Sex and gender differences in the treatment of Alzheimer's disease: A systematic review of randomized controlled trials

tIn recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influenceof sex and gender on Alzheimer’s disease (AD). Nevertheless, not enough attention has been paid totheir impact on treatment outcomes. The present study is aimed at systematically retrieve, review anddiscuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketedtreatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possiblesex and gender differences in their efficacy, safety and tolerability.A systematic review of literature was performed. None of the retrieved studies reported data on theefficacy, safety and tolerability of considered medications separately in male and female patients withAD. We thus analyzed 48 excluded studies of potential interest, that is, almost all of the currently availabletrials on the four considered drugs. Nearly all the considered RCTs recruited a larger number of femaleparticipants to mirror the sexually unbalanced prevalence of AD. Only two studies took into account thepotential influence of sex and gender on treatment efficacy, reporting no significant differences betweenmen and women. None of the studies investigated potential sex and gender differences in the safety andtolerability of the four considered treatments.The existence of sex and gender differences in the efficacy and tolerability of ChEIs and memantine inAD has, to date, drawn limited to no attention. However, a considerable amount of data, with an adequaterepresentativeness in terms of sex/gender distribution, seem to be already available for dedicated anal-yses on this topic. A greater effort should be made to collect and report data on those factors interactingwith sex and gender that may significantly influence clinical manifestations, outcomes, and trajectoriesover time of AD patients.