Written by Lindley Wells; Select sections of article written by and article reviewed by Dr. Bojana Jankovic Weatherly.
Polycystic ovarian syndrome (PCOS) is a common condition among women, affecting 6-12% (about 5 million women)[i] of women of reproductive age. PCOS is the most likely cause of anovulatory infertility and was previously diagnosed solely on the presentation of polycystic ovaries. As a result, PCOS has often been viewed or treated as a gynecologic condition, however it is now being better understood as a condition that involves the endocrine system and is both a gynecologic and metabolic condition. Due to the multifactorial nature of PCOS, in recent years there has been discussion around renaming the syndrome to, metabolic reproductive syndrome, estrogenic ovulatory dysfunction, or functional female hyperandrogenism.[ii]
Diagnostic Criteria
PCOS on average takes one year to properly diagnose and can be costly, time intensive and often involves working with multiple medical providers to get a formal diagnosis.[iii] Women with this condition often present differently and have a wide variety of symptoms which also adds a layer to the complexity to the diagnosis of PCOS. Diagnosis involves both blood testing as well as pelvic and/or abdominal ultrasound. Currently, diagnosis is most often based on the modified 2003 Rotterdam criteria. To be formally diagnosed with PCOS, an individual needs to present with at least two of the three categories below:[iv]
- Hyperandrogenism: it can be biochemical (elevated total testosterone or free testosterone; elevated DHEA-S and androstenedione can be considered) or based on clinical features such as hirsutism (excess facial or body hair) or acne
- Polycystic ovaries (20 or more follicles per ovary and an ovarian volume of 10 cm3 or greater)
- Oligo-anovulation (menstrual cycles greater than 35 days apart of having fewer than 8 menstrual cycles in a year)
The Rotterdam criteria has identified four specific phenotypes of PCOS. While this makes diagnosis more complex, it also enables more bio individualized treatment and care. The four phenotypes of PCOS include:
- Frank/Classic PCOS: Anovulation, hyperandrogenism, polycystic ovaries
- Non-Polycystic Ovary: Anovulation, hyperandrogenism, normal ovaries
- Ovulatory PCOS: Normal menstrual cycles, hyperandrogenism, polycystic ovaries
- Normoandrogenic PCOS: Anovulation, normal androgens, polycystic ovaries
Symptoms
The symptoms associated with PCOS can vary greatly between individuals, therefore it is essential for individuals who suspect PCOS to share any obvious symptoms with their medical providers. In turn it is important for medical providers to assess the entire clinical picture of the patient to ensure a potential PCOS diagnosis is not overlooked.
The most common symptoms associated with PCOS include:[v]
- Infertility
- Irregular menstrual cycles (missed cycles, no cycles, longer or shorter cycles)
- Acne
- Hirsutism (excess hair growth, often located around mouth and chin)
- Male pattern baldness
- Weight gain
- Acanthosis nigricans (patches of skin that become thicker and darker, generally located on neck, armpits, and groin)
- Enlarged or polycystic ovaries
- Mental health disorders (women with PCOS are at increased odds of depressive symptoms)[vi]
Pathophysiology
In healthy ovulating females, gonadotrophin releasing hormone (GnRH) is secreted by the hypothalamus (a region of the brain) which communicates with the pituitary gland (small gland at the base of the brain) which triggers the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH).[vii] These hormones then communicate with the ovaries and together stimulate hormone production, the normal growth of follicles in the ovaries, and ultimately ovulation.
Individuals with PCOS have an increased GnRH pulse frequency which leads to increased levels of LH and lower levels of FSH.[viii] When the ratio of LH:FSH is imbalanced this leads to excess androgen production which will continue to increase and can ultimately lead to the suppression of FSH. When FSH is suppressed, the follicles in the ovaries are growing but not to the point of maturity and therefore ovulation is not taking place or is very irregular.[ix] It is also common in women with PCOS to have very low progesterone which also fosters an environment for increased GnRH secretion and the cycle will continue to repeat itself in this hormonally imbalanced state. Additionally, PCOS is commonly associated with insulin resistance or hyperinsulinemia, which leads to increased androgen production, decreases the amount of circulating sex hormone binding globulin (SHBG) and can also lead to abnormal glucose and lipid levels. [x]
There is still much understanding and research to be done to best understand the pathophysiology of PCOS. It is suspected that some of the following factors play a role in the development of PCOS.[xi]
- Being of Hispanic or Latina descent (have higher prevalence of hyperandrogenism, insulin resistance, hypertension and hyperglycemia)[xii]
- Obesity
- Hyperinsulinemia
- Anovulation
- Having a first degree relative who had PCOS
- Increased concentrations of testosterone during pregnancy and in turn increased in utero exposure[xiii]
- Follicular stress in the endoplasmic reticulum environment
- Changes in the gut microbiome
- Inflammation
- Impaired methylation
- Gene expression/SNPs (single nucleotide polymorphisms) there are certain groups of genes that are more commonly implicated in those with PCOS [xiv]
Lab Abnormalities
Looking at blood test results in addition to getting an ultrasound can help to paint a clearer picture if PCOS is at play. Some of the most helpful labs to get may include:
- Insulin (fasting)
- Glucose (fasting)
- Oral glucose tolerance test with insulin
- Hemoglobin A1c
- DHEA-S
- SHBG
- LH
- FSH
- Estradiol
- Progesterone
- Free and Total Testosterone
- Lipid panel
- Thyroid panel
- Cortisol (AM or 24 hour)
- Vitamin D
- Inflammatory markers (Hs-CRP and homocysteine)
If you or someone you know suspects they may have PCOS we encourage you to reach out to a qualified healthcare provider to discuss your symptoms and potential treatment. In our clinic, we provide the diagnostic workup for PCOS and we work with individuals with PCOS to provide an integrative treatment approach incorporating personalized therapeutic approaches to manage your individual symptoms.
