Sex differences in hearing: Probing the role of estrogen signaling

Abstract

Hearing loss is the most common form of sensory impairment in humans, with an anticipated rise in incidence as the result of recreational noise exposures. Hearing loss is also the second most common health issue afflicting military veterans. Currently, there are no approved therapeutics to treat sensorineural hearing loss in humans. While hearing loss affects both men and women, sexual dimorphism is documented with respect to peripheral and central auditory physiology, as well as susceptibility to age-related and noise-induced hearing loss. Physiological differences between the sexes are often hormone-driven, and an increasing body of literature demonstrates that the hormone estrogen and its related signaling pathways may in part, modulate the aforementioned differences in hearing. From a mechanistic perspective, understanding the underpinnings of the hormonal modulation of hearing may lead to the development of therapeutics for age related and noise induced hearing loss. Here the authors review a number of studies that range from human populations to animal models, which have begun to provide a framework for understanding the functional role of estrogen signaling in hearing, particularly in normal and aberrant peripheral auditory physiology.

An overview of occupational noise-induced hearing loss among workers: epidemiology, pathogenesis, and preventive measures

“…Previous studies have shown that males experience more effects after exposure to occupational noise than females [ 1 , 66 ]. This may be due to males usually having greater exposure to noise at work than females due to differences in occupational categories, economic sectors of employment, and lifetime work history.…”

“…Another possible reason is the hormone-driven physiological differences between sexes. Several animal and human studies have demonstrated that women may be protected against hearing loss because of estrogen and its signaling pathways [ 66 ].…”

Synaptic migration and reorganization after noise exposure suggests regeneration in a mature mammalian cochlea

“…In addition to the species/strain differences (and ignoring effects of the observable inter-laboratory differences in immunostaining signal-to-noise), other sources of difference in synaptic recovery include sex 44 and age-at-exposure 4 . Here we studied primarily females, but saw no significant sex differences at 1 month post exposure (Fig.…”

Age‐related hearing loss: Why we need to think about sex as a biological variable

“…Given this neuroprotective role, it is perhaps unsurprising that there is a wealth of literature that estrogen, the classical estrogen receptors (ERs), and the estrogen-related receptors (ERRs) play a critical role in maintaining auditory function (Charitidi, Meltser, Meltser, Tahera, & Canlon, 2009;Delhez, Lefebvre, Lefebvre, Pequeux, Malgrange, & Delacroix, 2020;Hultcrantz, Simonoska, Simonoska, & Stenberg, 2006;Shuster, Depireux, Depireux, Mong, & Hertzano, 2019;Williamson, Zhu, Zhu, Pineros, Ding, & Frisina, 2020). Despite this, our understanding of the modes of action of estrogen in the cochlea are far from clear.…”