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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, South Korea.
Address reprint requests to: Byung Moon Kang, MD, University of Ulsan, College of Medicine, Asan Medical Center, 388-1, Department of Obstetrics and Gynecology, Poongnapdong, Songpa-ku, Seoul 138-736, South Korea; E-mail: bmkang@www.amc.seoul.kr.
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ABSTRACT |
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METHODS: Serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and hearing sensitivity were measured in 1830 postmenopausal women. Serum estradiol level was measured by radioimmunoassay, and dual energy x-ray absorptiometry was used to measure bone mineral densities of the lumbar vertebrae and femoral neck. Hearing sensitivity was evaluated by pure tone audiometry. Age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and the proportion of women on hormone replacement therapy were analyzed in women with and without hearing loss.
RESULTS: On univariate analysis, significant differences were found in mean age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and the proportion of women on hormone replacement therapy between the two groups (mean ± standard deviation, 59.4 ± 5.6 versus 56.9 ± 4.7 years, P < .001; 8.4 ± 3.8 versus. 9.9 ± 8.7 pg/mL, P < .001; 0.85 ± 0.14 versus 0.88 ± 0.15 g/cm2, P < .01; 0.65 ± 0.10 versus 0.68 ± 0.10 g/cm2, P < .005; 0.006% versus 0.03%, P < .05, respectively). On multiple logistic regression analysis, significant association was found between age and hearing loss and between serum estradiol level and hearing loss (P < .001, P = .02, respectively).
CONCLUSION: This study suggests that a lower level of serum estradiol possibly impedes hearing sensitivity in postmenopausal women.
As more organs are found to be influenced by the positive effects of estrogen, there is a growing interest in the possible favorable effects of estrogen in various tissues. Estrogen has been expected to have favorable effects on auditory systems by some investigators. The positive effect of estrogen on auditory brain stem response was demonstrated in ovariectomized rats.1 Estrogen receptors 
and ß were found in the inner ear cell nuclei at specific locations, both in the auditory pathways and in the water-ion regulating areas of mice and rats, which indicates that estrogen may have an effect on the inner ear and hearing functions.2
An epidemiologic study suggests that prevention of bone loss might also prevent age-related hearing loss to some degree. Clark et al3 demonstrated that postmenopausal women with lower bone mineral density of the femoral neck had an increased risk of having hearing loss. They proposed that decreased bone mineral density of the femoral neck might reflect demineralization of the cochlea and otic capsule that could be associated with sensorineural hearing loss. Recently, analyzing auditory brain stem responses of postmenopausal women, Caruso et al4 reported that women treated with hormone replacement therapy (HRT) showed wave latencies and interpeak latencies shorter than those in the control group. They suggested that estrogen might influence the neuronal plasticity, the metabolic levels of neurotransmitters, and thus the neuronal conduction time into the audiologic system.
Hearing loss is a frequently reported chronic disorder of the elderly, with approximately 30% of people over 65 years old and 50% of people over 75 years old experiencing some degree of hearing loss.5,6 Although mortality directly related to hearing loss is minimal, hearing loss has been associated with increased incidence of depression and social isolation and decreased cognitive function in the elderly.7,8
In spite of a growing interest in the quality of life of postmenopausal women and the diverse favorable effects of estrogen, little has been known as to whether estrogen or bone mineral density exerts any direct effect on the auditory system. This study was designed to clarify whether hearing sensitivity in postmenopausal women is associated with the serum estradiol level or bone mineral density. For that purpose, we analyzed age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, the current status of hormone use, and pure tone threshold in 1830 postmenopausal women.
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MATERIALS AND METHODS |
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Estradiol level was determined from a single serum sample collected from each woman between 8 AM and 10 PM. Serum estradiol level was measured by radioimmunoassay using an estradiol Maia kit (CIBA-Corning Diagnostics, East Walpole, MA). The lowest detection limit of the assay was 5 pg/mL. The inter- and intra-assay coefficients of variation at the lower end range of the assay were 8.5% and 4.3%, respectively. Dual energy x-ray absorptiometry using QDR-4500A (Hologic Inc., Waltham, MA) was used for measuring bone mineral densities of the L2, L3, L4 vertebrae and femoral neck. The coefficient of variation in measuring bone mineral density was 0.97% in the lumbar bone mineral density and 1.82% in bone mineral density of the femoral neck, respectively.
Pure tone thresholds of both ears were evaluated in all patients by screening audiometer (Voyager 522, Madsen Electronics, Taastrup, Denmark). Hearing loss was defined as a 40-dB hearing level at 1000 and 2000 Hz in one ear or a 40-dB hearing level at 1000 or 2000 Hz in both ears.9 The patients defined as having hearing loss by screening audiometry were transferred to the otologic department for an otoscopic examination and confirmative pure tone audiometry (Orbitel 922, Madsen Electronics). We excluded from this study 12 patients in whom specific otologic disorders, such as otitis externa, otitis media, serous labyrinthitis, and Meniere disease, were confirmed.
A total of 1830 patients were analyzed; 181 patients were in the hearing loss group and 1649 patients were in the control group. Fifty-six patients were defined as women on HRT and 1774 patients were defined as nonusers. Women on HRT were defined as those women who were using hormones at the time of the above-mentioned measurements.
