New tide for women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. The Rotterdam revised consensus meeting in 2003 proposed that oligomenorrhea, clinical or biochemical hyperandrogenemia, and the presence of polycystic ovaries should serve as the diagnostic criteria for PCOS. Metabolic syndrome is defined by a cluster of risk factors for cardiovascular disease, including visceral obesity, dyslipidemia, abnormal glucose tolerance, and hypertension. It is associated with substantially elevated risks for type 2 diabetes (5-fold) and cardiovascular disease (2to 3-fold). Recent studies indicate that the increasing prevalence of metabolic syndrome in developed and developing countries has become an important public health problem. Although the increased risk of atherosclerotic cardiovascular disease and hypertension in women with PCOS remains controversial, a variety of intriguing metabolic disturbances related to the risks for cardiovascular disease and hypertension, such as obesity, insulin resistance, dyslipidemia, and the metabolic syndrome, are commonly found in women with PCOS. Women with PCOS are characterized as having a high free androgen index, a low high density lipoprotein cholesterol (HDL-C), a low sex hormone binding globulin (SHBG), and an increased susceptibility to cardiovascular disease. Low HDL-C and low SHBG levels have been reported to be associated with insulin resistance and obesity in women with PCOS. In our previous study, we found a positive correlation between HDL-C and SHBG after adjusting for many anthropometric and metabolic factors. The low SHBG levels in women with PCOS are associated with a low HDL-C, independent of insulin resistance and obesity. Biologically, SHBG may mediate its effect on HDL-C through the regulatory effect of androgen on hepatic lipase activity. Because SHBG binds preferentially to testosterone, a decrease in SHBG increases the amount of circulating free testosterone. Our study also revealed that a lower level of SHBG was accompanied by a higher incidence of the metabolic syndrome. The effects of androgen on blood pressure are controversial, especially in women with PCOS who have a higher prevalence of obesity and insulin resistance than women without PCOS. Because elevated androgens, such as dehydroepiandrosterone sulfate (DHEAS) and testosterone (free and total), have been reported to be associated with insulin resistance, obesity, and lipid metabolism, elevated androgens may also raise the risk for cardiovascular disease. A recent study demonstrated that the bioavailable serum and total testosterone levels were significantly and positively correlated with both systolic and diastolic blood pressure in young women with PCOS, independent of insulin resistance, obesity, and dyslipidemia. The observed associations in this specific population suggest that the characteristic hyperandrogenemia in young women with PCOS is associated with their blood pressure and may possibly contribute to the risks of hypertension and cardiovascular disease that occur in middle age. Therefore, we concluded that the hyperandrogenemia and low SHBG levels in women with PCOS may contribute to the occurrence of the metabolic syndrome. Because of different dietary, genetic, and environmental factors, the prevalence of insulin resistance in women with PCOS, presenting as obesity and the metabolic syndrome, is quite different among different ethnicities. Asian women with PCOS have been reported to be less obese and have less apparent hyperandrogenic phenotypes than the other ethnicities, but the prevalence of androgen excess, insulin resistance, and polycystic ovaries appeared to be similar in comparison with other populations. A high prevalence of the metabolic syndrome (33.4%) in South American and Caucasian women with PCOS has been noted and is associated with a higher body mass index (after adjusting for age) and the high prevalence (66%) of a low HDL-C (<50 mg/dL). Using the modified criteria of the metabolic syndrome for Asians, we report a relatively low prevalence of the metabolic syndrome (16.0%) in women with PCOS. The prevalence of a low HDL-C, however, was similar to that in a report for other ethnicities. It is thus implied that the level of HDL-C may play an important role in women with PCOS, even in different ethnicities. To prevent the future development of cardiovascular disease and hypertension in women with PCOS, control of the metabolic dysregulation, as well as hyperandrogenism, should be considered.