Comparison of effects of simvastatin and metformin in women with PCOS: a randomized trial

Abstract

Statins are HMG-Co-A reductase inhibitors with pleiotropic effects including decreased cholesterol synthesis and reduction of oxidative stress. In ovarian theca cell cultures, statins inhibit proliferation, promote apoptosis and lower steroidogenesis reducing expression of CYP11 and 3ßHSD. Statins may also decrease oxidative stress inhibiting expression of NADPH subunits. Recently, we have evaluated the effects of simvastatin on women with polycystic ovary syndrome (PCOS), randomizing the subjects to the use of oral contraceptive pill (OCP) alone or in combination with simvastatin. In the presence of OCP, simvastatin reduced hyperandrogenism and improved lipid profile. This is the first trial comparing the use of simvastatin with metformin in women with PCOS not using any hormonal treatment. Prospective, randomized trial. Forty-one women with PCOS were enrolled and 34 completed the trial. Age of the women was 25.5 ± 4.3 (mean ± SD) and BMI was 23.6 ± 4.1. Patients were randomized to: simvastatin (S) alone (20 mg/day), metformin (M) alone (1,700 mg/day), and simvastatin+metformin (S+M). Evaluations were performed at baseline and after 3 months of treatment. All subjects were using barrier contraception. Data were analyzed using Student's t-test and Wilcoxon Sign-Rank test. S reduced total testosterone by 14% (P=0.005); M had no effect (decrease by 0.3%; P=0.9) while S + M decreased testosterone by 11% (P=0.02). Similarly, S decreased free testosterone by 12% (P=0.005) while M or M + S had no effect. In parallel, acne score improved following treatment with S by 46% (P=0.02); M or S + M had no effect. S also decreased total cholesterol by 22% while M had no effect (decrease by 2%). S + M reduced total cholesterol by 32%; this effect was greater than that of S alone (P<0.05). Similar effects of S were observed on LDL and triglycerides. Body mass index decreased minimally (by 2.5–3%) following each treatment (P<0.05). Insulin sensitivity index determined by a 2-hour glucose tolerance test increased following M (by 19%, P<0.05). This is the first study demonstrating that statin used alone significantly lowers hyperandrogenism and hyperandrogenemia in women with PCOS. Furthermore, as anticipated, simvastatin improves lipid profile. The effects of simvastatin are likely mediated by mechanisms distinctly different than those of metformin. We propose that statins use may represent a novel treatment of PCOS-related hyperandrogenism.