Summary: Women’s alcohol consumption has increased significantly to the same level as people’s, but women still face much greater health risks even at lower intake levels. A growing body of research is uncovering essential physiological gender disparities that influence why and how people drink, with pressure being a more prominent motivation for people.
To better understand these differences and to create more personalized, potent treatments, experts are now looking into mental circuits, cholinergic responses, and physiological influences. This job is particularly urgent, as alcohol-related fatalities and health problems are rising faster in women, but existing treatments have been mostly designed and tested on men.
Important Information
- Biological Vulnerability: Women metabolize alcohol differently, leading to higher blood alcohol levels and greater health risks at lower doses.
- Differences in the brains of women are related to alcohol use disorder and have distinct neuroimmune responses and stress-driven pathways.
- Tailored Treatments Needed: Current alcohol use disorder medications are based on male-focused research, underscoring the need for sex-specific therapeutics.
Source: Yale
Alcohol use disorder is a chronic disease that used to disproportionately affect men. However, for the first time in history, women are catching up.
Today, women in the United States are drinking and engaging in harmful alcohol use at rates on par with their male counterparts.
Men have historically been the focus of research on alcohol use disorder, which is characterized by an impaired ability to control alcohol use despite negative consequences.
However, researchers are discovering that men and women are motivated to drink for various reasons, and that women are more vulnerable to health risks as a result of the rise in alcohol use disorders in women.
Now, the , Yale Program on Sex Differences in Alcohol Disorder , is exploring the neurobiological drivers of drinking behavior and alcohol use disorder in women.
This work is assisting in the development of novel drugs that can treat alcohol use disorders based on studies involving primarily ( or largely exclusively ) men. This is a significant development considering the FDA’s currently approved treatments are based on this research.
” Alcohol use disorder is incredibly heterogenous”, says , Sherry McKee, PhD, professor of psychiatry at Yale School of Medicine ( YSM) and director of the Yale program.
Not every medication will work for everyone, according to the statement. And one of the key pieces that’s been missing in our research is a focus on sex and gender”.
Alcohol use is a growing problem for women’s health.
Last year, the Centers for Disease Control and Prevention , identified a disturbing trend—between 2016 and 2021, rates of alcohol-related deaths increased by 35 % in women ( and 27 % in men ). Some researchers believe that women’s social norm shifts may contribute to the rise in drinking.
” Women are now earning more, delaying marriage, and delaying childbirth”, says McKee.
” It’s thought that this may allow for more time and space for drinking.”
And, even among those who are married and starting families, alcohol companies have increasingly focused their marketing on women. Gendered alcoholic drinks like” Mom Water” have become more popular, and terms like “mommy juice” have started appearing in liquor stores.
” We’ve seen that marketing toward moms has normalized ‘ wine mom culture,'” says , Kelly Cosgrove, PhD, professor of psychiatry, of neuroscience, and of radiology and biomedical imaging at YSM.
The rise in drinking is suggested by research.  , One 2020 study  , found that the number of days in which women reported heavy alcohol use—at least four drinks within a couple of hours—rose by 41 %.
” It had to do with the amount of time people were at home and the stress they were feeling,” says Marina Picciotto, PhD, Charles B. G. Murphy Professor of Psychiatry at YSM.
The rise in alcohol use is especially concerning because women face greater drinking-related health risks at lower amounts of alcohol than men. We refer to this as the risk-severity paradox, according to McKee.
Studies have found that women who drink are at a disproportionately greater risk for brain damage, cognitive deficits, various cancers such as breast cancer, cardiovascular issues, liver injury, and immune system dysfunction.
Drinking is also linked to higher rates of suicide, physical and sexual assault, pregnancy- and perinatal complications, and other mental health issues. Furthermore, alcohol can cause hormonal imbalances and menstrual irregularities.
Alcohol-related deaths are rising faster among women and are also being caused by fewer alcohol-related deaths. Men need to drink at least 3.2 drinks per day to be at increased risk of premature death, whereas women , only need to consume 1.8.
Not even two drinks a day increase a woman’s risk, according to McKee.
These disparities are reflected in the health care system. Between 2006 and 2014, hospitalizations increased by 70 % and 43 %, and alcohol-related emergency room visits increased by 40 % and 43 % in women.
Why does alcohol disproportionately impact women?
Drinking partly increases the health risks for women because of their different alcohol metabolisms than men. Alcohol is not lipid-soluble. In other words, alcohol does not enter fat tissue when we consume it; instead, it simply disperses into tissue that contains water.
Women tend to have a lower percentage of body water and more fat tissue than men. They therefore have less fluid to dilute the alcohol, which results in a higher blood alcohol content ( BAC ).
Furthermore, the primary enzyme involved in the metabolism of alcohol—alcohol dehydrogenase—is as much as 40 % less active in women.
In consequence, a woman will have a higher BAC when a woman and a man of the same age and weight consume the same amount at the same rate.
” Let’s say they’re both 150 pounds and 48 years old, and they consume three drinks in two hours”, McKee says.
Because of this difference in how alcohol is metabolized, the man will be significantly under the legal drinking limit for driving, and the woman will be significantly under the legal drinking limit for both.
Current alcohol use disorder treatments don’t address underlying sex differences
As women continue to have more alcohol-related problems, they are also less likely than men to seek medical attention. McKee believes that societal stigma surrounding alcohol consumption is the primary reason for this reluctance.
Another challenge is that doctors do not take into account the sex-related differences when identifying and treating alcohol use disorders.
Women, for example, make up only about 13 % of participants studied in research on withdrawal, according to a review in , Frontiers in Psychiatry.
Medication trials for alcohol use disorder have also historically been conducted, primarily on male cohorts. Only 1 % of study participants involved in research on disulfiram—which, in 1948, became the first of the three FDA-approved medications for alcohol abuse —were women.
Another FDA-approved medication, naltrexone, is more likely to have side effects on women, such as nausea and sleep disturbances, making them less likely to continue taking the medication. Research has not revealed any sex differences related to acamprosate, the third FDA-approved medication.
The Yale Program on Sex Differences in Alcohol Disorder is conducting research into the main differences between male and female alcohol addiction mechanisms. One of its missions is to create more effective therapeutics tailored to women.  ,
Emerging research, for example, shows that drivers of alcohol use differ between sexes.
Women are more likely to drink to help manage stress, compared to men who are more likely to experience the positive aspects of alcohol, such as social connections and pleasure-seeking feelings.
” So, we’re developing medications that target stress pathophysiology”, says McKee.
This may be attributed to significant sex differences in the brain that, for example, emerge during adolescence, and particularly those that affect the interactions of three crucial neural systems, the prefrontal cortex, striatum, and amygdala.
The prefrontal cortex is responsible for executive functions such as impulse control and decision-making. The striatum activates when people engage in risk-taking scenarios and controls pleasure-seeking behaviors and processes rewards. The amygdala is associated with our emotional responses, especially those related to fear.
Studies of brain imaging have demonstrated that men have striatum activation, which increases their risk of engaging in risky behaviors.
The prefrontal cortex of women, on the other hand, develops earlier than in men—acting as a brake on impulsivity. Women also exhibit greater reactivity of the amygdala, which makes them more prone to anxiety and other mood disorders.
This may explain why women, unlike men, do not seek alcohol for the thrill of drinking, but rather to cope with negative emotions, McKee says.
These findings may also help explain why women who experienced significant stressors in early childhood, such as abuse or neglect, may be more prone to developing alcohol use disorders.
” The prefrontal cortex and the amygdala are key brain regions that interact with the experience of childhood adversity, childhood trauma, and stress”, says McKee.
Our working hypothesis is that these events will cause disorders like anxiety and depression to become internalized, which eventually lead to alcohol use. A lot of data suggest that this is a common pathway for alcohol use disorder in women”.
A closer examination of the differences between the female brain and the sex.
Yale School of Medicine researchers are now diving even deeper into understanding how differences in the brain may be uniquely driving alcohol use disorder in women. For instance, Cosgrove concentrates on the neuroimmune system.
” Most of us are familiar with the peripheral immune system—it keeps us healthy”, she says.
” But the brain has its own immune system, which is essential for good brain function, and we’ve been focusing on that.” It’s at the root of everything”.
The team at Cosgrove’s employs a radiotracer, a radioactive substance used in medical imaging, that binds to microglia, a crucial type of brain immune cell.
Microglia play a crucial role in maintaining brain health, and their dysfunction is associated with a range of neurodegenerative disease such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
The researchers are looking into whether there are differences between the microglia of men and women who have alcohol use disorder using positron emission tomography scans.
They are finding that women with alcohol use disorder have a greater deficit of microglia than their male counterparts.
According to Cosgrove, the findings are not surprising. The fact that women are more likely than men to suffer from autoimmune diseases such as multiple sclerosis points to differences underlying female immune processes.
She claims that “women have different immune systems inherently.”
Because immune dysfunction and inflammation are intertwined, when part of the neuroimmune system malfunctions, it can lead to increased or chronic inflammation.
Cosgrove’s study of neuroimmune differences between sexes might shed light on why women are more susceptible to alcohol-related complications like liver disease and other sex issues.
” These sex differences are likely driven by differences in inflammation”, says Cosgrove.
And we can consider various treatments and medications to address and manage this inflammation.
Cosgrove’s team is also working to identify other differences in the neuroimmune system that might be easier to therapeutically target.
” The protein TSPO, which is expressed by microglia,” is not an easy target to develop a medication for,” she says.
” But there are likely other targets that could give us new ideas for medication development”.
In the meantime, Picciotto is testing hypotheses raised by Cosgrove’s in mice. By feeding a blocker of microglia to female mice, for example, her team is studying how this alters their likelihood to choose alcohol over water when under stress.
They have found so far that reducing microglia by half has little to do with stress-induced alcohol consumption.
In future studies, they plan to investigate whether a greater deficit of microglia will impact mice behavior.
However, her team has demonstrated that reducing inflammation does not alter alcohol-seeking behaviors.
The researchers blocked signaling pathways known to promote inflammatory responses using a drug called apremilast. By reducing inflammation, this medication treats conditions like plaque psoriasis and psoriatic arthritis in humans.
They found that the drug reduced the likelihood of mice choosing alcohol over water.
Picciotto hopes to find out which specific subtypes of inflammatory responses are crucial in the context of alcohol use disorder in future studies.
” We’re interested in whether different circuits are engaged in response to stress-induced alcohol drinking in male and female mice”, she says.
” And we’re going to keep looking at the effects on neural signaling of these inflammatory responses.”
Envisioning a future of personalized therapies
Former U.S. Surgeon General Vivek Murthy released a report in January, further highlighting the urgent need for effective treatments for alcohol use disorder. The report, which was for the first time, communicated to the public.
The ongoing research at the Yale Program on Sex Differences in Alcohol Disorder is paving the way for a new era of more personalized therapeutics for women.
We’re only just getting started understanding what it is that makes the brain and body different for men and women who drink, says Picciotto.
McKee hopes her program will help contribute to a healthier society overall. Our goal is to make everyone better, she says. ” We really need to be focused on a personalized medicine perspective—particularly in regard to addiction and alcohol”.
No matter what stage of life a woman is in, she can develop alcohol use disorder. And there is no shame in seeking support, the researchers say.
” We think about adolescents as being particularly susceptible to problematic drinking, and they certainly are,” says Picciotto, but women are also at risk of developing problematic drinking habits throughout their lives. Research shows that alcohol use, for instance, is also on the rise among , women ages 60 and older.
There are options for women who need to reduce their drinking in stressful situations to seek help from stress-related life events, which may increase their alcohol intake in ways that are surprising to them.
For resources on finding quality, evidence-based care, women can visit the National Institute on Alcohol Abuse and Alcoholism ( NIAAA )  , Alcohol Treatment Navigator.
The Yale Program on Sex Differences in Alcohol Disorder is also enrolling in medication trials.
About this alcohol use disorder research news
Author: Colleen Moriarty
Source: Yale
Contact: Colleen Moriarty – Yale
Image: The image is credited to Neuroscience News
