Males Have Greater Drug Overdose Mortality Than Females

Males have a significantly greater rate of overdose mortality from synthetic opioids, heroin, and stimulant drugs compared to women, according to a paper published in Neuropsychopharmacology.

Investigators from the Icahn School of Medicine at Mount Sinai conducted a state-level analysis of epidemiological data on overdose mortality in order to determine if these differ across lifespan and if so, whether they can be accounted for by different levels of drug misuse. The investigators looked at rate of overdose death per 100,000 for synthetic opioids, such as fentanyl (but not methadone), heroin, cocaine, and psychostimulants with potential for misuse, such as methamphetamine. Included participants were categorized by 10-year age bins, ranging from 15 years to 74 years. The data were collected from all 50 states plus the District of Columbia for 2020–2021.

While overdose deaths due to opioids and stimulants have increased in recent years, these deaths have accelerated since the onset of the COVID-19 pandemic particularly among synthetic drugs and psychostimulants, the study authors wrote.

Preventing these deaths will involve the identification of vulnerability factors, which are believed to include sex and age. Along with the direct pathophysiological effects of the drug, other factors that could account for rates of overdose include family and social interactions and related trauma, propensity towards risky behaviors, and propensity to seek treatment.

For all 4 main drug categories (synthetic opioids, heroin, psychostimulants, and cocaine), the study authors observed that males had greater overall overdose mortality than females, after controlling for rates of drug misuse. The investigators also noted that the mean male/female sex ratio of mortality rates were relatively stable across all jurisdictions:

• Synthetic opioids: 2.5
• Heroin: 2.9
• Psychostimulants: 2.4
• Cocaine: 2.8

When categorizing into the 6 age bins of 10-year bands, the study authors observed that the sex difference generally survived age adjustment, especially once those involved in the analysis were aged between 25 and 64 years.

The study authors also examined the nation-level sex ratios in overdose mortality and learned that they were generally congruent with state-level findings. They cited the example for synthetic opioid overdoses at the national level for those aged 15 to 74 years; the male/female ratio of overdose mortality was 2.7.

“The study showed that for these drug categories, across the lifespan, after controlling for sex-specific levels of past-year drug misuse and for major demographic factors, males died from overdoses at an ~2–3 greater rate than females,” the study authors wrote. They mentioned that studies from other developed countries also show greater drug-induced mortality for males compared to their female counterparts.

Though the results of the study indicate that males across the country are reliably at greater risk of fatal overdose compared to females. Culture-bound differences, such as a propensity for risky behaviors, could be a contributing factor in this difference. Sex-specific biological vulnerability remains another possible explanation.

“These findings call for mechanistically-based research on risk and interventions for severe [opioid use disorder] outcomes in both males and females,” the investigators concluded. “Furthermore, these findings underscore that sex differences are important targets for investigation at multiple biological and behavioral levels, potentially leading to optimized prevention and intervention approaches to mitigate risk of overdose mortality, at different stages across the lifespan.”