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Thought Leadership | 17th January 2023

Why we really need to THINK about the pill

Read Time: 9 minutes

 

Your doctor recommends a drug that; may increase your risk of depression; could potentially increase your risk of some forms of cancer; might mean you put on weight; and even promote excess hair growth.1 Do you take it? 

If you’re already taking a form of hormonal birth control, ‘the pill’, then, like millions of women around the world, you have likely already experienced some of these less desirable side effects. Yet beyond the benefit of preventing pregnancy, few of us are fully aware of the other physiological considerations we should give ‘women’s liberator’. 

Reported implications of hormonal contraception on our physical health include an increased risk of stroke2 and certain cancers,3 and links to depression4 have also been reported, as well as a host of other potential side effects.1 So why do we persist in their use and what more should we know to enable us to improve our experiences and our choice of hormonal contraception methods?

A hard pill to swallow 

At a time when more people than ever are opting to forgo or delay having children,5,6 and when the reproductive choices of 1.2 billion women worldwide are restricted,7 the abandonment of existing hormonal contraception is simply not feasible.  

It’s beneficial that there are a host of hormonal contraceptive options available to women today, including the contraceptive injection, patch and implant.8 Despite the various options available, data from recent years suggests the oral contraceptive pill (‘birth control pill’, or ‘the pill’) was the foremost contraceptive choice in the UK and US, with 28% of UK women in 2018 and 25% of US women in 2022 electing to use it.9,10 

But users of the pill report troubling side-effects. An online survey of heterosexual women found that 4-36% of contraceptive pill users were likely to change their contraceptive method within the first 12 months, with the most common reason for change cited as unwanted side effects.11 

And yet, the pill remains ubiquitous; in 2019 it was the most popular contraceptive method of Northern and Western Europe.12 It seems that for most of us who opt for a long-term contraceptive option, the question isn’t whether to go on the pill, but rather, what side effects of the pill are we willing to put up with?

Hormonal contraception: a gulf in understanding 

Despite the dissatisfaction associated with the pill, the mini-pill (also known as the progesterone-only pill) recently become available over-the-counter in the UK for the first time in 2021.13,14 The same pill currently remains under consideration by the FDA to become available without a prescription for the first time in the USA.15 

While this provides women with favourable control over their own fertility, does sufficient public scientific information and understanding exist for the availability of the pill, without a prescription, to truly empower our choices? 

GPs themselves have suggested that they don’t possess confidence in their own capacity to prescribe contraception effectively. A 2021 survey performed by the Family Planning Association, revealed that of 1,023 GPs surveyed, across 914 practices in the UK, only 2% offered patients the full range of contraceptive methods, including hormonal, barrier and LARC (long-acting reversible contraception intrauterine) methods.16 More than half (54%) of respondents also reported that there is not enough time in a standard contraception appointment to talk through all contraceptive options with patients.16 

In the UK, this problem is confounded by the availability of contraception from multiple different sources, including GP surgeries, sexual health clinics, or pharmacies. While all the healthcare professionals situated within these sites can prescribe contraception, they aren’t all contraceptive specialists and are likely to default to one or two methods they are comfortable prescribing.17 

Despite the considerable gaps in GPs’ confidence in prescribing contraception, doctors still have the greatest influence on women’s choices of contraceptive method.11 Data shows that these doctors are most likely to suggest the contraceptive pill or male condom.11 

So perhaps it is little wonder that so many women report dissatisfaction with their pill; doctors and patients alike don’t seem to know enough about it to know what we can expect from it. 

What does the pill actually do? 

