Sex differences in smoking, alcohol consumption, and risk of Parkinson's disease: A nationwide cohort study

Objective: We assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD). Methods: This population-based cohort study examined data of 6,795,816 Koreans aged ≥40 years from the Korean National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years’ observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI). Results: 3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,154 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P < 0.0001 for interaction) and duration (P < 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P < 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014). Conclusion: Our data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.