Among the physiologic hormonal changes that occur in PCOS, reproductive endocrine function might especially influence the risk of metabolic derangement. Larger waist circumference, higher blood pressure, lower insulin sensitivity, and a greater degree of dyslipidemia are known to develop in PCOS women. As a result, the prevalence of metabolic syndrome was found to be higher in PCOS women, especially those with older age, obesity, and hyperandrogenemia status. In our study, metabolic syndrome was more prevalent in the hyperandrogenemia PCOS group than in non-hyperandrogenemia PCOS group. The prevalence of metabolic syndrome was 27.1% and 9.2% in hyperandrogenemia and non-hyperandrogenemia groups, respectively. Prevalence of metabolic syndrome was statistically significantly different between hyperandrogenemic PCOS and non-hyperandrogenemic PCOS, which is comparable to the results of two previous studies[4, 5]. Similar to previous studies, PCOS women with hyperandrogenemia in the present study had more obesity[4], and a higher level of abnormality among the components of metabolic syndrome[12], including blood pressure, waist circumference, fasting blood glucose, triglycerides, and HDL-C. In contrast, The present study had the difference in prevalence of metabolic syndrome according to difference of mean age, mean BMI, race and criteria for diagnosis of metabolic syndrome when compared with previous studies[4, 12]. Obesity and androgen excess in PCOS may involve the aggravation of metabolic abnormalities, such as increased visceral fat, decreased lipolysis in subcutaneous fat, insulin resistance in adipose tissue and skeletal muscle, and lipid metabolism[6]. These factors influence an increased risk of metabolic syndrome.
Many studies reported obesity and hyperandrogenism to be factors that influence the development of metabolic syndrome in PCOS women[4, 5]. However, hyperandrogenism and its associated parameters, including free androgen index and SHBG, were reported to be significantly associated with metabolic syndrome in non-obese PCOS women[13]. Another study found a significant difference in abnormal insulin resistance and lipid metabolism between PCOS with and without hyperandrogenism[5]. As such, several factors that relate to hyperandrogenism influence metabolic syndrome. Similar to previous study[13], we found age, BMI, free testosterone, and DHEA-S to be factors significantly associated with metabolic syndrome in Thai women with PCOS.
Although we found higher free testosterone and lower DHEA-S to be associated with metabolic syndrome, no association was observed for total testosterone. A recent study reported that high levels of circulating androgens derived from the adrenal gland, and that lower levels of ovarian androgens exert a beneficial effect on metabolic disturbances in PCOS women[14]. There are several mechanisms that might explain the protective effect of DHEA-S in PCOS women, including its effect on insulin function[14]. DHEA decreases gluconeogenesis by suppressing the activity and expression of glucose- 6-phosphatase and phosphoenolpyruvate carboxykinase[15]. DHEA-S increases glucose uptake in hepatocytes and increases insulin binding to its receptor[15]. High circulating levels of glucose or insulin might impact DHEA-S synthesis in the adrenal gland, which might be mediated via insulin action[16]. Therefore, a high DHEA-S might be a defensive effect to prevent a metabolic syndrome event. Our findings revealed free testosterone cut-off for diagnosing hyperandrogenemia to be the only parameter significantly associated with metabolic syndrome. Therefore, hyperandrogenemia using free testosterone cut-off should be considered a potential indicator for predicting metabolic syndrome in PCOS women.
Limitations
This study has some mentionable limitations. First and consistent with the retrospective nature of this study, some patient data may have been missing or incomplete, and no causal relationships could be conclusively established. Second, this was a single-center study. Third, metabolic syndrome is a multifactorial disorder, and our study was not able to adjust for other confounding factors, including nutritional status, exercise, lifestyle and smoking. Further prospective study is needed to support the findings of this study and to include and assess the aforementioned unevaluated factors.