Study Suggests Wine's "Matrix Effect" Enhances Polyphenol Benefits Beyond Isolated Alcohol

A recent scientific review proposes a paradigm shift in how wine and health are studied, advocating for a holistic approach that considers the "matrix effect" rather than focusing solely on isolated compounds. The study highlights how the interaction between polyphenols, alcohol, and other wine components can significantly influence both the bioavailability and biological effects of these compounds, raising questions about the effectiveness of supplements based on isolated ingredients or dealcoholized wine.

A Shift Toward the Matrix Effect

A review study¹ published in the International Journal of Molecular Sciences critically examined current methodologies in wine and health research and introduced the matrix effect concept—a complex interaction between various molecules within plant-based matrices that can trigger specific responses, often different from those observed with isolated constituents.

The study focused on three major polyphenols found in wine: tyrosol, hydroxytyrosol, and resveratrol, emphasizing how their lipophilic properties make them readily soluble in hydroalcoholic solutions, unlike most other polyphenolic compounds. This solubility difference is one reason for their higher bioavailability.

Key Findings on the Matrix Effect

The study demonstrates that wine has the most unique matrix among alcoholic beverages and can significantly impact the bioavailability of its phytocomplex formed during fermentation. The wine matrix plays a dual role: enhancing the absorption of beneficial compounds and inhibiting the carcinogenicity of alcohol metabolites.

The researchers identified at least thirteen polyphenols in wine as “potent inhibitors of pathways related to ethanol metabolism into acetaldehyde.” Additionally, three other polyphenols—epicatechin, epicatechin gallate, and epigallocatechin—were shown to attenuate acetaldehyde-induced double-strand DNA breaks by eliminating acetaldehyde.

Limitations of Alternative Products

The review provides evidence of the limitations of wine alternatives:

• Grape juice: Found ineffective as a matrix for quercetin and resveratrol absorption in both animals and humans. In contrast, adding 10% ethanol or whisky to the juice enabled effective absorption.
• Dealcoholized wine: Experiments in postmenopausal women yielded disappointing results, while regular red wine showed a reduced risk of cardiovascular disease.
• Red wine extracts (RWE): Showed inconsistent results in human studies, especially in terms of flow-mediated dilation (FMD) outcomes.

Implications and Recommendations

The findings suggest that ignoring the full wine matrix and focusing solely on isolated compounds (such as polyphenols) may lead to misleading conclusions—as is the case with dealcoholized wine or wine-based supplements. Alternatively, this narrow focus may also place undue emphasis on the toxic effects of a single component (alcohol), while overlooking the specific protective effects of other compounds (polyphenols) found in the same matrix.

Limitations and Considerations

• The holistic approach still requires more clinical trials for full validation;
• The specific nature of the wine matrix should be taken into account by public health authorities;
• The interaction among various matrix components demands further investigation;
• Consumption should always adhere to guidelines for moderate alcohol intake.

Conclusion

The study concludes that research on wine and health must move beyond classical molecular models toward concepts like the matrix effect and phytocomplexes. The wine matrix plays a crucial role in enhancing the bioavailability of beneficial compounds and/or inhibiting the carcinogenic effects of alcohol metabolites. This confirms the WHO Scientific Group’s recommendation to “investigate the potential protective effects of ingredients other than alcohol in alcoholic beverages.”

References:

1. Miraldi E, Baini G, Biagi M, Cappellucci G, Giordano A, Vaccaro F, Bertelli AAE. Wine, Polyphenols, and the Matrix Effect: Is Alcohol Always the Same? Int J Mol Sci. 2024 Sep 10;25(18):9796. DOI: 10.3390/ijms25189796.

Half of Brazilian Adults Consume Alcohol — and 1 in 5 Admit to Overdrinking, According to Datafolha

A national survey reveals the profile of alcohol consumption in Brazil: half of adults drink, and nearly 1 in 5 admit to overindulging.

A survey conducted by the Datafolha Institute¹ in April 2025 revealed that 49% of Brazilians aged 18 and over regularly consume alcoholic beverages. The largest group (20%) reported drinking once or twice a week, while 3% said they drink almost daily. Another 13% said they drink less frequently, about once a month or less.

