Service C Austin, Puri Dhruv, Hsieh Tung-Chin, Patel Darshan P
Department of Urology, University of California San Diego, San Diego, CA, USA.
Department of Urology, University of California San Diego, 9333 Genesee Avenue, Suite 320, La Jolla, CA 92121, USA.
Ther Adv Reprod Health. 2023 Mar 8;17:26334941221138323. doi: 10.1177/26334941221138323. eCollection 2023 Jan-Dec.
Access to reliable contraception is a pillar of modern society. The burden of unintended pregnancy has fallen disproportionately on the mother throughout human history; however, recent legal developments surrounding abortion have sparked a renewed interest in male factor contraceptives beyond surgical sterilization and condoms. Modern efforts to develop reversible male birth control date back nearly a century and initially focused on altering the hypothalamic-pituitary-testes axis. These hormonal contraceptives faced multiple barriers, including systemic side effects, challenging dosing regimens, unfavorable routes of delivery, and the public stigma surrounding steroid use. Novel hormonal agents are seeking to overcome these barriers by limiting the side effects and simplifying use. Non-hormonal contraceptives are agents that target various stages of spermatogenesis; such as inhibitors of retinoic acid, Sertoli cell-germ cell interactions, sperm ion channels, and other small molecular targets. The identification of reproductive tract-specific genes associated with male infertility has led to more targeted drug development, made possible by advances in CRISPR and proteolysis targeting chimeras (PROTACs). Despite multiple human trials, no male birth control agents have garnered regulatory approval in the United States or abroad. This narrative review examines current and emerging male contraceptives, including hormonal and non-hormonal agents.
获得可靠的避孕方法是现代社会的一大支柱。在整个人类历史中,意外怀孕的负担不成比例地落在了母亲身上;然而,近期围绕堕胎的法律发展引发了人们对除手术绝育和避孕套之外的男性避孕方法的新兴趣。现代开发可逆性男性节育方法的努力可以追溯到近一个世纪前,最初集中在改变下丘脑 - 垂体 - 睾丸轴。这些激素避孕药面临多重障碍,包括全身性副作用、复杂的给药方案、不利的给药途径以及围绕类固醇使用的公众污名。新型激素制剂正试图通过限制副作用和简化使用来克服这些障碍。非激素避孕药是针对精子发生各个阶段的制剂;例如视黄酸抑制剂、支持细胞 - 生殖细胞相互作用抑制剂、精子离子通道抑制剂以及其他小分子靶点。与男性不育相关的生殖道特异性基因的鉴定促使了更具针对性的药物开发,这得益于CRISPR和蛋白酶靶向嵌合体(PROTACs)技术的进步。尽管进行了多项人体试验,但在美国或国外,尚无男性避孕药获得监管批准。这篇叙述性综述探讨了当前和新兴的男性避孕药,包括激素和非激素制剂。