An editorial notes that this meta-analysis is a commendable effort to expand thinking about the role of lifetime exposure to reproductive hormones in the occurrence of postmenopausal depression. It adds that “given the small effect size and limitations of the studies used in this analysis, more direct evidence supporting a sustained and delayed neuroprotective effect of extended exposure to estradiol, cyclic progestins, and their neurosteroid derivatives is required to support use of hormonal therapy as a therapeutic approach to protecting against postmenopausal depression.”