Development of Novel Male Contraceptives

Abstract

Unintended pregnancy is surprisingly common, accounting for 40–50% of pregnancies worldwide. Contraception is the most effective means of preventing unintended pregnancy. Seventy percent of all contraceptives are used by women; however, some women are unable to use contraceptives due to health conditions or side effects. Many men wish to take a more active role family planning, but currently have only two effective male contraceptive options, condoms and vasectomy. Therefore, work to develop novel male contraceptives analogous to popular female methods, such as daily pills or long‐acting shots and implants, is underway. This paper will briefly discuss the pros and cons of condoms and vasectomies, and then review the research into novel methods of male contraception.

SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility

“…Medically, our work confirms that the dysregulation of SLC22A14, a riboflavin transporter localized at the IMM in the spermatozoa mid-piece that promotes FAO energy metabolism, can cause infertility in male mice but not female mice and emphasizes that such infertility is not accompanied by disruption of hormone levels or sexual ability. As common contraceptives use modes of action based on female reproductive physiology, there is a strong bias wherein women are perceived to be solely responsible for fertility management, leaving them to face the brunt of pharmacological side effects and causing societal bias issues ( Amory, 2020 ). The development of male contraceptives is now widely recognized as an unmet need for birth control ( Matzuk et al., 2012 ).…”

Retinoic acid receptor antagonists for male contraception: current status†

“…Inhibitors of enzymes involved in this process could potentially disrupt ATRA synthesis and thereby stop spermatogenesis. Indeed, suppression of spermatogenesis involving the ATRA pathway was demonstrated with a bisdichloroacetyldiamine analog (BDAD) [ 2 , 27 , 28 ]. WIN 18 446, one of the BDAD analogs, was used in a clinical study to treat over 60 men for 1 year and was shown to efficiently suppress sperm production in men [ 27 ].…”

“…The mechanism of suppression was subsequently elucidated when WIN 18 446 was shown to inhibit the enzymes aldehyde dehydrogenase ALDH1A1 and ALDH1A2 [ 29 , 30 ]. Using X-ray crystallography, direct binding studies, and enzymatic analyses, a recent report determined the structural basis of ALDH1A2 inhibition by WIN 18 446, and two novel and reversible small molecule inhibitors were identified which are being investigated for their property of not blocking alcohol metabolism [ 28 , 31 ]. Results provide a structural framework toward the rational design of potent and selective ALDH1A2 inhibitors that might be suitable for non-hormonal male contraception [ 28 ].…”

Deleterious effect of short-term gavage of an ethanol extract of cogon grass (Imperata cylindrica L.) roots on testis and epididymal sperm quality

“…In contrast, the development of male contraception remains limited. In principle, male contraception acts by blocking sperm from fertilizing the egg either by physical barriers or by inhibiting spermatogenesis [ 1 , 2 ]. One of the known methods is vasectomy, but it has a high failure rate and lacks complete reversibility [ 3 ].…”