Reproductive activity in females and males is coordinated through a communication pathway known as the hypothalamic-pituitary-gonadal axis (or HPG axis); coordination between the brain, pituitary gland and ovaries.1 

The system can be thought of as a type of feedback loop. The pituitary and brain work together to coordinate the activity of the ovaries and the ovaries in turn feedback to the pituitary and brain.18 Throughout the menstrual cycle, the brain releases a hormone called gonadotropin-releasing hormone (GnRH).19, 20 The frequency of release of GnRH depends on the stage of the menstrual cycle.21,22)  A high frequency release of GnRH pre-ovulation promotes the release of an egg, due to the GnRH-mediated increase in the pituitary hormone, luteinising hormone (LH).23, 20  GnRH and LH levels are subsequently reduced post-ovulation due to feedback from oestrogen and progesterone, hormones released from the ovaries.24, 25 Oestrogen and progesterone play crucial roles in preparing the female body for pregnancy.26 However, at the end of the menstrual cycle if pregnancy does not occur, oestrogen and progesterone levels decrease and high frequency of GnRH release returns to once again promote egg release.19 

Contraceptive pills contain oestrogen and progesterone, which effectively mimic the post-ovulatory phase. What sets those who take the pill apart from non-pill takers, is that rather than experiencing the natural fluctuation of hormones across the menstrual cycle, their bodies instead receive the same hormonal message every day; that the body does not need to release an egg.1 

This is all very clever, except that research is emerging to suggests that tinkering with these hormones and the systems that govern them has implications for all of the body’s systems that are influenced by female sex hormones.1 To quote Dr Sarah E. Hill, author of Your Brain on Birth Control, this is “Like dropping an atomic bomb on your house to blow out a candle”.1 So, what’s going wrong?

Not all hormones are created equally 

Most birth control pills are combination pills, which contain artificial versions of oestrogen and progesterone. While most pills use the same artificial oestrogen, there are many different versions of artificial progesterone, called progestins, in use.1 

While the artificial oestrogen used in the pill is synthesised from actual oestrogen, the majority of synthetic progestins in the pill are made from testosterone and not progesterone.1 This means that while progestins are synthesised to mimic progesterone and its influence within the body, they’re not a perfect match. 

Progestins therefore don’t bind to progesterone receptors in the same way as real progesterone does. What’s more, they bind to the testosterone receptors as well.1 This is why some pill-takers find that they experience masculinising effects such as acne, weight gain, and increase in hair growth in undesirable places.1 

To offer an example that demonstrates this in action; weight gain associated with the pill may be a product of the body maintaining a permanent luteal phase. During the first half of the cycle for someone not taking the pill, the body is sexually motivated to reproduce, meaning hunger and food intake are at their lowest. During the second half of the cycle (the one that the pill mimics) progesterone peaks and food intake is at its highest, because the body is preparing for the need to supply energy to a foetus.1  

So, for pill-takers who aren’t aware of this process, and aren’t adapting their diet to accommodate, being stuck in a perpetual artificial version of the luteal phase can cause weight gain.1 It’s also worth noting that evidence linking hormonal contraceptives to weight gain is strongest in those types of pill that have the highest ratio of progestin to oestrogen.1 

However, these hormones do not solely affect the cycle coordinating pregnancy, but they also control our emotional processing, learning, memory, social interactions, self-control, eating behaviours, language processing, and much more.1 Yet, very little investigation has taken place to understand the full extent to which the artificial hormones in the pill influence every other cell in the body that has hormone receptors for oestrogen and progesterone.

Why your progestin generation matters 

All progestins can be grouped into one of four generations, depending on the molecules they’re based on and when they first appeared on the market. The first three generations of progestin bind to testosterone receptors, and these pills tend to cause masculinising effects such as hair growth, weight gain and breakouts.1 This is because when the progestin binds to the testosterone hormone receptors of any cell, it makes that cell do whatever it’s supposed to do when that hormone is present; – regardless of whether it is a sex cell or not.1 

Each woman’s body can react differently to differing hormonal contraceptives.1 This means for women suffering unwanted masculinising effects of the contraceptive pill, they may want to look to the type of progesterone present in their pill, and research alternative options to discuss with their GP. 

Fourth generation progestins are generally considered superior,1 as they have been designed to act like the naturally produced progesterone.27 Unlike the prior generations, they possess lower androgenic (masculinising) effects, and have been reported to improve acne.28 They could also potentially be used for the treatment of polycystic ovary syndrome, a condition that results from unusually high androgen levels.29  

Of course, it would save a lot of time if woman could avoid the trial and error of trying different contraceptive pills to see which works for them. 

