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.