Male steroidal contraception

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.

Scroll to Top