Statins are one of the most prescribed classes of drugs, and atorvastatin is the most used drug in that class. People take statins to lower their blood cholesterol levels and reduce their risk of heart disease. However, statins may also lower levels of testosterone and other androgens. These are hormones that have important functions in male and female health and development.
What did we do?
We wanted to measure the effect of atorvastatin on testosterone and other androgens.We searched for all studies in the medical literature that compared the effect of different doses of atorvastatin to placebo or no treatment in males and females, and also reported on their levels of testosterone and other androgens . We looked for studies in which the treatments people received were decided at random. This type of study usually gives the most reliable evidence about the effects of a treatment. Studies could have participants of any age.
After we identified these studies, we compared the results, and summarized the evidence from all the studies. Finally, we rated our confidence in the evidence ("certainty of the evidence"), based on such factors such as study methods and sizes, and how consistent the findings were across studies.
What did we find?
We found six studies, involving a total of 265 participants. Studies were conducted in China, Finland, Iran, Turkey, the UK and the USA.
Evidence from four studies suggests that atorvastatin may have a potentially beneficial effect in females with polycystic ovary syndrome (PCOS), a set of symptoms that may develop in women with higher than normal androgen levels. In women with PCOS, atorvastatin helped to decrease total testosterone and other androgens.
We found two studies in men, where atorvastatin had no significant effect on total testosterone.
What does this mean?
The certainty of the evidence for all outcomes ranged from low to very low. Our statistical estimates for the effects of atorvastatin on testosterone and other androgens in males and females may be very different from the true effects. More studies are needed to answer this important question.
How up-to-date is this evidence?
The evidence from our review is current to November 2020.
We found no significant difference between atorvastatin and placebo 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.
Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial.
To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment.
To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment.
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work.
RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females.
Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence.
We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 μmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels.