HMG-CoA reductase inhibitors interfere with cholesterol synthesis and as such might theoretically blunt adrenal and/or gonadal steroid production. Results of clinical trials with drugs in this class have been inconsistent with regard to drug effects on basal and reserve steroid levels. However, clinical studies have shown that lovastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve, and does not reduce basal plasma testosterone concentration. Another HMG-CoA reductase inhibitor has been shown to reduce the plasma testosterone response to HCG. In the same study, the mean testosterone response to HCG was slightly but not significantly reduced after treatment with lovastatin 40 mg daily for 16 weeks in 21 men. The effects of HMG-CoA reductase inhibitors on male fertility have not been studied in adequate numbers of male patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Patients treated with lovastatin who develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should also be exercised if an HMG-CoA reductase inhibitor or other agent used to lower cholesterol levels is administered to patients also receiving other drugs (., ketoconazole, spironolactone, cimetidine) that may decrease the levels or activity of endogenous steroid hormones.
In AFCAPS/TexCAPS, the number of participants with consecutive elevations of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (> 3 times the upper limit of normal), over a median of years of follow-up, was not significantly different between the Lovastatin and placebo groups (18 [%] vs. 11 [%]). The starting dose of Lovastatin was 20 mg/day; 50% of the Lovastatin treated participants were titrated to 40 mg/day at Week 18. Of the 18 participants on Lovastatin with consecutive elevations of either ALT or AST, 11 (%) elevations occurred in participants taking 20 mg/day, while 7 (%) elevations occurred in participants titrated to 40 mg/day. Elevated transaminases resulted in discontinuation of 6 (%) participants from therapy in the Lovastatin group (n=3,304) and 4 (%) in the placebo group (n=3,301).