A narrative review on alcohol use in women: Insight into the telescoping hypothesis from a biopsychosocial perspective

Abstract

Background:

There has been a dramatic rise in alcohol consumption and alcohol use disorder (AUD) among women. Recently, the field has made substantial progress towards better understanding sex and gender differences in AUD. This research has suggested accelerated progression to AUD and associated health consequences in women, a phenomenon referred to as “telescoping”.

Objective:

To examine evidence for the telescoping hypothesis from a biopsychosocial perspective.

Methods:

This narrative review examined and integrated research on biological, psychological, and socio-environmental factors that may contribute to the development and progression of AUD in women.

Results:

Biopsychosocial research has revealed sex- and gender-specific risk factors and pathways to AUD onset and progression. Biological sex differences render females more vulnerable to alcohol-related toxicity across various biological systems, including the brain. Notably, sex and gender differences are consistently observed in the neural circuitry underling emotional and stress regulation, and are hypothesized to increase risk for an internalizing pathway to AUD in women. Psychological research indicates women experience greater negative emotionality and are more likely to use alcohol as means to alleviate negative emotions compared with men. Socio-environmental factors, such as familial and peer isolation, appear to interact with biological and psychological processes in a way that increases risk for negative emotionality and associated alcohol use in women.

Conclusion:

There appears to be a complex interplay of biopsychosocial factors that increase risk for AUD onset and progression in women through an internalizing pathway. Developing targeted interventions for women with AUD that specifically target internalizing processes are critical.

1. Introduction

Alcohol use has an enormous global burden [1], ranking among the leading cause of preventable death, disease, and injury [2]. Alcohol use is predominately a social phenomenon, however certain biological, psychological, and socio-environmental factors can increase an individual’s risk for heavy alcohol use and alcohol use disorder (AUD) [4]. The biopsychosocial model has been proposed to capture these biological (e.g., pharmacological), psychological (e.g., stress), and socio-environmental (e.g., family/peer influence) components that interact to contribute to the development and maintenance of AUD [4]. This model captures the complexity of addiction, which cannot be attributed to a singular cause.

Historically, men have exhibited higher rates of alcohol use and AUD compared with women. As such, alcohol research has largely focused on men [5]. The past few decades have seen a dramatic rise in alcohol use and AUD among women [6–9], with data from 2023 suggesting roughly equal prevalence of past-year alcohol use in men and women [10, 11]. Consequently, there has been a notable shift towards studying alcohol use and its effects on women [12–14]. This research has identified sex and gender as critical moderators of alcohol consumption and alcohol-related outcomes. Although findings have been mixed [15], a growing literature supports the “telescoping” effect among women, which suggests accelerated progression to AUD and alcohol-related health consequences in women compared with men [16].

2. Methods

This narrative review aims to synthesize research on sex and gender differences in biological, psychological, and socio-environmental factors that contribute to AUD onset and progression, and examine how these interrelated factors may contribute to telescoping in women. While prior articles have provided in-depth reviews of specific aspects of alcohol and AUD research [7, 17–29], this review offers a unique perspective by integrating findings from biological, psychological, and socio-environmental domains. We will use the definitions of sex and gender provided by the National Institutes of Health Office of Research on Women’s Health. “Sex” will be used to describe biological distinctions between males and females and refer to “sex assigned at birth”, while “gender” will be used to describe socially determined roles [30].

3. Recent shifts in alcohol use: A narrowing gender gap

Alcohol use and AUD are highly prevalent across all age groups in the United States (US), from adolescence to later stages of adulthood. According to the 2023 National Survey Data on Drug Use and Health (NSDUH), 16.7% of adolescents (ages 12-17), 68.1% of young adults (ages 18-25), and 67% of adults (ages 26+) reported consuming alcohol in the past year. Excessive alcohol use, including binge drinking—defined as consuming 4+ drinks for females and 5+ drinks for males on a single occasion—is associated with risk for developing an AUD and health consequences. The 2023 NSDUH data revealed that 3.9% of adolescents, 28.7% of young adults, and 22.7% of adults engaged in binge drinking in the past month [10]. Moreover, the prevalence of past-year AUD was reported at 2.9% among adolescents, 15.1% among young adults, and 10.3% among adults in the US [11].

Historically, women have consumed less alcohol and exhibited lower rates of AUD compared to men. However, over the past few decades, this gender gap in alcohol use, binge drinking, and AUD has narrowed [7]. National survey data from 2000 to 2016 suggests the number of women (ages 18+) who drink each year increased by 6%, while this number decreased by 0.2% for men. Similarly, the number of women who engaged in binge drinking increased by 14%, while it increased by only 0.5% for men [31]. In 2023, 64.6% of adult women and 69.5% of adult men consumed alcohol in the past year, with 19.3% of adult women and 26.2% of adult men engaging in binge drinking in the past month, according to the NSDUH [10]. The 2023 prevalence of past-year AUD was 7.8% among women and 12.9% among men [11]. Forecasting models predict this gender gap will continue to narrow through 2040 [32].