Men Still Drink More — and More Often

The survey showed that alcohol consumption is still more prevalent among men, with 58% of them reporting alcohol use, compared to 42% of women. Men also drink more frequently: 10% reported drinking three to seven days a week, compared to just 2% of women.

However, research shows that the number of women who drink has been increasing over the years. Data from the latest Alcohol and the Health of Brazilians report, based on Vigitel², showed that non-abusive alcohol use among women rose from 16.5% in 2010 to 22.8% in 2023, while abusive use went from 10.5% to 15.2% in the same period.

Age, Income, and Religion Influence Drinking Habits

Alcohol consumption is most prevalent among young adults aged 18 to 34, with 58% reporting drinking. This percentage decreases with age: it drops to 46% in the 45–59 age group and to 35% among those aged 60 and over.

Income also plays a role. Among those earning 5 to 10 times the minimum wage, 64% drink alcohol. In contrast, only 43% of those earning up to 2 minimum wages report drinking.

Religion is another influential factor: 27% of Evangelicals report consuming alcohol, compared to 58% of Catholics.

A 2023 survey by Ipec³, commissioned by CISA, showed similar findings: among 18–34-year-olds, only 25% abstain from drinking, while 23% drink weekly or every other week. Regarding religion, that study also found similar patterns, with 27% of Evangelicals and 50% of Catholics reporting alcohol use.

Underage Drinking Among Teenagers

The study also explored the behavior of 16- and 17-year-olds, analyzing this data separately. It found that 27% of teenagers in this age group already consume alcohol. This is concerning, as drinking at this stage of life can have harmful consequences for adolescent development.

How Much Are People Drinking?

Among regular drinkers, the average consumption was 4.5 drinks in the week prior to the survey. Each drink was counted as a glass, can, cup, or cocktail. Twenty-three percent of respondents said they consumed more than 6 drinks during that week.

Despite this, 81% of drinkers believe they drink in moderation, while only 18% admit to overdrinking—11% say they drink more than they should, and 7% say they drink far too much.

Decline in Consumption: Trend or Misperception?

When asked about their alcohol consumption over the past year, 53% said they had reduced their drinking, 35% said it had remained stable, and only 12% reported an increase.

However, the average consumption remains high: 4.5 drinks in the previous week, which may already indicate abusive use. Two key takeaways emerge:

1. A significant portion of the population still consumes alcohol at harmful levels.
2. There is a disconnect between how people perceive their own consumption and public health guidelines.

The Ipec³ survey supported this conclusion, finding that among heavy drinkers (estimated at 17% of the population at the time), 75% believed they were moderate drinkers, and only 13% recognized the need to change their habits.

These data reveal that a significant portion of people engage in harmful alcohol use without recognizing it as problematic, highlighting the urgent need for public policies to raise awareness about excessive drinking and its associated harms.

References:

1. Instituto Datafolha. (2025, abril). Consumo de álcool no Brasil. Instituto Datafolha. https://media.folha.uol.com.br/datafolha/2025/05/05/dtfpncnsmbblcllca128242fasdfa.pdf
2. Álcool e a Saúde dos Brasileiros: Panorama 2024 - CISA - Centro de Informações sobre Saúde e Álcool [Internet]. cisa.org.br. Disponível em: https://cisa.org.br/biblioteca/downloads/artigo/item/485-panorama2024
3. Álcool e a Saúde dos Brasileiros: Panorama 2023 - CISA - Centro de Informações sobre Saúde e Álcool [Internet]. cisa.org.br. Disponível em: https://cisa.org.br/biblioteca/downloads/artigo/item/426-panorama2023

Are There Medications for the Treatment of Alcoholism?

In addition to psychosocial interventions, there are medications that also play an important role in reducing alcohol consumption and managing alcohol dependence. Below, learn about the main pharmacological options available—their functions, effectiveness, and the challenges of access in Brazil.

The Role of Medication in Treating Alcohol Use

Harmful alcohol use affects over 2 billion people and is responsible for nearly 6% of all deaths worldwide.¹ Similar to other chronic multifactorial diseases, the pathophysiology of alcoholism is approximately 50% genetic and 50% due to environmental factors.¹ Despite these alarming statistics, it’s important to highlight that alcoholism is both preventable and treatable.

