Cholesterol-lowering statin drugs might influence a person's aggressive behaviors, increasing or decreasing their irritability and violent tendencies, a new clinical trial suggests.
Men taking statins typically become less aggressive, while women on statins tend to become more aggressive, according to findings published July 1 in the journal PLOS ONE.
"Clinicians should be aware of this, and it's not bad for patients to be aware of it," said lead author Dr. Beatrice Golomb, a principal investigator at the University of California, San Diego School of Medicine. "If an individual develops a behavioral change, in my view medication should always be considered as a possibility."
However, the effect appears to be minimal and needs to be verified with follow-up studies, said one outside expert, Robert Geffner, founding president of the Institute on Violence, Abuse & Trauma at Alliant International University in San Diego.
"If I am reading their study right, it looks like they're dealing with really low levels of aggression to begin with," Geffner, a psychology professor at the university, said. "That's interesting, but I'm not sure how meaningful it is."
For the study, researchers randomly assigned more than 1,000 adult men and postmenopausal women to take either a statin medication or a placebo for six months.
The trial was aimed at clarifying a rather muddy picture that has emerged on the role that low blood cholesterol and statins might play in violent behavior, Golomb said.
Prior research has shown that low blood cholesterol levels can increase a person's aggressive behavior, increasing or decreasing the rate of violent death, violent crime and suicide, she added.
Even though statins reduce blood cholesterol levels, the drugs theoretically should lower aggressive tendencies by reducing testosterone levels and improving the ability of cells to generate energy, Golomb continued. But statins also can alter a person's serotonin levels, causing sleep problems and increasing aggressive behavior, the researchers noted.
The participants' behavioral aggression was measured by tallying any aggressive acts they performed against other people, objects or themselves in the previous week. Researchers looked for a change in aggression from the start of the study to the end.
They found that statins typically tended to increase aggression in postmenopausal women, with a significant effect on those older than 45. The increase appeared stronger in women who started out with lower levels of aggression, according to the study.
Analysis of the male participants proved trickier. Three men assigned to take statins had very large increases in aggression. When they were included in the review, statins had no effect one way or the other on average aggressive behavior.
But when the three outliers were removed from the group, researchers observed a significant decline in aggressive behavior for male statin users.
Statins' effect on hormone levels appeared to influence behavior, Golomb said. Those who experienced a decrease in testosterone due to statins also experienced a decrease in aggression. Those who slept worse -- possibly due to statins' effect on serotonin levels -- experienced an increase in aggression.
The sleep finding helped account for the male outliers, as the two men with the biggest aggression increases both had developed much worse sleep problems, Golomb noted.
Geffner said that it's well-known that "hormones and neurotransmitters are definitely a player" in the way the brain functions.
But he questioned whether excluding the three aggressive male outliers was appropriate in the analysis, since this could be evidence of statins increasing violent behavior.
Geffner also noted that the study started out with 2,400 people, but that nearly 1,400 were left out because they either didn't meet the criteria for the study or declined to participate.
"I just have a lot more questions than answers at this point," he said. "I think there are interesting things to follow up on, but I have many questions."