[i] Centers for Disease Control and Prevention. (2022, December 30). PCOS (polycystic ovary syndrome) and diabetes. PCOS (Polycystic Ovary Syndrome) and Diabetes. https://www.cdc.gov/diabetes/basics/pcos.html
[ii] Azziz R. (2014). Polycystic ovary syndrome: what’s in a name?. The Journal of clinical endocrinology and metabolism, 99(4), 1142–1145. https://doi.org/10.1210/jc.2013-3996
[iii] Rasquin, L. I., Anastasopoulou, C., & Mayrin, J. V. (2022). Polycystic Ovarian Disease. In StatPearls. StatPearls Publishing.
[iv] Christ, J. P., & Cedars, M. I. (2023). Current Guidelines for Diagnosing PCOS. Diagnostics (Basel, Switzerland), 13(6), 1113. https://doi.org/10.3390/diagnostics13061113
[v] Ndefo, U. A., Eaton, A., & Green, M. R. (2013). Polycystic ovary syndrome: a review of treatment options with a focus on pharmacological approaches. P & T : a peer-reviewed journal for formulary management, 38(6), 336–355.
[vi] Cooney, L. G., Lee, I., Sammel, M. D., & Dokras, A. (2017). High prevalence of moderate and severe depressive and anxiety symptoms in polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction (Oxford, England), 32(5), 1075–1091. https://doi.org/10.1093/humrep/dex044
[vii] Raju, G. A., Chavan, R., Deenadayal, M., Gunasheela, D., Gutgutia, R., Haripriya, G., Govindarajan, M., Patel, N. H., & Patki, A. S. (2013). Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation. Journal of human reproductive sciences, 6(4), 227–234. https://doi.org/10.4103/0974-1208.126285
[viii] Abbara, A., & Dhillo, W. S. (2021). Targeting Elevated GnRH Pulsatility to Treat Polycystic Ovary Syndrome. The Journal of clinical endocrinology and metabolism, 106(10), e4275–e4277. https://doi.org/10.1210/clinem/dgab422
[ix] Morshed, M., Banu, H., Akhtar, N., Sultana, T., Begum, A., Zamilla, M., Tuqan, S., Shah, S., Hossain, A., Afrine, S., Rashid, E., Jahan, I., & Hasanat, M. (2021). Luteinizing Hormone to Follicle-Stimulating Hormone Ratio Significantly Correlates With Androgen Level and Manifestations Are More Frequent With Hyperandrogenemia in Women With Polycystic Ovary Syndrome. Journal Of Endocrinology And Metabolism, 11(1), 14-21.
[x] Purwar, A., & Nagpure, S. (2022). Insulin Resistance in Polycystic Ovarian Syndrome. Cureus, 14(10), e30351. https://doi.org/10.7759/cureus.30351
[xi] Harada M. (2022). Pathophysiology of polycystic ovary syndrome revisited: Current understanding and perspectives regarding future research. Reproductive medicine and biology, 21(1), e12487. https://doi.org/10.1002/rmb2.12487
[xii] Engmann, L., Jin, S., Sun, F., Legro, R. S., Polotsky, A. J., Hansen, K. R., Coutifaris, C., Diamond, M. P., Eisenberg, E., Zhang, H., Santoro, N., & Reproductive Medicine Network (2017). Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype. American journal of obstetrics and gynecology, 216(5), 493.e1–493.e13. https://doi.org/10.1016/j.ajog.2017.01.003
[xiii] Carrasco, A., Recabarren, M. P., Rojas-García, P. P., Gutiérrez, M., Morales, K., Sir-Petermann, T., & Recabarren, S. E. (2020). Prenatal Testosterone Exposure Disrupts Insulin Secretion And Promotes Insulin Resistance. Scientific reports, 10(1), 404. https://doi.org/10.1038/s41598-019-57197-x
[xiv] Khan, M. J., Ullah, A., & Basit, S. (2019). Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives. The application of clinical genetics, 12, 249–260. https://doi.org/10.2147/TACG.S200341