Safety and Efficacy Studies of an Implant for Male Contraception

依赖于促性腺激素持续抑制的男性生育控制的激素方法 分泌需要同时服用雄激素来维持雄激素的功能，包括 性欲。人口理事会率先开发了合成雄激素7a-甲基-19- 用于男性避孕的去甲睾酮。证据表明，蒙特的行为与其他动物很相似 雄激素抑制促性腺激素的分泌，从而将睾丸T水平降低到所需的水平以下 以维持精子发生。它在抑制促性腺激素方面比T强得多，因此使它 可通过硅橡胶植入物等缓释制剂长期释放。蒙特具有抵抗力 到5a-减少，潜在的优势是当用作避孕药时对前列腺更安全。在……里面 此外，通过转化为雌激素，它应该能够保持对骨骼的积极作用。 质量。因此，男性长期服用安非他明除了对健康有好处外，还有望带来健康益处。 避孕效果。植入物诱导无精子症的效果已在 以前的研究和进一步的研究都有必要证实男性使用安非他明的安全性和有效性 避孕。在目前的提案中，我们将在动物模型中研究甲硝唑的安全性和有效性。 以及在临床试验中。1)对肾脏酶的药理作用；2)骨生长的药理作用 将在动物模型中进行研究。3)Mment和a处理的雄性大鼠生育力研究的可逆性 长效孕激素将通过与雌性大鼠的交配试验进行。4)制裁的效果将是 在一项评估雄激素对血管参数作用的临床安全性研究中与T进行了比较。5)我们会 研制一种改进的皮下埋植剂缓释系统 (而不是以前研究中使用的空调)。MENT比MENT AC更受欢迎，因为它是活动的 体内的成分。6)将使用植入物和长效避孕药进行避孕效果研究 孕激素。

Hormonal methods of fertility control in men that depend on the sustained suppression of gonadotropin secretion require the concomitant administration of an androgen to maintain androgenic functions, including libido. 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 other androgens to suppress gonadotropin secretion, thereby lowering testicular T levels below the point needed to sustain spermatogenesis. It is much more potent than T in suppressing gonadotropins, thus making it feasible for long-term delivery via sustained release formulations such as silastic implants. MENT is resistant to 5a-reduction, with the potential advantage of being safer for the prostate when used as a contraceptive. In addition, through its conversion to estrogen, MENT should be able to maintain a positive effect on bone mass. Hence, the long-term use of MENT in men is expected to have health benefits in addition to its contraceptive effect. Efficacy of MENT Ac implants to induce azoospermia has been demonstrated in previous studies, and further research is warranted to confirm the safety and efficacy of MENT use for male contraception. In the current proposal we will investigate the safety and efficacy of MENT in animal models as well as in clinical trials. 1) The pharmacological effects of MENT on kidney enzymes and 2) bone growth will be investigated in animal models. 3) A reversibility of fertility study in male rats treated with MENT and a long-acting progestin will be conducted by mating tests with female rats. 4) The effect of MENT will be compared to T in a clinical safety study assessing androgen action on vascular parameters. 5) We will develop 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 active component in vivo. 6) A contraceptive efficacy study will be conducted using MENT implants and a longacting progestin.