Simvastatin effects on androgens, inflammatory mediators, and endogenous pituitary gonadotropins among fertility patients with polycystic ovary syndrome: results from a prospective randomized placebo-controlled clinical trial

Objective: To evaluate effects of simvastatin on selected biochemical parameters and reproductive outcome among patients with polycystic ovary syndrome (PCOS) who undergo in vitro fertilization (IVF). Methods: PCOS patients were randomized to receive either oral simvastatin 20mg/d (n=32) or placebo (n=32) in a prospective, double-blind randomized clinical trial (NCT 005-75601) in parallel with controlled ovarian hyperstimulation for IVF. All patients were determined to be at average risk for cardiovascular disease, based on high sensitivity C-reactive protein (hsCRP) measurement at entry. Following an eight-week treatment interval concluding at periovulatory hCG administration, selected clinical and laboratory parameters were measured. Results: Mean serum total testosterone level decreased by 25% in the simvastatin group, compared to a 10% reduction in the placebo group (p<0.001). A trend of lower serum LH levels was noted in experimental and control groups (29 vs. 22%, respectively) although this difference was not significant (p>0.05). Neither fasting insulin nor QUICKI were significantly impacted by simvastatin (p>0.05). As expected, total cholesterol was not modified among placebo patients but was significantly reduced following simvastatin (p=0.001). Additionally, hsCRP and VCAM-1 were both significantly lower after simvastatin therapy compared to controls (p≤0.005, for both). At study completion, no important change in BMI was observed in either group (p≥ 0.60). While oocyte maturation rate, fertilization rate and clinical pregnancy rate were all higher following simvastatin, none of these improvements were statistically significant. Conclusions: This report presents data from the first prospective, randomised, placebo-controlled clinical investigation of simvastatin in the setting of PCOS and IVF. Simvastatin appears to be compatible with gonadotropin therapy for IVF and can offer beneficial endocrine and cardiovascular effects for PCOS patients who undergo embryo transfer. While the observed improvements in reproductive function were mild, the reductions in hsCRP and VCAM-1 following simvastatin treatment were significant, suggesting the need for further clinical trials to clarify simvastatin’s impact on reproductive physiology.