Drug overdoses are an escalating cause of mortality in the United States, with potential sex differences across the lifespan. The objective of this study was to use state-level nationally representative data that includes the COVID-19 pandemic period to determine overdose mortality for specific drug categories across the lifespan of men and women. We used Centers for Disease Control and Prevention (CDC) Multiple Cause of Death 2020-2021 data on overdose mortality, for 50 states and District of Columbia, across 10-year age bins (age range: 15-74). The outcome measure was sex-specific crude overdose death rate (per 100,000) for: synthetic opioids excluding methadone (ICD-10 code: T40.4; e.g., fentanyl), heroin (T40.1), psychostimulants with abuse potential (T43.6; e.g., methamphetamine), and cocaine (T40.5). Multiple regression analyses adjusted for ethnic-cultural background and household net worth from Census data, and sex-specific rate of misuse of the relevant substances, from the National Survey on Drug Use and Health (2019-2020). For each of these major drug categories, men had greater overall overdose mortality than women. Although overall rates of mortality differed across jurisdictions, the sex ratio of mortality for each drug category was relatively stable (≈2- to 3-fold greater mortality in men vs women). These findings survived adjustment for state-level ethnic-cultural and economic variables, and for sex-specific misuse of each drug type (especially in the 25-34, 35-44, 45-54 and 55-64 age bins). These findings underscore the need for research into sex- and gender-based mechanisms underlying differential vulnerability in overdose mortality for these drugs, based on their diverse pharmacodynamics and pathophysiology.

The authors have declared no competing interest.

NIH-NIDA U01DA053625 (ERB), and NIDA 1RO1DA048301-01A1 (RZG)

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Source data were openly available at the beginning of the study, as de-identified data from the U.S. CDC multiple cause mortality data, obtained from the CDC WONDER platform (https://wonder.cdc.gov/mcd.html)

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