Hormonal Contraception for men: Past and Future

Regine Sitruk-Ware

Rockefeller University and Population Council, New York, NY, USA

Development of highly effective, practical, and acceptable non-traditional male contraceptives has proven to be a daunting challenge for more than three decades. Steroid hormones that inhibit gonadotropin secretion have been used in women for over 40 years as contraceptives. Similar approaches are being investigated in men. Methods of fertility control in men that depend on the sustained suppression of gonadotropins will require the concomitant administration of an androgen as an essential part of the method.

7a-methyl-19-nortestosterone (MENT™) is a synthetic androgen that is more potent than T for gonadotropin suppression and is resistant to 5a-reduction, with potential advantages when used as a contraceptive. MENT Acetate (MENT Ac) has diffusion characteristics that are well suited for delivery via subdermal implants. MENT Ac is rapidly hydrolyzed in vivo to MENT, the biologically active molecule. MENT Ac implants administered once were able to suppress spermatogenesis to a degree comparable to those reported in studies with multiple injections of TE or testosterone undecanoate (TU) or with T implants in normal men. The prostate sparing effect of MENT has previously been shown in a study in castrated cynomolgus monkeys where the effect of MENT was directly compared with that of testosterone. Doses of MENT that will completely replace testosterone for its anabolic and antigonadotropic actions will be less stimulatory to the prostate. Hence the use of MENT in men over long-term is expected to have a health benefit.

New areas of basic research include the genomic and proteomic as well as studies of enzymes involved in the reproductive system. Identifying specific genes and the proteins induced by these genes and finding molecules that specifically antagonize gene action will open new avenues for the development of contraceptives that do not modify the hormonal profile of the individual. The new methods will be targeted to specific interactions within the reproductive system at the level of the ovary and testis, as well as between spermatozoa and the ovum. Genes involved in the regulation of human reproduction are explored first in animal models but these models must then be validated by studies in humans. These new approaches also require the engineering of original drug-delivery methods that reach the target very specifically but do not interact with other tissues in the body.

This futuristic approach still keeps in mind the need for better access to existing contraceptive methods, as well as the discovery of new contraceptives that are simple to use, safe, reversible and inexpensive.