Hormone replacement therapy diminishes hearing in peri-menopausal mice.
We recently discovered that progestin in hormone replacement therapy (HRT) for post-menopausal women has detrimental effects on the ear and central auditory system [Guimaraes, P., Frisina, S.T., Mapes, F., Tadros, S.F., Frisina, D.R., Frisina, R.D., 2006. Progestin negatively affects hearing in aged women. Proc. Natl. Acad. Sci. - PNAS 103, 14246-14249]. 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 peri-menopausal 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 30-45 kHz) 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.
Price
Katharine
K
Department of Otolaryngology, University of Rochester School of Medicine & Dentistry, 601 Elmwood Avenue, Rochester, NY 14642-8629, USA.
Zhu
Xiaoxia
X
Guimaraes
Patricia F
PF
Vasilyeva
Olga N
ON
Frisina
Robert D
RD
D000818:Animals; D001307:Auditory Perception / Q000187:drug effects; D002979:Climacteric / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000502:physiology; D006309:Hearing / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008593:Menopause / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D011304:Presbycusis / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors
D012739:Gonadal Steroid Hormones; D011372:Progestins; D004958:Estradiol