Abstract:
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.
摘要:
获得可靠的避孕方法是现代社会的支柱。在整个人类历史上,意外怀孕的负担不成比例地落在母亲身上;然而,最近围绕堕胎的法律发展引发了人们对手术绝育和避孕套以外的男性因子避孕药的新兴趣。发展可逆男性节育的现代努力可以追溯到近一个世纪,最初集中在改变下丘脑-垂体-睾丸轴。这些荷尔蒙避孕药面临多重障碍,包括全身副作用,具有挑战性的给药方案,不利的交货路线,以及围绕类固醇使用的公众耻辱。新型激素剂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药物;如视黄酸抑制剂,支持细胞-生殖细胞相互作用,精子离子通道,和其他小分子靶标。与男性不育相关的生殖道特异性基因的鉴定导致了更有针对性的药物开发,CRISPR和蛋白水解靶向嵌合体(PROTACs)的进展使之成为可能。尽管进行了多项人体试验,在美国或国外,没有男性节育人员获得监管部门的批准。这篇叙述性综述研究了当前和新兴的男性避孕药,包括荷尔蒙和非荷尔蒙药物。