Abstract
Existing evidence indicates that both iron deficiency anemia and sickle cell anemia have been previously associated with hearing loss. However, human data investigating the association between anemia and auditory threshold shifts at different frequencies in the adolescent, adult and elderly population are extremely limited to date. Therefore, this cross-sectional study used the dataset from the US National Health and Nutrition Examination Survey from 2005 to 2012 to explore differences in low- or high-frequency hearing thresholds and hearing loss prevalence between participants with and without anemia. A total of 918 patients with anemia and 8213 without anemia were included. Results indicated that low- and high-frequency pure tone average were significantly higher in patients with anemia than that in those without anemia in the elderly, but not in adult or adolescent population. In addition, the prevalence of low-frequency hearing loss but not high-frequency hearing loss was also higher in patients with anemia than in those without anemia in the elderly population. After adjusting various confounders, multiple regression models still indicated that patients with anemia tended to have larger threshold shift. In conclusion, anemia was associated with auditory threshold shifts in the elderly population, especially those vulnerable to low-frequency hearing loss.
Keywords: anemia, hearing loss, auditory threshold shifts, pure tone average
1. Introduction
Approximately 466 million people worldwide have disabling hearing loss in 2018 [1], and unaddressed hearing loss poses an annual global cost of US$ 750–790 billion [2]. In the United States, the number of adults with hearing loss (pure tone average (PTA), >25 dB) is estimated to gradually increase from 44.1 million in 2020 to 73.5 million by 2060 [3]. Hearing loss is a sensory impairment caused by multiple factors including gene mutations, environmental noise, viral infection, autoimmune disease, labyrinthine membrane rupture, vascular events (e.g., vascular disease/alteration of microcirculation, vascular disease associated with mitochondriopathy, vertebrobasilar insufficiency, red blood cell deformability, sickle cell disease and cardiopulmonary bypass), and blood disorders [4]. Anemia is the most common blood disorder and also remains the major global public health problems. Existing evidence indicated that both iron deficiency anemia (IDA) and sickle cell anemia (SCA) have been previously associated with hearing loss [5,6].
In a Taiwan population-based study, Chung et al. found that the odds ratio (OR) for having a previous IDA diagnosis among patients aged ≥18 years with sudden sensorineural hearing loss was 1.34 (95% confidence interval (CI), 1.11–1.61), which was most pronounced among those aged ≤44 years compared with controls (OR, 1.91; 95% CI, 1.35–2.72) [7]. US cohort studies by Schieffer et al. also showed that children and adolescents with IDA have an increased risk of developing sensorineural hearing loss (OR, 3.67; 95% CI, 1.60–7.30); increased odds of sensorineural hearing loss (OR, 1.82; 95% CI, 1.18–2.66) but conductive hearing loss (OR, 1.51; 95% CI, 0.54–3.28) among adults with IDA [8,9]. In addition, a prospective case-control study by Aderibigbe et al. indicated that the average hearing thresholds of patients with SCA aged 16–48 years were significantly higher than controls aged 15–39 years in both right and left ears (right hearing thresholds: 16.7 ± 13.0 vs. 11.1 ± 9.1 dB; left hearing thresholds: 12.8 ± 9.4 vs. 9.6 ± 5.8 dB) [10].
Although IDA and SCA mechanisms that lead to hearing loss differ, hemoglobin may play a common and critical role in the deterioration of hearing function. In addition, typical changes in age-related hearing loss usually start with a hearing loss on high frequencies [11], and there are rare reports of low-frequency hearing loss occurring in old age. To date, human data investigating the association between anemia and auditory threshold shifts at different frequencies in the adolescent, adult and elderly population are extremely limited. Therefore, we use the dataset from the National Health and Nutrition Examination Survey (NHANES) to explore differences in low- or high-frequency hearing thresholds and hearing loss prevalence between participants with and without anemia.
2. Materials and Methods
2.1. Database
The data used in this cross-sectional study were derived from the NHANES in the United States (https://wwwn.cdc.gov/nchs/nhanes/). This survey includes information about questionnaires, demographic data, laboratory tests, and physical examinations, among others. All the study participants in the NHANES are sampled from the residents in the United States. Its research protocols were approved by the Research Ethics Review Board of National Center for Health Statistics. All participants provided written informed consents. Because we only used de-identified secondary data from NHANES, this study was exempted from full review by the Institutional Review Board.