Besides psychosocial interventions—such as individual and group psychotherapy—that play an extremely important role in treating alcohol dependence, there are medications that can assist in this process. These drugs help regulate the brain chemicals responsible for increasing the urge to drink, and they can also reduce anxiety or alleviate withdrawal symptoms when someone stops drinking, such as tremors, weakness, or hallucinations.

Pharmacological Treatment for Alcoholism

Currently, treatment is based on three main medications: disulfiram, naltrexone, and acamprosate, which are approved by the U.S. Food and Drug Administration (FDA).³ A recent review study demonstrated the efficacy of pharmacological treatment, even when compared to the significant effects of placebos.² The main drugs evaluated in the study were acamprosate, disulfiram, nalmefene, naltrexone (oral and injectable), baclofen, gabapentin, topiramate, and varenicline. The study showed that these medications—approved or recommended by international guidelines—help reduce both the frequency and intensity of alcohol use, as well as cravings. Although the effects are modest, the findings reinforce that their use can offer significant benefits, especially when combined with psychosocial support.

Disulfiram

Disulfiram⁴⁵ was one of the first medications approved by the FDA for the treatment of alcoholism. It inhibits the enzymes that break down alcohol into acetaldehyde. Inhibiting the enzyme acetaldehyde dehydrogenase leads to a buildup of acetaldehyde in the body, resulting in the disulfiram–ethanol reaction, characterized by severe nausea, vomiting, or even seizures. In other words, the medication is intended to create an aversive response to alcohol by producing unpleasant physical effects when alcohol is consumed shortly after taking the drug.⁵

Despite its proven efficacy and long history of use, disulfiram is currently not being marketed in Brazil, which limits its availability as a treatment option.

Naltrexone

Naltrexone⁴⁵ is used as an adjunct to psychosocial interventions in treating alcoholism. It works pharmacologically as an opioid receptor antagonist, reducing the pleasurable effects of alcohol, the desire to drink, and the feelings of euphoria associated with alcohol use. Alcohol indirectly stimulates the activity of endogenous opioids by promoting the release of peptides such as enkephalins and beta-endorphins. These peptides enhance dopamine activity in a brain region called the nucleus accumbens, mediating the rewarding effects of alcohol.

Another mechanism of naltrexone involves the inhibitory action of these endogenous peptides on GABAergic interneurons in the ventral tegmental area. These interneurons normally inhibit dopamine neurons. Therefore, opioid antagonists like naltrexone reduce alcohol consumption by blocking these receptors and interrupting the mesolimbic dopamine pathway.

Some studies suggest two types of drinkers may respond differently to treatment: “relief drinkers” and “reward drinkers.”⁶ Relief drinkers consume alcohol to relieve negative emotional states like anxiety, whereas reward drinkers are driven by alcohol’s pleasurable effects and have a strong craving for it.

Research has shown that reward drinkers tend to respond better to naltrexone.⁶ For example, in young adults, one study found that patients with high levels of both reward and relief motivation responded better to naltrexone treatment compared to placebo.⁷⁸

Note: Naltrexone is available in oral formulations in Brazil. The long-acting injectable form, which is common in some countries, is not commercially available in Brazil at this time, limiting its use in certain cases.

Acamprosate

Acamprosate⁴⁵ has also proven effective in treating alcohol dependence. It inhibits the brain’s excitatory glutamate activity, particularly by acting on NMDA receptors when these receptors become hyperactive. Acamprosate is considered a partial co-agonist of the NMDA receptor. Animal studies have shown that this medication reduces glutamate-induced calcium reuptake in neurons, suppresses conditioned responses to alcohol, reduces withdrawal effects, and inhibits glutamate-induced brain hyperexcitability and c-fos gene expression.⁵ There are also studies suggesting it acts on the GABAergic system, enhancing GABA reuptake in the thalamus and hypothalamus, which may help modulate dopaminergic activity in the nucleus accumbens and reduce the rewarding effects of alcohol.⁴

Challenges of Pharmacological Treatment in Brazil

Pharmacological treatment of alcoholism in Brazil faces significant challenges—particularly after disulfiram was discontinued by its manufacturer in 2019. Currently, naltrexone remains available by prescription and is provided free of charge in some municipalities, such as São Paulo. Acamprosate is not available on the national market. This limited availability can undermine treatment effectiveness—especially when combined approaches involving both medication and psychosocial support are not accessible. These circumstances highlight the urgent need for public policies to ensure the availability and accessibility of essential medications for fighting alcoholism.

