7 alpha-methyl-nortestosterone (MENT): the optimal androgen for male contraception

Abstract

Many methods of contraception involve the use of drugs that affect the secretion of hormones essential for reproduction. Oestrogens and progestins have been used for contraction in women as inhibitors of gonadotrophin secretion and ovulation. Similarly, androgens must be used in methods of fertility control for men that block gonadotrophin secretion. Androgen supplementation currently involves large, frequent doses of testosterone esters that are associated with wide fluctuations of plasma testosterone levels. Hence, there is a need for an androgen preparation that provides appropriate, continuous replacement doses over long periods. To achieve this goal, 7 alpha-methyl-19-nortestosterone (MENT), a synthetic androgen that is considerably more potent than testosterone, is suitable. As a consequence, it is feasible to administer this androgen as a substitute for testosterone for 1 year by subdermal implants. Another important feature of MENT is that it does not undergo 5 alpha- reduction in prostate as does testosterone. As a consequence, a dose of MENT sufficient to maintain normal muscle mass and gonadotrophin secretion will not hyperstimulate the prostate because its action in this organ is not amplified as is that of testosterone. Thus, MENT can be administered to men with the assurance that it will be less prone to cause diseases of the prostate than testosterone.

Conclusions: (i) MENT is the first androgen that has a health benefit compared to testosterone; (ii) MENT will be promoted as one component of a two-implant system for male contraception, the other component being an implant that will release an LHRH analogue; (iii) MENT has potential uses in patients with a variety of disorders, including hypogonadism, prostatic hyperplasia and muscle wasting.

PIP: Androgens are needed in male fertility control methods to impede gonadotropin secretion. Large and frequent doses of testosterone esters are used to induce this effect, but these large and frequent doses are linked to wide fluctuations of plasma testosterone levels. Thus, men need a contraceptive that supplies effective, appropriate, continuous replacement doses over long periods. The synthetic androgen 7alpha-methyl-19-nortestosterone (MENT) can likely address this problem. Studies in primates, rats, and adult men show that it is much more potent than testosterone and can be administered via subdermal implants in effective amounts, which mimic physiologic doses and effects of testosterone, for 12 months. There will most likely be 2 subdermal implants, 1 releasing MENT and the other releasing a luteinizing hormone releasing hormone. Unlike testosterone, MENT is not reduced (5alpha-reduction) to a 5alpha-dihydrosteroid in the prostate. If MENT is administered in a dose sufficient to not disturb normal muscle mass and gonadotropin secretion, it will not hyperstimulate the prostate. Thus, it is less apt to cause benign prostatic hypertrophy and, possibly, prostate cancer than is testosterone. MENT is the first androgen to promote health (i.e., reduction of the incidence of prostate disease). Clinicians may also be able to use MENT to treat hypogonadism, prostatic hyperplasia, and muscle wasting.