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July 15, 2015
Statins Tend to Decrease Aggression in Men, Raise It
in Some Women San Diego—Statins have behavioral effects in users, but whether aggression increases or decreases varies by gender, according to a new study. That’s according to the results of a new randomized trial, published online recently by PLOS ONE, which found that aggressive behavior typically declined among men on statin therapy compared to placebo but often increased in women. “Many studies have linked low cholesterol to increased risk of violent actions and death from violence, defined as death from suicide, accident and homicide,” said lead author Beatrice A. Golomb, MD, PhD, professor of medicine at the University of California, San Diego School of Medicine. “There have been reports of some individuals reproducibly developing irritability or aggression when placed on statins. Yet in contrast to prestatin lipid-lowering approaches, clinical trials and meta-analyses of statin use (in which most study participants were male) had not shown an overall tendency toward increased violent death. We wanted to better understand whether and how statins might affect aggression.” Background information in the article notes that previous studies have raised questions about adverse behavioral changes with statins, such as irritability or violence, but findings have been inconsistent. For this blinded study, researchers randomly assigned more than 1,000 adult men and postmenopausal women to either simvastatin, pravastatin, or a placebo for 6 months. Male and female study cohorts were separately randomized, and analyzed separately. A weighted tally of actual aggressive acts against others, themselves or objects in the previous week was used to measure behavioral aggression in study subjects. Other measurements included testosterone levels and reported sleep problems, which can affect aggression and which, in past studies, have been tied to simvastatin use. Results indicate that, for postmenopausal women, especially those older than age 45 years, the typical effect was increased aggression. In fact, the greatest increase appeared to be in women who began with lower aggression at baseline. The results in men were more mixed, but when three “outliers”—all men who took statins and displayed significant increases in aggression—were removed from the calculations, a decline in aggressive behavior for male statin users was notable, especially for those on pravastatin. The strongest effect was in younger men who tend to be more aggressive, but Golomb explained that “actually the effect was most evident in less aggressive men.” The authors explain that a larger drop in testosterone on simvastatin was linked, on average, to a greater decrease in aggression, while a greater increase in sleep problems on simvastatin was tied to heightened aggression. They point out that the sleep issue helped explain the outliers; both men were on simvastatin and had developed more serious sleep problems. “The data reprise the finding that statins don't affect all people equally—effects differ in men versus women and younger versus older,” Golomb added. “Either men or women can experience increased aggression on statins, but in men the typical effect is reduction.”
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