There is however positive progress being made, as the contraceptives market is beginning to offer non-hormonal contraceptive solutions, and R&D in the area is increasing; driven by a desire to overcome contraceptive side effects.30 

But why we don’t have more answers on the full effects of hormonal contraception on our bodies, hinges on the same reasons as to why women suffer in healthcare across the board: research, funding, and politics.1 

Science works in a way that systematically discourages research on women; with fierce competition to publish quickly. Arguably, it’s easier and cheaper to study men in clinical settings, as you needn’t worry about their monthly hormonal cycles;1 and historically, those conducting studies (men) choose research areas relating to their personal interest.31 

As Hill puts it, the person you think of as you, is very much ‘a product of the biological processes going on in your body. And huge among the mediators of these processes are your hormones’.1 It’s time we gave them the attention they deserve. 

References 

1. Hill, SE, Your Brain on Birth Control. London: Penguin Random House 2019. 2. Li F, Zhu L, He H, et al. Oral Contraceptive Use and Increased Risk of Stroke: A Dose–Response Meta-Analysis of Observational Studies. Front Neurol. 2018; 10: 993. Available from: doi 10.3389/fneur.2019.00993. 3. Michels KA, Brinton L, Pfeiffer RM, et al. Oral Contraceptive Use and Risks of Cancer in the NIH-AARP Diet and Health Study. Am J Epidemiol. 2018 Aug; 187(8): 1630–1641. Available from: doi 10.1093/aje/kwx388. 4. Wessel Skovlund C, Steinrud Mørch L, Vedel Kessing V, et al. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154-1162. Available from: doi:10.1001/jamapsychiatry.2016.2387. 5. The World Bank. Fertility rate, total (births per woman). Available from: https://data.worldbank.org/indicator/SP.DYN.TFRT.IN [Accessed January 2023]. 6. Eurostat. Women are having their first child at an older age. Available from: https://ec.europa.eu/eurostat/web/products-eurostat-news/-/ddn-20200515-2 [Accessed January 2023]. 7. United Nations. Progress On the Sustainable Development Goals: The Gender Snapshot 2022. Available from: www.unwomen.org/sites/default/files/2022-09/Progress-on-the-sustainable-development-goals-the-gender-snapshot-2022-en_0.pdf [Accessed January 2023]. 8. NHS. Which method of contraception suits me? Available from: https://www.nhs.uk/conditions/contraception/which-method-suits-me/ [Accessed January 2023]. 9. Statista. Distribution of women using user dependent and long lasting reversible contraceptives (LARCs) in England in 2021/22, by age. Available from: https://www.statista.com/statistics/573210/contraceptive-use-among-women-by-type-and-age-in england/#:~:text=Health%20System-,Contraceptive%20use%20among%20women%20in%20England,22%2C%20by%20type%20and%20age&text=In%20the%20period%202021%2F22,acting%20reversible%20contraceptives%20(LARCs) [Accessed January 2023]. 10. Cooper DB, Patel P, Mahdy H. Oral Contraceptive Pills. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430882/ [Accessed January 2023]. 11. Johnson S, Pion C, Jennings V. Current methods and attitudes of women towards contraception in Europe and America. Reprod Health. 2013; 10: 7. Available from: doi: 10.1186/1742-4755-10-7. 12. Statista. Prevalence of contraceptive use among women of reproductive age (15-49 years) in Europe in 2019, by method and region. Available from: https://www.statista.com/statistics/1268282/contraceptive-methods-of-women-in-europe-by-region/ [Accessed January 2023]. 13. GOV.UK. First progestogen-only contraceptive pills to be available to purchase from pharmacies. Available from: https://www.gov.uk/government/news/first-progesterone-only-contraceptive-pills-to-be-available-to-purchase-from-pharmacies [Accessed January 2023]. 