Edited by Lauren Dayes
While women’s health has historically been a neglected area of research, there has been a societal push in recent years to increase awareness and understanding of many common conditions in this field. One area of consideration is Polycystic Ovary Syndrome (PCOS). This condition is one of the most common endocrine disorders affecting reproductive aged women and is primarily characterized by ovulatory dysfunction (oligo- or amenorrhea) and excess androgen production (hyperandrogenism). Research has suggested that the etiology of PCOS can be tied to interactions between genetic and environmental factors, however a specific cause is still unknown.
PCOS has a complex, heterogeneous pathophysiology including genetic, inflammatory and metabolic components.
Disrupted GnRH Secretion
PCOS disrupts the hypothalamic-pituitary-ovarian (HPO) axis, with a higher frequency of gonadotropin-releasing hormone (GnRH) release leading to increased frequency of luteinizing hormone (LH) release and unchanged follicle-stimulating hormone (FSH) release, thus resulting in an elevated LH/FSH ratio. This hormonal imbalance results in impaired folliculogenesis leading to anovulation and excess ovarian androgen production.
Insulin contributes to hyperandrogenism in PCOS by indirectly lowering sex hormone-binding globulin (SHBG) and acting alone or with LH to increase androgen production in ovarian theca cells. The combination of increased androgens and decreased SHBG levels correlates with insulin resistance.
Excess Androgen Production
Overexpression of CYP--C17 enzyme present in ovarian theca cells has been shown in PCOS. This dysregulation leads to greater efficiency in conversion of androstenedione to testosterone.
Many genes and their encoded proteins have been suggested to form the genetic basis of PCOS. Two examples are Anti-Müllerian hormone (AMH) and Glucokinase regulatory protein (GCKR). However, the exact mechanisms involved, and their clinical relevance, are not well-understood.
It is postulated that pro-inflammatory cytokines as well as inflammatory marker C-reactive protein (CRP) are involved in the pathogenesis of PCOS. Inflammation associated with PCOS is linked to risk of obesity, cardiovascular disease, and Type 2 diabetes mellitus.
Patients with PCOS may have all or only some of the following symptoms:
Signs of hyperandrogenism (hirsutism, acne, alopecia)
Anovulation or oligo-ovulation
Associated metabolic features (including clinical manifestations of insulin resistance)
Psychological challenges (depressive symptoms)
Long term complications of PCOS include infertility, endometrial hyperplasia, endometrial cancer, as well as metabolic issues such as diabetes and cardiovascular disease.
Diagnosis of PCOS can be challenging due to the variability of symptom presentations as well as lack of consensus on precise diagnostic criteria. The Rotterdam guidelines are the most widely used diagnostic criteria. According to these guidelines, diagnosis of PCOS is made when a patient has at least two of:
Hyperandrogenism or hyperandrogenemia
Oligo-ovulation or anovulation
Polycystic ovaries (by ultrasound)
Regardless of the criteria used, exclusion of other associated disorders with similar clinical presentation such as thyroid dysfunction, hyperprolactinemia or congenital adrenal hyperplasia should be investigated.
The treatment approach for PCOS should always follow an individualized plan based on the patient’s goals and current symptoms. This plan may change over time depending on the patient’s specific needs (i.e., gender-affirming therapy, family planning, etc.).
For women who are obese or overweight, a weight loss goal of 5 to 10% is recommended in most guidelines to improve hyperandrogenism and insulin resistance. Some alternative strategies such as Orlistat, GLP-1 agonists, or bariatric surgery may be considered in some patients. However, there is a lack of long-term studies focused on clinical outcomes (beyond just weight loss) in this population. Recognize that weight loss may not be a primary goal for the patient, and support lifestyle changes for general health.
Diet recommendations are similar to those for the general population. Insufficient evidence exists to support recommendation of a specific diet over another, however caloric restriction in general has shown beneficial for women with PCOS.
Similar to diet, evidence is lacking in this population to recommend specific type and intensity of exercise. However, incorporating regular physical activity is recommended (150 minutes per week of moderate intensity physical activity) to improve cardiovascular and metabolic risk factors.
Select pharmacologic therapies based on target symptoms.
PCOS is an incredibly common condition with a complex pathophysiology and multiple off-label treatment options. It is important for practitioners to recognize the burden experienced by women with PCOS and create treatment plans tailored to a patient’s individual needs. Overall, it is crucial for health care providers to increase their awareness and understanding of PCOS to support women and improve their quality of life.
Bartelme KM. Polycystic Ovary Syndrome. In: O’Connell MB, Smith JA, eds. Women’s Health Across the Lifespan. 2nd ed. McGraw-Hill; 2019;chap 11. Accessed June 12, 2022. https://accesspharmacy-mhmedical-com.proxy.lib.uwaterloo.ca/content.aspx?bookid=2575§ionid=213570437
Gnanadass SA, Prabhu YD, Gopalakrishnan AV. Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update. Arch Gynecol Obstet. 2021;303:631–643. https://doi.org/10.1007/s00404-020-05951-2
Havelock J. Polycystic ovary syndrome. B C Med J. 2018;60(4):210–216. https://bcmj.org/articles/polycystic-ovary-syndrome
Maple Leaf Medical Centre. PCOS – polycystic ovary syndrome. Published September 19, 2019. Accessed June 12, 2022. https://mapleleafmedical.com.au/blog/2019/9/21/pcos-polycystic-ovary-syndrome
Mayo Clinic. Polycystic ovary syndrome (PCOS). Accessed June 12, 2022. https://www.mayoclinic.org/diseases-conditions/pcos/symptoms-causes/syc-20353439
Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol. 2018;182:27–36. doi:10.1016/j.jsbmb.2018.04.008
Shaw N, Rosenfield RL. Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents. In: Post T, ed. UpToDate. UpToDate; 2022. Accessed June 11, 2022. www.uptodate.com
Saydam BO, Yildiz BO. Weight management strategies for patients with PCOS: current perspectives. Expert Rev Endocrinol Metab. 2021;16(2):49–62. https://doi.org/10.1080/17446651.2021.1896966
Shaw N, Rosenfield RL. Diagnostic evaluation of polycystic ovary syndrome in adolescents. In: Post T, ed. UpToDate. UpToDate; 2022. Accessed June 11, 2022. www.uptodate.com
Shaw N, Rosenfield RL. Etiology and pathophysiology of polycystic ovary syndrome in adolescents In: Post T, ed. UpToDate. UpToDate; 2022. Accessed June 11, 2022. www.uptodate.com