2.2. Study Participants Selection and Anemia Definition
This study attempted to identify the association between anemia and auditory threshold shifts. Therefore, study participants aged 12 years and older were only limited to 2005–2012 NHANES individuals who underwent both audiometric examinations and with complete blood count results. Those with incomplete audiometric exams or missing laboratory tests for hemoglobin were excluded from this study. A total of 9131 US participants were recruited in this cross-sectional study. We then classified the study participants into two groups: patients with and without anemia. Anemia was defined based on the World Health Organization recommendations. Male participants with the serum hemoglobin level of <13 g/dL or female participants with the serum hemoglobin level of <12 g/dL were identified as patients with anemia [12]. Finally, 918 patients with anemia and 8213 without anemia were included in this study.
2.3. Audiometric Measures
According to the NHANES protocols, audiometric examinations excluded participants who could not tolerate headphones because of ear pain at the exam time. Those using hearing aids (not able to remove them) during the test were also excluded. All audiometry examinations were carried out by professionally trained audiologists from the National Institute for Occupational Safety & Health using the interacoustics model AD226 audiometer (with standard TDH-49 headphones and Etymotic EarTone 3A insert earphones). The hearing threshold test in this study was conducted on both right and left ears at 0.5, 1, 2, 3, 4, 6, and 8 kHz across an intensity range of −10 to 120 decibels (dB). Full audiometric protocols and procedures are available online.
2.4. Auditory Threshold Shifts and Hearing Loss Definition
In the relevant analyses of this study, PTA thresholds of hearing at 0.5, 1, and 2 kHz were identified as the low-frequency PTA (low PTA) and PTA thresholds of hearing at 3, 4, and 6 kHz were identified as the high-frequency PTA (high PTA) [13]. Additionally, this cross-sectional study identified patients with PTA at 0.5, 1, and 2 kHz thresholds of ≥15 dB in either ear as those with low-frequency hearing loss (LFHL). Patients who met the criteria for PTA at 3, 4, and 6 kHz thresholds of ≥15 dB in whichever ear were defined as the high-frequency hearing loss (HFHL). Furthermore, patients who experienced any hearing loss of ≥15 dB (including HFHL or LFHL) were identified as those with overall hearing loss (HL).
2.5. Covariate Measurement
To eliminate the potential effects of some confounders and investigate the actual relationship between anemia and HL, participants’ age group, sex, race, hypertension, diabetes, coronary heart disease, heart failure, and stroke were considered in the regression models. In this study, the race was categorized as non-Hispanic white, non-Hispanic black, or others (including Mexican American, other Hispanic, and other races). In addition, participants were considered to have medical history of hypertension, coronary heart disease, heart failure, and stroke if participants self-reported to have medical history about these diseases according to their physicians. Moreover, patients self-reported to have diabetes by physicians or other health professionals or receive diabetic medications were identified as diabetes cases.
2.6. Statistical Analysis
All analyses were performed with the SAS system (SAS System for Windows, ver. 9.4, SAS Institute Inc., Cary, NC, USA). This study used the chi-squared tests to explore differences in age group, sex, race, hypertension, diabetes, coronary heart disease, heart failure, and stroke, LFHL, HFHL, HL, between participants with and without anemia. Independent t-tests were further conducted to compare differences in low PTA and high PTA between participants with and without anemia. Additionally, regression models were carried out to estimate the effects of anemia on PTA thresholds of hearing. A two-sided p-value of 0.05 was used to determine the statistical significance of this study.
3. Results
This study consisted of 918 participants with anemia and 8213 without anemia. Table 1 shows the demographic characteristics and comorbidities of participants with anemia and controls without anemia. Relevant findings indicated that there were significant differences in age group (p < 0.001), sex (p < 0.001), and race (p < 0.001) between the two groups. In addition, the prevalence of hypertension (p < 0.001), diabetes (p < 0.001), coronary heart disease (p < 0.001), heart failure (p < 0.001), and stroke (p < 0.001) between participants with anemia and controls without anemia was significantly different.
Table 1.
