In an innovative preclinical study published in Nature Communications on December 30, researchers at Weill Cornell Medicine discovered a direct link between oestrogen levels and binge drinking in females. The findings shed light on a previously unexplored aspect of alcohol consumption disorders and suggest possible paths for focused treatment. 

"We know a lot less about what drives alcohol drinking behaviour in females because most studies of alcohol use have been done in males," explained Dr. Kristen Pleil, the study's senior author and associate professor of pharmacology. The study reveals circulating oestrogen as a major cause of binge drinking in women, particularly during periods of high hormonal activity. This discovery sheds light on the molecular reasons underlying known sex disparities in alcohol intake tendencies. 

The findings are especially significant in light of previous research revealing that women consumed more heavy alcohol than males during pandemic lockdowns. According to Dr. Pleil, this behaviour has serious health consequences because "many studies show that this pattern of drinking enhances alcohol's harmful effects." Women have seen an increase in alcohol-related hospital visits and consequences during and after the pandemic, highlighting the need for gender-specific research and interventions. 

In earlier research, Dr. Pleil's group found that female mice that drank a lot had more activity in a certain neuronal circuit in the bed nucleus of the stria terminalis (BNST). Building on previous research, the new study found that ooestrogen increases brain activity, particularly during high-ooestrogen periods of the oestrous cycle. 

"When a female takes her first sip from the bottle containing alcohol, those neurones go crazy," according to Dr. Pleil. "And if she's in a high-oestrogen state, they go even crazier." This increased brain activity causes females to "front-load," or consume a considerable amount of alcohol within the first 30 minutes of availability. 

One of the study's most striking findings was how quickly oestrogen took effect. In the normal process, oestrogen binds to nuclear receptors and changes gene activity over hours. But in this case, the hormone attaches directly to receptors on the surface of BNST neurones and changes their activity in minutes. Researchers proved this novel mechanism by using chemically produced oestrogen, which was unable to penetrate cells but still caused binge drinking. 

"We believe this is the first time anybody has shown that during a normal oestrous cycle, endogenous oestrogens made by the ovaries can use such a rapid mechanism to control behaviour," according to Dr. Pleil. This rapid effect contributes to the increased alcohol consumption observed during high-oestrogen conditions. 

The study also identifies potential treatments for alcohol consumption disorders. The team identified the oestrogen receptors involved in this process, as well as the signalling pathways. Interestingly, men share the same receptors and circuits, but the brain produces their oestrogen locally from testosterone. 

Targeting this pathway may lead to novel treatments. For example, blocking the enzyme that produces oestrogen could preferentially lower alcohol consumption during hormonal surges. "Putting this drug together with chemicals that change the effects of the chemicals made by the BNST neurones could possibly lead to a new, more targeted way to treat alcohol use disorder," says Dr. Pleil. 

This study is a huge step forward in understanding the biochemical basis of binge drinking in females. The discovery of estrogen's quick and direct influence on brain circuits paves the way for gender-specific treatments that could alleviate the terrible health effects of alcohol consumption disorders.