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Recently significant progress was made in understanding the mechanisms by which the two estrogen receptors (alpha and beta) are involved in different pathways of estrogen action in a wide variance of tissues. Divergent responses of cells and tissues to estrogens or their ligands have been attributed to various isoforms and signaling pathways of estrogen receptors. Both subtypes of estrogen receptors have been identified in the cochlea and there are indications that they have neuroprotective effects but there is still limited information on the role and specific mechanisms of these two receptors in the auditory system. This review will examine the molecular and functional actions of the two estrogen receptor subtypes, the pivotal role they play in the auditory system and their therapeutic strategies for protecting against hearing loss.