Gender-related protection from or vulnerability to severe CNS diseases: Gonado-structural and/or gonado-activational? A meta-analysis of relevant epidemiological studies

•Molecular research has found multitudes of neuroprotective actions of estrogen.•Epidemiology of brain diseases reveals gender differences in risk for brain diseases.•We conduct a meta-analysis of gender differences in risk for brain diseases.•We find substantial gender differences as a function of type of brain disease.•However we find no modulation coming from gonadal activation (puberty) or deactivation (menopause, andropause). A vast scientific literature has dealt with gender-specific risk for brain disorder. That field is evolving toward a consensus to the effect that the estrogen hormone family is outstandingly and uniquely neuroprotective. However, the epidemiology relevant to this general outlook remains piecemeal. The present investigation strategically formats the relevant epidemiological findings around the world in order to quantitatively meta-analyze gender ratio of risk for a variety of relevant severe central nervous system (CNS) diseases at all three gonadal stages of the life cycle, pre pubertal, post adolescent/pre menopausal, and post menopausal. The data quantitatively establish that (1) no single epidemiological study should be cited as evidence of gender-specific neuroprotection against the most common severe CNS diseases because the gender-specific risk ratios are contradictory from one study to the other; (2) risk for severe CNS disease is indeed significantly gender-specific, but either gender can be protected: it depends on the disease, not at all on the age bracket. Our assay of gender-specific risk for severe brain disease around the world has not been able to support the idea according to which any one gender-prevalent gonadal steroid hormone dominates as a neuroprotective agent at natural concentrations.