Clinical Education Center
Polycystic Ovary Syndrome (PCOS)—Making Sense of a Misunderstood Condition
Polycystic Ovary Syndrome (PCOS)—Making Sense of a Misunderstood Condition
Polycystic ovary syndrome (PCOS) is a commonly misunderstood condition with a misleading name.
Dr. Andrea Dunaif, Charles F. Kettering Professor of Endocrinology and Metabolism, Northwestern University Feinberg School of Medicine, explains that the high-risk form of PCOS is a significant metabolic disorder, which is straightforward for any primary care provider to diagnose. She also reviews the background and rationale for renaming the condition.
Correcting a Common Misunderstanding
“PCOS is a very important metabolic disorder with long-term health consequences, especially increased risk for prediabetes and diabetes,” notes Dr. Dunaif. “Primary healthcare providers should be aware that the high-risk form is very easy to diagnose and does not require an ovarian ultrasound examination.
“There’s been a lot of miscommunication about PCOS being a complex condition due to differing opinions about definitions. However, the high-risk form is straightforward to diagnose with simple hormonal tests. Importantly, the diagnosis does not require an assessment of the ovarian morphology. The idea that ovarian ultrasonography was required for the diagnosis was quite daunting to non-obstetrician/gynecologists and has become a barrier to a diagnosis being made by primary care physicians.”
A Simple Diagnosis – Applying the NIH Criteria
Diagnosing PCOS is more straightforward than commonly understood, explains Dr. Dunaif. “In 1990, there was a conference sponsored by the National Institutes of Health (NIH) during which the first diagnostic criteria were developed,1 known as the NIH Criteria. These criteria were based on a survey of all conference participants, experts in the field, on what they thought were the key features of the condition. This meeting established two criteria: evidence of androgen excess, either clinical, which is usually hirsutism, or elevated circulating androgens in the blood, primarily total or free testosterone; and chronic anovulation, indicated by irregular menstrual cycles, usually prolonged and infrequent, i.e., less than 8 menses per year. The diagnosis required that other conditions that could present similarly to PCOS were excluded. These disorders include mild forms of inherited adrenal 21-hydroxylase deficiency, prolactin-secreting pituitary tumors, and hypothyroidism.
“Once these other conditions are excluded, one documents the hyperandrogenism by clinical examination and/or blood test. Combined with a history of infrequent menstrual cycles indicative of chronic anovulation, the NIH criteria for the diagnosis of PCOS are met. This diagnosis does not require an ovarian ultrasound, so any healthcare provider can perform the evaluation.”
PCOS – A Misnomer
“The name PCOS is actually a misnomer,” notes Dr. Dunaif, “because there are no cysts in the ovaries. What had been called cysts are really normal structures: the ovarian follicles. These follicles contain the maturing egg. Because of the hormonal imbalance, the maturation of these follicles is arrested when they are approximately 10 mm in size. There is also an increase in the number of ovarian follicles in polycystic ovaries for reasons that are poorly understood.
“At the time of the NIH conference in 1990, it was already known that the polycystic ovarian morphology was a non-specific finding. Twenty percent to thirty percent of young women with regular menses have polycystic ovarian changes. Some of these women may have subtle hormonal changes but many are completely hormonally normal with regular, ovulatory menstrual cycles.”
The Rotterdam Criteria
There was a conference in Rotterdam in 2003 during which the diagnostic criteria for PCOS were modified.1 The so-called Rotterdam Criteria, analogous to the NIH Criteria, were based on expert opinion and not a formal consensus process. Ovarian morphology assessed by ultrasound was added as a diagnostic criterion. Two of three of the following criteria were required for the diagnosis of PCOS: 1) hyperandrogenism, 2) chronic anovulation and 3) polycystic ovarian morphology. The Rotterdam Criteria added two new diagnostic categories to the NIH diagnostic category: 1) women with hyperandrogenism and polycystic ovarian morphology who have regular menstrual cycles and 2) women with irregular menstrual cycles and polycystic ovarian morphology but no hyperandrogenism.
“Implementing the Rotterdam Criteria is problematic for physicians who do not perform their own ovarian ultrasound examinations because of a lack of awareness outside the reproductive endocrinology community of the assessment of polycystic ovarian morphology,” notes Dr. Dunaif. “Standard pelvic ultrasound reports rarely provide the information needed to determine if the criteria for polycystic ovarian morphology, such as the number and size of ovarian follicles, are met. It is still possible to diagnose PCOS according to the NIH criteria without ovarian ultrasound but confusion about the need for ovarian ultrasound is a disincentive for primary care providers to evaluate women for PCOS. However, since the Rotterdam Criteria were established, there has been extensive research comparing the PCOS sub-groups. This research has led to the recognition that it’s the NIH sub-group that’s at high risk for prediabetes, diabetes and metabolic syndrome.”
