Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options

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.

Male animal sterilization: history, current practices, and potential methods for replacing castration

“…The method is performed under general anesthesia, typically involving a simple incision of the scrotum in men and inguinal incision in dogs and cats ( 153 , 158 ). Vasectomy is one of the most common, convenient, and effective methods of sterilization/contraception in men, with nearly 500,000 being performed annually in the United States ( 196 , 197 ). Although vasectomy is considered safe and reliable, a few complications have been shown to arise post-surgery, such as infections, chronic scrotal pain, and sperm granulomas ( 198 ).…”

“…Hormones, including steroids and synthetic peptides, have been explored for controlling male reproduction. However, the focus has been on reversible contraception for both men and domestic or wildlife animals ( 21 , 156 , 182 , 197 , 403–406 ) rather than inducing sterility. For instance, anabolic steroids such as testosterone undecanoate can be used alone or with a progestin to temporarily suppress gonadotropins, leading to azoospermia, or the absence of sperm.…”

The landscape of male contraception

“…Over the past century, significant progress has been made to elucidate effective contraception methods further. 3 Most of this research has focused on developing and improving female contraceptives via physical devices such as diaphragms, vaginal rings, implants, and intrauterine devices (IUDs), and oral birth control pills or injections. Recently, more attention has been focused on male contraception.…”

Sperm Toolbox – A selection of small molecules to study human spermatozoa

“…In parallel, a deeper understanding of the sperm function and possible interventions for male infertility is required to counter declining birth rates. Recently, the application of advanced technologies has helped to move the human fertility field forward, revealing new potential targets for both contraception and fertility, and new compounds as contraceptive candidates (reviewed by (Anderson and Johnston, 2023;Service et al, 2023). A key part of this effort is the development of mechanistic insight and drug candidates that affect the behaviour and properties of human spermatozoa (Balbach et al, 2023;Carlson et al, 2022;Faber et al, 2023;Hau et al, 2022).…”