Etiology and Definition

Polycystic ovary syndrome (PCOS) is a common disorder of reproductive hormone dysfunction, often with associated metabolic abnormalities, that affects 5-8% of women of reproductive age. The disorder typically emerges in adolescence when a normal menstrual pattern is not established and there is clinical evidence of androgen excess. It is characterized by the triad of oligo-ovulation or anovulation, clinical or biochemical hyperandrogenism, and ovarian cysts (≥12 immature follicles) (the Rotterdam criteria). Various expert bodies prioritize these elements differently for establishing the diagnosis, and few require the presence of all 3. Hyperandrogenism with ovulatory dysfunction (with exclusion of other causes) is most often considered sufficient for diagnosis in the USA. Abnormalities commonly associated with PCOS include obesity, insulin resistance, and the metabolic syndrome, but the phenotype is variable (see Table 546-1 on the Nelson Textbook of Pediatrics website at www.expertconsult.com).

Pathology Pathogenesis and Genetics

PCOS has a high concordance rate in twins, and in some studies either epigenetic or dominant inheritance patterns are observed. Nonetheless, a consistent hereditary pattern has not been identified.

Gonadotropic dysregulation with increased luteinizing hormone (LH) pulsatility and abnormally high ratios of circulating LH to follicle-stimulating hormone (FSH) are found in many patients with PCOS. Increased ovarian production of androgen in response to LH and impaired folliculogenesis owing to lower FSH are attributed to this gonadotropic pattern. Abnormal regulation of gonadotropin-releasing hormone agonist (GnRH) and abnormal gonadotropin secretion more likely reflect the abnormal hormonal milieu of the syndrome than explain its origin (Fig. 546-1). An increased ratio of circulating levels of LH to FSH is not a diagnostic criterion for PCOS.

Figure 546-1 Schematic of pathophysiology of polycystic ovary syndrome and mechanism of therapeutic drugs. DHT, dihydrotestosterone; LH, luteinizing hormone; SHBG, sex hormone binding globulin; OCPs, oral contraceptive pills.

(Adapted from Hassan A, Gordon CM: Polycystic ovary syndrome in adolescence, Curr Opin Pediatr 19[4]:389–397, 2007.)

Alterations in activities of steroidogenic enzymes that would explain ovarian androgenic hyperfunction are seen in PCOS subjects, but they are not consistently present in all patients; it is unclear whether these alterations cause PCOS or are a consequence of ovarian dysregulation. The mass of ovarian stromal cells responsible for androgen production is increased, and surgery that reduces this ovarian component (ovarian wedge resection, or laparoscopic ablative procedures) reduces circulating androgen levels and often restores ovarian cyclicity. Patients with hyperandrogenic congenital or adult-onset adrenal hyperplasia exhibit PCOS-like ovarian dysfunction that can be reversed by reducing the adrenal-derived androgens with glucocorticoid therapy. A primary role for androgen excess in the pathophysiology of all instances of PCOS seems unlikely; many patients have minimal hyperandrogenism, and elimination of androgen excess (with GnRH agonists) does not affect associated insulin resistance.

Measures of insulin resistance are greater and more prevalent among women with PCOS than controls even when accounting for BMI. Insulin enhances ovarian androgen production directly and contributes to elevations of free testosterone levels through its suppression of hepatic production of sex steroid–binding globulin. Treatment with insulin sensitivity–enhancing agents that can reduce insulin levels is associated with modest reductions in measures of androgen excess and, in some patients, restoration of regular ovulation. The association of insulin resistance with weight might explain the appearance of features of PCOS among some women who gain weight and the resolution of PCOS among affected women who lose weight.

Clinical Manifestations

PCOS commonly becomes manifest as puberty progresses, but its onset can occur later during young adulthood. PCOS is a lifelong disorder (though with some evidence for amelioration with age or weight loss) (Table 546-2). Clinical hallmarks are menstrual abnormalities and manifestations of hyperandrogenism. Ovulation is typically irregular or absent, and menses are consequently irregular or absent. When they do occur, menses may be relatively normal in character as a consequence of a preceding ovulation. In many women, protracted periods of unopposed estrogen exposure without ovulation can terminate erratically in bleeding that is abnormally prolonged and/or heavy.

Table 546-2 LIFELONG HEALTH COMPLICATIONS