Cardiometabolic risk in women with PCOS

Introduction

It is well known that in young women with PCOS, the cardiovascular (CV) risk is increased . In fact, in these patients, all CV risk factors including atherogenic dyslipidemia, LDL (low-density lipoproteins) levels, C-reactive protein, hypertension, and metabolic syndrome are elevated . In addition, several markers of clinical and subclinical atherosclerosis, including carotid intima-media thickness and coronary artery calcium may be altered .

The concept of CV risk factors was introduced by the original Framingham investigators and risk factors are antecedents of atherosclerosis whose levels predict subsequent cardiovascular events and are targets for therapy . In the general population, there is a good correlation between cardiovascular risk and cardiovascular diseases . On the contrary, in women with PCOS, most data suggest that the increased cardiovascular risk does not translate into a proportionally high number of CV diseases . The exact mechanisms of this discrepancy are unclear but may depend on changes in hormone production that occur in PCOS patients moving from young to late adult reproductive age and menopause . In addition, most original data on CV risk in PCOS were obtained in US patients diagnosed by NIH (National Institutes of Health) criteria and may not reflect the heterogeneity of the syndrome and the low prevalence of obesity in some populations.

CV risk factors in different PCOS phenotypes

PCOS is a very heterogeneous disorder that may present with at least four different phenotypes (A, B, C, D) . CV risk seems to be different depending on the phenotype with a higher prevalence of risk factors in patients diagnosed by NIH criteria (phenotypes A and B) compared to the other PCOS Phenotypes (C and D). In fact, these last phenotypes are generally considered mild forms of PCOS with little or no metabolic disturbances and no need for follow-up for risk of type 2 diabetes or cardiovascular alterations.

However, our recent data in a large population of women with PCOS (1215 patients) have shown that also phenotype C presents important metabolic alterations with considerable risk for developing type 2 diabetes and cardiovascular diseases . In fact, while patients with phenotype C have a lower prevalence of obesity, type 2 diabetes, and metabolic syndrome compared to the phenotypes A and B, their metabolic alterations are significantly more common than in controls.

Moreover, in patients with phenotype C, prediabetes and lipid alterations are as common as in PCOS patients with phenotype A ( Figs. 1–3 ) suggesting that phenotype C cannot be considered a PCOS phenotype with no metabolic alterations. Instead, these patients, while not presenting fertility problems, should be carefully evaluated for metabolic alterations and will need close follow-up because they present important cardiovascular and metabolic risks.

In our study, only normoandrogenic (phenotype D) women with PCOS have a normal metabolic status suggesting that the role of increased androgens in inducing metabolic alterations may be more important than previously thought. However, our experience with this subgroup of PCOS patients is limited and larger groups of patients with phenotype D (with a careful diagnosis of normal androgen levels) should be evaluated.