Hormonal Contraception for men: Past and Future

Hormonal Contraception for men: Past and Future

Regine Sitruk-Ware

Rockefeller University and Population Council, New York, NY,


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.


(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.

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