Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study

Background: Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS. Methods: A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations. Results: The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] mu mol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] mu mol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin. Conclusions: Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.