The effect of atorvastatin on adrenal and ovarian hyperandrogenemia in patients with polycystic ovary syndrome.
Thozhukat Sathyapalan1, Karen A Smith2, Anne-Marie Coady3, Eric S Kilpatrick2 & Stephen L Atkin1
Context: Hyperandrogenemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (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 levels in patients with PCOS.
Objective: This randomized double blind placebo controlled study was conducted to study the effects of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS.
Intervention: Forty medication naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. Subsequently, a 3 month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were the changes in androstenedione and DHEAS concentrations.
Results: The mean (S.D.) baseline androstenedione (5.6 (0.9) vs 5.5(1.3) nmol/l; P=0.58) and DHEAS (7.1 (1.0) vs 7.2 (1.2) μmol/l; P=0.72) levels were comparable between two groups. There was a significant reduction of androstenedione (5.6 (0.9) vs 4.7 (0.7) nmol/l; P=0.03) and DHEAS (7.1 (1.0) vs 6.0 (0.9) μmol/l; P=0.02) with atorvastatin compared to placebo. Three months treatment with metformin maintained the reduction of androstenedione and DHEAS levels with atorvastatin compared to 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 levels and indicating that the reduction of the hyperandrogenaemia is due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.