Scientists Reveal Why Women Are More Easily Addicted to Cigarettes

A newly discovered brain circuit may explain why women tend to become hooked on nicotine more quickly than men.

Smoking remains a leading cause of preventable disease and death in the United States, with more than 480,000 Americans killed by smoking every year, according to the U.S. Centers for Disease Control and Prevention. As of 2021, roughly 11 percent of American adults reported smoking cigarettes, with men slightly more likely to smoke than women.

However, while fewer women might smoke on average, previous studies have shown that women are more likely to develop a nicotine addiction and tend to become addicted more quickly with lower nicotine exposures.

"Studies show that women have a higher propensity to develop addiction to nicotine than men and are less successful at quitting," Sally Pauss, a doctoral student at the University of Kentucky College of Medicine in Lexington who led the project under the supervision of associate professor Terry Hinds Jr., said in a statement.

"Our work aims to understand what makes women more susceptible to nicotine use disorder to reduce the gender disparity in treating nicotine addiction."

The Role of Estrogen

One clear difference between men and women is their production of estrogen. Therefore, the researchers trawled through a large library of genes known to be activated by this hormone, specifically those expressed in our brains. Only one class of candidate genes fit this criteria: those coding for a group of proteins called olfactomedins, which play a diverse range of roles in the early development and functional development of the nervous system.

The researchers then performed a series of studies with human uterine cells and rats to better understand the interactions between olfactomedins, estrogen and nicotine. Through their experiments, an interesting feedback loop emerged: estrogen activates olfactomedins, which, in turn, are suppressed in the presence of nicotine in areas of the brain involved in reward and addiction. In other words, this olfactomedin intermediary could be driving individuals to seek out nicotine to satisfy these reward circuits.

Making It Easier for Women To Quit Smoking

"If we can confirm that estrogen drives nicotine seeking and consumption through olfactomedins, we can design drugs that might block that effect by targeting the altered pathways," Pauss said. "These drugs would hopefully make it easier for women to quit nicotine."

The researchers said that this knowledge could be particularly useful for those taking estrogen in the form of oral contraceptives or hormone replacement therapy, which might increase the risk of developing a nicotine use disorder.

The findings will be presented at the annual meeting of the American Society for Biochemistry and Molecular Biology on March 25 in San Antonio.

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