Do Statins Decrease Endogenous Testosterone?
Yes, statins do cause a modest but statistically significant decrease in total testosterone levels in men, though the clinical significance remains uncertain as bioavailable and free testosterone may not be affected.
Evidence from Research Studies
Effect in Men with Normal Testosterone
The most robust evidence comes from multiple meta-analyses and population studies:
A 2013 meta-analysis of 5 randomized controlled trials involving 501 men (mainly middle-aged with hypercholesterolemia) demonstrated that statins lowered total testosterone by -0.66 nmol/L (95% CI -0.14 to -1.18) 1.
A 2024 systematic review and meta-analysis found that statins reduced total testosterone by 55.02 ng/dL in cross-sectional studies (p<0.00001) and by 13.12 ng/dL in randomized controlled trials (p=0.03), though this decrease was not sufficient to drop levels below the normal range 2.
The Rotterdam Study, a large population-based investigation of 4,166 men, showed that current statin use was associated with significantly lower total testosterone (β -1.14 to -1.24 nmol/L) and non-SHBG-bound testosterone (β -0.42 nmol/L), with a dose-dependent trend 3.
Mechanism and Biological Plausibility
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis 4. Since cholesterol is the precursor for testosterone biosynthesis, this mechanism provides biological plausibility for testosterone reduction 3, 5.
Critical Nuance: Total vs. Bioavailable Testosterone
An important clinical caveat emerges from a 2009 study of 355 men with type 2 diabetes: while statins (particularly atorvastatin) were associated with lower total testosterone (11.9 vs. 13.4 nmol/L, p=0.006), there was no significant effect on bioavailable testosterone, free testosterone, or hypogonadal symptoms 6. This suggests the reduction may be clinically less relevant than the numbers suggest.
Statin-Specific Differences
Atorvastatin appears to have the most pronounced effect, with a dose-response relationship where doses ≥20 mg resulted in total testosterone levels of 9.6 nmol/L compared to 13.4 nmol/L in untreated men (p=0.017) 6. Simvastatin use was not associated with significant testosterone reductions 6.
Duration and Reversibility
The effect appears with both short-term (1-6 months) and longer-term use (>6 months), with no association found between past statin use and testosterone levels, suggesting reversibility upon discontinuation 3.
Clinical Implications
Assessment Recommendations
When evaluating hypogonadism in men taking statins, particularly atorvastatin, measuring bioavailable or free testosterone is recommended rather than relying solely on total testosterone 6. Total testosterone measurements may lead to diagnostic error in this population, as the reduction in total testosterone may not reflect true androgen deficiency.
Monitoring Considerations
While guidelines recommend measuring testosterone levels in men with erectile dysfunction 4, clinicians should be aware that statin use may artificially lower total testosterone without causing true hypogonadism 6.
Magnitude of Effect
The testosterone reduction, while statistically significant, is modest (approximately 10-55 ng/dL depending on the study design) and typically does not result in levels below the normal range 2. The clinical relevance of this reduction remains uncertain, as symptoms of hypogonadism were not increased in statin users 6.
Common Pitfalls to Avoid
- Do not diagnose hypogonadism based solely on total testosterone in men taking statins, especially atorvastatin at doses ≥20 mg 6
- Do not assume the testosterone reduction is clinically significant without assessing bioavailable or free testosterone and clinical symptoms 6
- Be aware of the dose-dependent effect, particularly with atorvastatin 6
- Consider that the testosterone reduction may be reversible upon statin discontinuation 3