Birth Control Pills for PCOS

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Birth Control Pills for PCOS

Polycystic ovarian syndrome (PCOS) is a hormonal condition affecting around 1 in 10 women worldwide, and is usually characterised by irregular periods, increased testosterone levels and many small follicles in the ovaries.

It is not currently known what truly causes PCOS, but it is thought that family history, genetics, hormones and lifestyle are all influencing factors.

Due to a hormonal imbalance in women with PCOS, symptoms often include extra body hair, acne, weight gain, and infertility.

Birth control pills are a first-line treatment option for women who have been diagnosed with PCOS, and who do not wish to get pregnant.1

Birth control pills inhibit ovulation and the subsequent overproduction of androgens from the ovaries which occurs in women with PCOS. This in turn helps reduce the severity of symptoms.

Birth Control Options for PCOS

There are two main types of birth control pills; the combined oral contraceptive pill (COCP), which contains the hormones progesterone and oestrogen, and the progesterone-only (or progestin-only) contraceptive pill (POP), which is also known as the mini pill.

Commonly prescribed COCP formulations for PCOS include:

  • Ethinylestradiol/Levonorgestrel (e.g. Alesse, Aviane, Microgynon, Nordette, Seasonique, Vienva)
  • Ethinylestradiol/Desogestrel (e.g. Enskyce, Marvelon, Micrette, Reclipsen)
  • Ethinylestradiol/Drospirenone (e.g. Yasmin, Yaz, Loryna)
  • Ethinylestradiol/Cyproterone acetate (e.g. Diane, Estelle)
  • Ethinylestradiol/Norethindrone (e.g. Loestrin, Balzvia, Junel)
  • Ethinylestradiol/Norgestimate (e.g. Sprintec, Ortho Tri-Cyclen)

Commonly prescribed progesterone-only pill formulations for PCOS include:

  • Dienogest
  • Desorgestrel (Cerazette)
  • Drospirenone (Slynd)

Current COCPs mostly contain ethinylestradiol, which is a modified synthetic form of estradiol (a hormone made in the ovaries), although some contain estradiol valerate (a natural form of the hormone estradiol). Combinations using lower doses of ethinylestradiol or higher doses of estradiol valerate were developed to reduce the adverse side effects associated with liver response.

Interestingly, there are many forms of progestins available as components of COCPs. These are usually catergorized as first, second, third or fourth generations according to the time of development. First and second generation progestins were chemically related to testosterone. However, over the last 30 years, new progestins have been developed to reduce the unwanted effects on androgens (and glucocorticoids).

First and second generation progestins, such as norethindrone and norgestrel respectively, have androgenic properties which increase metabolic side effects. However, third generation progestins, such as norgestimate, have minimal androgenic properties which decreases the metabolic side effects.2 Fourth generation progestins not only decrease metabolic side effects, but they are also anti-androgenic (suppresses androgen production and binding).3

In theory, COCPs are more effective than POPs for treating PCOS because they address a broader range of hormonal imbalances associated with the condition. COCPs contain both oestrogen and progesterone, which work together to suppress androgen production (e.g. testosterone), and therefore reduce androgen-related symptoms such as acne and excess body/facial hair. The oestrogen in COCPs increases the production of a protein called sex hormone-binding globulin (SHBG), which further lowers free androgen levels in the blood. Additionally, COCPs are considered to be more effective at regulating and managing irregular periods, which are often a symptom of PCOS. There is also research to suggest that some COCPs can improve insulin sensitivity, which is important when treating PCOS, as insulin resistance is linked with PCOS.4,5 In contrast, POPs, which only contain progesterone, are less effective at controlling androgen levels and regulating the menstrual cycle, so may not be as effective at reducing symptoms associated with PCOS.

However, there is a lack of definitive proof surrounding this. It is important to consider that PCOS affects women in different ways, with differing symptoms and severities. Therefore, what may work for one woman may not work for another, and COCPs may not necessarily be the right treatment. In addition, there is a lack of large clinical trials that directly compare COCPs and POPs in treating PCOS, so there is no clear and definitive evidence that COCPs are more beneficial and in which cases. It is also important to consider the potential side effects and risks of each treatment, as COCPs come with more risks such as blood clots. Therefore, it’s important to always discuss treatment options for PCOS with a healthcare professional.

COCPs with Second-Generation Progestins

COCPs with second-generation progestins such as levonorgestrel have a lower risk of VTEs and cardiovascular events when compared to third and fourth-generation progestins.

However, second-generation progestins tend to have higher androgenic activity compared to later generations, which may lessen its effectiveness on symptoms such as acne, oily skin, facial/body hair growth, bloating, weight gain and mood changes.