These gender-specific trends in alcohol use is particularly notable among adolescents and young adults. Although adolescent alcohol use has been declining, the rate of decrease has been slower among girls compared to boys [9, 31]. The 2023 NSDUH revealed that alcohol use was higher among adolescent girls (19.2%) compared to boys (14.7%) [10]. A similar pattern emerged among young adults, with 69.8% of women versus 66.4% of men reporting alcohol use in the past year [10]. Additionally, in 2023, the prevalence of AUD was higher among females in both adolescents (girls: 3.8% versus boys: 2.0%) and young adults (girls 15.1% versus boys: 15.0%) [11].

4. The development and progression of alcohol use disorder in women

AUD is a chronic relapsing disorder characterized by a cycle of binge/intoxication, withdrawal/negative affect, and anticipation/preoccupation [33]. Women and men appear to differ in the etiology and clinical course of AUD. The telescoping hypothesis has been used to describe the accelerated progression of AUD in women [16]. While women initiate alcohol use at an older age, they progress more rapidly from first use of alcohol to heavy drinking episodes, the onset of AUD and treatment-seeking status [34]. Studies have shown that women consume lower amounts of alcohol relative to men but do not differ in their AUD severity [35, 36]. Additionally, women, versus men, with AUD present with a more severe and complicated clinical course, marked by more psychiatric comorbidities (i.e., mood disorders) [37], stronger alcohol craving [38], greater difficulty quitting [39], and greater likelihood of relapse in response to stressful events or drug-related cues [18]. The following sections examine how several biological, psychological, and socio-environmental factors may contribute telescoping in women.

a. Biological factors

i. Pharmacology

Due to biological differences, females and males metabolize alcohol at different rates [40]. Females have a lower percentage of water and a higher percentage of fat in their bodies than men [41]. As alcohol is water-soluble, but not fat-soluble, females achieve a higher blood alcohol concentration than males following the same amount of alcohol consumption [42]. Additionally, females have lower levels of gastric alcohol dehydrogenase—the alcohol metabolizing enzyme that breaks ethanol down before it reaches the bloodstream [43]. Therefore, blood alcohol concentration levels rise faster, get higher, and stay elevated for longer in women than men [43, 44]. This may contribute to greater alcohol-related toxicity and vulnerability to AUD, and associated health consequences, in women compared with men [45, 46]

ii. Neurobiology

Chronic, heavy alcohol use is associated with long-lasting brain changes most pronounced in reward, cognitive, and emotional control networks. Both human neuroimaging and preclinical work have documented a sexually dimorphic pattern of alcohol-related brain changes [19–21, 56]. Although conflicting findings have been reported [57], human neuroimaging work has observed distinct patterns of brain atrophy in men and women following chronic alcohol use [19–21, 56, 58]. These patterns are nuanced and appear to change across the lifespan. Girls and boys differ in their brain developmental trajectory during adolescence and young adulthood, which may render them differentially susceptible to the neurotoxic effects of alcohol on their developing brain. Heavy alcohol use has been associated with decreased cortical thickness and volume in male youth but with increased cortical thickness and volume in female youth [59–62]. One study showed that binge drinking was associated with greater ventral striatal volume in college-age women, but smaller volume in college-age men [62]. This pattern appears to reverse in adulthood, with structural imaging studies in adults generally showing that women tend to have greater brain atrophy and more pronounced hypothalamic-pituitary-adrenal (HPA) axis dysfunction following chronic alcohol exposure, compared with men [63–65].

Functional neuroimaging studies have also revealed gender differences in the functional neural circuitry underlying alcohol cue reactivity, cognitive processes, and emotional regulation [21]. These differences emerge in adolescence but evolve as alcohol use increases [21]. One study found that alcohol-naïve girls exhibited greater activation in frontal regions in response to visual alcohol cues compared to alcohol-naïve boys. Following moderate-to-heavy alcohol use, however, this pattern of reversed, such that girls showed lower activation than boys in response to alcohol-related cues [66]. In terms of cognitive processes, adolescent girls who binge drink have been found to exhibit decreased activation in frontal, temporal, and cerebellar brain regions during a spatial working memory task compared with sex-matched controls [67]. This pattern of activation has been associated with worse sustained attention and working memory performance in girls. Sex differences in the neural circuitry underlying emotional regulation and the stress response also emerge in adolescence (i.e., persistent amygdala activation in response to negative emotional stimuli in girls) [68].

