What causes PCOS?

Research has shown that genetic and environmental factors contribute to the development of PCOS, but its exact cause remains unknown.

The symptoms of PCOS tend to run in families, so genetics have long been a focus of PCOS research.

Recent research suggests that there are 19 possible changes, or variants, in genes that can increase a person’s risk of developing PCOS.1 These variants could explain why the features and symptoms of PCOS are so different from one person to the next.

Although PCOS usually is considered to be a condition related to the ovaries, researchers found these genetic variants in both females and males. In fact, males with these genetic variants experienced cardiac and metabolic symptoms similar to those experienced by females with PCOS.2

Researchers identified subtypes of PCOS based on these genetic variants. One group of NICHD-funded researchers identified two subtypes: reproductive, which has higher reproductive hormone levels; and metabolic, which had higher Body Mass Index (BMI), insulin, and glucose levels.3

Other NICHD-funded work found four subtypes,4 which they called “clusters.” The genetic clusters correlated with distinct sets of symptoms: the obesity/insulin resistance cluster had higher BMI; the hormonal/menstrual cycle changes cluster had increased age at first menstruation; the blood markers/inflammation cluster had decreased blood markers, including platelets; and the metabolic changes cluster had high triglycerides and metabolic hormone levels.

Research conducted in animal models suggests that exposure to increased levels of androgen hormones in the womb may also increase the likelihood of PCOS in offspring.5,6

What causes the symptoms of PCOS?

Many symptoms of PCOS result from an imbalance of hormones, chemicals that control functions in the body.

The ovaries, testes, and adrenal glands produce reproductive hormones that are involved in regulating reproductive processes and health. One reproductive hormone, called estrogen, plays a role in regulating the menstrual cycle (in females), breast health, bone development, and other important functions.7 Another such hormone, called androgen, contributes to hair growth, muscle development, sperm production (in males), and voice deepening.8

People with PCOS have higher levels of androgens and may have lower levels of estrogen. High levels of androgens can interfere with signals from the brain that control ovulation, making it occur sporadically or not at all. High androgen levels can also cause ovarian follicles—small, fluid-filled sacs where eggs grow and mature—to stop developing and clump together.9,10 Androgen levels also play a role in increased hair growth and acne.10

Many people with PCOS also have problems with another hormone called insulin, which helps move sugar (also called glucose) from the bloodstream into cells to use as energy. When cells don't respond normally to insulin, the level of sugar in the blood rises. High insulin levels are linked to a skin condition called acanthosis nigricans, which results in thickened dark, velvety patches of skin.10

In addition, the body produces more and more insulin to get glucose into the cells. To balance out the high levels of insulin, the body makes more androgens,9 which contribute to symptoms of PCOS. It is difficult to disrupt this cycle, which is why treating PCOS can be challenging.

Citations

  1. Welt C. K. (2021). Genetics of polycystic ovary syndrome: What is new? Endocrinology and Metabolism Clinics of North America, 50(1), 71–82. PMID: 33518187
  2. Zhu, J., Pujol-Gualdo, N., Wittemans, L. B. L., Lindgren, C. M., Laisk, T., Hirschhorn, J. N., & Chan, Y. M. (2022). Evidence from men for ovary-independent effects of genetic risk factors for polycystic ovary syndrome. The Journal of Clinical Endocrinology and Metabolism, 107(4), e1577–e1587. PMID: 34969092
  3. Dapas, M., & Dunaif, A. (2022). Deconstructing a syndrome: Genomic insights into PCOS causal mechanisms and classification. Endocrine Reviews, 43(6), 927–965. PMID: 35026001
  4. Stamou, M. I., Smith, K. T., Kim, H., Balasubramanian, R., Gray, K. J., & Udler, M. S. (2024). Polycystic ovary syndrome physiologic pathways implicated through clustering of genetic loci. The Journal of Clinical Endocrinology and Metabolism, 109(4), 968–977. PMID: 37967238
  5. Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G., & Azziz, R. (2011). Polycystic ovary syndrome: etiology, pathogenesis, and diagnosis. Nature Reviews: Endocrinology, 7(4), 219–231. PMID: 21263450
  6. Tata, B., Mimouni, N. E. H., Barbotin, A. L., Malone, S. A., Loyens, A., Pigny, P., Dewailly, D., Catteau-Jonard, S., Sundström-Poromaa, I., Piltonen, T. T., Dal Bello, F., Medana, C., Prevot, V., Clasadonte, J., & Giacobini, P. (2018). Elevated prenatal anti-Müllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nature Medicine, 24(6), 834–846. PMID: 29760445
  7. Delgado, B. J., & Lopez-Ojeda, W. (2023). Estrogen. In StatPearls. StatPearls Publishing. PMID: 30855848
  8. Nassar, G. N., & Leslie, S. W. (2023). Physiology, Testosterone. In StatPearls. StatPearls Publishing. PMID: 30252384
  9. Rodriguez Paris, V., & Bertoldo, M. J. (2019). The mechanism of androgen actions in PCOS etiology. Medical Sciences (Basel, Switzerland), 7(9), 89. PMID: 31466345
  10. American College of Obstetricians and Gynecologists. (2022) FAQs: Polycystic ovary syndrome (PCOS). Retrieved July 26, 2024, from https://www.acog.org/en/womens-health/faqs/polycystic-ovary-syndrome-pcos external link
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