Hearing in menopausal women and in women with Turner syndrome, a model for hearing matured in an estrogen-deficient environment

Sammanfattning: Epidemiological studies have shown that women have better high-frequency hearing than men in virtually all age groups, regardless of noise-exposure, and that agerelated hearing decline starts after age 30 in men but not until after the age of 50 in women. This coincides with the menopausal transition in most women, thus leading us to hypothesize that the menopause triggers auditory deterioration. This may be due to reduced levels of endogenous circulating estrogens, which are known to have protective effects on the auditory system. Turner syndrome is a chromosomal aberration affecting 1:2000 newborn girls, in which all or part of one X chromosome is absent. This leads to ovarian dysgenesis and little or no endogenous estrogen production. These women have, among many other syndromal features, a high occurrence of ear and hearing problems, and neurocognitive dysfunctions, including reduced visual-spatial abilities. It is assumed that estrogen deficiency is at least partially responsible for these problems. One objective of this thesis was to describe the prevalence of hearing loss and to classify audiometric configurations in a group of 143 healthy middle-aged women in the general population with respect to menopausal stage and hormone replacement therapy (HRT). A follow-up study including 101 of these women was performed 7.5 years later to describe the rate of hearing decline during the menopausal transition. Another objective was to perform a battery of hearing tests in a group of 30 adult women with Turner syndrome (TS), aimed at localizing the lesion causing the sensorineural hearing impairment and assessing central auditory function, primarily sound localization. Further we carried out a longitudinal study of hearing thresholds in a group of 69 TS women to determine whether the factors initial age, initial hearing level, karyotype, and presence/absence of a mid-frequency dip influences the rate of decline and could serve as prognostic markers. The main findings in middle-aged women in the general population are that although they have close to normal median hearing thresholds, a large proportion has significant high-frequency losses and dips, which are overlooked if only an average of thresholds at 0.5-4 kHz is used to determine prevalence of hearing impairment. Further, the menopause per se seems to be the starting point for an accelerated period of hearing decline, rather than age alone. In TS women we showed that cochlear dysfunction is the major cause for the sensorineural impairment. Phase audiometry, a test for sound localization, showed mild disturbances in the TS women compared to the reference group, suggesting that auditory-spatial dysfunction is another facet of the recognized neurocognitive phenotype in TS. Further, the rate of hearing decline in women with TS is comparable to that seen in 70-90-year-old women in the general population, regardless of initial age, hearing level, karyotype, or presence of a mid-frequency dip. The presence of a mid-frequency dip is an especially strong predictor for a future high rate of highfrequency hearing decline with subsequent social consequences.