The effect of statins on aggression appears to differ based on sex and age, as a study published in PLOS ONE found that aggression increased in postmenopausal women taking statins but actually decreased in men.

Researchers at the University of California, San Diego School of Medicine conducted a double-blind, sex-stratified study where 1,016 adults were randomly assigned to simvastatin 20mg, pravastatin 40mg, or placebo for six months. Actual behavioral aggression during the previous week, including verbal assaults, assaults against objects, assaults against others, and assaults against self, was measured using the Overt-Aggression-Scale-Modified–Aggression-Subscale (OASMa). Testosterone levels and reported sleep problems were also noted during the study.

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Women aged ≥45 years were significantly more likely to experience aggression and the effect was stronger in those who had lower aggression at baseline. After excluding three outliers, men had a significant decrease in aggression with statin therapy; this effect was most evident in men who were less aggressive at baseline. Changes in testosterone and sleep predicted aggression, as a larger drop in testosterone with simvastatin was associated with a greater drop in aggression. A greater increase in sleep problems in those taking simvastatin was also significantly linked to a greater rise in aggression.

Lead author Beatrice A. Golomb, MD, PhD, proposed that factors like oxidative stress and cell energy could play a role in the biological explanations linking statins to behavior.

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