COCPs with Third-Generation Progestins

COCPs with third-generation progestins have low androgenic activity, making them more suited to women with concerns about acne, oily skin or excess body hair as they are less likely to aid acne or hair growth than second-generation progestins.5

COCPs are also less likely to cause weight gain or water retention compared to first and second-generation progestins due to the lower androgenic activity. However, there is a higher VTE risk than first and second generation progestins.

COCPs with Fourth-Generation Progestins

COCPs with fourth-generation progestins differ from other generations of progestins as they have anti-androgenic effects, and are thereforeunlikely to cause side effects such as acne, excessive hair growth and weight gain.

In addition, drospirenone (derivative of spironolactone) has diuretic effects, which can reduce water retention, bloating and blood pressure.6 However, COCPs containing fourth-generation progestins are associated with a slightly higher risk of blood clots (VTEs) compared to second and third-generation progestins.

The effectiveness of fourth-generation progestins can also vary significantly between each other. For example, drospirenone has been found have a greater effect on serum SHBG concentrations and total testosterone concentrations compared to dienogest.7

Best Birth Control Pill for PCOS

Determining the best birth control pill for managing PCOS is challenging, as effectiveness can vary based on factors such as an individual’s symptoms, age, lifestyle and existing health conditions.

For women with PCOS and hirsutism, research suggests that ethinylestradiol and cyproterone acetate has a better effect compared to other COCPs. However, it has also been associated with more side effects such as VTE. Therefore, COCPs containing newer estrogens and other anti-androgenic progestins (e.g. drospirenone) may be more beneficial.8

For adolescents with PCOS, it is not recommended to prescribe COCPs as alternative treatments such as a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET) leads to healthier and better insulin-sensitive condition, with a more normal post-treatment ovulation rate than COCPs.9 Studies also show that in adolescents with PCOS, follistatin levels rise significantly after six months on birth control pills, which is associated with worsening insulin resistance and liver fat.10

For women diagnosed with PCOS who are concerned about weight gain, this should be discussed when considering treatment using birth control pills. Although no difference in waist circumference has been identified between COCPs, body fat mass and lipid accumulation product has been found to increase with the use of the pill compared to no/other treatments, especially COCPs containing CPA.11,12 While laboratory studies show that unbound estrogen can promote insulin resistance, so the optimal dose of ethinylestradiol may vary for each woman.13,14

Research suggests that COCPs with fourth-generation progestins may also improve metabolism, as LDL levels have been found to decrease, and HDL levels increase compared to previous generation COCP treatment.5 Additionally, newer natural oestrogens also do not appear to negatively affect carbohydrate metabolism and have a beneficial effect on lipid metabolism compared to ethinylestradiol.15 This is one probable explanation why BMI was lower in women with PCOS after treatment with third and fourth-generation COCPs (specifically desogestrel and drospirenone).16 However, all of these findings were from low-quality trials, and require further investigation.

Side Effects of Birth Control Pills

Although there are numerous potential benefits to treating PCOS with birth control pills, and birth control pills generally improve PCOS symptoms, it is also important to consider the possible side effects and risks to this treatment option.

In some cases, birth control pills can cause weight gain in for women with PCOS who are already predisposed to insulin resistance or metabolic challenges. Therefore, it is important to monitor closely and continue diet and lifestyle modification to manage this risk.

Progestin-only pills and/or COCPs containing second-generation progestins can potentially worsen insulin resistance in women with PCOS, due to increased androgenic activity. However, COCPs containing fourth-generation progestins should have a minimal negative impacts on insulin sensitivity and androgen levels.

Studies suggest that there is an increased risk of blood clots when using birth control pills, especially COCPs containing fourth-generation progestins.17 Although this risk remains low in most women, it is increased by factors such as smoking, prolonged immobilisation, age (>35 years), obesity and family history.18 Therefore, it is a risk that should be considered and discussed with a healthcare professional before starting treatment.

In some cases, women may experience an initial worsening of acne when starting birth control pills due to the body adjusting to hormonal changes. However, this side effect is usually temporary and acne typically improves over time as androgen levels are regulated.

Alternatives to Birth Control for PCOS

The alternative treatments to birth control for PCOS typically fall into two categories; anti androgens and anti-diabetics.

Anti-androgen medication such as spironolactone, flutamide, bicalutamide and finasteride is often used to treat PCOS where birth control is poorly tolerated or where there has been a sub-optimal response after a minimum of 6 months.19

Anti-diabetic medication such as metformin, pioglitazone, sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide-1 analogs is often used in cases of PCOS and severe metabolic dysfunction.

