Context: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and cardiovascular risks including dyslipidemia and systemic inflammation. In vitro, statins decrease proliferation and steroidogenesis of ovarian theca-interstitial cells.

Objective: To compare effects of two treatments of PCOS: simvastatin plus oral contraceptive pill (OCP) vs. OCP alone.

Design: In a prospective, cross-over trial 48 women with PCOS were randomized to either simvastatin plus OCP for 12 weeks followed by OCP alone for an additional 12 weeks; or to OCP alone for 12 weeks, and subsequently simvastatin plus OCP for an additional 12 weeks. Evaluations were performed at baseline, after 12 weeks (cross-over) and after 24 weeks. Data were analyzed using a random effects model.

Setting: Academic medical center.

Primary outcome: Serum total testosterone.

Results: Total testosterone decreased by 38% following Statin+OCP, while OCP alone led to a 26% decrease; the statin-attributable effect was significant (P < 0.004). Free testosterone declined by 58% following Statin+OCP, significantly more than the 35% decline following OCP alone (P = 0.006). Hirsutism decreased by 8.1% after Statin+OCP, a greater effect than the 4.7% decrease after OCP alone (P = 0.02). Statin decreased LH, but not FSH or prolactin. Statin + OCP decreased total and LDL cholesterol, respectively, by 7.5% and 20%. OCP alone led to a 5% increase of total cholesterol without effect on LDL cholesterol. Statin prevented OCP-induced increase of triglycerides. C-Reactive Protein decreased by 45% following Statin+OCP, a significantly different effect (P = 0.006) than a 6% increase following OCP alone. Soluble vascular cell adhesion molecule-1 decreased by 18% following Statin+OCP, a greater decline than the 10% decrease following OCP alone (P = 0.01).

Conclusions: Simvastatin improved endocrine/clinical aspects of PCOS and had beneficial effects on lipid profile and markers of systemic inflammation.