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男性避孕的激素方法:接近现实。

Hormonal approaches to male contraception: approaching reality.

作者信息

Wu Frederick C W

机构信息

Department of Endocrinology, Manchester Royal Infirmary, University of Manchester, Oxford Rd, Manchester M13 9WL, United Kingdom.

出版信息

Mol Cell Endocrinol. 2006 May 16;250(1-2):2-7. doi: 10.1016/j.mce.2005.12.017. Epub 2006 Mar 31.

Abstract

The 'pre-testicular' suppression of gonadotrophins is the most likely approach for reversible therapeutic male fertility control to reach imminent clinical application. Maintenance of spermatogenesis depends on adequate gonadotrophin and intratesticular testosterone concentrations. Hormonal contraception for men interrupts this physiological axis by various means of gonadotrophin suppression; this interferes with spermatogonial differentiation and meiosis entry resulting in reversible azoospermia or severe oligozoospermia in virtually all men. Clinical trials have confirmed that high contraceptive efficacy, similar to female hormonal contraceptives, can be reliably attained with few side effects. However, the simultaneous suppression of Leydig cell steroidogenesis mandates the requirement for testosterone replacement in hormonal male contraception. Combination regimens of new synthetic progestins and androgens at various stages of development are being investigated with the lead products poised to go into phase III trials. Heterogeneity in response to spermatogenesis suppression has been observed within and between population; the mechanisms are unclear. This new method of reversible and effective contraception has registered high acceptability in surveys of both men and women. The recent entry of pharmaceutical companies into this area of research and development has considerably enhanced the prospects of translating years of academic efforts into new products which provide added family planning choice for many couples.

摘要

促性腺激素的“睾丸前”抑制是可逆性治疗性男性生育控制最有可能实现即将临床应用的方法。精子发生的维持依赖于足够的促性腺激素和睾丸内睾酮浓度。男性激素避孕通过多种抑制促性腺激素的方式中断这一生理轴;这会干扰精原细胞分化和减数分裂进入,几乎在所有男性中导致可逆性无精子症或严重少精子症。临床试验已证实,与女性激素避孕类似,男性激素避孕能可靠地实现高避孕效果,且副作用很少。然而,同时抑制睾丸间质细胞类固醇生成使得男性激素避孕中需要补充睾酮。正在研究处于不同开发阶段的新型合成孕激素和雄激素的联合方案,其领先产品准备进入III期试验。在人群内部和人群之间都观察到了对精子发生抑制反应的异质性;其机制尚不清楚。这种可逆且有效的避孕新方法在男性和女性调查中都获得了很高的可接受性。制药公司最近进入这一研发领域,大大增强了将多年学术努力转化为新产品的前景,这些新产品为许多夫妇提供了更多的计划生育选择。

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