Are there any Male Contraceptive Pills?

In previous posts, we have described many different types of birth controls: non-hormonal; hormonal; IUDs; and the emergency contraceptive pill. Even though there are plenty of options, much of the responsibility for birth control has fallen on women. Since multinational surveys suggest that most men would use contraception if available [1] why aren’t there any male birth control pills? Would there be one in the future?

Before answering these questions, it is important to understand how sperm production (spermatogenesis) is regulated in the body. This process involves the hypothalamus (a region of the brain), the pituitary gland (a gland in the brain), and the testes (the male reproductive organs). It is named the hypothalamic-pituitary-testicular (HTP) axis [2].

First, the hypothalamus secretes gonadotropin-releasing hormone (GnRH), which travels to the pituitary gland, stimulating production and releasing both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These are the same hormones in the menstrual cycle (more information here), however, in males, FSH and LH will stimulate the production of testosterone in the testes [3]. Testosterone has many functions such as regulation of spermatogenesis, development of male sexual characteristics, and maintenance of bone and muscle mass [4]. When enough testosterone is produced, it signals the hypothalamus to stop secreting GnRH and, therefore, the secretion of FSH and LH is also inhibited [2].

Although male contraceptives have not reached the market yet, extensive research has been conducted over the last 40 years [1]. Nowadays, male hormonal contraception options are based on the administration of testosterone (either alone or in combination with progestin or GnRH) to suppress LH and FSH to levels below what’s required to produce sperm [5, 6] in the form of injections, gel, and implants [7]. There is a prototype of the “male pill”, but so far, this needs to be taken 2-3 times per day and can cause significant toxicity in the liver [1]. Moreover, there is also a similar device to an IUD called the intra-vas device (IVD) that would be placed inside the vas deferens (the tube that transports mature sperm [8]) to filter the sperm out and prevent pregnancies [7], however, this is still in the very early stages of research.

There are factors that have slowed the progress in this field despite decades of research [1,5]. For example:

• Since these prototypes are still developing, the side effects are unclear, especially long-term. Without knowing this, it can not be approved by regulatory agencies.

• There is less funding for these methods due to market uncertainties, potential side effects, and the lack of long-term studies.

• Clinical trials showed racial variations in sperm suppression. Some studies showed that Caucasians achieved less complete suppression than Asians [9], while there is not enough data from Latinos and African descent populations.

• Furthermore, brief periods where sperm concentration rises have been observed, which could increase the likelihood of contraception failure. This needs to be taken into consideration and studied intensively before releasing it into the market.

• A female-directed contraceptive must suppress the release of one egg per menstrual cycle, while a male contraceptive has to suppress 15-200 million sperm/mL of ejaculate, making it more difficult.

• It requires 6-8 weeks to be effective as sperm production requires approximately 72 days. Therefore, additional contraceptive is required to avoid pregnancy.

• Even though these contraceptive methods are reversible, it takes a longer time to be effective or to start producing sperm again once stopped the contraceptive. After biweekly injections or daily gels, recovery will be 2.5-4 months while IVD recovery is 5-10 months.

Many women are unable or unwilling to tolerate female contraceptives due to side effects. The development of simple, safe, effective, and reversible male contraceptives could reduce unplanned pregnancies while also allowing couples to share the burden and benefits of contraception. Even though it has been a slow process, over the last decade there have been significant achievements in this field, and further funding could accelerate this process - perhaps a “male pill” will be a reality in the near future!

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Written by: María

Edited by: Natasha

BioDecoded is a volunteer group committed to sharing accurate scientific information. If you have any questions about this topic or would like to learn more, please comment below or send us your questions.

References:

1. Thirumalai A and Page S.T (2020). “Male hormonal contraception”. Annual Review of Medicine 71:1, pp. 17-31. Available at: https://www.annualreviews.org/doi/10.1146/annurev-med-042418-010947?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed

2. Handelsman, D. (2020) "Androgen Physiology, Pharmacology, Use and Misuse", MDText.com, Inc. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279000/ (Accessed: 19 April 2023).

3. Gilbert, S. (2000) "Spermatogenesis", Sinauer Associates. Available at: https://www.ncbi.nlm.nih.gov/books/NBK10095/ (Accessed: 19 April 2023).

4. Nassar, G. and Leslie, S. (2023) "Physiology, Testosterone", StatPearls Publishing, p. Available at: https://www.ncbi.nlm.nih.gov/books/NBK526128/ (Accessed: 19 April 2023).

5. Wang, C. and Swerdloff, R. (2010) "Hormonal approaches to male contraception", Current Opinion in Urology, 20(6), pp. 520-524. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078035/

6. Page, S., Blithe, D. and Wang, C. (2022) "Hormonal Male Contraception: Getting to Market", Frontiers in Endocrinology, 13. Available at: https://www.frontiersin.org/articles/10.3389/fendo.2022.891589/full

7. His Turn: 8 Options in the Pipeline for Male Birth Control (2023). WebMD. Available at: https://www.webmd.com/sex/birth-control/ss/options-in-the-pipeline-for-male-birth-control (Accessed: 19 April 2023).

8. Vas Deferens: Function, Anatomy & Conditions (2023). Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/body/22763-vas-deferens (Accessed: 19 April 2023).

9. Liu, P. et al. (2008) "Determinants of the Rate and Extent of Spermatogenic Suppression during Hormonal Male Contraception: An Integrated Analysis", The Journal of Clinical Endocrinology & Metabolism, 93(5), pp. 1774-1783. Available at: https://academic.oup.com/jcem/article/93/5/1774/2598758?login=false