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Effect of statins on aggression varies according to age, sex
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Men and women experienced different effects on aggression from treatment with statins, with men exhibiting a decrease and women an increase in aggression, according to results from the UCSD Statin Study.
In the parallel-design, double blind trial, researchers evaluated the influence of statin use on aggression in 692 men and 324 postmenopausal women between 2000 and 2005. Patients were stratified by sex and randomly assigned 20 mg simvastatin, 40 mg pravastatin or placebo for 6 months. Aggression, measured according to the Overt-Aggression-Scale-Modified-Aggression-Subscale (OASMa), was the primary outcome of the study. Other evaluated factors included serotonin levels and self-reported sleep problems.
Men exhibited a decrease in behavioral aggression with statin use, particularly with pravastatin, with a 1-point change on OASMa after treatment (P = .038). Three statin users experienced a marked increase in aggression, with an OASMa change of 40 points or more, which offset an otherwise significant difference between statin users and those who received placebo, the researchers noted. Excluding these outliers, an OASMa decrease of 1.3 occurred among statin users (P = .0009), along with a decrease of 1.4 in the simvastatin group (P = .0015) and of 1.2 in the pravastatin group (P = .0083).
The decrease in aggression was more pronounced among patients aged 40 years or younger, who exhibited an OASMa difference of –1.4 (P = .026). Men who did not exhibit aggression at baseline were protected against manifestations of aggression, with a –2.4 difference observed between statin users and those who received placebo (P = .0016).
The researchers noted that testosterone was reduced among men who received statins, particularly simvastatin. This reduction in testosterone was predictive of a decrease in aggression (beta level = 0.64; P = .034), particularly among those treated with simvastatin (beta level = 1.29; P = .009). However, men treated with statins also exhibited increased sleep problems, which were predictive of an increase in aggression (beta level = 2.2; P < .001), particularly with simvastatin (beta level = 3.3; P < .001).
Among postmenopausal women, researchers observed a borderline significant increase in aggression with the use of statins, which became statistically significant after the exclusion of one patient who was of younger age and surgically menopausal (beta level = 0.7; P = .039). This increase was significant among women aged at least 45 years (beta level = 0.68; P = .048) and persisted at age cutoffs of at least 50 years or at least 55 years. The researchers also noted that women with low aggression at baseline experienced a more pronounced increase in aggression than those with higher baseline aggression (beta level = 0.84; P = .006).
“The data reprise the finding that statins don’t affect all people equally — effects differ in men vs. women and younger vs. older [patients],” Beatrice A. Golomb, MD, PhD, professor of medicine at University of California, San Diego School of Medicine, said in a press release. “Either men or women can experience increased aggression on statins, but in men the typical effect is reduction.” – by Adam Taliercio
Disclosure: The researchers report no relevant financial disclosures.
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