In adults with AUD, sex and gender differences in the neural processes related to reward and cognition are mixed [21]; however, functional imaging studies have consistently shown sex- and gender-differences in the neural circuitry underlying emotional and stress regulation [56, 69–74]. A recent study found that women with AUD tend to exhibit a greater brain response to stress in affective regulation and self-referential processing regions (e.g., amygdala) compared to men with AUD [69]. These sex and gender differences in the stress response are hypothesized to provide neural evidence for increased risk and progression of AUD in women through an internalizing pathway [68].

Neuroimaging findings largely align with the telescoping hypothesis and may explain sex/gender differences in the development and clinical course of AUD. Sex/gender differences in alcohol’s effect on the brain are also supported by preclinical work, which has identified sex differences in dopaminergic, GABAergic, glutamatergic, and adenosinergic brain systems following chronic alcohol exposure [19, 75].

iii. Endocrinology

The endocrine system controls the production and regulation of hormones in the body [26, 76–78]. There is a bidirectional relationship between alcohol use and endocrine system functioning; alcohol use has been shown to disrupt endocrine system functioning, while hormonal fluctuations can, in turn, impact alcohol’s effects on the brain, and alcohol use behavior [56, 78]. Alcohol-induced hormonal dysregulation can disrupt a wide range of essential functions [79], including neuronal function [56]. Preclinical and clinical research has linked chronic alcohol consumption with higher estradiol levels and decreased progesterone levels in both males and females [78]. Additionally, both acute and chronic alcohol consumption use has been associated with increases in testosterone levels in women [78, 80, 81], but this association has not been consistently observed in men [78, 82, 83]. Higher levels of estradiol and testosterone have both been linked with earlier initiation of drinking in adolescence, as well as altered functional connectivity within a key emotional regulation brain network [84].

Furthermore, different phases of the menstrual cycle, characterized by fluctuations in estrogen and progesterone levels, are associated with variations in binge drinking, alcohol craving, consumption, and subjective response to alcohol [12, 85–87]. For example, data suggest that alcohol craving is greater during the follicular phase compared to the luteal phase of the menstrual cycle [88]. Women who use hormonal contraceptives do not demonstrate a shift in craving throughout their cycle [88]. Furthermore, research indicates differences in alcohol-related behaviors, such as consumption and craving, between women with natural menstrual cycles and those who use hormonal contraceptives [88]. In sum, research supports a bidirectional relationship between alcohol use and endocrine function. Additional research is needed to better understand how hormonal and menstrual related factors could specifically contribute to AUD vulnerability in women.

b. Psychological factors

i. Negative affect, stress, and psychiatric illness

Negative affect has consistently been linked to the onset of alcohol use and misuse, and is thought to play an important role in the development and progression of AUD [18, 89–91]. Negative affect is more prevalent among women than men [92], and may be a gender-specific risk factor for AUD. Adolescent girls and boys differ in their motivating factors for initiating alcohol use [20, 89, 93], such that girls more frequently cite coping and negative reinforcement motives for alcohol initiation (i.e., using alcohol to alleviate negative affect and stress), while boys more frequently cite enhancement and positive reinforcement motives (i.e., using alcohol to enhance positive feelings) [42, 56, 90, 94]. These gender differences in drinking motives extend to adulthood, such that there is a stronger association between negative affect and alcohol use, including binge and heavy drinking, in women than in men [38, 95, 96]. Studies have also identified a stronger relationship between internalizing symptoms (i.e., negative mood) and alcohol problems in women than in men [97, 98]. Women with AUD report more frequent heavy alcohol use during negative emotional states compared with men with AUD [99]. Overall, these data indicate that women are both more likely to experience negative affect and to use alcohol to alleviate negative affect compared with men [56]. This marks one critical factor contributing to AUD vulnerability in women, as research has shown individuals who endorse coping motives (i.e., drinking to reduce negative affect) are at increased risk for alcohol-related problems and AUD compared with individuals who endorse enhancement (i.e., drink to increase positive mood) or social motives (i.e., drink for social reward) [100–104].

Negative affect and stress are common psychological symptoms associated with psychiatric illness, such as mood and anxiety disorders. These disorders are highly relevant to the development of, prognosis for, and treatment outcomes in AUD [56, 91, 105, 106]. Women have a higher prevalence of psychiatric illness than men, making this risk factor is especially salient among women [107, 108]. Furthermore, the relationship between psychiatric comorbidity and problematic alcohol use is stronger in women than in men [56]. Indeed, studies have shown that drinking to cope with symptoms of mood and anxiety disorders is more common among women than men [109, 110]. As such, psychiatric comorbidity may be implicated in sex differences in alcohol use and in the development of AUD.

