Strategies for the Prevention of Long-term Health Consequences of PCOS
Strategies to prevent long-term health morbidities are critical for women who have been diagnosed with PCOS. Since the exact etiology of PCOS is unclear, and the impact of early life intervention on disease progression is unclear, it is not possible to recommend a specific plan for those at risk for developing PCOS. A recent study using the letrozole PCOS rat model studied the effect of exercise and demonstrated that with high-intensity exercise, the levels of testosterone, luteinizing hormone, fasting insulin, and leptin were lower, suggesting that exercise could prevent the progression or severity of the disorder.
For adult women with a diagnosis of PCOS, routine screening for associated metabolic abnormalities is recommended. Screening for IGT and T2DM should be done by employing the 2-hour fasting oral glucose tolerance test (75 g load, with glucose measured at 0 and 2 hours). While many women with PCOS will have normal fasting glucose, many of those will have IGT based on a 2-hour postprandial glucose level between 140 and 200 mg/dL, highlighting the importance of testing in this population to establish risk for developing T2DM (Fig. 4). Cardiovascular risk should be assessed with blood pressure, glucose, lipid profile, waist circumference, and assessment of levels of physical activity, nutrition, psychosocial stress, and smoking. Rescreening for T2DM should occur every 3 to 5 years as per a recent clinical guidelines, or sooner if additional risk factors develop.
Scattergrams of fasting blood glucose levels on the horizontal axis versus 2-hour postprandial glucose levels on the vertical axis in 254 women with polycystic ovarian syndrome (PCOS) by the NIH 1990 criteria after a 75-g oral glucose challenge. Points on the graph reflect the diagnostic status of the study subjects after their 2-hour levels based on WHO criteria which define normal glucose tolerance (NGT; 2-hour glucose below 140 mg/dL), impaired glucose tolerance (IGT; 2-hour glucose over 140 mg/dL), and diabetes mellitus (DM; fasting glucose above 125 mg/dL or 2-hour glucose above 200 mg/dL). The vertical lines depict minimum levels for impaired fasting glucose (110 mg/dL) and diabetes (fasting glucose of 126 mg/dL) by the 1997 ADA criteria. Many diabetic PCOS women will be missed with a single fasting glucose level, hence the need for all women with PCOS to undergo a glucose tolerance test at initial visit and at regular intervals thereafter. (Modified with permission from figure provided by R.S. Legro, based on data from Legro et al.88)
In terms of treatment, lifestyle intervention including diet and exercise regimens should be considered first-line therapy for women with PCOS, particularly those who are overweight or obese. These interventions generally help improve ovulatory function, at least in part, in a large proportion of women and reduce fasting serum insulin levels. Hirsutism also improved, although modestly, in some of these women. The particular type of diet, as long as it is hypocaloric, has not been shown to have any significant difference in outcome.
Metformin, a biguanide which suppresses hepatic gluconeogenesis and acts peripherally as an insulin sensitizer, is indicated for women with IGT who fail to lose weight by lifestyle changes alone, as it reduces the progression to T2DM.[90,93] A meta-analysis of pooled results from 31 clinical trials in 4,570 participants, 620 of which had known PCOS, suggested that metformin treatment has significant benefits for women with PCOS in terms of reducing BMI, increasing HDL, reducing LDL, reducing insulin resistance, and decreasing new-onset diabetes by 40%. The benefits were still observed when the analysis was restricted to those with PCOS, with the exception of a lesser reduction in fasting insulin values. More recently, another meta-analysis suggested that the combination of metformin and lifestyle changes in PCOS may be more effective in reducing weight than lifestyle changes alone. In those women with PCOS who also have altered lipid profiles statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors are more effective than placebo at reducing total cholesterol, triglyceride levels, and LDL levels, and should be used per standard indications.
Semin Reprod Med. 2017;35(3):271-281. © 2017 Thieme Medical Publishers