Male steroidal contraception

R.A. Anderson

MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh, UK

Contraceptive methods for men have not benefited from the advances in steroid chemistry in the last half century. This provides a stark contrast to female methods, which have been transformed and are available in a range of preparations enhancing compliance and efficacy. Potential approaches to male contraception include hormonal suppression of the pituitary gonadotrophins and thus spermatogenesis, direct testicular actions on spermatogenesis, and methods targeting post-testicular spermatogenic maturation in the epididymis. While all three offer potentially attractive methods, the hormonal is the only one in clinical studies. The ability of exogenous testosterone to suppress spermatogenesis was first reported in the 1940s. Large efficacy studies were undertaken by WHO in the early 1990s, confirming that a steroidal approach was feasible and offered good contraceptive efficacy. Subsequent studies have explored addition of a range of progestogens to testosterone administration, utilising the progestogen to provide most of the gonadotrophin suppression, with the testosterone mostly for ‘add back’ replacement to prevent hypogonadism. This allows a large reduction in the dose of testosterone required, and thus avoids the side effects noted in the purely testosterone-based WHO studies. A major issue has been incomplete suppression of spermatogenesis in a proportion of men, although Chinese and Asian men show more consistent induction of azoospermia. A Phase III trial using the longer acting injectable testosterone undecanoate is underway in China at present. Recent testosterone/progestogen combinations have show more consistent induction of azoospermia in caucasian men. In our studies using testosterone pellets with either oral desogestrel or etonogestrel implants, we have achieved azoospermia in all men, although groups sizes have been small (n=15 approx). The advent of synthetic androgens with differential metabolism such as the prostate-sparing 7-methyl-19-nortestosterone allow for the exploration of non-contraceptive health benefits. These results, together with the increasing involvement of the pharmaceutical industry, provide grounds for cautious optimism that a ‘male pill’ will become a reality.