The opioid epidemic has claimed more than half a million lives in the U.S. since 1999, about three-quarters of them men, according to the National Institutes of Health (NIH). Although men’s disproportionate rates of opioid abuse and overdose deaths are well-documented, the reasons for this gender disparity are not well understood.
A new study in rats by researchers at Washington University School of Medicine in St. Louis suggests that one underlying cause may be biological. Male rats in chronic pain gave themselves increasing doses of an opioid — specifically, fentanyl — over time, while female rats with the same pain condition kept their intake at a constant level, similar to what is seen in people. The behavioral difference was driven by sex hormones, the researchers found: treating male rats with the hormone estrogen led to them maintain a steady level of fentanyl intake.
The findings, published March 10 in the journal Neuron, indicate that differences in how men and women use and misuse opioids may be driven by their hormones, and that a deeper understanding of how sex hormones interact with chronic pain could open up new approaches to addressing the opioid epidemic.
“These data suggest that men may be inherently predisposed to misuse opioids in the context of pain because of their balance of sex hormones,” said lead author Jessica Higginbotham, a postdoctoral researcher in the lab of Jose Moron-Concepcion, PhD, the Henry Elliot Mallinckrodt Professor of Anesthesiology at WashU Medicine and the paper’s senior author. “We focused on estrogen in this study, but I doubt the effect we saw is due to estrogen alone. It is more likely to be the balance of all the sex hormones in the body that influences risk. Men and women have the same sex hormones, just in different amounts, and our data suggest that females have a more protective balance than males. But if that balance changes, the risk of developing opioid use disorder could change, too.”