It is also important to consider that alcohol use can, in turn, lead to greater negative affect and psychological stress, and worsen the course of psychiatric comorbidities [18]. Negative affect is a central feature of alcohol withdrawal, and is associated with alcohol craving during this stage of the addiction cycle [91]. A study of adults in addiction treatment observed higher depression and alcohol craving during withdrawal in women, as well as a stronger relationship between depression and craving in women than in men [38]. Taken together, this literature indicates that negative affect plays a critical role in differentiating women and men across all stages of addiction, and may render women vulnerable to AUD onset, progression and relapse.

ii. Cognitive function

Chronic, heavy alcohol use, as exhibited in AUD, is consistently associated with long-term deficits in cognitive processes, including in memory, executive function, emotion and psychosocial skills, visuospatial cognition, and psychomotor abilities [27, 125]. Such deficits are central to addiction phenomenology, and have been associated with the preoccupation-anticipation stage of the addiction cycle [33, 126]. Cognitive deficits observed in women largely parallel those observed in men with AUD [27]. While conflicting findings have been reported [127, 128], there is data suggesting an accelerated rate of development of cognitive deficits in women, compared to men, with AUD. Consistent with the telescoping hypothesis, women may experience cognitive deficits earlier in their AUD course or following lower levels of lifetime alcohol consumption [129].

There is also evidence suggesting unique deficits in emotional and social cognition processes in women, relative to men, with AUD [27]. Alexithymia—a condition marked by challenges in identifying, understanding, and expressing emotions—is more prevalent in women than men with AUD [130]. Alexithymia has been hypothesized to act as a moderator of the relationship between depression and alcohol craving in AUD [131–133], a relationship that is more robust in women than men [38]. Women with AUD also exhibit greater difficulties in decoding or inferring other’s emotions, indicative of theory of mind deficits, relative to men with AUD.

iii. Subjective response to alcohol

Subjective response to alcohol refers to an individual’s perceived experience of alcohol’s effects [134, 135] and is a key determinant of alcohol consumption and problems [136]. Subjective response varies between individuals and is thought to arise from a combination of genetic and environmental factors [136]. Robust longitudinal research has shown that greater stimulating effects of alcohol and lower sedative effects of alcohol are both phenotypes associated with risk for AUD [137–141]. Although several early studies found no evidence for gender differences in subjective response [137, 142], a recent study (N=250) of heavy drinkers found that females exhibited lower alcohol-induced stimulation and alcohol craving during alcohol administration compared with males [143]. An alcohol-administration study of social drinkers (N=24) also found that women experience lower levels of alcohol-induced stimulation compared with men [124]. This is in line with the finding that men more commonly drink for positive reinforcement (i.e., stimulation) than women [56]. Another study (N=30) found women felt less high, nauseated, and uncomfortable during alcohol intoxication than men [144]. Taken together, these clinical data suggest women—both social and heavy drinkers—experience a lower level of response to the stimulating and aversive effects of alcohol. Low level of response to the aversive effects of alcohol use has been associated with increased risk for AUD [137]; therefore, it is possible this pattern of response contributes to risk for AUD in women. Larger studies are needed to replicate findings. Interestingly, preclinical data has found that females may actually be more sensitive than males to the acute rewarding effects of alcohol [20, 54, 55], which may be related to greater alcohol-induced dopamine release in the nucleus accumbens in females compared with males [54]. Additional work is also needed to reconcile findings from clinical versus preclinical studies.

c. Socio-environmental factors

i. Family/peer support

There is a nonlinear relationship between age and alcohol consumption across the lifespan. For both women and men, alcohol use increases during adolescence, peaks around ages 18 to 22, and subsequently decreases in the mid-20s [145, 146]. Early initiation of alcohol use is a predictor of binge drinking and AUD [147]. Psychosocial factors, such as parental and peer social support, play a gender-specific role in the onset of alcohol use among adolescent girls and boys. Notably, lack of family social support and peer interactions appear to drive onset of alcohol use more strongly in girls than boys [148]. These psychosocial factors, particularly social support, continue to have a similar gender-specific role in their impact on alcohol use throughout adulthood. In adults, a lack of social support has been linked to negative affect and AUD symptom severity in women, but not in men [148].

ii. Traditional gender roles

Both women and men typically begin to reduce their drinking in their mid-20s, a phenomenon referred to as “maturing out.” This normative reduction in drinking is attributed to social factors, such as role transitions, including marriage, career development, and parenthood [149]. Being married and a parent are both associated with lower risk of AUD onset and a reduction in AUD symptoms, even when accounting for “maturing out” effects [150–152]. Historically, traditional gender roles (i.e., expectations for women to assume primary caretaking responsibilities) have led to lower alcohol consumption in women, and greater alcohol consumption among men. For example, women with childcare responsibilities may have less time available to drink, be under the influence of alcohol, or recover from a drinking episode [153]. There has also been less social acceptance of drinking in women [154, 155]. Traditional gender roles and norms have evolved over recent decades, and such changes are thought to contribute to the narrowing gender gap in alcohol use and AUD. Specifically, higher education attainment and rates of employment outside the home in women, later age at first marriage, and older age at childbearing have been suggested to contribute to this trend [42, 156, 157].