Comparisons of age, bone mineral densities, serum estradiol level, and the proportion of women on HRT between women with and without hearing loss were performed using Student t test and Fisher exact test. Multiple logistic regression analysis was used for estimating odds ratios for the association of hearing loss and the factors with P < .2 in Student t test. The lumbar and femoral neck bone mineral densities were analyzed separately using a multiple logistic regression model because there was strong correlation between the two variables. Serum estradiol level and current status of hormone use were also analyzed separately for the same reason. Results with P < .05 were considered significant.
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There have also been several reports that suggested the favorable effects of estrogen on the auditory system in humans. When comparing the hearing of elderly men and women from the normal population, there is a gender difference. In a large cohort study of 70–75 year olds, Jönsson et al11 reported that hearing in the 4–8 kHz region of the men was generally poorer than that of the women. In Turner syndrome, a chromosomal disorder (45, XO) associated with a loss of estrogen production, women often develop an early presbyacusis.12 It was reported that young female subjects had shorter auditory brain stem response latencies and larger amplitudes than young male subjects, but interestingly, the amplitude values of postmenopausal women closely approached the male values.13 Swanson and Dengerink14 reported earlier that pure tone thresholds at 4 kHz during the menstrual phase, in which the circulating level of estrogen was lowest, were poorer than at the time of ovulation or during the luteal phase.
We analyzed age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, the current status of hormone use, and pure tone threshold in 1830 postmenopausal women. Significant differences were observed in all parameters between women with and without hearing loss. However, multiple logistic regression analyses have shown that only age and serum estradiol level were significantly associated with hearing loss. It may be difficult to explain why the current status of hormone use did not seem to have influenced hearing sensitivity, although the findings of the present study are in concordance with previous research12–14 in that estrogen could have a favorable effect on pure tone thresholds. This study might have some limitations as a retrospective cross-sectional design, considering that the optimal way of searching for causality of hearing loss would be a prospective cohort study. One of the limitations is the low number of women on HRT, which consisted of only 56 of 1830 women in this study. It is possible that this extremely low number of women on HRT contributed to the statistically insignificant association between the current status of hormone use and hearing sensitivity in the present study.
Other factors that might have influenced these results could be the diverse HRT regimens and unpredictable compliance. We could not have any information about the HRT regimens. At present, little is known about the definite role of progesterone as well as estrogen on the auditory system. Caruso et al4 reported that women treated with estrogen replacement therapy showed shorter latencies than those treated with combined HRT, whereas some investigators have suggested favorable effects of progesterone on the auditory system by evaluating auditory brain stem response.15–17 Although we could not examine components of auditory brain stem response in this study, it could be supposed that various regimens of HRT make it difficult to find out whether estrogen replacement has any effect on hearing sensitivity or not. Further prospective randomized trials are needed for identifying the definite role of sex steroids on the auditory system.
As our study included only 56 of 1830 postmenopausal women on HRT, the averages of serum estradiol level in women with and without hearing loss were below the 10 pg/mL range. Only taking account of the difference of averages between the two groups with its standard deviation, one might argue against finding any clinical significance from this current study. However, comparing the proportion of women with hearing loss between the different serum estradiol range subgroups, we could find a tendency indicating decreased incidence of hearing loss with increased level of estradiol. Among women with a serum estradiol level of less than 10 pg/mL, 10–30 pg/mL, and more than 30 pg/mL, the proportions of women with hearing loss were 11.6%, 6.7%, and 2.8%, respectively (P = .002). The little difference of the averages of serum estradiol level between the two groups could result mainly from the low number of women on HRT.
Clark et al3 reported that postmenopausal women with hearing loss had significantly lower bone mass of the femoral neck after adjustment for age. They suggested that demineralization of the petrous temporal bone might be one biologic factor contributing to hearing loss in the elderly. They supposed that further studies including a third bone site, such as the lumbar region of the spine that contains a higher proportion of trabecular bone, would help to clarify the association between bone mass and hearing loss.
On univariate analysis, we found a significant difference of bone mineral densities of the lumbar vertebrae and femoral neck between women with and without hearing loss. However, multiple logistic regression analysis shows that bone mineral densities were not the factors associated with hearing loss risk. These findings suggest that hearing sensitivity in postmenopausal women is determined mainly by age and serum estradiol level. Bone mineral density may not influence hearing loss risk independent of its relationship with age and serum estradiol level. Our findings are contradictory to the previous report3 in that there was no significant association between bone mass and hearing loss risk after adjusting for age and serum estradiol level, and in that the lumbar region of the spine did not correlate better with hearing sensitivity than the femoral neck. More credibility could be given to the present study compared with the previous one3 because we had a larger number of women and a consistent way of measuring bone mineral density in which all of the patients were evaluated with the same absorptiometer.
In summary, from analyses of age, bone mineral densities, serum estradiol level, and the current status of hormone use of 1830 postmenopausal women, we found that not only age but also serum estradiol level could significantly influence hearing loss risk. In spite of some limits owing to the cross-sectional study design, our findings strongly suggest that estrogen has a favorable effect on the hearing sensitivity of postmenopausal women. Further prospective studies are needed to clarify the definite role of sex steroids on the auditory system.
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Footnotes |
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Received October 11, 2001. Received in revised form January 10, 2002. Accepted January 31, 2002.
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REFERENCES |
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2. Stenberg AE, Wang H, Sahlin L, Hultcrantz M. Mapping of estrogen receptors alpha and beta in the inner ear of mouse and rat. Hear Res 1999;136:29–34.[Medline]
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16. Elkind-Hirsch KE, Wallace E, Stach BA, Jerger JF. Cyclic steroid replacement alters auditory brainstem responses in young women with premature ovarian failure. Hear Res 1992;64:93–8.[Medline]
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