It is also crucial to stress that pharmacological treatment should not occur in isolation. Its success depends heavily on the integration with psychotherapeutic approaches, such as Cognitive Behavioral Therapy (CBT).³ Furthermore, treatment options continue to evolve, and other drug combinations may be considered, particularly for addressing co-occurring conditions.

These medications should always be used under the guidance of a psychiatrist. The most appropriate treatment varies depending on each person's unique characteristics, drinking patterns, and any emotional, physical, or interpersonal issues resulting from alcohol use.

References:

1. Fairbanks, Jeremiah, et al. "Evidence-based pharmacotherapies for alcohol use disorder: clinical pearls." Mayo Clinic Proceedings. Vol. 95. No. 9. Elsevier, 2020.
2. Carvalho, Cainã Salmon Lima, Guilherme Soares Carvalho, and Nadine Cunha Costa. "Avanços no tratamento farmacológico do alcoolismo: revisão integrativa." Brazilian Journal of Development 7.1 (2021): 11271-11283.
3. Agabio R, Lopez-Pelayo H, Bruguera P, Huang SY, Sardo S, Pecina M, et al. Efficacy of medications for the treatment of alcohol use disorder (AUD): A systematic review and meta-analysis considering baseline AUD severity. Pharmacological Research. 2024 Nov;209:107454.
4. Santos, Samuel Mororó Pereira, and Leonardo Guimarães de Andrade. "FÁRMACOS PARA O TRATAMENTO DO ALCOOLISMO." Revista Ibero-Americana de Humanidades, Ciências e Educação 8.3 (2022): 558-567
5. Castro, Luís André, and Danilo Antonio Baltieri. "Tratamento farmacológico da dependência do álcool." Brazilian Journal of Psychiatry 26 (2004): 43-46.
6. Mann, Karl, et al. "Precision medicine in alcohol dependence: a controlled trial testing pharmacotherapy response among reward and relief drinking phenotypes." Neuropsychopharmacology 43.4 (2018): 891-899.
7. Roos CR, Bold KW, Witkiewitz K, Leeman RF, DeMartini KS, Fucito LM, et al. Reward drinking and naltrexone treatment response among young adult heavy drinkers. Addiction. 2021
8. Roos, Corey R., Karl Mann, and Katie Witkiewitz. "Reward and relief dimensions of temptation to drink: construct validity and role in predicting differential benefit from acamprosate and naltrexone." Addiction biology 22.6 (2017): 1528-1539.

Understanding Relapse in Alcohol Dependence

Relapse is a complex phenomenon and a significant challenge in the treatment of Alcohol Use Disorder (AUD). Despite advances in psychological and pharmacological treatments, a considerable portion of individuals return to drinking after a period of abstinence. Estimates indicate that up to 60–70% of people may relapse within the first six months after treatment.¹ Understanding what characterizes a relapse, which factors increase its risk, and how to prevent it is essential for promoting long-term recovery.

What is relapse—and how does it differ from a lapse?

Although often used interchangeably, relapse and lapse represent different situations in the recovery process. A lapse is an isolated episode of alcohol use that may occur during recovery but does not necessarily imply a return to previous patterns of problematic drinking. A relapse, on the other hand, is understood as a broader process involving a return to a sustained and problematic pattern of alcohol consumption.

Studies highlight that relapse should be analyzed both as a discrete event (e.g., any alcohol use after a period of abstinence) and as a more complex process influenced by multiple factors over time. This distinction is important, as not every lapse leads to a relapse—and recognizing this can help avoid feelings of failure that might discourage continuation of treatment.

Factors that increase the risk of relapse

Research points to specific factors that significantly raise the risk of relapse.¹ One such factor is anhedonia, or the inability to feel pleasure in daily activities. Individuals with high levels of anhedonia are more likely to return to drinking after treatment. Another important factor is smoking: people who continue smoking during treatment for AUD have a higher risk of relapse compared to former smokers or non-smokers.