Traditional gender roles also pose significant barriers for women with AUD to access treatment. Specific barriers have included concerns about childcare, pregnancy (e.g., lack of services for pregnancy, fear of prosecution, fear of losing custody after giving birth), resistance from family members and/or romantic partners, and poor social support [158]. As a result, women have historically been less likely to receive AUD treatment than men [159–161]. The odds of women utilizing any alcohol-related treatment are 47% lower than the odds for men [162]. Additionally, women with AUD are more likely to go to primary health care than to specialty AUD treatment [162]. Treatment settings that offer childcare, prenatal care, treatment for co-occurring psychological problems, and supplemental social services can help reduce barriers for women with AUD [25].

iii. Trauma and early life stress

Trauma exposure is a significant risk factor for alcohol use, particularly among women [163–169]. Longitudinal studies have shown that trauma exposure predicts future alcohol use among women [164, 167, 169]. Women who have experienced trauma consume more alcohol and experience more alcohol-related consequences compared to women without trauma exposure [170, 171]. Additionally, the severity of trauma exposure and the presence of current trauma symptoms are strong predictors of alcohol relapse in women, a pattern that is not consistently observed in men [172]. Furthermore, girls and women are more likely to experience sexual abuse and violent victimization, forms of trauma that carry the highest risk for heavy drinking and AUD [91, 173, 174]. Negative affect is also a common psychological symptom associated with trauma, and coping motives have been shown to mediate the relationship between trauma and drinking [175–179].

Trauma, as well as psychological stress, that occurs early in life—or early life stress (ELS)—is an especially potent risk factor for AUD [180–182]. Such experiences are hypothesized to sculpt the developing brain in a way that increases risk for psychiatric illness, including AUD [183]. History of ELS is also linked to worse clinical course; one study found individuals with AUD and a history of ELS present with greater negative emotionality compared with diagnostic controls with no ELS history [184]. Women appear to be more vulnerable than males to adverse ELS-related health outcomes, including heavy alcohol use and relapse [172, 185, 186]. This is mirrored by greater ELS-related biological changes (e.g., neural, immune) in women than in men [187, 188]. Furthermore, gender differences in the pathway to alcohol misuse have been observed [175]. For example, one study found that coping motives mediated the relationship between childhood abuse and alcohol consequences in women, but enhancement motives mediated this relationship in men [189]. Indeed, women tend to experience more ELS-related internalizing symptoms, which may be related to sex-differences in the effects of ELS on the development of the neural circuitry thought to underlie emotional regulation [186].

5. Alcohol-related health consequences among women

The rise in alcohol use and AUD in women has been accompanied by increases in alcohol-related health consequences among women. From 2006 to 2014, alcohol-related emergency department visits increased more in women (up by 5.3%) than in men (up by 4.0%) [191]. Similarly, between 1993 and 2010, alcohol-related hospital inpatient diagnoses in adults in the US increased by 90% in women compared to 30% in men [192]. Additionally, women with AUD have a higher risk of mortality than men (relative risk: 4.6 in women, 3.4 in men) [193]. In 2016, it was estimated that women experienced approximately 681,000 deaths and lost roughly 26.1 million disability-adjusted life years (DALYs) to alcohol consumption worldwide [194].

Increased risk for alcohol-related health consequences in women is widely supported by biopsychosocial research. This literature has shown that alcohol—even when used at low and moderate levels—has enduring consequences on health and functioning [194], and that some of these detrimental health effects may be different in women and men [7, 45]. The telescoping hypothesis has also been used to describe faster progression to alcohol-related health problems in women than men [16]. Women experience physiological complications (i.e., liver disease, sleep disturbances) from alcohol use with lower levels of consumption and within a shorter time frame compared to men [195]. As described in prior sections, biological factors may contribute to greater alcohol-related toxicity and vulnerability to health consequences in women than men [45, 46]. Distinct health outcomes are not just determined by biology; socio-environmental influences differentially affect women and men, and how they respond to addictive substances [13]. For example, traditional gender roles and expectations can pose significant barriers to treatment among women, leading to untreated health problems. Table 2 summarizes research examining alcohol’s effects on liver and cardiovascular function, sleep, breast cancer, and pregnancy.

