Effects of Simvastatin and Oral Contraceptive Agent on Polycystic Ovary Syndrome: Prospective, Randomized, Crossover Trial

Abstract

There is increasing evidence that statins improve the lipid profile and also have cardioprotective effects that include an anti-inflammatory action and improved endothelial dysfunction. Preliminary findings from a 12-week trial suggest that women with polycystic ovary syndrome (PCOS) had lower total testosterone levels and a better lipid profile when given simvastatin plus an oral contraceptive pill (OCP) rather than an OCP alone. The final results of this trial, after a crossover of treatments and follow-up for 24 weeks, now are available. The 48 women entered into the study were prospectively randomized to receive simvastatin plus OCP for 12 weeks followed by OCP alone for 12 weeks longer, or OCP alone for 12 weeks and then combined treatment. Simvastatin was given orally in a daily dose of 20 mg. The OCP contained 20 μg of ethinyl estradiol and 150 μg of desogestrelpo. Total serum testosterone declined 38% after combined treatment but only by 26% with OC alone, a highly significant difference. The corresponding figures for free testosterone levels were 58% and 35%. Hirsutism decreased by about 8% with combined treatment and by less than 5% with OCP treatment; this difference also was significant. Similar effects on levels of dehydroepiandrosterone sulfate accompanied the two treatment regimens. Simvastatin therapy correlated with decreased levels of luteinizing hormone, but no changes in follicle-stimulating hormone or prolactin. Total cholesterol decreased by 7.5% with combined treatment but increased modestly on OCP alone. Both treatments were associated with increases in high-density lipoprotein cholesterol. With combined treatment, low-density lipoprotein cholesterol decreased by 20%. Triglycerides did not change with combined treatment but rose by one-fifth on OCP alone. OCP treatment led to a modest but significant negative effect on glucose metabolism. Both combined treatment and OCP correlated with a significant increase in fasting insulin. Statin therapy significantly improved markers of systemic inflammation including high-sensitivity C-reactive protein and soluble vascular cell adhesion molecule. No significant changes in body mass index were noted, and none of the subjects developed symptoms of muscle damage or biochemical evidence of liver dysfunction. These findings show that simvastatin therapy can substantially lessen clinical and endocrinological elements of PCOS and, at the same time, decrease cardiovascular risk factors.