Polycystic Ovary Syndrome: 5 Things You Might Not Know

Peter Kovacs, MD, PhD

Disclosures

August 02, 2019

More than 80 years ago, physician colleagues Irving Stein and Michael Leventhal noticed a pattern among some of the infertile women with menstrual irregularities they were seeing in their practice. They published their observations in a landmark report[1] describing seven women who exhibited the triad of clinical symptoms — "polycystic" ovaries, hirsutism, and amenorrhea — associated with polycystic ovary syndrome (PCOS) to this day. Here are five key facts everyone should know about this common condition.

1. "Polycystic" is a misnomer.

PCOS isn't the first condition to be saddled with a name that is later found to be inaccurate or misleading. What Stein and Leventhal characterized as epithelial cysts are really immature antral follicles.[2] The misnomer is unfortunate because it suggests that ovarian cysts are the defining feature of PCOS. Moreover, except in adolescents, the ovarian morphology isn't the most important feature used to diagnose the condition. Similarly, a woman with polycystic ovaries but no hormonal or metabolic aberrations does not have PCOS. But to date, experts haven't been able to agree on a new name for this syndrome that adequately represents its anatomic, clinical, and metabolic manifestations.[3]

2. Far from rare, PCOS affects as many as 1 in 10 women.

Since the syndrome was first described by Stein and Leventhal, the diagnostic criteria for PCOS have changed, and it is now estimated that as many as 10% of women may be affected,[4,5] although many remain undiagnosed. PCOS is also a diagnosis of exclusion. Other conditions with overlapping features (Cushing syndrome, androgen-producing tumors, medications with androgenic side effects, congenital adrenal hyperplasia) must first be ruled out.

Currently the most widely accepted criteria are the Rotterdam criteria, which state that PCOS can be diagnosed when two out of the following three criteria are met[4]:

  • Oligo- or anovulation

  • Clinical or laboratory evidence of androgen excess

  • Polycystic ovaries

Other diagnostic criteria put more emphasis on the hormonal and metabolic features and less on ultrasound findings (Table).

Table. Diagnostic Criteria for PCOS

Guideline Source Diagnostic Criteria
National Institutes of Health Anovulation
Clinical or laboratory hyperandrogenism

Both required
2003 Rotterdam criteria Oligo-, anovulation
Clinical or laboratory hyperandrogenism
Polycystic ovaries

2 of 3 required
Androgen Excess and PCOS Society Cinical or laboratory hyperandrogenism
Oligo-, anovulation
Polycystic ovaries

2 of 3 required; androgen excess must be present

Some patients with PCOS have regular menstrual cycles, but 85%-90% have more than 35 days between cycles or have fewer than nine cycles annually. Hyperandrogenemia (elevated free testosterone, free androgen index, or DHEA levels) and/or clinical evidence of androgen excess (hirsutism, acne, clitoromegaly, male body habitus) are present in up to 80% of affected women.[6] Polycystic ovaries are defined as having 12 or more small (2-9 mm) follicles per ovary, although some authors suggest a much higher number (> 25 per ovary).[6,7]

Diagnosis becomes more challenging in teenagers and perimenopausal women. Among adolescents, cycle irregularity and acne are already common, and follicle counts tend to be high. Elevated serum androgen levels may be the most consistent marker for PCOS in teens, but all three Rotterdam criteria should be present to establish the diagnosis.[7] In perimenopausal years, cycles tend to become more regular and follicle counts lower in women with PCOS. Furthermore, age-related declines in ovarian and adrenal androgen secretion make the diagnosis challenging in menopausal women.[8]

Although not diagnostic, certain findings are more common in women with PCOS, including obesity (at least 50%), elevated luteinizing hormone levels, insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, hypertension, endothelial dysfunction, hypercoagulability, and endometrial hyperplasia.

Some affected women have expressed frustration with the process of evaluation and diagnosis that they underwent to find out what was wrong with them — why they couldn't lose weight or become pregnant, or why their menstrual periods were irregular, not to mention the acne and distressing growth of body hair. In recent crowdsourced data, 1 in 3 women reported that it took at least 2 years to be diagnosed with PCOS, and almost half saw three or more healthcare professionals along the way.[9] Nor were women satisfied with the information they received about their condition, giving particularly low marks to primary care providers, whom they judged as unqualified to manage PCOS. A mere 15% were satisfied with the information they received at the time of diagnosis.[9]

3. It's the most common cause of female infertility.

The underlying cause of infertility among women with PCOS is oligo-ovulation or anovulation. In fact, 90% of women with oligo- or amenorrhea have PCOS.[7] The lack of ovulation isn't the only strike against fertility, because obesity, poorer oocyte quality, and an adverse endometrial environment can also impair a woman's chance of conceiving. In addition to the assessment of ovarian function, the couple should undergo a proper, full infertility evaluation (male factor infertility, tubal status, etc.). If the rest of the evaluation is normal, regular ovulation must be restored to improve fertility.

