Male Predominance in West Virginia Unintentional Overdose Deaths is Influenced by Alcohol and Co-Intoxicants.

Background: To examine sex differences in overdose (OD) mortality based upon substances involved.

Methods: A retrospective database analysis of West Virginia OD decedents (12,666 unintentional OD deaths, 2005-early 2023). Exposures were substances judged to contribute to death. The main outcome measure was determination of male to female death ratios with varying co-intoxicant involvement, particularly related to alcohol and fentanyl. Secondary outcomes included associations of fentanyl concentrations with alcohol concentrations and male sex, including fentanyl (F) and inactive metabolite norfentanyl (N) concentration variability between sexes.

Results: Alcohol co-intoxication in OD deaths was associated with higher male:female death ratios, from 2.0 (alcohol absent) to 3.3 (alcohol present). There was a greater increase over time in alcohol involvement in recent deaths involving females compared to males (relative increases of 52% vs. 6%, respectively). Male:female ratios with alcohol and fentanyl co-involvement ranged from 5.9:1 (only two drugs involved) to 2.4:1 (= 5 substances), with females significantly more likely to have multiple substances contributing to death. Overall, males had statistically significantly larger fentanyl (F) to norfentanyl (N) median concentration ratios compared to females (8.8 vs. 6.9, respectively). Multivariable analyses found alcohol presence was associated with a statistically significant 22% reduction in predicted fentanyl concentrations.

Conclusions: Male:female ratios in unintentional OD deaths were higher with greater alcohol involvement and lower with fewer co-intoxicants. Fentanyl and norfentanyl concentration differences by sex were observed. It is important to determine possible contributors to sex differences in OD death rates to better target prevention and treatment initiatives.