Safety and Efficacy Studies of an Implant for Male Contraception

依赖于持续抑制促性腺激素的男性生育控制的激素方法 分泌需要伴随给予雄激素以维持雄激素功能，包括 性欲人口理事会率先开发了合成雄激素7 α-甲基-19- 去甲睾酮（MENTO）用于男性避孕。有证据表明，MENT的作用与其他 雄激素抑制促性腺激素分泌，从而降低睾丸T水平低于所需的点 来维持精子的生成它在抑制促性腺激素方面比T强得多，因此使其 对于通过缓释制剂如硅橡胶植入物的长期递送是可行的。MENT耐药 到5a-减少，具有当用作避孕药时对前列腺更安全的潜在优点。在 此外，通过其转化为雌激素，MENT应该能够保持对骨的积极作用 马萨诸塞州因此，男性长期使用MENT，除了其对健康的益处外， 避孕效果。MENTAc植入体诱导无精子症的有效性已在以下研究中得到证实： 以前的研究，以及进一步的研究是必要的，以确认安全性和有效性的MENT用于男性 避孕。在本提案中，我们将在动物模型中研究MENT的安全性和有效性 以及临床试验。1)MENT对肾酶和2）骨生长的药理作用 将在动物模型中进行研究。3)在接受MENT和a治疗的雄性大鼠中进行的生育力可逆性研究 将通过与雌性大鼠的交配试验来进行长效雷公藤多甙。4)MENT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)我们将 开发和配制改进的皮下植入物递送系统，用于持续释放MENT （而不是以前研究中使用的MENT Ac）。MENT优于MENT Ac，因为它是活性的 体内成分。6)将使用MENT植入物和长效 我是克里斯汀

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.