Table 2.

Health consequences of alcohol use in women

Liver	• Liver disease in the United States has risen in recent decades [196].  • Historically, men have experienced higher rates of alcohol-related liver injury compared with women, which may be related to their higher frequency and quantity of alcohol consumption [23].  • Alcohol-related liver injury is increasing among women [23].     ○ Between 1998 to 2012, there was a 240% increase in liver disease among women ages 15-39 versus a 90% increase among same-aged men [196].  • Women exhibit increased susceptibility for, and faster progression of, alcohol-related liver cirrhosis and its end-stage effects, which have been linked to differences in alcohol metabolism [44, 197, 198].     ○ Lower levels of gastric alcohol dehydrogenase and hepatic enzymes may contribute to increased risk for alcohol-related liver injury in women [44, 198].
Cardiovascular	• Moderate and high levels of alcohol consumption dose-dependently impact cardiovascular health.  • Alcohol-related complications include increased blood pressure and incidence of hypertension, and cardiac complications, such as acute cardiac arrhythmia, cardiomyopathy, and heart failure [199, 200].  • A meta-analysis of 20 cohort studies found that men who consumed 1 to 2 alcohol-containing drinks per day had increased risk for hypertension, whereas similar consumption in women was not associated with increased risk for hypertension [201].  • Another meta-analysis of 12 cohort studies found that low alcohol consumption in women may actually be protective for hypertension [202].  • Men may also be more susceptible to alcohol-related increases in systolic and diastolic blood pressure than women [203].
Sleep	• Due to its sedative properties, alcohol has been used anecdotally as a sleep aid.     ○ Particularly at descending levels of blood alcohol concentration, alcohol intoxication can increase subjective sleepiness and decrease latency to fall asleep [204].  • However, acute alcohol consumption may actually lead to a decrease in subjective sleep quality by decreasing rapid eye movement (REM) stage sleep in the beginning of the night and increasing wakefulness later in the night [205].  • Such disturbances in sleep have been associated with increased risk of relapse, alcohol misuse, and other psychiatric comorbidities [28].  • In general population studies, women exhibit greater alcohol-related sleep disruptions compared with men [204, 206].  • Poor sleep is also associated with greater alcohol-related problems in women than in men [207].
Breast Cancer	• Alcohol is classified as a Group 1 carcinogen by the International Agency for Research on Cancer, indicating there is sufficient evidence that it can cause cancer in humans [208].  • Alcohol consumption is associated with the development of various cancers including colorectal, liver, esophageal, head and neck, and breast cancer.  • Roughly 5% of breast cancer cases are attributed to alcohol use [209, 210].  • The relative risk of developing breast cancer significantly increases with higher levels of alcohol consumption [210, 211].  • Binge drinking, where blood alcohol concentration reaches 0.08 g/dL, has also been associated with a higher risk for breast cancer [212].  • Alcohol consumption is associated with increased levels of sex hormones and decreased folate absorption, both of which are potential factors mediating the heightened risk of breast cancer associated with alcohol use [213, 214].
Fetal Alcohol Spectrum Disorder	• Women have unique pregnancy-related risks of alcohol use.  • Maternal alcohol use during pregnancy increases risk for miscarriage, premature birth, birth defects, and low birth weight and is associated with fetal alcohol spectrum disorder (FASD) [215].  • FASD is a serious condition that occurs in roughly 1 out of every 1,000 live births in the United States [216].  • FASD occurs in utero and can cause permanent damage to the fetuses’ central nervous system.  • Children with FASD experience a number of physical, cognitive, behavioral, and functional impairments that may require intensive and costly care throughout the lifespan [217, 218].

6. Conclusion, Future Directions, and Limitations

a. Integrating Biological, Psychological, and Socio-environmental Factors: Evidence for telescoping among women

This narrative review explored sex and gender differences in the onset and progression of AUD through a biopsychosocial lens. Although not supported by all research [15], data largely suggests that sex and gender differences in these domains may lead to distinct pathways to, and trajectories of, AUD in women and men. To begin, biological sex differences render females more vulnerable to alcohol-related toxicity across various biological systems, including the brain.. Both preclinical and clinical studies indicate adult women are more prone to brain changes and HPA axis dysfunction following chronic alcohol exposure, compared with men [63–65]. Specifically, sex and gender differences are consistently observed in emotional and stress regulation circuitry, and are hypothesized to increase risk for an internalizing pathway to AUD in women. Indeed, psychological research supports that women experience greater negative emotionality and more likely to drink for negative reinforcement, while men are more likely to drink for positive reinforcement [42, 56, 90, 94]. Coping motives are a critical factor contributing to AUD vulnerability in women, as research has shown that individuals who endorse coping motives are at greater risk for AUD compared with those who endorse enhancement or social motives [100–104]. Studies have also found a stronger relationship between depression and craving during withdrawal in women than in men [38], indicating that negative affect plays a critical role in differentiating women and men across all stages of addiction, from initiation to maintenance, and relapse.

