Will 2022 bring a ‘Male Pill’ and why haven’t we got one already?

By Isabella Kwiecinski

Trials of a male contraceptive pill have been successful at preventing pregnancy in mouse models. Isabella Kwiecinski discusses how this form of non-hormonal contraceptive works and the safety concerns that need to be addressed before its clinical use.

In 1950, one of the most influential and politically significant medications was introduced, the female contraceptive pill. Despite centuries of pharmacological discoveries, the oral contraceptive pill has been the only one influential enough to earn its simple nickname ‘the pill’ [1]. Its release forced a shift in social attitudes towards sexual intercourse and challenged religious, social and political viewpoints. Women were liberated and finally given reproductive autonomy.

Since its invention over 70 years ago, the pill has undergone little change, with the risk of blood clots the same today as it was in the early 1960s. Instead, during the 1990s, research moved to look for new contraceptive methods, such as implants, intrauterine devices (IUDs) and injections, giving women even more choice and control over their fertility [1].

In the decades since the pill first became available, creating a male counterpart which is equally as effective, and that avoids unwanted side effects, has proven difficult. Currently, men are limited to condoms or vasectomies. Whilst barrier contraception such as condoms are one of the most popular choices for contraception, many people feel they cannot rely on them, with the failure rate estimated at 14% [2]. The other option for men who wish to take contraception into their own hands is a vasectomy, which is typically irreversible. This option is not accessible to everyone, as there are long NHS wait lists across the UK and many men must undergo counselling to ensure the procedure is right for them. Moreover, getting a vasectomy is particularly problematic younger males who may wish to have children later in life [3]. Their limited options mean that many men rely on their female partner to protect against conception, leaving women to carry this physical and mental burden.

In the decades since the pill first became available, creating a male counterpart which is equally as effective, and that avoids unwanted side effects, has proven difficult.

Over the last 20 years support, and demand, for a male pill has been growing, with several pharmaceutical companies developing their own. Many approaches have tried to mirror what was successful in the female pill—altering levels of our androgens. The female contraceptive pill targets oestrogen and progesterone, leaving the woman sterile whilst she takes the medication. Yet trials in men targeting the male hormonal counterpart, testosterone, have shown many adverse side effects, such as weight gain, depression, acne and sexual dysfunction. In past trials it was decided that these risks outweigh the benefits. As well as issues with the developing drugs, other companies have simply given up on their studies due to the challenges of social acceptance and male adherence [4]. Yet in a critical appraisal carried out by the BMJ the adverse effects of the female and male hormonal contraceptive pill were compared, finding that the side effects occurred with very similar frequencies. This discovery led researchers to believe that there is an ‘implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods’ [5].

Excitingly, a new male contraceptive is set to be trialled in humans later this year, having shown 99% efficacy in mouse trials with no side effects to note. The new contraceptive method is a non-hormonal pill with the active compound of the drug being YCT529. This compound blocks RAR-a proteins which are crucial in cell growth, sperm formation and embryonic growth. By blocking this protein the role of vitamin A in sperm development is inhibited, leading to sterility. Although RAR protein inhibitors have been trialled as a male contraceptive method in the past, none have shown the specificity that YCT529 has shown. This means that the other bodily functions of vitamin A are not impacted, and adverse effects are avoided [6].

The development of a male contraceptive pill could provide a shift in social and political views surrounding the role of women, contraception, and reproductive autonomy, similar to the revolution in beliefs that came with the first pill in the 1950s.

In the past, adverse effects have been recorded in both the male and female contraceptive pill, with weight gain, depression and changes in sex drive seen in both genders when taking hormonal contraception. These side effects, coupled with traditional attitudes surrounding contraception, have led to many male contraceptive pills failing in the development stages. There has been a recent shift in mindset that if the risks and adverse effects are equal for men and women, men ought to have the same rights to contraception as women do and given the ability to make the choice for themselves [5]. Nonetheless, many of the side effects that have been observed in trials of male pills have been viewed within common society as ‘emasculating’, with a study carried out in Bristol showing 71% of men were not prepared to tolerate any side effects from their contraception [7]. Challenging these beliefs which have been established within society over the past century is vital in the development of the male pill.

Another potential barrier for the male pill is trust and adherence. In a survey of 132 men and 165 women, 80.9% of men reported that they would be compliant with an oral medication but only 65.6% of women believed that their male partner would be compliant. Furthermore, 74.2% of women reported that they would continue their current form of contraception regardless of whether their partner was taking a male contraceptive [8].

Researchers to believe that there is an ‘implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods’.

Abbe & Roxby (2019), reference 5

The development of a male contraceptive pill could provide a shift in social and political views surrounding the role of women, contraception, and reproductive autonomy, similar to the revolution in beliefs that came with the first pill in the 1950s. The introduction of a male contraceptive pill would allow men more freedom and choice in their fertility and would make contraception a shared burden between genders. Whilst a male pill is clearly necessary in providing equality within contraception, challenging existing social beliefs, and working past bias surrounding acceptable risk in men is a huge barrier to its use.


References:

  1. Verma Liao, P. and Dollin, J., 2012. Half a century of the oral contraceptive pill: historical review and view to the future. Can Fam Physician., [online] Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3520685/ [Accessed 10 April 2022].
  2. Samra, O., 2022. How Often Do Condoms Fail?. [online] eMedicineHealth. Available at: https://www.emedicinehealth.com/ask_how_often_do_condoms_fail/ article_em.htm#doctors_response [Accessed 10 April 2022].
  3. nhs.uk. 2021. Vasectomy (male sterilisation). [online] Available at: https://www.nhs.uk/ conditions/contraception/vasectomy-male-sterilisation/ [Accessed 10 April 2022].
  4. Wang, C. and Swerdloff, R., 2010. Hormonal approaches to male contraception. Current Opinion in Urology, 20(6), pp.520-524.
  5. Abbe, C. and Roxby, A., 2019. Adverse effects of Male Contraception: How Much is Too Much?. British Medical Journal, [online] Available at: https://blogs.bmj.com/bmjsrh/ 2019/12/04/adverse-effects-male/ [Accessed 10 April 2022].
  6. Huzar, T., 2022. The pill for men: Mice study shows 99% effectiveness. [online] Medicalnewstoday.com. Available at: https://www.medicalnewstoday.com/articles/safeand-99-effective-birth-control-pill-for-men-may-soon-become-reality#The-birth-controlburden [Accessed 10 April 2022].
  7. M, B., 1998. Men’s views on male hormonal contraception-a survey of the views of attenders at a fitness centre in Bristol, UK. [online] PubMed. Available at: [Accessed 9 May 2022].
  8. Windsperger, A., Art, K., Epp, A., Greiner, A., Tash, J. and Nangia, A., 2012. Male and female public opinion regarding a possible male contraceptive pill. Fertility and Sterility, 98(3), pp.S6-S7.

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