4 Polycystic Ovary Syndrome

Suggested citation:  Endocrine Society. Endocrine Facts and Figures: Reproduction and Development. First Edition. 2017

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of young women in the US today 77-79.

The currently accepted diagnostic criteria issued by the 2003 Rotterdam PCOS consensus workshop group (sponsored by the European Society of Human Reproduction and Embryology/American Society of Reproductive Medicine) states that PCOS should include two of the following three criteria: oligo-anovulation, hyperandrogenism (clinical or biochemical), and polycystic ovary morphology on ultrasound 80,81.

It is important to note that many studies of PCOS used the previous NIH criteria established in 1990 that required both hyperandrogenism and oligo-anovulation, which included a group of women with PCOS who could have more severe symptoms and metabolic complications 82. The Androgen Excess and PCOS Society PCOS definition requires the presence of hyperandrogenism (clinical or biochemical) associated with ovulatory dysfunction (either oligo-anovulation or PCOs) 83. Clinical practices use the Rotterdam criteria for the diagnosis of PCOS. Research studies may use all three criteria (Rotterdam, NIH, and AE-PCOS).

In order to make the diagnosis of PCOS, clinicians must also exclude conditions that could cause symptoms of PCOS, such as thyroid disease, elevated prolactin, estrogen deficiency, CAH, and Cushing’s syndrome 80-83.

For the purpose of this Facts and Figures report, we use the Rotterdam criteria to define PCOS.

4.1 PREVALENCE AND INCIDENCE

Table 13. Global prevalence and phenotypes for polycystic ovary syndrome based on 2003 Rotterdam criteria.
Severe PCOS Hyperandrogenism and chronic anovulation Ovulatory PCOS Mild PCOS
Periods Irregular Irregular Normal Irregular
Androgen concentration High High High Mildly raised
Risks Potential long-term Potential long-term Unknown Unknown
Ovaries on ultrasonography Polycystic Normal Polycystic Polycystic
Insulin concentrations Increased Increased Increased Normal
Prevalence in affected women* 61% 7% 16% 16%
Abbreviations: PCOS, polycystic ovary syndrome.
Notes: *, Azziz et al. 2006 83

Source: Table adapted from Norman et al. 2007 84

4.2 COST BURDEN OF DISEASE

A 2005 study by Azziz et al. reported a cost of approximately US $5.46 billion (in 2017 dollars, estimated using an online inflation calculator) to evaluate and provide care to reproductive-aged PCOS women in the US 85. Diagnostic evaluation accounted for a minor part of the total costs (roughly 2%). The majority of the costs are attributable to treatment of T2DM, menstrual dysfunction, or abnormal uterine bleeding. Therefore, more widespread screening for PCOS would likely be cost-effective, as it would lead to earlier diagnosis and interventions that can prevent and control symptoms and prevent the development of T2DM. In particular, prevention or early diagnosis and optimal treatment of T2DM prevents future complications, such as CVD and associated morbidity, mortality, and health care-related costs (Table 14) 85.

Table 14. The overall health care-related economic burden of polycystic ovarian syndrome patients during their reproductive years.
Procedure Annual costs in millions of US dollars (% of total costs, in 2017 US dollars)*
Initial evaluation $130 (2.3)
Treatment
Menstrual dysfunction /AUB $1,768 (30.9)
Infertility $698 (12.2)
Type 2 DM $2,313 (40.4)
Hirsutism $815 (14.2)
Total cost $5,725 (100.0)
Abbreviations: AUB, Abnormal uterine bleeding; DM, diabetes mellitus; US, United States.
Notes: *, costs were updated to 2017 figures using an online inflation calculator.

Source: Azziz et al. 2005 85

4.3 DEMOGRAPHIC DIFFERENCES

Several studies have demonstrated or reported significant ethnic differences in the prevalence of cardiovascular risk factors in PCOS. These observations mirror known CVD risk factor differences, such as a higher prevalence of the MetS, insulin resistance, and T2DM in Hispanic women. Whether these ethnic differences will interact with PCOS to greatly increase overall CVD risk factors is not clear. There is no evidence for differences in subclinical tests of atherosclerosis 86,87.