Socio-environmental factors appear to interact with biological and psychological processes in a way that may further increase risk for negative emotionality and associated alcohol use in women. For example, a lack of social support has been associated with negative affect and AUD symptom severity in women, but not in men [148]. Sex differences in emotional regulation neural circuitry may predispose women to such adverse outcomes. Additionally, alcohol use is often incongruous with traditional gender roles and expectations, contributing to the stigmatization of alcohol use and related problems among women. Such stigmatization can exacerbate feelings of social isolation and negative affect.

In conclusion, there appears to be a complex interplay of biological, psychological, and socio-environmental factors that heightens women’s vulnerability for AUD through an internalizing pathway. Understanding these factors and their interactions is crucial for developing targeted interventions that address the specific needs of women with AUD. Indeed, research on AUD in women has led to the development of women-only and female-specific treatments. Programs such as Female-Specific Cognitive Behavioral Therapy (FS-CBT) have demonstrated efficacy in reducing alcohol consumption, relieving internalizing symptoms, and addressing interpersonal problems among women [219]. These programs incorporate language, examples, and material tailored to women, along with modules focused on social support, interpersonal functioning, self-confidence, coping strategies for mood problems and negative affect, and psycho-education about women and alcohol [220]. The success of these female-specific interventions underscores the importance of sex-specific research in informing effective treatment approaches.

b. Future directions

Sex and gender-specific research has already begun to shape more effective treatments for women with AUD (i.e., FS-CBT); however, this is only the beginning. A more comprehensive understanding of sex-differences in AUD—particularly at a biological level—is essential to develop better pharmacological treatments for women. While pharmacotherapy holds tremendous promise for improving AUD treatment, the majority of FDA-approved medications for AUD were developed based on research in men. Consequently, sex and gender differences in AUD pharmacotherapy have not been adequately examined [24]. A 2020 review of randomized clinical trials of US FDA approved medications for AUD (disulfiram, acamprosate, naltrexone) found that only 4.9% of studies examined the effects of gender on treatment response [221]. Similarly, much of the preclinical support for AUD pharmacotherapies originates from studies conducted in males [24]. While research is limited, there are some studies suggesting sex and gender moderate response to AUD pharmacotherapy [24]. For example, naltrexone and varenicline may be more effective in reducing drinking in men than in women [222–226], while baclofen may show greater efficacy in improving alcohol use outcomes in women [227–231]. Additionally, studies on acamprosate, naltrexone, baclofen, and varenicline have reported poorer tolerability and more severe side effects in women compared to men [24]. Most of these studies, however, were not designed to assess sex and gender differences in medication response, so their findings should be interpreted with caution. There is a clear need for studies designed to evaluate sex and gender effects, and for greater representation of women in clinical trials [232].

Recent research initiatives have begun to prioritize the investigation of sex and gender differences in AUD research at both clinical and preclinical levels. Given that stress and negative reinforcement appear to be key motivating factors for alcohol use in women [18], many studies are focusing on stress-reactivity processes and the neurobiological bases for negative reinforcement drinking in women. While these initiatives mark significant progress in the field, substantial gaps in knowledge remain. Several additional critical areas for future research are outlined in table 3. The field must prioritize research in these areas and integrate findings from biological, psychological, and socio-environmental domains to advance healthcare for women with AUD.

Table 3.

Critical areas for future research

Biological	• Increasing evidence suggests that women and men exhibit differences in brain structure and function even before the onset of alcohol use [233], yet few empirical studies have tested how these pre-existing differences might influence the development and progression of addiction.  • There is growing literature suggesting sex differences in brain adaptations to alcohol. A 2017 review of structural imaging studies in substance use disorders found that of the studies that included males and females, only 26% evaluated sex differences [234]. Notably, 85% of these studies identified sex-dependent effects of substance use on brain volume, underscoring the need to include sex as a biological variable in alcohol neuroscience research.  • Women experience tremendous hormonal shifts across the lifespan, as well as lasting brain-related changes associated with pregnancy, but our understanding of how these fluctuations affect their risk for alcohol use and its consequences is also limited. There are also important opportunities for translation; preclinical data suggests the menstrual cycle impacts alcohol use, but clinical research in this area is limited.
Psychological	• Women with AUD experience higher rates of co-occurring psychiatric and medical conditions, yet we lack a comprehensive understanding of how to tailor treatments for this complex clinical presentation.
Social	• Women encounter significant social barriers when seeking treatment for AUD; therefore, it is essential to understand and address these barriers to ensure equitable access to care.

