Obesity occurs in more than 50% of patients with PCOS. The body fat is usually deposited centrally (android obesity), and a higher waist-to-hip ratio is associated with insulin resistance indicating an increased risk of diabetes mellitus and cardiovascular disease (30). Among women with PCOS, there is widespread variability in the degree of adiposity by geographic location and ethnicity. In studies in Spain, China, Italy, and the United States, the percentage of obese women with PCOS were 20%, 43%, 38%, and 69%, respectively (31).
Insulin resistance resulting in hyperinsulinemia is commonly exhibited in PCOS. Insulin resistance may eventually lead to the development of hyperglycemia and type 2 diabetes mellitus (32). About one-third of obese PCOS patients have impaired glucose tolerance (IGT), and 7.5% to 10% have type 2 diabetes mellitus (33). These rates are mildly increased in nonobese women who have PCOS (10% IGT; 1.5% diabetes, respectively), compared with the general population of the United States (7.8% IGT; 1% diabetes, respectively) (34,35).
Abnormal lipoproteins are common in PCOS and include elevated total cholesterol, triglycerides, and low-density lipoproteins (LDL); and,low levels of high-density lipoproteins (HDL), and apoprotein A-I (30,36). According to one report, the most characteristic lipid alteration is decreased levels of HDL2α (37).
Other observations in women with PCOS include impaired fibrinolysis, as shown by elevated circulating levels of plasminogen activator inhibitor, an increased incidence of hypertension over the years (which reaches 40% by perimenopause), a greater prevalence of atherosclerosis and cardiovascular disease, and an estimated sevenfold increased risk for myocardial infarction (36,38–41).
Pathology Macroscopically, ovaries in women with PCOS are two to five times the normal size. A cross-section of the surface of the ovary discloses a white, thickened cortex with multiple cysts that are typically less than a centimeter in diameter. Microscopically, the superficial cortex is fibrotic and hypocellular and may contain prominent blood vessels. In addition to smaller atretic follicles, there is an increase in the number of follicles with luteinized theca interna. The stroma may contain luteinized stromal cells (42).
The hyperandrogenism and anovulation that accompany PCOS may be caused by abnormalities in four endocrinologically active compartments: (i) the ovaries, (ii) the adrenal glands, (iii) the periphery (fat), and (iv) the hypothalamus–pituitary compartment (Fig. 31.5).
In patients with PCOS, the ovarian compartment is the most consistent contributor of androgens. Dysregulation of CYP17, the androgen-forming enzyme in both the adrenals and the ovaries, may be one of the central pathogenetic mechanisms underlying hyperandrogenism in PCOS (43). The ovarian stroma, theca, and granulosa contribute to ovarian hyperandrogenism and are stimulated by LH (44). This hormone relates to ovarian androgenic activity in PCOS in a number of ways.
1.
Total and free testosterone levels correlate directly with LH levels (45).
2.
The ovaries are more sensitive to gonadotropic stimulation, possibly as a result of CYP17 dysregulation (43).
3.
Treatment with a gonadotropin-releasing hormone (GnRH) agonist effectively suppresses serum testosterone and androstenedione levels (46).
4.