14. Hall R. Contraceptive ‘mini pills’ to be offered over the counter in UK. Available from: https://www.theguardian.com/society/2021/jul/08/contraceptive-pill-will-be-available-over-the-counter-for-the-first-time [Accessed January 2023]. 15. Reuters. FDA to review first ever over-the-counter birth control pill. https://www.reuters.com/business/healthcare-pharmaceuticals/perrigo-unit-submits-approval-application-fda-otc-birth-control-pill-2022-07-11/ [Accessed January 2023]. 16. FPA.org.uk. Survey finds worrying gaps in GP contraceptive provision. Available from: https://www.fpa.org.uk/survey-finds-worrying-gaps-in-gp-contraceptive-provision/ [Accessed January 2023]. 17. Mihalia S. Understanding the contraception crisis. Available from: https://www.femtechworld.co.uk/features/understanding-the-contraception-crisis/ [Accessed January 2023]. 18. Blair JA, McGee H, Bhatta S, et al. Hypothalamic-pituitary-gondal axis involvement in learning and memory and Alzheimer’s disease: more than “just” estrogen. Frontiers in Endocrinology; 2015 March. Available from: doi: 10.3389/fendo.2015.00045. 19. Barbieri RL. The endocrinology of the menstrual cycle. Methods in Molecular Biology, vol 1154. Humana Press, New York, NY. Available from: /doi.org/10.1007/978-1-4939-0659-8_7. 20. Casteel CO and Singh G. Physiology, Gonadotropin-Releasing Hormone. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from:https://www.ncbi.nlm.nih.gov/books/NBK558992/#:~:text=GnRH%20secretion%20and%20pulsatility%3A&text=In%20women%2C%20the%20frequency%20of,hours%20in%20the%20secretory%20phase. 21. Perret RM and McArdle CA. Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network. Front. Endocrinol., 20 November 2013 Sec. Pituitary Endocrinology. Available from: doi.org/10.3389/fendo.2013.00180. 22. Hutchens EG, Ramsey KA, Howard LC, et al. Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 h in estradiol‐pretreated women. Physiol Rep. 2016 Aug; 4(16): e12891. Available from doi: 10.14814/phy2.12891. 23. Cleveland Clinic. Luteinizing Hormone. Available from: https://my.clevelandclinic.org/health/body/22255-luteinizing-hormone [Accessed January 2023]. 24. Shaw ND, Histed SN, Srouji SS, et al. Estrogen Negative Feedback on Gonadotropin Secretion: Evidence for a Direct Pituitary Effect in Women. J Clin Endocrinol Metab. 2010 Apr; 95(4): 1955–1961. Available from: doi: 10.1210/jc.2009-2108. 25. Bosch E, Alviggi C, Lispi, M, et al. Reduced FSH and LH action: implications for medically assisted reproduction. Human Reproduction, Volume 36, Issue 6, June 2021. Available from: doi.org/10.1093/humrep/deab065. 26. John Hopkins Medicine. Hormones During Pregnancy. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/staying-healthy-during-pregnancy/hormones-during-pregnancy [Accessed January 2023]. 27. Sitruk-Ware R. New progestogens: a review of their effects in perimenopausal and postmenopausal women. 2004;21(13):865-83. Available from: doi: 10.2165/00002512-200421130-00004. 28. Stacey D. 8 Types of Progestin in Combination Birth Control Pills. Available from: https://www.verywellhealth.com/different-progestin-types-906936 [Accessed January 2023]. 29. Healthline. Your Guide to Anti-Androgens. Available from: https://www.healthline.com/health/anti-androgen#what-are-they/ [Accessed January 2023]. 30. Kent C. The Future Is Non-Hormonal: Contraceptive Market Crawls Into The 21st Century. Available from: https://invivo.pharmaintelligence.informa.com/IV146782/The-Future-Is-Non-Hormonal-Contraceptive-Market-Crawls-Into-The-21st-Century?vid=Pharma [Accessed January 2023]. 31. Onyx Health. Women’s Healthcare: Where is the woman’s voice? https://onyxhealth.com/womens-healthcare/ [Accessed January 2023].

 

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