What are the differences between men and women in substance use disorders regarding epidemiology, clinical presentation, progression, and treatment response?

Sex and Gender Differences in Substance Use Disorders

Women with substance use disorders demonstrate a more vulnerable clinical profile characterized by faster progression to dependence ("telescoping"), higher rates of psychiatric comorbidity, and greater psychological distress at treatment entry, while men more commonly initiate substance use through illicit sources and show different patterns of treatment utilization.

Epidemiological Differences

Prevalence Patterns

• Historically, men have shown higher rates of substance use and dependence, including heroin, though this gender gap has been narrowing over the past two decades 1, 2, 3, 4
• For prescription opioids specifically, the pattern diverges: some studies report higher rates of recent or regular use in women, but higher rates of abuse in men 1
• The convergence of male/female prevalence ratios represents a significant epidemiological shift that requires updated clinical approaches 4

Initiation and Source of Substances

• Women seeking treatment for opioid use disorder are significantly more likely to first obtain opioids from legitimate medical prescriptions, while men more commonly obtain substances from illicit sources initially 1
• This difference in initiation pathway has critical implications for prevention strategies and early intervention 1

Clinical Presentation and Disease Progression

The Telescoping Phenomenon

• Women demonstrate "telescoping"—a significantly faster transition from initial substance use to problematic use and dependence compared to men 1, 3, 4
• This accelerated progression occurs across multiple substance classes and represents a consistent finding in addiction research 3, 4
• The telescoping effect means women develop severe substance use disorders more rapidly despite potentially starting use later than men 3

Psychiatric Comorbidity

• Women with substance use disorders present with substantially higher rates of co-occurring psychiatric conditions and greater psychological distress at treatment entry 1, 5, 3, 6
• Women show more consistent vulnerability across multiple predictors, including unemployment, co-occurring psychiatric disorders, and polysubstance use 5
• The presence of major depressive episodes is an important predictor of service utilization in both sexes, but women with this comorbidity face compounded challenges 6
• Women with substance use disorders are at higher risk for intimate partner violence, sexual and reproductive health complications, and loss of child custody 3

Treatment Entry Characteristics

• Women face multiple barriers affecting access and entry to substance abuse treatment that are distinct from those faced by men 2
• Despite these barriers, once women enter treatment, gender itself is not a predictor of treatment retention, completion, or outcome 4
• For men, lack of prior treatment history is the strongest predictor of substance use at discharge and treatment dropout 5

Biological and Pharmacological Differences

Hormonal Influences

• Endogenous gonadal hormones significantly impact opioid effects, with estrogens diminishing opioids' antinociceptive effects and influencing methadone metabolism 1
• Evidence demonstrates interactions and crosstalk between opioid and estrogen receptors that affect both pain relief and rewarding effects of opioids 1
• Differential sex effects of methadone on testosterone levels and naltrexone on cortisol levels have been documented 1

Neurobiological Differences

• Preclinical work demonstrates sex-specific effects of acute opioid withdrawal and subsequent opioid replacement therapy (methadone or buprenorphine) on regional brain metabolism in the anterior cingulate, amygdala, and striatum 1
• Pharmacokinetic responses to substances differ between sexes, contributing to variations in treatment response 3
• Women are nearly twice as likely to develop adverse drug events, some requiring hospitalization, likely due to sex differences in drug pharmacokinetics 1

Treatment Response and Outcomes

Social Determinants of Health

• Women demonstrate more consistent vulnerability across social determinants of health, with unemployment, housing instability, and lack of health insurance showing stronger associations with poor treatment outcomes 5
• Health insurance coverage is associated with better outcomes for both sexes, but the protective effect is more consistent in women 5
• Housing instability and criminal justice involvement show sex-specific effects on treatment completion and substance use at discharge 5

Treatment Utilization Patterns

• Males with comorbid major depressive episodes show greater likelihood of emergency room visits and inpatient service use compared to females with similar comorbidity 6
• Barriers to substance treatment are remarkably similar between sexes, with attitudinal factors being the most common barriers in both groups 6
• Women are less likely to enter substance abuse treatment than men over the lifetime, but once engaged, gender does not predict retention or completion 4

Medication-Specific Considerations

• Women tend to receive suboptimal doses of guideline-recommended medications and are less often prescribed these medications compared to men 7
• Sex-specific dosing adjustments may be necessary given differences in drug metabolism and adverse event profiles 1

Critical Research Gaps

Underrepresentation in Research

• Women represent less than 15% of participants across reviewed neuroimaging studies of opioid use disorder, with 37.7% of studies including only male participants 1
• This severe underrepresentation is part of a larger problem in addiction research and clinical trials generally 1
• No studies have adequately examined sex differences despite clear evidence of differential clinical presentations and treatment responses 1

Clinical Implications

Clinicians must recognize that women with substance use disorders require earlier intervention given their accelerated disease progression, more intensive psychiatric screening and treatment given higher comorbidity rates, and careful attention to social determinants including housing, employment, and healthcare access. 1, 5, 3

For men, particular attention should be paid to engaging those without prior treatment history, as this represents the strongest predictor of poor outcomes in this population 5

Treatment programs should be designed with sex-specific considerations rather than assuming gender-neutral approaches, given the substantial differences in clinical presentation, progression, biological responses, and treatment barriers 2, 3, 4