The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.

Methods: A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.

Results: Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).

Conclusions: Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.

Figure 1

Selection process for the placebo-controlled randomized trials of the effects of statins on testosterone.

Figure 2

Funnel plots of placebo-controlled randomized trials examining the effects of statins on testosterone by sex and for men and women together.

Figure 3

Forest plots of placebo-controlled randomized trials examining the pooled effects of statins on testosterone for men (top panel), women (middle panel) and both sexes (bottom panel). In Kazerooni et al. [32], the reported SD was much smaller than in other trials, whereas the reported SD multiplied by the square root of the sample size was similar to the SDs reported in other trials. If we were to assume that the reported SD was actually the standard error, the pooled estimate for women would be -0.40 nmol/l (95% CI -0.83 to 0.03) and the overall pooled estimate would be -0.44 nmol/l (95% CI -0.80 to -0.08). Mean = mean difference; SD = standard deviation.