2012 Evidence-based Methodology Workshop on PCOS
The NIH organized an evidence-based methodology workshop on PCOS in December 2012 during which all the evidence in the field was presented to an impartial panel of experts. In their Executive Summary, the expert panel concluded that the name PCOS was inaccurate and an impediment to progress in the field.2 The expert panel recommended that the name be changed to something that more accurately reflects the complex endocrine and metabolic features of the syndrome.
Identifying High-Risk Patients
“There is now general agreement that the NIH criteria identify the sub-group of affected women who are at highest metabolic risk,” notes Dr. Dunaif. “The prevalence of this group among pre-menopausal women is about 7%.3 These women have about a four-fold increased risk of getting type 2 diabetes, independent of obesity and other risk factors, such as oral contraceptive use.” 4-6
In the U.S., about 30% of women with the high-risk form of PCOS already have impaired glucose tolerance, also known as prediabetes, and about 10% already have type 2 diabetes. About 70% of obese women with PCOS have metabolic syndrome.5-6 These prevalence rates are well above the population prevalence rates for these conditions in young women.7
Women who meet NIH criteria for the diagnosis of PCOS should also be screened for diabetes and metabolic syndrome. “Screening for prediabetes and diabetes requires a two-hour post oral glucose tolerance test glucose level because the major abnormality in glucose homeostasis in PCOS is insulin resistance,” notes Dr. Dunaif. “Because of insulin resistance, glucose uptake after a glucose load is reduced in PCOS. Fasting glucose levels reflect glucose production by the liver, which remains relatively normal in young women with PCOS. Therefore, fasting glucose levels are frequently normal in women with PCOS who have impaired glucose tolerance and, even type 2 diabetes. Similarly, hemoglobin A1C levels can be in the normal range in women with PCOS who have impaired glucose tolerance. Therefore, hemoglobin A1C levels cannot be used to screen women with PCOS for prediabetes and type 2 diabetes.
“Unfortunately, there are no FDA-approved medications for the treatment of PCOS. Further, since we do not know the cause of PCOS, treatment remains symptomatic and determined by the major symptom profiles: hyperandrogenic symptoms such as hirsutism, metabolic issues, mainly obesity and prediabetes, irregular menstrual cycles or infertility.”
“Following the 2012 NIH conference proposing a name change for PCOS, there have been a number of suggestions in editorials about what the name should be,” concludes Dr. Dunaif. “A formal process that includes experts in the field as well as representatives from patient groups has been underway for approximately one year. The process includes international surveys of patients and healthcare providers regarding their attitudes toward the name. The majority felt that the name should be changed. However, the new name has not yet been finalized.”
1. Evidence-based Methodology Workshop on Polycystic Ovary Syndrome. Final Report. National Institutes of Health. https://prevention.nih.gov/docs/programs/pcos/FinalReport.pdf Accessed November 10, 2016.
2. Panel recommends changing name of common disorder in women. Press Release. National Institutes of Health. January 23, 2013 https://www.nih.gov/news-events/news-releases/panel-recommends-changing-name-common- disorder-women. Accessed November 10, 2016.
3. March WA, Moore VM, Willson KJ, Philips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544-51. doi:10.1093/humrep/dep399. Epub 2009 Nov 12
4. Elting MW, Korsen TJM, Bezemer PD, Schoemaker J. Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Hum. Reprod. 2001;16 (3): 556-560. doi:10.1093/humrep/16.3.556
5. Ehrmann, D.A., Barnes, R.B., Rosenfield, R.L. et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999; 22:141–146.
6. Legro, R.S., Kunselman, A.R., Dodson, W.C. et al. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J. Clin. Endocrinol. Metab. 1999; 84:165–169.
7. National Health and Nutrition Examination Survey. Centers for Disease Control and Prevention http://www.cdc.gov/nchs/nhanes/ Page last updated: February 24, 2016. Accessed November 10, 2016
Andrea Dunaif, M.D.
Charles F. Kettering Professor of
Endocrinology and Metabolism
Northwestern University Feinberg
School of Medicine