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This chapter briefly reviews recent advancements in the search for a non-feminizing estrogen alternative that can mimic estrogen's positive effects on cognitive health without eliciting an undesirable impact on reproductive and cardiovascular systems. The discussion focuses on two avenues of translational development, tissue-selective and subtype-selective estrogen receptor (ER) modulators (SERMs), in particular ERβ-selective phytoSERMs as a natural approach for potentially promoting neurological health and preventing age-associated cognitive impairment and risk of Alzheimer's disease in both genders.