Among women with a higher body mass index, weight loss should be the first-line treatment. The loss of as little as 5% of body weight can have a favorable effect on ovarian function. For women who do not conceive after lifestyle intervention, metformin (an insulin-sensitizing drug) has been shown to improve ovulation and live birth rates.[10]

Clomiphene citrate is the recommended first choice for ovulation induction, successfully inducing ovulation in up to 80% of women with PCOS. The effect seems to be superior to metformin.[11,12] Combining the drug with metformin (especially in women who are resistant to clomiphene citrate) may further improve its efficacy.[10,12] As an alternative, aromatase inhibitors may induce ovulation without negative endometrial effects.

Women who do not respond to oral agents can consider gonadotropin stimulation or laparoscopic ovarian drilling. Gonadotropins are typically started at a low dose with slow increases if needed in a step-up protocol. Gonadotropins are highly effective in inducing folliculogenesis but often lead to a multifollicular response, increasing the risk for ovarian hyperstimulation syndrome and multiple-gestation pregnancy. The use of in vitro fertilization with elective embryo cryopreservation and subsequent single embryo transfer may avoid these complications in women who are sensitive to stimulation.[13] Adding metformin can lower the risk for hyperstimulation.[14]

The management of ovulatory infertility should begin with the least invasive approach (lifestyle intervention), moving stepwise toward more invasive (in vitro fertilization) treatments. Safety for the patient (avoiding ovarian hyperstimulation) and the pregnancy (avoiding multiple gestations) must be kept in mind, and in certain cases this may require moving on to a more invasive strategy sooner or even right away.

4. PCOS isn't just a reproductive disorder.

The health consequences of PCOS traverse not only a woman's childbearing years but her entire lifespan. A meta-analysis based on 30 studies found the risk for insulin resistance to be increased 2.48-fold, the risk for diabetes 4.43-fold, and the risk for metabolic syndrome 2.88-fold.[15] It is therefore recommended to screen women with PCOS (especially those with high BMI) with an oral glucose tolerance test and lipid profile.

Cardiovascular disease (CVD) risk factors (elevated LDL cholesterol/triglycerides, low HDL cholesterol, increased carotid intima thickness, increased coronary calcification, increased left ventricular volume, diastolic dysfunction, endothelial dysfunction) and obesity are significantly more common than in age-matched women without PCOS.[5,16]

It is controversial whether these CVD risk factors translate into increased CVD morbidity or mortality, however. In a recent study, among reproductive-aged women diagnosed with PCOS, the risk for myocardial infarction, stroke, or CVD-related death was not increased.[17]

The picture gets even more complicated as affected women enter menopause. The higher risks for glucose intolerance, diabetes, dyslipidemia, and metabolic syndrome persist into menopause in women with PCOS. The risk for hypertension, however, does not seem to be higher, and data are inconsistent on the risk for myocardial infarction, stroke, or CVD, with several studies finding no increased risk for CVD among menopausal women with PCOS.[17,18,19]

The Endocrine Society recommends lifestyle changes to avoid the metabolic complications of PCOS that persist after a woman's reproductive years. For women who do not achieve health goals with diet and exercise, metformin is a key option.[16]

Insulin resistance is undoubtedly involved in the pathomechanism of PCOS, but for a long time it was unclear what came first. Did insulin resistance cause the syndrome or did the endocrine abnormalities induce insulin resistance? Currently it is believed that insulin resistance is responsible for the endocrine and metabolic changes of PCOS.

5. A link with cancer is plausible.

An association between PCOS and various cancers has long been studied. PCOS is accompanied by long-periods of unopposed estrogen exposure, which could induce endometrial hyperplasia and subsequent endometrial cancer. Recent data suggest a threefold increased risk for endometrial cancer among women with PCOS, as well as an increased risk for ovarian cancer.[20]

Insulin might play a role in cancer risk as well, by increasing mitogenic activity of certain insulin binding sites in the endometrial stroma.[21] Furthermore, the hormonal regulation of endometrial cell death via apoptosis, influenced by the normal menstrual cycle, is shifted toward survival in women with PCOS, potentially providing cancer cells with a survival advantage.[21] These findings have led to studies to evaluate the role of insulin-sensitizing medications in the prevention or treatment of cancer. Preliminary findings suggest a protective role.[22]

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