Additionally, the amount of time a person has been abstinent before starting treatment plays a relevant role. People who had stopped drinking more recently before beginning treatment showed higher relapse rates over the following months.

A study that monitored individuals in real time using Ecological Momentary Assessment (EMA) found that everyday stress is a direct trigger for relapse.³ Participants who reported high stress levels were more likely to drink in the hours that followed, indicating that stress acts as an immediate trigger—not just a general risk factor. The research also observed that as stress increased throughout the day, so did the craving to drink, suggesting that alcohol may be used as a way to relieve momentary tension, which reinforces the risk of relapse.

Prevention: What works?

Relapse prevention involves strategies that address the aforementioned risk factors. Interventions that treat depressive symptoms (such as anhedonia), encourage smoking cessation, and strengthen coping skills in stressful situations are especially effective. Ongoing support after the end of formal treatment is also crucial, helping to identify early warning signs and prevent a lapse from progressing into a full relapse. Understanding relapse as a process—rather than simply a “failure”—allows professionals and patients to develop more realistic, empathetic, and personalized recovery plans.

Relapse in alcohol use disorder is a common and multifaceted phenomenon that can be prevented with evidence-based strategies. Understanding the difference between a lapse and a relapse, identifying risk factors such as anhedonia, smoking, and short prior abstinence, and offering continuous support are key steps to building a more solid recovery. Relapse does not mean the end of the road—with the right support, it’s possible to get back on track with confidence and self-awareness.

References:

1. Nguyen, L. C., Durazzo, T. C., Dwyer, C. L., Rauch, A. A., Humphreys, K., Williams, L. M., & Padula, C. B. (2020). Predicting relapse after alcohol use disorder treatment in a high-risk cohort: The roles of anhedonia and smoking. Journal of psychiatric research, 126, 1–7. https://doi.org/10.1016/j.jpsychires.2020.04.003
2. Reyes-Huerta, H. E., Vacio, Á., Pedroza, F., Salazar, M., & Martínez, K. (2018). The Recovery from Alcohol Consumption: Analysis of the Construct of Relapse. International journal of psychological research, 11(1), 70–82. https://doi.org/10.21500/20112084.3252
3. Eddie, D., Barr, M., Njeim, L., & Emery, N. (2021). Mean Versus Variability: Disentangling Stress Effects on Alcohol Lapses Among Individuals in the First Year of Alcohol Use Disorder Recovery. Journal of studies on alcohol and drugs, 82(5), 623–628. https://doi.org/10.15288/jsad.2021.82.623

Oral Minoxidil and Alcohol Hangover: Is There a Connection?

In recent years, low-dose oral minoxidil has become an increasingly popular treatment option for various types of alopecia (hair loss). While the topical form of the medication has been used for decades, the oral version has gained traction due to its practicality and effectiveness. However, like any medication, it is important to be aware of its possible side effects and interactions. A recently observed interaction deserves special attention: the potential intensification of alcohol hangover symptoms.

What is low-dose oral minoxidil?

Minoxidil was originally developed as a medication for hypertension, typically used in doses of 10 to 40 mg daily for this purpose. Its most well-known side effect, hair growth, led to the development of the topical version for alopecia treatment.

Currently, low-dose oral minoxidil (0.25–5 mg daily) is used "off-label" (usage not approved in the official label) for various types of hair loss, such as androgenetic alopecia (male or female pattern baldness), telogen effluvium, alopecia areata, and even some scarring alopecias.

A multicenter study published in 2021 with 1,404 patients showed that low-dose oral minoxidil has a good safety profile.³ The most common side effects include hypertrichosis (excessive hair growth in unwanted areas), dizziness, fluid retention, tachycardia, headache, and periorbital edema.

The possible relationship with alcohol hangover

A recent comment published in the International Journal of Dermatology by Alhanshali et al. (2024) brought attention to a possible interaction between oral minoxidil and alcohol that had not been widely documented: exacerbation of hangover symptoms.

