Female hormone influences on auditory system aging are not completely understood. Because of widespread clinical use of hormone replacement therapy (HRT), it is critical to understand HRT effects on sensory systems. The present study retrospectively analyzed and compared hearing abilities among 124 postmenopausal women taking HRT, treated with estrogen and progestin (E؉P; n ‫؍‬ 32), estrogen alone (E; n ‫؍‬ 30), and a third [non-hormone replacement therapy (NHRT; n ‫؍‬ 62)] control group. Subjects were 60 -86 years old and were matched for age and health status. All had relatively healthy medical histories and no significant noise exposure, middle-ear problems, or major surgeries. Hearing tests included pure-tone audiometry, tympanometry, distortion-product otoacoustic emissions (DPOAEs), transient otoacoustic emissions, and the hearing-in-noise test (HINT). The HINT tests for speech perception in background noise, the major complaint of hearing-impaired persons. Pure-tone thresholds in both ears were elevated (poorer) for the E؉P relative to the E and control groups. For DPOAEs, the E؉P group presented with lower (worse) levels than the E and control groups, with significant differences for both ears. For the HINT results, the E؉P group had poorer speech perception than the E and control groups across all background noise speaker locations and in quiet. These findings suggest that the presence of P as a component of HRT results in poorer hearing abilities in aged women taking HRT, affecting both the peripheral (ear) and central (brain) auditory systems, and it interferes with the perception of speech in background noise.estrogen ͉ hearing loss ͉ hormone replacement therapy ͉ presbycusis ͉ progesterone A ge-related hearing loss (presbycusis) is the number one communication disorder, and it is one of the top three chronic medical conditions of elderly persons. Because of the widespread prescription of hormone replacement therapy (HRT), it is critical to determine the effects of HRT on sensory systems in postmenopausal females. Sensory function declines with age, yet the effects of HRT on hearing, balance, vision, and the chemical senses are not assessed in HRT drug development.Estrogen (E) and progestin (P) actions have been linked to key sensory and CNS processes and disorders such as cognition, memory, dementia (Alzheimer's disease), epilepsy, depression, and others. For instance, Rice et al.(1) reported differences between E alone and EϩP in rates of cognitive decline, showing E alone as beneficial and the presence of P as detrimental. Shumaker et al. (2) reported that the use of EϩP increased the risk for dementia in elderly females. Klaiber et al. (3,4) demonstrated that the effects of P seem opposed to those of E for mood changes. Stein and Hoffman (5) reported opposite effects of E and P in the treatment of acute brain trauma, attributing to P overall qualities of a neuroprotection agent. Klein et al. (6) suggested a protective effect of E on eye-lens opacities.The effects of sex hormones on hearing and ...

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We recently discovered that progestin in hormone replacement therapy (HRT) for postmenopausal women has detrimental effects on the ear and central auditory system (Guimaraes et al., Proc. Nat. Acad. Sci. -USA, 103: 14246-9). To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen+progestin) and estrogen alone on hearing in perimenopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion product otoacoustic emissions (DPOAEscochlear outer hair cell system) were employed. Middle age female CBA mice received either a timerelease, subcutaneous implanted pellet of estrogen+progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen+progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen+progestin treatment group in the high and middle frequency ranges (15-29 and 30-45kHz) after as early as 2 months of treatment (p<0.01 and p<0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen +progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen+progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

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