Hormonal methods of fertility control in men that depend on the sustained suppression of gonadotropinsecretion require the concomitant administration of an androgen to maintain androgenic functions, includinglibido. The Population Council has pioneered the development of the synthetic androgen, 7a-methyl-19-nortestosterone (MENT ) for male contraception. The evidence suggests that MENT acts much like otherandrogens to suppress gonadotropin secretion, thereby lowering testicular T levels below the point neededto sustain spermatogenesis. It is much more potent than T in suppressing gonadotropins, thus making itfeasible for long-term delivery via sustained release formulations such as silastic implants. MENT is resistantto 5a-reduction, with the potential advantage of being safer for the prostate when used as a contraceptive. Inaddition, through its conversion to estrogen, MENT should be able to maintain a positive effect on bonemass. Hence, the long-term use of MENT in men is expected to have health benefits in addition to itscontraceptive effect. Efficacy of MENT Ac implants to induce azoospermia has been demonstrated inprevious studies, and further research is warranted to confirm the safety and efficacy of MENT use for malecontraception. In the current proposal we will investigate the safety and efficacy of MENT in animal modelsas well as in clinical trials. 1) The pharmacological effects of MENT on kidney enzymes and 2) bone growthwill be investigated in animal models. 3) A reversibility of fertility study in male rats treated with MENT and along-acting progestin will be conducted by mating tests with female rats. 4) The effect of MENT will becompared to T in a clinical safety study assessing androgen action on vascular parameters. 5) We willdevelop and formulate an improved subdermal implant delivery system for the sustained release of MENT(rather than MENT Ac used in previous studies). MENT is preferred over MENT Ac as it is the activecomponent in vivo. 6) A contraceptive efficacy study will be conducted using MENT implants and a longactingprogestin.
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