Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial

Epidemiological and clinical studies have suggested that powerful cholesterol lowering may have adverse effects on mood and psychological well-being. Inhibition of cholesterol biosynthesis by simvastatin (a hydroxymethyl glutaryl coenzyme A reductase inhibitor) may also reduce steroid hormone biosynthesis. To explore if mood changes are related with steroid hormone levels, we designed a randomized double-blind placebo-controlled crossover trial. The separate and combined effects of a Mediterranean-type diet intervention and treatment with simvastatin 20 mg/day PO for 12 weeks were studied in 120 hypercholesterolemic but otherwise healthy middle-aged men. Psychological functioning was assessed with questionnaires, and steroid hormone levels in blood were assayed radioimmunologically before and after the treatments. Simvastatin resulted in a statistically significant increase of depression and somatization without changes in the anxiety, hostility or aggression scores. Mood changes seemed to be unrelated with the statistically significant but clinically insignificant decline in serum testosterone levels and unrelated with the increase in serum dehydroepiandrosterone levels.