Practical Pearls: Polycystic Ovarian Syndrome

She is sitting in your office waiting room. That fat, hairy woman for whom you can pretty much guarantee her chief complaint —amenorrhea, abnormal hair growth or knee pain. You know the Pandora’s Box of diagnoses she really should be worried about: diabetes, hyperlipidemia, endometrial cancer. So many problems, so little time, so little compensation.

The average woman with polycystic ovarian syndrome (PCOS) fits this picture, but not all do. Approximately 30% of women with PCOS are thin.¹ The chief complaints of women affected by PCOS are infertility, abnormal uterine bleeding, hirsutism and acne.² PCOS affects approximately 6% to 7% of reproductive-age women³ and can be diagnosed, by meeting two of three criteria set in 2003 by the Rotterdam Consensus: hyperandrogenism (either clinically or biochemically), oligomenorrhea or amenorrhea, and polycystic ovaries noted on ultrasound.⁴ The Androgen Excess Society expanded the definition in 2006 by requiring hyperandrogenism to be present among the three Rotterdam criteria.⁵ Potential diagnoses of hyperandrogenims such as androgen-secreting tumors, Cushing’s syndrome, non-classical congenital adrenal hyperplasia, exogenous androgens and acromegaly must be excluded.

No clear etiology of PCOS has been defined. Insulin resistance with subsequent decreased levels of sex hormone-binding globulin and more available circulating androgen is central to the pathophysiology. Hyperinsulinemia can stimulate further androgen production by the ovaries and by the adrenal glands. Obesity can independently exacerbate PCOS and its symptoms. The physical exam reveals many aspects of PCOS. Through excessive hair growth, male-pattern baldness and acne, hyperandrogenism can significantly impact women’s lives. Hirsutism can be evaluated using the Ferriman-Gallwey score (Figure 1). First described in 1961, this scale was modified in 2001 for grading 19 corporal locations with a score of 0 (no hair growth) to 4 (extensive hair growth). These locations include upper lip, chin, lower abdomen and inguinal area.6 Acne also may disfigure with deep pustular nodules along the patient’s cheeks, jawline, chin and upper neck (Figure 2). A pelvic exam can demonstrate clitoromegaly, a subtle but important finding on physical exam, and ovarian enlargement. A transvaginal ultrasound will give the classic appearance of "string-of-pearls" for polycystic ovaries (Figure 3).

Oligomenorrhea and other menstrual irregularities are common complaints. Oligomenorrhea is defined as menstrual cycles occurring at an interval of less than 21 days or greater than 35 days. With the lack of a moliminal symptom such as breast tenderness or mood-changes, oligomenorrhea can be suggestive of anovulation. These women often seek medical attention for infertility and, with ovarian stimulation, are prone to hyperstimulation and pregnancies complicated by multiple gestations. Without ovulation, women with PCOS are at increased risk of endometrial cancer as they age.

The prevalence of concomitant cardiometabolic syndrome is between 33% and 47%. This is from two to three times that of the general population and may be related to obesity. Therefore, those with PCOS should be screened regularly for cardiovascular risk factors.

Approximately 70% of American women with PCOS have dyslipidemia⁷ with mildly elevated low-density lipoprotein (LDL)⁴, low high-density lipoprotein (HDL) cholesterol and higher triglycerides than normal. This often responds to lifestyle intervention. It is wise to remember that statins are contra-indicated in women at risk for pregnancy. Cholesevelam is the only lipid modifying agent that is pregnancy class B. All agents except statins (which are class X) are class C. Target goals are those for metabolic syndrome in patient with PCOS (3 of 5 characteristics including low HDL cholesterol (50 mg/dL in women), high Triglycerides (>150 mg/ dL) , elevated fasting glucose (>110 mg/ dL) and elevated waist circumference(>35 inches in Caucasians and >3.5 inches in Asians. Carbohydrate intolerance also needs to be assessed at regular intervals, because the incidence of impaired glucose intolerance is approximately 20% a year.⁸ Screening for diabetes is recommended in any patient with PCOS, regardless of age, given that inherent insulin resistance often is aggravated by obesity. Acanthosis nigricans can herald this insulin resistance on physical exam, marking the neck, axillae, chest and vulva with its classic velvety, hyperpigmented appearance. A quantitative scale of acanthosis nigricans has been devised and validated to aid with longitudinal evaluation. Notably, patients with PCOS also often have excess skin tags.

To properly evaluate this prevalent disorder, the American College of Obstetrics and Gynecology⁴ recommends examining the patient for the stigmata mentioned above. Additionally, assessment for cardiometabolic syndrome in blood pressure, waist circumference, body mass index, fasting lipid panel and a complete metabolic profile, including fasting glucose and liver enzymes, should be completed. Liver enzymes need to be evaluated for fatty liver and/ or nonalcoholic steatohepatitis (NASH Hyperandrogenism should be documented by obtaining a free androgen index [the ratio of testosterone to sex hormonebinding globulin (SHBG)] and exclusion of other etiologies by obtaining a thyroidstimulating hormone level, a prolactin and 17-hydroxyprogesterone level at 0800hrs to rule out non-classic congenital hyperplasia, hypothyroidism and/or hyperprolactinemia. A pelvic ultrasound to document polycystic ovaries also is recommended, because it also evaluates for endometrial pathologies. Evaluation for Cushing’s syndrome and androgensecreting tumors is left to the discretion of the practitioner. Cushing’s syndrome, likewise, usually has characteristic stigmata and patients with virilizing ovarian or adrenal tumors usually have rapid onset virilization with serum androgens (T or DHEAS) in a very high range. Additionally, patients with PCOS often have depression and/or anxiety disorders^10,11 for which they should be screened and diagnosed.

The evaluation of a patient with polycystic ovarian syndrome takes time¹² and likely needs to be spread over several visits. This allows you to tackle the multiple complaints your female patient has to offer and permits her Pandora’s Box of medical complexities to be addressed effectively and comprehensively.

Disclosure statement: Dr. Lambert has no disclosures to report.