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Try out PMC Labs and tell us what you think. Learn More. The gender gap in substance use disorders SUDscharacterized by greater prevalence in men, is narrowing, highlighting the importance of understanding sex and gender differences in SUD etiology and maintenance.

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Biological sex differences are evident across an array of systems, including brain structure and function, endocrine function, and metabolic function. Gender i. Adverse medical, psychiatric, and functional consequences associated with SUDs are often more severe in women. However, men and women do not substantively differ with respect to SUD treatment outcomes. Although several trends are beginning to emerge in the literature, findings on sex and gender differences in SUDs are complicated by the interacting contributions of biological and environmental factors.

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Future research is needed to further elucidate sex and gender differences, especially focusing on hormonal factors in SUD course and treatment outcomes; research translating findings between animal and human models; and gender differences in understudied populations, such as those with co-occurring psychiatric disorders and gender-specific populations, such as pregnant women. Historically, research on substance use disorders SUDs has disproportionately focused on males. However, there are numerous biological, psychological and social differences between men and women that may affect the development, maintenance and treatment of SUDs Greenfield, Brooks, et al.

In this manuscript, we provide a critical overview of sex and gender differences in SUDs, with a focus on human research. In this article, we will review studies of sex and gender differences, as well as literature that addresses topics specific to females e. Although we will cover the range of types of SUDs, where possible, we will attempt to disentangle findings across drug classes e. Search terms and methods for this review were adopted from a review ly published by our group that examined sex and gender differences in SUD treatment entry, retention, and outcome Greenfield, Brooks, et al.

Our search terms included: g ender, sex, sex factors, gender identity, female, male, gender differences, sex, sex differences, women, gender-specific, substance-related disorders, substance-induced disorders, substance abuse treatment centers, drug users, prescription drug misuse, alcohol-related disorders, alcohol-induced disorders, alcoholism, alcohol drinking, and opioid-related disorders.

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We expanded our methods to include a brief overview of biological sex differences and the epidemiology of SUDs. This current review of gender differences in the prevalence and incidence of substance use includes recent government publications reporting data from population-based surveys. In our review sex and gender differences in the etiology of substance use, as well as substance use in pregnancy, we also included seminal manuscripts published before On the topic of treatment, we only included manuscripts published since through April, in order to highlight the most recent findings.

This yielded a total of papers, which were reviewed for relevance to the current review. A of biological differences exist between males and females in the acute and long-term effects of alcohol and other drugs. These differences reflect sexual dimorphisms in brain, endocrine e. Among the most consistent findings in this area is that females and males metabolize alcohol differently.

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Females exhibit lower levels of alcohol dehydrogenase the enzyme that metabolizes ethanol activity in the gastric mucosa relative to males. Combined with lower total body water relative to males, this in higher blood alcohol concentrations in women, even after consumption of equivalent quantities of alcohol Baraona et al.

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This metabolic difference in greater intoxication for females relative to males when the same amount of alcohol is consumed. Sex differences in the metabolism of other substances have not been consistently demonstrated. Substantial heterogeneity within sexes in metabolic processes, as well as the contribution of multiple metabolic pathways to the clearance of substances may obscure sex differences in drug metabolism DeVane, Nonetheless, findings to date suggest that the metabolism of substances and, accordingly their effects cannot be assumed to be consistent for males and females.

Research on sex differences in the acute subjective effects of substances has yielded equivocal. For example, several studies of sex differences in the rewarding effects of substances e. Heterogeneity in study methodology, such as dosing and study population, might contribute to mixed.

One study enrolling participants with and without frequent marijuana use found that males without frequent marijuana use produced greater subjective ratings of THC abuse liability compared to their female counterpartswhereas there were no sex differences among frequent marijuana smokers Haney, Subjective drug effects may be further influenced by variation in ovarian hormones, which are often not measured and thus may present a source of variability among females that obscures true sex differences.

Studies of menstrual cycle phase have found that the follicular phase is associated with greater reports of drug liking and pleasant subjective effects relative to the luteal phase S. Equivocal findings highlight the importance of refined examination of menstrual cycle phases i. Allen et al.

Sex and gender differences in substance use disorders

Indeed, studies that have involved the exogenous administration of ovarian hormones have yielded more consistent than studies of naturally occurring fluctuations. Among postpartum women, progesterone treatment has been associated with less cocaine relapse Yonkers et al.

Neuroimaging research has identified a of sex differences in brain volume and function in response to various substances; however, many studies have not detected sex differences, have not tested sex differences, or were insufficiently powered Lind et al. Structural neuroimaging studies suggest that there may be sex-specific neural consequences of substance use. Similar findings have been reported in smokers Franklin et al.

