The benefit-to-risk ratio of common treatments in PCOS: effect of oral contraceptives versus metformin on atherogenic markers.

OBJECTIVE To compare the effects of oral contraceptives (OCPs) and metformin on atherogenic markers, including serum levels of advanced glycated end products (AGEs) and C-reactive protein (CRP), in lean women (Body Mass Index below 25 kg/m(2)) with polycystic ovary syndrome (PCOS), defined by NIH criteria. DESIGN Prospective open-label study. RESULTS One hundred and twenty women with PCOS were treated for 6 months with one of the following treatments: ethinylestradiol plus cyproterone acetate (OCP 1, n=40) or ethinylestradiol plus drospirenone (OCP2, n=40) or metformin (MET, n=40). The three groups were age and BMI-matched (mean age: 22 ± 0.56 yrs in group OCP1; 23.24 ± 0.64 yrs in group OCP2; 21.50 ± 0.53 yrs in group MET; mean BMI 21.80 ± 0.35 kg/m(2) in group OCP1; 22.37 ± 0.48 kg/m(2) in group OCP2; 23.03 ± 0.67 kg/m(2) in group MET). At 6 months serum AGEs were decreased in group OCP1 (P=0.005) and group MET (P=0.001), whereas these were marginally decreased in group OCP2 (P=0.069). Treatment with metformin was associated with a greater percent decrease of AGEs. CRP was decreased with metformin (P<0.001), but was increased with OCPs (P<0.001). CONCLUSIONS This study evaluates common therapeutic options in women with PCOS by reconsidering and prioritizing the goals of treatment. OCPs and metformin appear to have differential effects on atherogenic molecules in lean PCOS patients, but metformin was superior in reducing serum AGEs and CRP. Clinicians should individualize the benefit-to-risk ratio of pharmaceutical intervention in women with PCOS in order to choose the formulation with the greatest overall efficacy as well as safety in terms of cardiovascular risk.