Study links statin to higher aggression in women

A new study on the effects of statin on behavior reveals the drug increases aggressive behavior in women while reducing aggression in men.

The research conducted by the University of California, San Diego School of Medicine, which involved more than 1,000 adult men and postmenopausal women, reveals higher aggression level among the latter group, particularly among those older than 45. Compared to placebo, the rise in aggression appeared stronger in women who began with lower aggression at baseline.

The findings for men were more complex. Three male participants who took statins, with no one taking placebo, showed significant increase in aggression. No average effect was shown after analysis, but a decline in aggressive behavior for male statin users was significant when the “outliers” were removed from the analysis. It was stronger among younger men who tend to be more aggressive, although actually the effect was most evident in less aggressive men, according to lead author Beatrice A. Golomb.

 Statin effects on testosterone and sleep contributed to the bidirectional effects as shown by further examination. 

 Ms. Golomb, MD, PhD, professor of medicine, said: “Changes in testosterone and in sleep problems on simvastatin each significantly predicted changes in aggression. A larger drop in testosterone on simvastatin was linked, on average, to a greater drop in aggression. A greater rise in sleep problems on simvastatin was significantly linked to a greater rise in aggression. The sleep finding also helped account for the outliers: The two men with the biggest aggression increases were both on simvastatin, and both had developed ‘much worse’ sleep problems on the statin.”

 The study, published in the online issue of PLOS ONE, is the first randomized trial to explore the effects of station on behavior. Previous studies of this hugely popular drug class for managing blood cholesterol levels and reducing heart disease risks have raised concerns about adverse behavioral changes, including irritability or violence, but findings have been inconsistent.

 One early hypothesis states lower levels of cholesterol may reduce brain serotonin. Low brain serotonin activity is linked to violence, one of the most consistent findings in biological psychiatry. Although whole blood serotonin, which can relate inversely to brain serotonin, was not a predictor in this study, testosterone and sleep were, for those on simvastatin. Dr. Golomb postulates that other factors, including oxidative stress and cell energy, may play a role.

“Many studies have linked low cholesterol to increased risk of violent actions and death from violence, defined as death from suicide, accident, and homicide. There have been reports of some individuals reproducibly developing irritability or aggression when placed on statins. Yet in contrast to pre-statin 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,” Dr. Golomb stated.

 Participants in the research were given either a statin—simvastatin or pravastatin—or a placebo for six months. The participants and researchers did not know who was receiving the drug or the placebo.

 The researchers measured behavioral aggression using a weighted tally of actual aggressive acts against others, self, or objects in the prior week. They also measured testosterone levels and reported sleep problems. Simvastatin is known to affect both measures, while both testosterone and sleep can affect aggression. Because it was shown that statin use affected the genders differently, the male and female participants were separately randomized and analyzed separately.

Dr. Golomb noted that the findings help clarify seeming inconsistencies in the scientific literature.

“The data reprise the finding that statins don’t affect all people equally—effects differ in men versus women and younger versus older. Female sex and older age have predicted less favorable effects of statins on a number of other outcomes as well, including survival.”