epithelium, thereby resulting in the early disappearance of spermatozoa from the ejaculate. This regimen did not cause any changes in plasma HDL or other lipoproteins or affect liver function test results.
