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 (DPOAEs-cochlear outer hair cell system) were employed. Middle age female CBA mice received either a time-release, 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.
Keywords: Aging, Hearing Loss, Presbycusis, HRT, Otoacoustic Emissions, Progestin, Progesterone, Estrogen, Auditory Brainstem Response, Sex Hormones