It has long been known that age‐related hearing loss (ARHL) is more common, more severe, and with an earlier onset in men compared to women. Even in the absence of confounding factors such as noise exposure, these sexdifferences in susceptibility to ARHL remain. In the last decade, insight into the pleiotrophic nature by which estrogen signaling can impact multiple signaling mechanisms to mediate downstream changes in gene expression and/or elicit rapid changes in cellular function has rapidly gathered pace, and a role for estrogen signaling in the biological pathways that confer neuroprotection is becoming undeniable. Here I review the evidence why we need to consider sex as a biological variable (SABV) when investigating the etiology of ARHL. Loss of auditory function with aging is frequency‐specific and modulated by SABV. Evidence also suggests that differences in cochlear physiology between women and men are already present from birth. Understanding the molecular basis of these sex differences in ARHL will accelerate the development of precision medicine therapies for ARHL.

中文翻译：

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与年龄相关的听力损失：为什么我们需要将性视为一个生物学变量。

众所周知，与女性相比，年龄相关性听力损失 (ARHL) 在男性中更常见、更严重且发病更早。即使在没有诸如噪声暴露等混杂因素的情况下，这些对 ARHL 易感性的性别差异仍然存在。在过去的十年中，对雌激素信号传导可以影响多种信号传导机制以介导基因表达的下游变化和/或引起细胞功能的快速变化的多效性的认识迅速加快，并且雌激素信号传导在生物途径中的作用赋予神经保护作用正变得不可否认。在这里，我回顾了为什么我们在调查 ARHL 的病因时需要将性别视为生物学变量 (SABV) 的证据。随着年龄的增长，听觉功能的丧失是频率特异性的，并受 SABV 的调节。证据还表明，女性和男性之间的耳蜗生理差异从出生就已经存在。了解 ARHL 中这些性别差异的分子基础将加速 ARHL 精准医学疗法的发展。