Demographic characteristics and comorbidities of subjects with anemia and the controls without anemia (n = 9131).
| Variable | Subjects with Anemia (n = 918) | Subjects without Anemia (n = 8213) | p Value | ||
|---|---|---|---|---|---|
| No. | % | No. | % | ||
| Age Group (Years) | <0.001 | ||||
| ≤19 | 313 | 34.1 | 3675 | 44.8 | |
| 20–29 | 72 | 7.8 | 721 | 8.8 | |
| 30–39 | 73 | 8.0 | 664 | 8.1 | |
| 40–49 | 85 | 9.3 | 629 | 7.7 | |
| 50–59 | 68 | 7.4 | 673 | 8.2 | |
| 60–69 | 74 | 8.1 | 610 | 7.4 | |
| ≥70 | 233 | 25.4 | 1241 | 15.1 | |
| Sex | <0.001 | ||||
| Male | 367 | 40.0 | 4292 | 52.3 | |
| Female | 551 | 60.0 | 3921 | 47.7 | |
| Race | <0.001 | ||||
| Non-Hispanic white | 224 | 24.4 | 3285 | 40.0 | |
| Non-Hispanic black | 446 | 48.6 | 1871 | 22.8 | |
| Other | 248 | 27.0 | 3057 | 37.2 | |
| Ever had diagnosis | |||||
| Hypertension | 329 | 35.8 | 1835 | 22.3 | <0.001 |
| Diabetes | 128 | 13.9 | 570 | 6.9 | <0.001 |
| Coronary heart disease | 44 | 4.8 | 212 | 2.6 | <0.001 |
| Heart failure | 42 | 4.6 | 154 | 1.9 | <0.001 |
| Stroke | 49 | 5.3 | 178 | 2.2 | <0.001 |
Table 2 displays the high PTA, low PTA, and prevalence of LFHL, HFHL, and HL in participants with and without anemia. Results showed that participants with anemia had significantly higher low PTA (right ear: 15.04 dB vs. 11.64 dB; left ear: 15.57 dB vs. 11.56 dB) and high PTA (right ear: 23.82 dB vs. 18.55 dB; left ear: 24.71 dB vs. 19.51 dB) in both ears compared to participants without anemia. Moreover, the HL was found in 64.16% of participants with anemia and in 54.60% of controls without anemia (p < 0.001). LFHL was observed in 42.59% of participants with anemia and in 32.66% of controls without anemia (p < 0.001). Furthermore, the HFHL was found in 61.44% of participants with anemia and in 51.88% of controls without anemia (p < 0.001).
Table 2.
High-PTA, low-PTA, and prevalence of hearing loss in subjects with and without anemia.
| Variables | Total (n = 9131) | Subjects with Anemia (n = 918) | Subjects without Anemia (n = 8213) | p Value | |||
|---|---|---|---|---|---|---|---|
| n, % | n, % | n, % | |||||
| Low-PTA (dB) | |||||||
| Right Ear | 11.98 ± 12.58 | 15.04 ± 14.45 | 11.64 ± 12.31 | <0.001 | |||
| Left Ear | 11.97 ± 12.71 | 15.57 ± 15.37 | 11.56 ± 12.31 | <0.001 | |||
| High-PTA (dB) | |||||||
| Right Ear | 19.08 ± 20.74 | 23.82 ± 23.06 | 18.55 ± 20.39 | <0.001 | |||
| Left Ear | 20.04 ± 21.35 | 24.71 ± 23.80 | 19.51 ± 20.99 | <0.001 | |||
| Hearing Loss | |||||||
| HL | 5073 | 55.56 | 589 | 64.16 | 4484 | 54.60 | <0.001 |
| LFHL | 3073 | 33.65 | 391 | 42.59 | 2682 | 32.66 | <0.001 |
| HFHL | 4825 | 52.84 | 564 | 61.44 | 4261 | 51.88 | <0.001 |
Low-PTA, pure tone average at low frequencies; High-PTA, pure tone average at high frequencies; LFHL, low-frequency hearing loss; HFHL, high-frequency hearing loss; HL, hearing loss.
Because age is an important factor in the development of HL, Table 3 further displays the high PTA, low PTA, and prevalence of LFHL, HFHL, HL in participants with and without anemia according to the age group. Independent t-tests presented that participants with anemia had a significantly greater low PTA and high PTA than those without anemia among the elderly population (aged ≥ 60 years) in both ears. The prevalence of LFHL was also higher in participants with anemia than that in those without anemia. However, no significant difference in low PTA and high PTA was observed between patients with and without anemia among adult and adolescent population.
Table 3.
