Age-dependent sex ratios of motor neuron disease: French nationwide study and meta-analysis.

OBJECTIVE:To examine the relation of age with male-to-female (M/F) ratios and incidence rates of motor neuron disease (MND) in a French nationwide study and meta-analysis of incidence studies. METHODS:We used data from the French National Health Insurance databases. Patients with incident MND (2010-2014) were identified based on drug claims (riluzole), hospitalization records, death records, and long-term chronic disease benefits. We estimated age-specific M/F incidence ratios using Poisson regression. Poisson, Gompertz, and multistep models were used to model the relation between age and incidence. We performed a meta-analysis (n = 28 studies) and used meta-regression to examine the relation of age with incidence rates and ratios. RESULTS:In France, we identified 10,848 patients with incident MND (6,021 men, 4,827 women). Incidence was higher in men than in women in all age groups. M/F ratios were significantly different across age groups and followed a quadratic trend (p < 0.001). Between 20 and 49 years, the average M/F ratio was 2.26 (95% confidence interval [CI] = 1.96-2.62); it was 1.41 (95% CI = 1.35-1.47) between 50 and 84 years, and 1.88 (95% CI = 1.64-2.17) after 85 years. Incidence was lower in women than men at younger ages, but increased more steeply in women than men. Similar patterns were observed in the meta-analysis of incidence studies, especially in 19 higher-quality studies. CONCLUSION:The relation between age and M/F incidence ratios of MND follows a quadratic U-shaped pattern with an abrupt drop after the fifth decade. The change in M/F ratios before and after menopause suggests that reproductive/hormonal protective factors have a role in women and should prompt further studies to explore this hypothesis.