Women With Alcohol Use Disorder Have a Different Disease

Alcohol affects men and women very differently, especially women dependent on alcohol. For five years, the Yale Program on Sex Differences in Alcohol Use Disorder (AUD), headed by Dr. Sherry McKee, has led pioneering research highlighting distinct neurobiological, psychological, and treatment-related differences between men and women with AUD. While controversial, this body of work suggests female alcohol use disorder is uniquely different from the disorder in men. Consequently, women with AUD need a sex-specific approach.

The Yale Specialized Center of Research Excellence (SCORE), funded by an $8.4 million grant, focuses on developing sex-specific treatments for AUD, addressing women’s unique needs. Ongoing clinical trials are evaluating the efficacy of treatment medications in women, like naltrexone and varenicline, aiming to tailor pharmacological interventions based on sex-specific responses.

Sherry McKee, PhD, Professor Yale Department of Psychiatry

Source: Yale University School of Medicine / With Permission

"Alcohol use disorder is incredibly heterogeneous," says Sherry McKee, PhD, professor of psychiatry at Yale School of Medicine (YSM) and director of the Yale SCORE program. "Not every medication is going to work for every person. And one of the key pieces that’s been missing in our research is a focus on sex ….”

A recent Yale press release highlights significant differences between women and men regarding AUD, binge drinking, metabolism, the risk of overdose/poisoning, and treatment. Despite alcohol being a Group 1 carcinogen, meaning it’s known to cause cancer in humans, and the World Health Organization (WHO) declaring no level of alcohol consumption as safe, alcohol consumption continues to rise. In fact, alcohol risks are more pronounced and life-threatening in women.

Who Drinks More? A Change in the Pattern

Throughout history, men have consumed more alcohol than women. But the Yale Program reports women in the US have caught up to or passed men. This is causing serious health problems. The Centers for Disease Control and Prevention (CDC) reported between 2016-2021, alcohol-related deaths increased by 35% in women and 27% in men. Studies also show from 2006-2014, emergency room visits related to alcohol use rose by 70% in women versus 58% in men. Also, from 2000-2015, alcohol-related hospitalizations increased by nearly 70% in women versus 43% in men.

The number of alcohol-related deaths is not only rising faster among women but is also driven by smaller amounts of alcohol. Men must consume at least 3.2 drinks per day for an increased risk of premature death, whereas women only need to consume 1.8 drinks. Although binge drinking remains more common among men, the gender gap is narrowing as rates among women increase.

Blood Alcohol Differences

The primary enzyme metabolizing alcohol—alcohol dehydrogenase—is 40% less active in women. As a result, when a woman and a man of the same age and weight drink the same amount, the woman will experience a greater blood alcohol concentration (BAC).

"Let us say they are both 150 pounds and 48 years old, and they consume three drinks in two hours," McKee says. "The man will be significantly under the legal drinking limit for driving, and the woman will be over the legal drinking limit, just because of this difference in how alcohol is metabolized."

Women are more susceptible to alcohol poisoning due to faster intoxication and higher BACs, even with lower alcohol intake. In addition, women are more prone to alcohol-related liver diseases, such as hepatitis and cirrhosis. Here’s another key factor: Women are more likely than men to consume alcohol in response to stress/negative emotions.

Brains, Alcohol, and Females

A woman's prefrontal cortex of the brain develops earlier than men's, acting as a brake on impulsivity. The prefrontal cortex manages executive functions such as impulse control and decision-making. Another part of the brain, the amygdala, is associated with emotional responses, especially fear-related reactions. Women show greater reactivity of the amygdala than men, making them more susceptible to anxiety or other mood disorders. This may explain why women, unlike men, drink alcohol to cope with negative emotions. McKee says these findings may also explain why women who suffered major stressors in early childhood, such as abuse or neglect, might be especially vulnerable to developing alcohol use disorder.

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These research findings reveal men and women have a very different AUD disease, with men more driven by rewards and women more influenced by stress and emotional regulation.

Increased Health Risks in Women Who Drink

Women who drink are at a disproportionately greater risk than men for brain damage from drinking, as well as cognitive deficits, various cancers, including breast cancer, cardiovascular issues, liver injury, and immune system dysfunction. Female alcoholics often present with atypical cardiovascular symptoms (e.g., fatigue, nausea, shortness of breath) rather than chest pain. Women also have worse outcomes post-heart attack, partly due to delayed diagnosis and treatment.

Drinking is associated with a greater risk of mental health issues and suicide in women, as well as pregnancy and perinatal-related complications. Furthermore, alcohol can cause hormonal imbalances and menstrual irregularities. Fluctuations in estrogen and progesterone levels in women impact alcohol metabolism and sensitivity, influencing drinking behaviors and relapse risks.

Men release more dopamine than women in response to alcohol consumption, which may explain differences in alcohol reward, craving, and heavy drinking between the sexes. Scientists are also investigating neuroimmune and hormonal influences to understand alcohol’s sex-specific effects to develop more effective treatments.

Research utilizing positron emission tomography (PET) scans has revealed women with AUD may experience greater deficits in microglial cells—critical components of the brain’s immune system—compared to men. These findings suggest neuroinflammation plays a significant role in women’s AUD and treatments targeting this inflammation could be beneficial.

Alcohol consumption signals a potential threat to the brain’s immune system and activates microglia to initiate repair functions. Now, a new Yale-led study in the journal Biological Psychiatry, in press, May 22, 2025, reveals a surprising finding: Women with alcohol use disorder have lower levels of microglia than healthy women. This is not the case for men.

What Women With AUD Need

Women need sex-specific AUD diagnosis, prognosis, and treatment. Yale’s experts remind us AUD medications like Antabuse and Naltrexone were approved after studies primarily performed on men. In addition, research indicates naltrexone is more likely to have side effects in women, such as nausea and sleep disturbances, making women less likely to stick with treatment.

The Yale researchers hope to develop effective treatments for women with AUDs. Currently, they are looking at Pregnenolone, a naturally-occurring neurosteroid, for its potential to reduce alcohol cravings and anxiety by modulating the stress response system. A 12-week clinical trial is currently underway to assess its efficacy.

Although originally approved for high blood pressure, another drug, prazosin, is being evaluated for its ability to decrease alcohol intake and cravings, particularly in individuals with drinking associated with stress and anxiety. In addition, guanfacine is being studied for its potential to address the “dark side of addiction,” such as stress-induced relapse, with a focus on sex-specific responses to treatment.

Summary

Historically, alcohol use disorder research has focused on men. But as AUD in women rises, researchers have found men and women drink for different reasons, and women face greater health risks. Men are more likely to drink to experience pleasure and social connections, while women are more likely to drink to manage stress and anxiety. "So, we are developing medications that target stress pathophysiology," says McKee.