Oral Testosterone for Male Hormonal Contraception

男性荷尔蒙避孕需要注射外源性睾酮来抑制脑下垂体 促性腺激素卵泡刺激素和促黄体生成素。目前注射睾酮的方法包括肌肉注射， 植入物，或每日透皮贴片或凝胶，因为口服睾丸素(与其他 类固醇)被认为不切实际。然而，我们最近已经表明口服给药 当联合使用时，睾丸素(以睾丸酮enanthate的形式)可导致正常的血清睾酮水平 使用5-α-还原酶抑制剂度他雄胺。我们认为口服的睾丸素醋酸酯 此外，度他雄胺可能是男性激素避孕方案中有用的一部分。然而，没有任何信息 存在关于口服睾酮抑制正常人促性腺激素释放和精子发生的能力 男士是这项提议的主题。具体来说，我们在这项建议中的目标是： 1)确定口服不孕酮与度他雄胺合用的最佳剂量。 男性在四周内的促性腺激素分泌。 2)确定口服睾酮/度他雄胺和孕激素的最佳剂量组合 用于抑制男性促性腺激素分泌的醋酸甲羟孕酮，为期八周。 3)确定口服睾酮组合对生精抑制的程度， 度他雄胺和醋酸甲羟孕酮在六个月内。 这份意见书中提出的实验将探索口服睾丸素和度他雄胺的能力。 与甲羟孕酮联合在男性体内起到激素避孕药的作用。睾丸素 Enanthate、Dutasteride和甲羟孕酮醋酸酯都可以在市场上买到，可以安全使用 在人类身上。这些创新的研究将深入了解口服睾丸素和孕激素的效用。 男性避孕中促性腺激素抑制的生理学及口服睾酮的影响 男性荷尔蒙环境下维持情绪和性功能的用药 避孕方法。此外，这项工作可能有助于开发新的雄激素疗法。 对于睾丸素缺乏的男性。这些研究将极大地促进努力创造一个可用的、有吸引力的 为男性提供可逆的口服荷尔蒙避孕药，并帮助实现“男性避孕药”的梦想。 演出现场(S)(组织、市、州) 美国华盛顿州西雅图华盛顿大学 小灵通398(04/06版)第114页表格第2页

Male hormonal contraception requires the administration of exogenous testosterone to suppress the pituitary gonadotropins FSH and LH. Current methods of testosterone delivery include intramuscular injections, implants, or a daily transdermal patch or gel, since oral administration of testosterone (in contrast to other steroids) was thought to be impractical. Nevertheless, we have recently shown that oral administration of testosterone (in the form of testosterone enanthate) results in normal levels of serum testosterone when coadministered with the 5-alpha-reductase inhibitor dutasteride. We believe that oral testosterone enanthate plus dutasteride might be a useful part of a male hormonal contraceptive regimen. However, no information exists about the ability of oral testosterone to suppress gonadotropin release and spermatogenesis in normal men¿the subject of this proposal. Specifically, our aims in this proposal are: 1) To determine the optimal dose of oral testosterone enanthate plus dutasteride to suppress gonadotropin secretion in men over a four week period. 2) To determine the best dose combination of oral testosterone/dutasteride and the oral progestogen medroxyprogesterone acetate to suppress gonadotropin secretion in men over an eight week period. 3) To determine the degree of spermatogenic suppression induced by combinations of oral testosterone, dutasteride and medroxyprogesterone acetate over a six month period. The experiments proposed in this submission will explore the ability of oral testosterone plus dutasteride combined with medroxyprogesterone to function as a hormonal contraceptive in man. Testosterone enanthate, dutasteride and medroxyprogesterone acetate are all commercially available and are safe for use in humans. These innovative studies will provide insight into the utility of oral testosterone and progestogens for male contraception, the physiology of gonadotropin suppression and the impact of oral testosterone administration on the maintainence of mood and sexual function in the setting of a male hormonal contraceptive regimen. In addition, this work might assist in the development of novel androgen therapies for men with testosterone deficiency. These studies will greatly inform efforts to create a usable, attractive reversible oral hormonal contraceptive for men, and help bring the dream of a "male pill" to fruition. PERFORMANCE SITE(S) (organization, city, state) University of Washington, Seattle, WA, USA PHS 398 (Rev. 04/06) Page 114 Form Page 2