polycystic ovary syndrome (PCOS) and combined oral contraceptive pill (COC)

Last edited 10/2021 and last reviewed 08/2022

Management of clinical manifestations of PCOS, such as menstrual irregularities and hyperandrogenism symptoms, includes lifestyle changes and combined hormonal
contraceptives (COCs)

• COCs contain oestrogen that exerts antiandrogenic properties by triggering the hepatic synthesis of sex hormone-binding globulin that reduces the free testosterone levels
• also the progestogen present in COCs and in progestogen-only contraceptives suppresses luteinizing hormone secretion
• also some types of progestogens directly antagonize the effects of androgens on their receptor and also reduce the activity of the 5 alpha reductase enzyme
• progestogen component vary in terms of composition and affinity to receptors of other steroid hormones (mineralocorticoids, glucocorticoids, androgens, and oestrogen)

Polycystic ovary syndrome (PCOS) is a complex condition with high risk for dyslipidemia, dysglycaemia, venous thromboembolism, cardiovascular disease and metabolic syndrome.

• because the combined oral contraceptive (COC) use has also been associated with impaired fasting glucose, insulin resistance and increased risk of
  thromboembolism disease, it is rationale to think that the combination of oral contraceptive and PCOS could make it worse or increase the risks (1)
• despite the complex pathophysiological mechanisms and multiple phenotypes of PCOS, combined oral contraceptives (COCs) are the first-line option for the treatment of all women with PCOS not seeking to become pregnant, and they exert many beneficial effects in these women (2,3,4)

A review showed (1):

• consistent beneficial effect of COCs, particularly for hyperandrogenemic PCOS patients
• benefit size of COC’s use by normoandrogenemic PCOS patients is uncertain and need more investigation
• effects of COC use on carbohydrate metabolism of women with PCOS are still unresolved since most studies are observational but the current results demonstrated that COCs do not make their levels worse and may improve insulin sensitivity
• impact of COCs on lipids of PCOS patients seems to be clearer and most preparations increase total cholesterol, high-density lipoprotein cholesterol and triglycerides
• in summary, it is important to balance the potential benefits and risks of the COCs individually before prescribing them for PCOS women

Thee Androgen Excess and PCOS Society

• has a protocol for the treatment of hirsutism in PCOS in which the COCs of choice are those containing progestogens with a greater antiandrogen potential, such as cyproterone, chlormadinone, and drospirenone (5)

However, PCOS is related to clinical and metabolic comorbidities that may limit the prescription of CHCs. Clinicians should be aware of risk factors, such as age, smoking, obesity, diabetes, systemic arterial hypertension, dyslipidemia, and a personal or family history, of a venous thromboembolic event or thrombophilia (4)

The combined oral contraceptive in PCOS and risk of dysglycaemia (6):

• in a study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCs had a reduced risk of dysglycemia across all BMI subgroups

Reference:

• de Medeiros SF. Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndromeReproductive Biology and Endocrinology (2017) 15:93 DOI 10.1186/s12958-017-0313-y
• Mendoza N, Simoncini T, Genazzani AD. Hormonal contraceptive choice for women with PCOS: a systematic review of randomized trials and observational studies. Gynecol Endocrinol. 2014;30:850-60.
• Korytkowski MT, Mokan M, Horwitz MJ, Berga SL. Metabolic effects of oral contraceptives in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1995;80:3327-34.
• Sanches de Melo A et al. Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits.Open Access Journal of Contraception 2017:8 13-23
• Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E.American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 1. Endocr Pract. 2015;21(11):1291-1300
• Kumarendran B et al. Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study. Diabetes Care 2021 Oct; dc210437.