4.4 LIFE EXPECTANCY AND MORTALITY

4.4.1 Cardiovascular Risk Factors

Due to the high prevalence of obesity in PCOS and association of PCOS and androgen excess with insulin resistance 88, several studies have demonstrated a higher prevalence of cardiovascular risk factors in PCOS. Independent of BMI, women with PCOS have higher low-density lipoprotein (LDL) cholesterol (“bad cholesterol”) and triglycerides along with lower high-density lipoprotein (HDL) cholesterol (“good cholesterol”) 88,89. Although studies have not consistently reported higher blood pressure in women with PCOS, women with PCOS might be at risk for hypertension, especially later in life 90-94. Because increases in abdominal adiposity and insulin resistance are characteristic of PCOS, these women also have a high prevalence of the MetS 95. Asymptomatic women with PCOS have early signs of CVD, such as increased left atrial size, increased left ventricular mass index, lower left ventricular ejection fraction, increased carotid artery intima-media thickness, increased coronary artery calcification, and diastolic dysfunction 96-101.

In spite of evidence that women with PCOS have an increased prevalence of cardiovascular risk factors, there is limited data to make conclusions about any increase in event rates of heart disease, stroke, and death. Smaller studies failed to find an increase in cardiovascular event rates 102,103. In larger retrospective studies, incidences of stroke and mortality were only increased in women with PCOS who developed T2DM 104. Although some studies suggest that features of PCOS are more common in women with coronary artery disease and cardiovascular events, it is not clear that these women would have been diagnosed with PCOS before menopause 81.

 4.4.1.1 Type 2 Diabetes Mellitus

T2DM is considered a CVD equivalent, conferring the same risk of having a cardiovascular event as a prior cardiovascular event. T2DM also erases the female cardioprotective advantage, resulting in a similar cardiovascular risk for women with T2DM as men. Prediabetes is present in as many as 35% of US women and adolescents with as many as 3-10% with T2DM 81. T2DM is a clear target for prevention in lowering the risk for morbidity and mortality in women with PCOS.

Table 15. Cardiovascular risk in women with polycystic ovarian syndrome.
At risk—PCOS women with any of the following risk factors:
Hypertension
Dyslipidemia (increased LDL-cholesterol and/or non-HDL-cholesterol)
Cigarette smoking
Impaired glucose tolerance
Family history of premature CVD (<55 years of age in male relative; <65 years of age in female relative)
Obesity (especially increased abdominal adiposity)
Subclinical vascular disease
At high risk–PCOS women with:
MetS
OSA
T2DM
Overt vascular or renal disease, CVD
Abbreviations: CVD, cardiovascular disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; OSA, obstructive sleep apnea, PCOS, polycystic ovary syndrome, T2DM, type 2 diabetes mellitus.
Notes: According to the Androgen Excess and Polycystic Ovary Syndrome Society, women with PCOS should be stratified as being either at high risk or at risk for CVD based the criteria shown above Wild et al. 2010 88.

Source: Table adapted from Legro et al. 2013 81.

4.4.2 Cancer

Because less-frequent menses (a symptom of PCOS) is linked to an increased risk for endometrial hyperplasia, two meta-analyses examined whether there is an also an increased risk for endometrial cancer associated with PCOS. The analyses reported that women with PCOS have a 2.7- to 3-fold increased risk for developing endometrial cancer 105,106. Whether this could be due to other risk factors for endometrial cancer, such as obesity, T2DM, and infertility instead of PCOS itself is not known 81.

PCOS has not been associated with breast cancer, and data are lacking linking PCOS with uterine leiomyosarcoma or vaginal, vulvar, or cervical cancers 106,107.

4.4.3 Psychosocial Issues

Women with PCOS have a higher prevalence of depression and anxiety 108. Psychosocial issues include: PCOS adolescents facing issues of self-presentation, young adult women with PCOS having fertility concerns, and women of all ages with PCOS having concerns related to eating, weight, and androgen excess 109,110.