c. Limitations

While this narrative review offers valuable insights, including a broad overview of alcohol research in women, it is important to acknowledge several inherent limitations with this approach. First, narrative reviews do not adhere to a strict methodology for study selection, which could result in an inconsistent and non-exhaustive review of the existing literature. Although this review focused on key biological, psychological, and socio-environmental factors contributing to alcohol use in women, it did not encompass all relevant factors (i.e., genetics, alcohol expectancies, socioeconomic status, religion). Additionally, this narrative review included studies of varying quality without systematically assessing or weighing them based on methodological rigor. Therefore, the conclusions drawn should be interpreted with caution and considered in conjunction with findings from systematic reviews and meta-analyses.

Table 1.

Biological, psychological, and socio-environmental factors in the development and progression of AUD in women

- Women progress more rapidly than men from first use of alcohol to heavy drinking episodes, onset of AUD, and treatment-seeking status [34–36]  - Women with AUD report stronger alcohol craving, have more difficulty quitting drinking, and are more likely to relapse in response to stressful events or drug-related cues compared with men [18, 37–39]
Biological Factors	Pharmacological: Blood alcohol concentration levels rise faster, get higher, and stay elevated longer in women than men [40–44]. Neurobiological: Preclinical and clinical work have observed distinct patterns of alcohol-related brain changes [19–21, 56, 58]; adult women tend to have greater brain atrophy and more pronounced hypothalamic-pituitary-adrenal (HPA) axis dysfunction following chronic alcohol exposure, compared with men [63–65]. Functional imaging studies also consistently show sex differences in the neural circuitry underlying emotional and stress regulation [21, 56, 69–74]. Endocrinological: There is a bidirectional relationship between alcohol use and endocrine system functioning; alcohol use has been shown to disrupt endocrine system functioning, while hormonal fluctuations can, in turn, impact alcohol’s effects on the brain, and alcohol use behavior (56, 78). Different phases of the menstrual cycle are associated with variations in alcohol craving, consumption, and subjective response to alcohol [12, 85–87].
Psychological Factors	Negative Affect: Women more frequently report using alcohol use to alleviate negative affect and stress (coping motives, negative reinforcement), while men more frequently report using alcohol to enhance positive feelings (enhancement motives, positive reinforcement) [42, 56, 90,94]. Studies have also observed a stronger relationship between depression and craving during withdrawal in women than men, suggesting that negative affect plays a critical role in differentiating women and men across all stages of addiction, from initiation to maintenance, and relapse [38], and may render women at greater risk for AUD progression and relapse [91]. Psychiatric Illness: Women with AUD present with more psychiatric comorbidities, and the relationship between psychiatric illness and problematic alcohol use is stronger among women than men [107, 108]. Executive Function: While conflicting findings have been reported [127, 128], there is data suggesting an accelerated rate of development of cognitive deficits in women, compared to men, with AUD [27, 129]. Additionally, there is evidence suggesting unique deficits in emotional and social cognition processes in women, relative to men, with AUD (e.g., Alexithymia) [27]. Sensitivity to Alcohol: Human laboratory data suggest women experience a lower level of response to the stimulating and aversive effects of alcohol compared with men [124, 143]. On the other hand, preclinical work has found that females are more sensitive to the acute rewarding effects of alcohol [20, 54, 55].
Socio-environmental Factors	Familial/Peer Support: Lack of social support has been linked to negative affect and AUD symptom severity in women, but not in men [148]. Traditional Gender Roles: Changes in traditional gender roles and norms (i.e., higher education attainment and rates of employment outside the home among women, later age at first marriage, older childbearing) in recent decades are thought to contribute to the narrowing gender gap in alcohol use and AUD [42, 156, 157]. Trauma & Early Life Stress: Women with trauma exposure consume more alcohol and experience more alcohol-related consequences compared to women without trauma exposure [164, 167, 169]. Girls and women are more likely to experience sexual abuse and violent victimization, which are forms of trauma that confer the highest risk for heavy drinking and AUD [91, 173, 174]. Trauma, as well as psychological stress, that occurs early in life—or early life stress (ELS)—is an especially potent risk factor for AUD [180–182]. Women appear to be more vulnerable than males to adverse ELS-related health outcomes, including heavy alcohol use and relapse [172, 185, 186], which is mirrored by greater ELS-related biological changes (e.g., neural, immune) in women than in men [187, 188].