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.
