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The effects of atorvastatin on testosterone levels in males and females : a systematic review and meta-analysis Shawish, MHD Ismail


Background: Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolemia and dyslipidemia. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgens levels caused by atorvastatin might cause negative effects except for conditions such as polycystic ovary syndrome (PCOS), where reduction of excessive levels of androgens is potentially beneficial. Objectives: To quantify the magnitude of the effects of atorvastatin as compared to placebo or no treatment on total testosterone, free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulfate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs). Methods: We searched major databases (CENTRAL, MEDLINE, EMBASE) and other sources for randomized controlled trials (RCTs) comparing atorvastatin with placebo or no treatment on testosterone levels in males and females. Two authors independently screened the citations, extracted the data and assessed the quality of the included studies. We used mean difference with 95% confidence interval to report effect size of continuous outcomes and a fixed effect model to combine the effect sizes across studies, and risk ratio to report effect size of the dichotomous outcome (WDAEs). iv Results: We included six RCTs involving 265 participants. Participants in two of the studies were male with normal or mild dyslipidemia (N=140). Participants in four of the studies were female with PCOS (N=125). Compared to placebo, atorvastatin had no significant effect on total testosterone levels (MD -0.20 [-0.77, 0.37] nmol/L in males. Atorvastatin may reduce total testosterone, FAI, androstenedione, and DHEAS in females by -0.27 (-0.50, -0.04) nmol/L, -2.59 (-3.62, -1.57), -1.37 nmol/L (-2.26, -0.49), and -0.64 μmol/l (-1.12, -0.16), respectively. Furthermore, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L [0.23, 5.99] compared to placebo. Conclusions: Compared to placebo atorvastatin had no significant effect on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.

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