A recent study examining death records in the United States revealed that men faced a significantly higher risk of overdose deaths involving opioids and stimulant drugs compared to women in 2020-2021. The research, published in Neuropsychopharmacology, showed that men had 2-3 times higher rates of overdose mortality from opioids (such as fentanyl and heroin) and psychostimulants (such as methamphetamine and cocaine).
While it is known that men use drugs more frequently than women, the study highlighted that this disparity alone does not account for the difference in overdose deaths. Instead, a combination of biological, behavioral, and social factors likely contribute to the increased mortality risk for men.
The motivation behind the study was driven by the alarming increase in overdose deaths related to opioids and stimulant drugs in the United States, particularly during the COVID-19 pandemic. This increase in overdose mortality has disproportionately affected men, with higher rates compared to women. Understanding the reasons behind this sex difference in overdose mortality is crucial for developing effective interventions and strategies to prevent fatal overdoses and mitigate the harms of drug use.
The researchers recognized the need to explore whether the higher mortality rate among men was solely due to their higher rates of drug use or if there were additional factors at play. They hypothesized that men may use drugs more frequently or in higher doses, which could increase their risk of death from overdose. Conversely, they also considered the possibility that women may have certain protective factors that reduce their risk of fatal overdose compared to men.
“Though men and women are being exposed to the modern, fentanyl-contaminated drug supply, something is leading men to die at significantly higher rates. It may be that men use drugs more frequently or in greater doses, which could increase their risk of death, or there may be protective factors among women that reduce their risk of death compared to men,” said study co-author Nora Volkow, director of the National Institute on Drug Abuse, in a news release. “Understanding the biological, behavioral, and social factors that impact drug use and our bodies’ responses is critical to develop tailored tools to protect people from fatal overdose and other harms of drug use.”
The researchers utilized the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) platform, which provides access to nationally representative data on overdose mortality. They conducted a state-by-state analysis to examine variations in overdose mortality rates by drug category (synthetic opioids, heroin, psychostimulants such as methamphetamine, and cocaine), state, and age.
To account for the differences in rates of drug misuse between men and women, the researchers used state-level data from the National Surveys on Drug Use and Health (NSDUH) conducted by the Substance Abuse and Mental Health Services Administration. This data allowed them to estimate and control for rates of drug misuse among men and women separately.
By analyzing the data from these two sources, the researchers aimed to determine if the higher rates of overdose deaths among men persisted even after accounting for differences in drug misuse rates. They also investigated whether the sex differences in overdose mortality varied across different drugs, states, and age groups.
The researchers found that men have a significantly greater rate of overdose mortality from opioids and psychostimulants compared to women. It was observed that for synthetic opioids (e.g., fentanyl), men had a significantly higher rate of overdose death compared to women (29.0 deaths per 100,000 people for men versus 11.1 for women). The same pattern was found for heroin (5.5 deaths per 100,000 people for men versus 2.0 for women), psychostimulants (13.0 deaths per 100,000 people for men versus 5.6 for women), and cocaine (10.6 deaths per 100,000 people for men versus 4.2 for women).
Importantly, the higher overdose death rate in men was consistently observed across different age groups (15-74 overall) and across states, even after considering other demographic factors. This highlights the robustness of the sex difference in overdose mortality, indicating that males in the US are reliably at a greater risk of fatal overdose than females.
While it is known that men report misusing drugs more than women, the magnitude of the difference in overdose mortality between men and women was substantially greater than the difference in reported drug misuse. For instance, men had a 2.8 times greater rate of cocaine overdose mortality compared to women, whereas men only had a 1.9 times greater rate of cocaine misuse compared to women. This suggests that factors beyond drug use patterns contribute significantly to the higher mortality risk in men.
The researchers hypothesize that the sex differences in overdose mortality can be attributed to a combination of biological, behavioral, and social factors. At the biological level, men may have a greater vulnerability to the toxicity of drugs compared to women. However, this vulnerability would have to be shared across different drug categories with distinct pharmacodynamic targets and pathophysiological mechanisms. Thus, additional research is needed to unravel the specific biological mechanisms contributing to the sex differences.
Behavioral factors may also play a role, as men may engage in riskier drug use behaviors compared to women, such as injecting alone, taking large doses, or using untrusted suppliers. Additionally, there may be cultural and gender-related differences that influence the propensity for risky behaviors, which could contribute to the disparity in overdose mortality.
The study confirmed that men have significantly higher rates of overdose mortality from opioids (such as fentanyl and heroin) and psychostimulants (like methamphetamine and cocaine) compared to women. This observation goes beyond the differences in drug use rates between men and women. The magnitude of the disparity in overdose deaths suggests that biological, behavioral, and social factors likely contribute to the increased mortality risk for men.
But the study, like all research, includes some limitations. The researchers note that the availability of state- and sex-level data on drug misuse after 2019 is limited, and they recognize that population-based surveys may underestimate overall illicit drug use. They also acknowledge that there may be reporting biases that could affect the observed sex differences in overdose mortality or drug misuse.
The findings emphasize the importance of further research into the underlying mechanisms and interventions for overdose outcomes in both males and females, the researchers said. They also highlight the need to investigate sex differences at multiple biological and behavioral levels to develop effective prevention and intervention approaches for reducing overdose mortality risk at different stages of life.
“These data emphasize the importance of looking at the differences between men and women in a multilayered way,” said Eduardo R. Butelman Ph.D., assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai and a lead author on the study. “Moving forward, it will be important for researchers to continue to investigate how biology, social factors, and behaviors intersect with sex and gender factors, and how all of these can impact addictive drug misuse and overdose deaths.”
The study, “Overdose mortality rates for opioids and stimulant drugs are substantially higher in men than in women: state-level analysis“, was authored by Eduardo R. Butelman, Yuefeng Huang, David H. Epstein, Yavin Shaham, Rita Z. Goldstein, Nora D. Volkow, and Nelly Alia-Klein.