There is also research to suggest that lifestyle and dietary changes can help to manage insulin resistance, which is commonly associated with PCOS.20 For example, focusing on a diet consisting of non-starchy vegetables and foods with fibre and healthy fats, and reducing the amount of processed foods consumer can help to reduce spikes in glucose levels, and help to manage insulin resistance. However, any changes in lifestyle and diet should be discussed with a healthcare professional.

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Final Tip from Fertility SCIENCE

PCOS is a complex condition that affects women differently, and the treatment options, including birth control pills, must be tailored to the individual.

Currently, COCPs are often the preferred choice due to their direct effects on the ovaries, reducing androgen-related symptoms, improving insulin sensitivity, and regulating periods. The associated risks, especially with COCPs containing fourth-generation progestins, should be carefully considered as there is a risk of blood clots.

Even though birth control pills are widely used, and can be an effective treatment for managing PCOS, no single treatment is perfect for all women. Each option carries potential benefits and risks, and effectiveness can vary greatly depending on the individual.

In the future, the growth of personalised medicine and alternative therapies will offer more tailored, and potentially effective, solutions for symptom control and overall quality of life for women with PCOS.21

Read More:

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References

  1. Teede H J, et al. (2018). Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. https://www.fertstert.org/article/S0015-0282(18)30400-X/fulltext ↩︎
  2. Phillips A, et al. (1992). Preclinical evaluation of norgestimate, a progestin with minimal androgenic activity. https://www.ajog.org/article/S0002-9378(12)90410-X/abstract ↩︎
  3. Oguz S H and Yildiz B O, (2021). An Update on Contraception in Polycystic Ovary Syndrome. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090477/ ↩︎
  4. Cagnacci A, et al. (2003). Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel. https://academic.oup.com/jcem/article/88/8/3621/2845304 ↩︎
  5. Forslund M, et al. (2023). Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis. https://academic.oup.com/ejendo/article/189/1/S1/7223903 ↩︎
  6. Krattenmacher R, (2000). Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. https://www.contraceptionjournal.org/article/S0010-7824(00)00133-5/abstract ↩︎
  7. Morgante G, et al. (2020). Evaluation of different antiandrogenic progestins on clinical and biochemical variables in polycystic ovary syndrome. https://www.tandfonline.com/doi/full/10.1080/13625187.2020.1736546 ↩︎
  8. Heikinheimo O, et al. (2022). Systemic hormonal contraception and risk of venous thromboembolism. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.14384 ↩︎
  9. Ibáñez L, et al. (2020). Toward a Treatment Normalizing Ovulation Rate in Adolescent Girls With Polycystic Ovary Syndrome. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182125/ ↩︎
  10. Díaz M, et al. (2023). Circulating follistatin concentrations in adolescent PCOS: Divergent effects of randomized treatments. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1125569/full ↩︎
  11. de Medeiros S F, et al. (2024). Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials. https://link.springer.com/article/10.1007/s00404-024-07637-5 ↩︎
  12. Amiri M, et al. (2021). Effects of oral contraceptives on serum concentrations of adipokines and adiposity indices of women with polycystic ovary syndrome: a randomized controlled trial. https://link.springer.com/article/10.1007/s40618-020-01349-8 ↩︎
  13. Root-Bernstein R, et al. (2014). Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2014.00118/full ↩︎
  14. Dasgupta S, et al. (2023). Randomized control trial to compare effects of ultra-low dose (Ethinylestradiol 20 μg or 15 μg) with low dose (Ethinylestradiol 30 μg) hormonal pills on lipid discordance in non-obese PCOS women. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663401/ ↩︎
  15. Jensen J T, (2010). Evaluation of a new estradiol oral contraceptive: estradiol valerate and dienogest. https://www.tandfonline.com/doi/full/10.1517/14656561003724713 ↩︎
  16. Amiri M, et al. (2020). A comparison of the effects of oral contraceptives on the clinical and biochemical manifestations of polycystic ovary syndrome: a crossover randomized controlled trial. https://academic.oup.com/humrep/article/35/1/175/5698584 ↩︎
  17. Practice Committee of the American Society for Reproductive Medicine, (2017). Combined hormonal contraception and the risk of venous thromboembolism: a guideline. https://www.fertstert.org/article/S0015-0282(16)62847-9/fulltext ↩︎
  18. Yildiz B O, (2015). Approach to the Patient: Contraception in Women With Polycystic Ovary Syndrome. https://academic.oup.com/jcem/article/100/3/794/2838953 ↩︎
  19. Alesi S, et al. (2023). Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00339-5/fulltext ↩︎
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  21. Calcagno M, et al. (2024). A bitter pill to swallow: adjustments to oral contraceptive pill use in polycystic ovary syndrome. https://www.tandfonline.com/doi/full/10.1080/14656566.2024.2371977 ↩︎

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