One study linked PCOS with bipolar disorder 111. However, this likely refers to both the disorder and its treatment regime 112. Valproate treatment is associated with weight gain and the development of polycystic ovaries, relative hyperandrogenemia, and oligomenorrhea, 113,114. In addition, in vitro studies have shown that valproate increases androgen production (similar to what is seen in polycystic ovaries) 115.

4.4.4 Long-Term Outcome of Children Born to Mothers with Polycystic Ovary Syndrome

Children of PCOS women have an increased risk for developing PCOS (similar to other first-degree relatives) 116,117, and some studies have reported that offspring of PCOS mothers can experience reproductive and metabolic abnormalities 118,119. However, current data are limited regarding long-term reproductive and metabolic risks for this group. Furthermore, not all children of PCOS mothers develop PCOS, and for those that do, symptoms may not emerge until puberty 120. There is currently no test that screens girls for PCOS.

4.5 KEY TRENDS AND HEALTH OUTCOMES

4.5.1 Diagnosis

4.5.1.1 Anti-Müllerian Hormone

Developing follicles release Anti-Müllerian Hormone (AMH), and clinicians use AMH to predict ovarian reserve and fertility. PCOS women generally have higher AMH levels than women without PCOS, and these levels correlate with PCOS presentation and follicle numbers 121,122.

It has been difficult to define a threshold for using AMH to diagnose PCOS, largely because there is no international standard for AMH assays. AMH assays would be helpful in diagnosing adolescent girls, as irregular menses occur more frequently during puberty and might normalize later in adolescence. AMH could replace an assessment with transvaginal ultrasound during adolescence in terms of evidence for anovulatory accumulation of multiple immature follicles 121,122.

4.5.1.2 Ultrasound

A recent task force report (recognizing advances in imaging technology) recommends changes to the polycystic ovarian morphology (PCOM) definition. The task force recommends a threshold of ≥25 follicles when the imaging technology affords maximal resolution (i.e., a transducer frequency ≥8 MHz)123. In the absence of such technology, clinicians could still use ovarian volume (OV) rather than follicle number for routine daily practice 123. Current definitions and recommendations for the diagnosis of PCOS have not been updated to include these criteria.

4.5.1.3 Diagnosis in Adolescents

Normal adolescents might experience irregular menses during puberty that later normalizes, making PCOS diagnoses challenging. Therefore, effectively diagnosing PCOS in adolescents is an area for future development 81,124.

4.5.2 Treatment

4.5.2.1 Hormonal Contraceptives

Hormonal contraceptives (HC) (i.e., oral contraceptives, patch, or vaginal ring) treat menstrual abnormalities and hirsutism/acne concurrently in women with PCOS. Therefore, we recommend HCs as first-line management 81.

The benefit of oral HCs versus patch or vaginal ring has not been determined, although there might be different risk-benefit ratios among preparations. Some data suggests that extended-cycle HCs (vs. cyclic therapy) may provide better hormonal suppression and prevent ovarian function from rebounding during the period when patients are not taking oral HCs 120.

4.5.2.2 Metformin in Adults

We do not recommend metformin as first-line treatment for treating obesity or preventing pregnancy complications or cutaneous manifestations. However, we do recommend metformin for women with PCOS who have impaired glucose tolerance or T2DM and unable to modify their lifestyle. For women with PCOS who cannot take or do not tolerate HCs, we recommend metformin as second-line therapy for menstrual irregularity 81.

In women with PCOS, we also recommend metformin for treating hirsutism 125 and cardiovascular risk factors in patients at metabolic risk to prevent CVD and T2DM 126. Patients should not use metformin for hirsutism, and evidence is lacking regarding metformin treatment for acne 127,128.

Clinicians should consider lifestyle management and weight loss as first-line therapy for women with PCOS who are at increased metabolic risk 126.

4.5.2.3 Other Medications

Women with PCOS should not take insulin sensitizers, such as inositols or thiazolinediones, due to lack of benefit and safety concerns (respectively). In addition, clinicians should not prescribe statins for hyperandrogenism and anovulation in women with PCOS, unless these women meet current indications for statin therapy 81.

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