Khandaker · Journal of women's health (2002) 2025 · Retrospective population-based time-series and trend analysis · n=564,418

Sex Differences in Opioid-Related Mortality Trends in the United States, 1999-2020: By Age, Race/Ethnicity, Region, and Opioid Type.

Cited 2 times in the scientific literature.

Level 3 - non-randomized controlled study

Retrospective population-based longitudinal registry and trend analysis of national vital statistics

PubMed 40824729 · doi:10.1177/15409996251369454 · record verified 2026-08-26

What was done

Researchers retrospectively analyzed national mortality records from the National Center for Health Statistics Multiple Cause of Death Files from 1999 through 2020. Opioid-related overdose deaths were identified using ICD-10 underlying and multiple-cause codes. Sex-stratified mortality trends across age groups, race/ethnicity, geographic region, and opioid type were evaluated using piecewise linear regression to estimate annual percentage changes (APCs) with weighted Bayesian information criteria and empirical quantile confidence intervals.

What was found

A total of 564,418 opioid-related overdose deaths were analyzed from 1999 to 2020. Men had a significantly higher mortality burden than women (mortality rate ratio = 2.11; 95% CI: 2.09, 2.12) and a faster overall rate of increase (APC = 14.9; 95% CI: 11.4, 21.0 vs. APC = 8.0; 95% CI: 7.0, 8.8 for women). However, relative mortality increases were steeper in women than in men among individuals under 45 years of age, residents of the Northeastern United States, and deaths involving synthetic opioids.

Why it matters

These findings delineate divergent trajectories in the overdose epidemic, demonstrating that while interventions must continue addressing the high absolute burden in men, prevention and harm reduction must adapt to accelerating risk in younger women and synthetic opioid exposures.

Limits

The study relies entirely on death certificate ICD-10 coding, which is susceptible to misclassification, toxicology testing variability, and historical underreporting of specific opioid subtypes. The abstract omits exact numerical subgroup rates and APCs, and vital statistics lack the clinical, behavioral, and socioeconomic context necessary to determine underlying causal mechanisms.

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