Moreover, females may be more susceptible to the negative effects of chronic cocaine Ide et al. Research examining neural response to substance-related cues e. For example, women demonstrate greater neural activation to cocaine cues relative to men Volkow et al. A study of stress- and cue-induced cocaine craving found greater neural reactivity to stress cues in women and drug cues in men Potenza et al.

Striatal dopamine release—which is reflective of activation of the brain reward pathways—is higher in men relative to women in response to stimulants Munro et al. Although further research is needed to fully understand the impact of these volumetric and functional differences, these studies provide an initial indication of neural correlates of observed sex gender differences in SUDs, such as greater stress-related vulnerabilities in women see below. Of note, these differences may be attributable to biological as well as gender-related differences e.

Taken together with the extensive preclinical evidence for biological differences between males and females, these data suggest that sex differences in the biology of substance use are evident, but may be subject to key moderators e.

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Prospective studies deed to clarify whether differences are present prior to drug exposure are needed to better understand the drivers of these differences as well as their functional consequences. Moreover, these findings suggest that sex differences are complex and cut across multiple systems ranging from metabolism and substance effects to brain structure and function.

Accordingly, research attempting to disentangle the effects of sex on substance use must consider these multiple levels of analysis to better understand the nature of these differences and their implications for men and women. Nonetheless, this body of research clearly suggests that we cannot assume that males and females will respond similarly to substances, and therefore inclusion of both sexes in research on this topic is essential.

The historical gap in SUD prevalence between men and women characterized by higher prevalence in men is narrowing worldwide Keyes et al. The epidemiology of SUDs varies internationally, and is affected by culture and policies that influence the access to and acceptability of using substances.

Although there is ificant variation across cultures, in general, men are more likely to have access to substances relative to women; this difference in access appears to for much of the gender difference in the prevalence of substance use. Given international variability, we will focus on the prevalence and incidence of substance use and SUDs in the U. Unless otherwise specified, all prevalence estimates are from the National Survey on Drug Use and Health, an annual, population-based survey of US citizens ages 12 years and older.

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Inan estimated Women also displayed lower rates of binge drinking i. Although a greater proportion of adult men tend to use alcohol, and display problematic use i. For example, data show no gender differences among adolescents i. This gap also appears to be closing for older adults in the U.

Nicotine dependence is present in However, tobacco use prevalence has declined among both males and females over the past decade CBHSQ, Across this period, women have consistently displayed lower rates of tobacco use than men CBHSQ, In Decreases in past-month tobacco use have been particularly rapid among adolescents, with 4. The decrease in use of tobacco products has been accompanied by an increase in other forms of nicotine administration. For example, electronic cigarette use is now more prevalent among adolescents than tobacco use.

According to Monitoring the Future Study in9. Large-scale data on electronic cigarette use is not yet available among adults. In7. However, 8.

Biological sex differences in substance use

This gender parity among adolescents appears to be driven by prescription drug misuse, with adolescent girls reporting higher rates of past-month use than boys 2. Among adults, prescription drugs are among the only substance class for which past-month prevalence of misuse is similar in adults of both genders 2. Recent trends in illicit drug use differ by drug class. Likewise, rates of past-year marijuana use have increased in both genders from — The peak risk period for onset of substance use is late adolescence Vega et al.

However, this has not been demonstrated for all substances e. This discrepancy may reflect cohort differences, with some evidence that telescoping is not evident in younger cohorts P. Specifically, the telescoping effect has primarily been identified among women who are already in treatment, and likely represent those with more severe SUDs, whereas population-based surveys have failed to replicate the telescoping effect. Thus, this effect might be present only among women who are vulnerable to more severe SUDs, with mitigation of this effect when simultaneously examining women who represent the wide range of substance use severity.

In other words, a subset of women may be vulnerable to a rapid progression to severe SUDs.

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There is also variation by substance type in the likelihood of transition from use to dependence i. For many illicit substances, such as heroin, cocaine, and methamphetamine, use is characterized by a chronic course i. Receipt of treatment is associated with more favorable course of illness in both genders, particularly when treatment is initiated early and sustained over time E. SUDs are associated with ificant mortality. Despite reductions in smoking over time, it remains the leading preventable cause of death in the U.

Department of Health and Human Services, Drug overdoses—currently predominated by the epidemic of opioid overdose—continue to escalate in the U. Although overdose death is more common among men, the rate of increase in overdose death is rising more rapidly in women relative to men, and accordingly this gender gap is narrowing CDC, Among those in SUD treatment, mortality remains elevated relative to gender- and age-matched population estimates, with women exhibiting a 5-fold greater mortality rate relative to the general population compared with 3-fold greater mortality in men; however this difference was not statistically ificant Lindblad et al.