The authors reported that after prescribing low-dose oral minoxidil to hundreds of patients, they observed about 10 cases in which patients reported a significant worsening of hangover symptoms after alcohol consumption, including:

• More intense headaches
• Increased nausea
• Greater light sensitivity

How does this interaction occur?

The exact mechanisms of this interaction are not yet fully understood, but some hypotheses are proposed:

• Additive vascular effects: Both minoxidil and alcohol cause vasodilation, which could potentially influence alcohol absorption and/or metabolism, intensifying its effects.
• Overlap of side effects: Some minoxidil side effects, such as headache and dizziness, are also common hangover symptoms, possibly resulting in an additive effect.
• Enzymatic alterations: A study cited by the authors demonstrated that ethanol can increase the activity of phenol sulfotransferase (SULT1A1) in the intestine, an enzyme crucial for the bioactivation of minoxidil. This enzymatic interaction could theoretically modify the metabolism of both substances.

Alcohol hangover: understanding the phenomenon

To better understand this interaction, it is important to define what an alcohol hangover is. "Veisalgia" (the medical term for hangover) is defined as "a combination of negative physical and mental symptoms that can be experienced after a single episode of alcohol consumption, beginning when blood alcohol concentration approaches zero."

Main symptoms include:

• Fatigue
• Headache
• Increased thirst and dry mouth
• Nausea and vomiting
• Dizziness
• Sensitivity to light and sound
• Tremors
• Excessive sweating
• Tachycardia (rapid heartbeat)
• Anxiety and irritability

The mechanisms causing hangover are multifactorial and include:

• Dehydration and electrolyte imbalance
• Gastrointestinal disturbances
• Low blood sugar
• Alterations in sleep and biological rhythms
• Inflammation
• Effects of components other than ethanol present in beverages (congeners)
• Alcohol metabolites, especially acetaldehyde

Recommendations for patients using oral minoxidil

Based on these observations, the authors make several recommendations for patients using low-dose oral minoxidil:

• Avoid taking minoxidil on days of heavy alcohol consumption: In clinical practice, doctors have advised patients not to take their minoxidil dose on days they plan to drink large amounts of alcohol.
• Monitor individual response: Since this interaction seems to affect only a small percentage of patients, it is important that each person observes how their body reacts to the combination of minoxidil and alcohol.
• Inform your doctor: If you use oral minoxidil and notice intensified hangover symptoms after alcohol consumption, inform your dermatologist for proper guidance.

Final considerations

It is important to emphasize that the interaction between oral minoxidil and alcohol still requires further studies to precisely establish its prevalence, mechanisms, and mitigation strategies. Most patients using low-dose oral minoxidil likely will not experience this interaction, but being aware of the possibility allows for safer medication use.

As with any medication, oral minoxidil should only be used under medical prescription and supervision. If you are considering starting this treatment for hair loss, discuss all possible interactions and side effects with your dermatologist to make an informed choice.

It is also worth remembering that responsible alcohol consumption is always recommended, regardless of medication use. Staying hydrated, not drinking on an empty stomach, and respecting your body’s limits are fundamental practices to reduce risks associated with alcohol consumption.

References:

1. Alhanshali L, Desai D, Nohria A, Shapiro J, Lo Sicco K. Oral minoxidil and the exacerbation of alcohol hangover symptoms. Int J Dermatol. 2024;63(7):975-976. doi: 10.1111/ijd.17195
   2. Swift R, Davidson D. Alcohol hangover: mechanisms and mediators. Alcohol Health Res World. 1998;22(1):54-60.
   3. Vañó-Galván S, Pirmez R, Hermosa-Gelbard A, Moreno-Arrones OM, Saceda-Corralo D, Rodrigues-Barata R, et al. Safety of low-dose oral minoxidil for hair loss: a multicenter study of 1404 patients. J Am Acad Dermatol. 2021;84(6):1644-51. doi: 10.1016/j.jaad.2021.02.054
   4. Maiti S, Chen G. Ethanol up-regulates phenol sulfotransferase (SULT1A1) and hydroxysteroid sulfotransferase (SULT2A1) in rat liver and intestine. Arch Physiol Biochem. 2015;121(2):68-74. doi: 10.3109/13813455.2014.992440
   5. Verster JC, Scholey A, van de Loo AJAE, Benson S, Stock AK. Updating the definition of the alcohol hangover. J Clin Med. 2020;9(3):823. doi: 10.3390/jcm9030823
   6. Minoxidil and alcohol/food interactions [Internet]. Drugs.com; [cited 2025 May 14].

