Every few months, headlines from the media report on the development of a new “male pill” or an exciting new form of male contraception. What is the reality and how can you advise your patients on the availability of reversible male contraceptives?
Is a new, reversible male contraceptive about to go on the market?
Unfortunately, no.
Many media reports on new male contraceptives come from preliminary studies that are often years away from being commercially available to men. Many studies report data from animals where a drug or agent has been administered and sperm output is halted. Research at this stage must undergo years of further development and clinical evaluation – with a high risk of failure – before a marketable product is available.
The only effective and reversible male contraception option on the market is the condom, with a “real world’ failure rate of ~13% per year[1].
Why has the development of new male contraceptives been so difficult?
One hurdle is a simple mathematical equation; a contraceptive needs to block the production of one egg (oocyte) per month in women compared to approximately one thousand sperm per heartbeat in men. Male contraceptives need to work very effectively at blocking sperm production.
A second major hurdle has been a lack of investment in research and development. Pharmaceutical companies have preferred to invest in the development of therapies to treat diseases, especially chronic disorders for which there is a large market and perceived need, rather than the higher risk and expositive strategy of developing agents to be administered over the long term to otherwise healthy men.
Male hormonal contraception is a promising approach
Over the past three decades, a wide variety of hormonal contraceptives have been trialled. These methods involve the administration of hormones, particularly androgen and progestin-like compounds. These suppress the release of gonadotrophins (FSH and LH) from the pituitary, resulting in the suppression of the synthesis of testicular testosterone and the production and release of sperm from the testes. These formulations contain androgenic agents that maintain peripheral androgen action.
Many of these formulations are very effective at suppressing sperm output. The complete suppression of sperm counts to undetectable (azoospermia) is achievable in many, but not all, men and has a contraceptive efficacy comparable to the most effective female contraceptives[4]. Suppression of sperm counts to less than one million per mL of ejaculate is achievable in around 95% of men, with a contraceptive efficacy similar to female oral contraceptives[1],[2].
Challenges in getting a male hormonal contraceptive to the market
Despite these promising results from many clinical trials, challenges remain.
A small proportion of men fail to achieve adequate sperm count suppression for unknown reasons. Side effects occur and vary with formulation but are generally similar to those experienced by women taking hormonal contraceptives. These include acne, weight gain and impacts on libido (though men tend to report increased libido compared to decreased libido in women).
Some formulations are associated with adverse changes in circulating lipoproteins. Effects on depression and mood with some formulations are a cause for concern, and these endpoints need to be monitored carefully in future clinical trials[2].
Male hormonal contraceptive research requires further investment so that formulations with optimal efficacy, safety, and acceptability are brought to market. Unfortunately, at present there is little interest from the pharmaceutical industry but work continues in the US public sector on innovative hormonal methods approaches.
What other male contraceptives are in the pipeline and where are they in their development?
Non-hormone-based contraceptive approaches are also being investigated. The Male Contraceptive Initiative is investing in research on a wide range of options to help bring a variety of marketable male contraceptives closer to reality. Various pharmaceutical agents that act on the testis to block sperm production have been investigated, but many have not progressed to further development.
Other approaches aim to reversibly block sperm motility or the transport of sperm into the ejaculate. For example, the injection of a substance into the vas deferens to reversibly block sperm output has been trialled, but a return to normal fertility after removal has been questioned by pre-clinical data[5].
The ultimate goal is to define formulations with the most favourable risk/benefit profiles. It is important to consider that female hormonal contraceptives are also associated with side effects and risks yet are still widely prescribed. Weighing up the risks and benefits for both partners is an important consideration when it comes to deciding on a contraceptive method.
What to tell your patients about male contraceptives
There is no male contraceptive on the market, yet. Research is ongoing and needs investment and public support.
The leading candidates are based on hormonal contraception and – like female hormonal contraceptives – different methods are being trialed for their safety, efficacy, and acceptability. Large, multi-center trials have established the effectiveness and relative safety of hormonal contraceptives, but much more research needs to be done to identify the ideal formulations.
Different methods, including physical barriers and non-hormone-based pharmaceuticals that specifically target sperm production, are also being investigated for their suitability as reversible contraceptives.
References
[1] Sundaram, A., B. Vaughan, K. Kost, A. Bankole, L. Finer, S. Singh, and J. Trussell, Contraceptive Failure in the United States: Estimates from the 2006-2010 National Survey of Family Growth. Perspect Sex Reprod Health, 2017. 49(1): p. 7-16.
[2] Thirumalai, A. and J.K. Amory, Emerging approaches to male contraception. Fertil Steril, 2021. 115(6): p. 1369-1376.
[3] McLachlan, R.I., L. O’Donnell, P.G. Stanton, G. Balourdos, M. Frydenberg, D.M. de Kretser, and D.M. Robertson, Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men. J Clin Endocrinol Metab, 2002. 87(2): p. 546-56.
[4] Trussell, J., Contraceptive failure in the United States. Contraception, 2011. 83(5): p. 397-404.
[5] Waller, D., D. Bolick, E. Lissner, C. Premanandan, and G. Gamerman, Reversibility of Vasalgel male contraceptive in a rabbit model. Basic Clin Androl, 2017. 27: p. 8.
