The Future of 'The Pill'

Almost half of all pregnancies around the world are unintended, according to UNFPA’s 2022 report on the State of the World Population. A way to reduce this is by improving the accessibility, variety and acceptability of reproductive health. This includes contraception, which is the use of artificial methods to prevent pregnancy.

When we think about contraceptives, we mainly think about the countless methods women can choose from, including injections, patches and coils. The most well-known female method is ‘the Pill’. The drug prevents ovulation, which prevents the release of an egg during the monthly menstrual cycle, so the egg cannot be fertilized. It also thickens the mucus around the cervix, so it becomes impenetrable to sperm. 

Inventing this birth control pill marked a significant milestone in the women's rights movement. In 1951, American nurse, feminist and birth control crusader Margaret Sanger challenged Gregory Pincus, a biologist, to develop a hormonal contraceptive in the form of a pill. Around the same time, chemist Carl Djerassi, working for Syntex, synthesized norethindrone, an artificial progesterone. Pincus knew that high hormone levels inhibited ovulation in laboratory animals. By 1953, he trialled a birth control pill for women, known as ‘the Pill’. In 1960, the US Foods and Drug Administration approved it as an oral contraceptive, giving Sanger a victory for American women to control their fertility.

Despite this, female contraceptives carry some major responsibilities and burdens. For instance, female methods of birth control tend to be more expensive. This is because most require at least one visit to the doctor, as well as a renewal of the prescription. Women at reproductive age spend 68% more on out-of-pocket health costs than men. With the pill, one hormone pill is taken each day at about the same time for 21 to 28 days, depending on the size of the pack. In addition, there are more undesirable side effects. This is mainly a problem with hormonal methods containing progestin and/or oestrogen. This is a major issue with the pill, including nausea, bloating, mood changes, irregular bleeding and more.

In contrast to the widespread use of female contraceptives since the 1960s, scientists did not begin developing new types of male contraceptives until the 1970s. A half century had passed since they began researching 'modern' contraceptives for women. These possible hormonal methods of men's birth control, despite being safe and effective, all ran into similar difficulty - undesirable side effects. For example, an androgen and progestin approach to hormonal male contraception reported side effects including weight gain, mood changes and libido changes.

This has resulted in men only having two options - condoms and a vasectomy. Consequently, women have borne most, if not all, the financial and health-related burdens of contraception.

But that may change. Recent advancements in male contraceptive research have sparked curiosity about the plausibility of a male pill.

Currently in preclinical study, the proposed pill aims to work as an on-demand contraceptive, only taken as needed. A single dose of TDI-11861 acts as a soluble adenylyl cyclase (sAC) inhibitor. sAC is a cytosolic enzyme which, when activated by bicarbonate, is necessary for sperm cell motility. Therefore, by interfering with sAC, the pill produces sperm that cannot propel themselves forwards, hence unable to make contact with and fertilize an egg.

The study demonstrated that, when tested on mice, the drug was effective. Male mice were infertile for around 2 hours, exhibited normal mating behaviour, and returned to full fertility the next day. Scientists found that with sAC-inhibited male mice after 52 attempts, female mice were not impregnated, whereas with an inactive control substance male mice impregnated ⅓ of their mates. In a BBC interview, Dr Stephanie Page, an endocrinologist and professor at the University of Washington School of Medicine stated that “translating findings in mice and even in non-human primates to humans has been particularly challenging [especially] in the area of reproductive health… there’s quite a lot more to do.”.

In the event that the drug is successfully tested on humans and approved, we could soon see a future when ‘the Pill’ no longer applies to only women, but to men as well. It is critical to note that the development of a male contraceptive pill should not replace female contraceptives. Instead, it should be considered a complementary option that offers additional choice and control for men and women. By empowering men to take greater responsibility for reproductive health, the new male contraceptive pill could lead to a more balanced distribution of responsibility between partners. This could reduce the burden women have borne for decades. While there is still more research to be done, the future looks promising for an inclusive, accessible approach to contraception.

References

Abbe, C. R. (2020, September 1). Focus: Sex & Reproduction: Male Contraception. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513428/#__ffn_sectitle

Balbach, M., Ghanem, L., Rossetti, T., Kaur, N., Ritagliati, C., Ferreira, J., Krapf, D., Molina, L. C. P., Santi, C. M., Hansen, J. P., Wachten, D., Fushimi, M., Meinke, P. T., Buck, J., & Levin, L. R. (2021). Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization. Molecular Human Reproduction, 27(9). https://doi.org/10.1093/molehr/gaab054

Balbach, M., Rossetti, T., Ferreira, J., Ghanem, L., Ritagliati, C., Myers, R. W., Huggins, D. J., Steegborn, C., Miranda, I. C., Meinke, P. T., Buck, J., & Levin, L. R. (2023). On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-36119-6

BBC News. (2023a, February 14). Male contraceptive pill prototype stops sperm swimming. https://www.bbc.com/news/health-64635446.amp

BBC News. (2023b, February 15). Male contraceptive pill a real possibility, say scientists - BBC News [Video]. YouTube. https://www.youtube.com/watch?v=Wh9JXi6Yzgg

Campo-Engelstein, L. (2012). Contraceptive Justice: Why We Need a Male Pill. AMA Journal of Ethics, 14(2), 146–151. https://doi.org/10.1001/virtualmentor.2012.14.2.msoc1-1202

Davis, N. (2023, February 17). Male contraceptive taken shortly before sex shows promise, say scientists. Contraception and Family Planning | the Guardian. https://amp.theguardian.com/society/2023/feb/17/male-contraceptive-taken-shortly-before-sex-shows-promise-say-scientists

Gorvett, Z. (2023, February 23). The weird reasons there still isn't a male contraceptive pill. https://www.bbc.com/future/article/20230216-the-weird-reasons-male-birth-control-pills-are-scorned

M Kaunitz, MD, A. (2022, November 28). Patient education: Hormonal methods of birth control (Beyond the Basics). UpToDate. https://www.uptodate.com/contents/hormonal-methods-of-birth-control-beyond-the-basics#H3

Male contraceptive disables sperm. (2023, March 7). National Institutes of Health (NIH). https://www.nih.gov/news-events/nih-research-matters/male-contraceptive-disables-sperm 

Murdoch, F. E., & Goldberg, E. (2014). Male contraception: Another holy grail. Bioorganic & Medicinal Chemistry Letters, 24(2), 419–424. https://doi.org/10.1016/j.bmcl.2013.12.004

NCI Dictionary of Cancer Terms. (n.d.). National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/contraception 

Nearly half of all pregnancies are unintended—a global crisis, says new UNFPA report. (2022, March 30). United Nations Population Fund. https://www.unfpa.org/press/nearly-half-all-pregnancies-are-unintended-global-crisis-says-new-unfpa-report 

On-demand male contraceptive shows promise in preclinical study. (2023, February 23). ScienceDaily. https://www.sciencedaily.com/releases/2023/02/230214153913.htm 

The High Costs of Birth Control - Center for American Progress. (2012a, February 15). Center for American Progress. https://www.americanprogress.org/article/the-high-costs-of-birth-control/ 

The High Costs of Birth Control - Center for American Progress. (2012b, February 15). Center for American Progress. https://www.americanprogress.org/article/the-high-costs-of-birth-control/ 

Wikipedia contributors. (2023, February 22). Soluble adenylyl cyclase. Wikipedia. https://en.m.wikipedia.org/wiki/Soluble_adenylyl_cyclase