Estrogen and Alcohol: Can Hormones Influence Alcohol Consumption in Women?

Research suggests that estrogen may influence excessive alcohol consumption among women. A study published in Nature Communications shows how this hormone affects brain pathways in female mice related to motivation and stress, pointing to a possible biological mechanism that could increase female vulnerability to alcohol.

Excessive alcohol consumption among women has been increasing in recent years. And although abusive alcohol use causes serious health damage to anyone, alcohol impacts women’s health significantly due to biological and physiological differences compared to men.

Some studies have mentioned that hormonal factors, such as estrogen, can drive alcohol-related behaviors.¹–³ Based on this, a study published in Nature Communications⁴ investigated how estrogen might regulate alcohol consumption behavior in female mice and which brain and molecular pathways are involved in this process.

To investigate the role of estrogen in excessive alcohol consumption in females, researchers observed alcohol intake throughout the estrous cycle (similar to the menstrual cycle in humans) and applied the Drinking in the Dark (DID) protocol, which simulates binge drinking episodes. Additionally, they performed hormonal manipulations by administering estrogen and selective blockers of membrane-associated estrogen receptor alpha (ERα), responsible for rapid, non-genomic hormonal action. Finally, they used electrophysiological techniques to assess the activity of CRF neurons (corticotropin-releasing factor – a peptide involved in the stress response) in the bed nucleus of the stria terminalis (BNST), aiming to identify how this hormonal pathway influences neuronal excitation and alcohol-seeking behavior.

The study results demonstrated that estrogen exerts a direct and significant influence on excessive alcohol consumption behavior in female mice. It was observed that during the phases of the estrous cycle when estrogen levels were highest, females showed a marked increase in ethanol intake, suggesting a relationship between hormonal peaks and vulnerability to compulsive consumption. When estrogen was administered exogenously, consumption also increased, confirming this association. Conversely, blocking ERα estrogen receptors reduced this behavior. Moreover, estrogen increased the activity of CRF neurons in the BNST, a brain region linked to stress and motivation, indicating that this hormonal pathway directly contributes to alcohol-seeking behavior.

Can We Apply These Findings to Women?

Although the findings of this study in mice offer important clues about how estrogen may influence excessive alcohol consumption in females, caution is needed when applying these conclusions directly to women.

Animal models are essential for understanding biological mechanisms but do not reflect the full complexity of human experiences, which involve social, emotional, and cultural factors, especially regarding alcohol use. Additionally, the study analyzed only the acute effects of estrogen in a specific brain region, leaving open how this hormone may act in contexts of chronic use or in association with other human variables.

Still, the results suggest a possible biological mechanism that may help explain women’s greater vulnerability to the harmful effects of alcohol. Therefore, these findings reinforce the need for further research with women that investigates the role of sex hormones in motivation for alcohol consumption, aiding the development of more effective and gender-sensitive prevention and treatment strategies.

References:

1. Johnson CS, Mermelstein PG. The interaction of membrane estradiol receptors and metabotropic glutamate receptors in adaptive and maladaptive estradiol-mediated motivated behaviors in females. 2022 Jan 1;33–91.
2. Torres VC, Feng B, Yang X, Patel N, Schaul S, Ibrahimi L, et al. Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice. Translational Psychiatry. 2024 Feb 27;14(1).
3. Chen H, Lu Y, Xiong R, Rosales CI, Coles C, Hamada K, et al. Effect of a brain‐penetrant selective estrogen receptor degrader (SERD) on binge drinking in female mice. Alcoholism/Alcoholism, clinical and experimental research. 2022 May 29;46(7):1313–20.
4. Zallar LJ, Rivera-Irizarry JK, Hamor PU, Pigulevskiy I, Rico Rozo AS, Mehanna H, et al. Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice. Nature Communications [Internet]. 2024 Dec 30 [cited 2025 Feb 5];15(1). Available from: https://www.nature.com/articles/s41467-024-54737-6