High-PTA, low-PTA, and prevalence of hearing loss in subjects with and without anemia according to the age group.
| Variables | Elderly Population (≥60 Years Old) | Adult Population (20–59 Years Old) | Adolescent Population (≤19 Years Old) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects with Anemia (n = 307) | Subjects without Anemia (n = 1851) | p Value | Subjects with Anemia (n = 298) | Subjects without Anemia (n = 2687) | p Value | Subjects with Anemia (n = 313) | Subjects without Anemia (n = 3675) | p Value | |
| Low-PTA (dB) | |||||||||
| Right Ear | 28.07 ± 15.23 | 25.13 ± 15.32 | 0.002 | 9.93 ± 8.98 | 9.24 ± 9.15 | 0.213 | 7.14 ± 7.41 | 6.60 ± 6.15 | 0.212 |
| Left Ear | 29.25 ± 16.49 | 25.01 ± 15.30 | <0.001 | 10.55 ± 10.09 | 9.21 ± 8.84 | 0.028 | 6.93 ± 6.90 | 6.51 ± 6.57 | 0.278 |
| High-PTA (dB) | |||||||||
| Right Ear | 48.20 ± 20.40 | 45.22 ± 21.57 | 0.024 | 15.44 ± 13.56 | 15.82 ± 14.30 | 0.231 | 7.88 ± 8.55 | 7.12 ± 7.16 | 0.129 |
| Left Ear | 50.54 ± 20.50 | 47.00 ± 21.52 | 0.007 | 15.79 ± 13.05 | 16.98 ± 14.85 | 0.140 | 7.87 ± 8.57 | 7.52 ± 7.83 | 0.490 |
| Hearing Loss | |||||||||
| HL | 306 (99.67) | 1825 (98.60) | 0.163 | 185 (62.08) | 1655 (61.59) | 0.870 | 98 (31.31) | 1004 (27.32) | 0.130 |
| LFHL | 268 (87.30) | 1494 (80.71) | 0.006 | 80 (26.85) | 717 (26.68) | 0.952 | 43 (13.74) | 471 (12.82) | 0.640 |
| HFHL | 305 (99.35) | 1820 (98.33) | 0.216 | 178 (59.73) | 1606 (59.77) | 0.990 | 81 (25.88) | 835 (22.72) | 0.202 |
Note: Low-PTA, pure tone average at low frequencies; High-PTA, pure tone average at high frequencies; LFHL, low-frequency hearing loss; HFHL, high-frequency hearing loss; HL, hearing loss.
To reduce the potential effects of confounders, the regression models were used to investigate the relationships between PTA and anemia according to different age groups (Table 4). After adjusting various confounders, multiple regression models still indicated that patients with anemia tended to have higher hearing thresholds. Anemia was also significantly positively associated with the hearing thresholds, including both high PTA and low PTA, in the overall and elderly population. β coefficients of the high PTA comparing participants with anemia to controls without anemia were 2.35 for the right ear (p < 0.001) and 2.33 for the left ear (p < 0.001), and β coefficients of the low PTA were 1.53 for the right ear (p < 0.001) and 2.25 for the left ear (p < 0.001) in the overall population. Additionally, β coefficients of the high PTA comparing participants with anemia to controls without anemia were 3.76 for the right ear (p = 0.002), and 4.03 for the left ear (p = 0.001) and β coefficients of the low PTA were 3.55 for the right ear (p < 0.001) and 4.64 for the left ear (p < 0.001) in the elderly population. Additionally, this study performed the regression models to investigate the relationships between PTA and anemia according to different sexes and ethnic groups (Supplementary Table S1). After adjustments, anemia was positively associated with the hearing thresholds, including both high PTA and low PTA, in women, men, non-Hispanic white, and non-Hispanic black populations.
Table 4.
Regression analyses of relationships between pure tone average and anemia according to different age groups.
| Models | Variables | High-PTA (dB) | Low-PTA (dB) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Right Ear | Left Ear | Right Ear | Left Ear | ||||||
| β | p Value | β | p Value | β | p Value | β | p Value | ||
| Model 1 a | All Patients with Anemia | 5.27 | <0.001 | 5.20 | <0.001 | 3.40 | <0.001 | 4.01 | <0.001 |
| Elderly Patients with Anemia | 2.99 | 0.024 | 3.54 | 0.007 | 2.93 | 0.002 | 4.24 | <0.001 | |
| Adult Patients with Anemia | −0.38 | 0.662 | −1.20 | 0.182 | 0.69 | 0.213 | 1.34 | 0.015 | |
| Adolescent Patients with Anemia | 0.76 | 0.077 | 0.35 | 0.455 | 0.54 | 0.144 | 0.42 | 0.278 | |
| Model 2 b | All Patients with Anemia c | 2.35 | <0.001 | 2.33 | <0.001 | 1.53 | <0.001 | 2.25 | <0.001 |
| Elderly Patients with Anemia d | 3.76 | 0.002 | 4.03 | 0.001 | 3.55 | <0.001 | 4.64 | <0.001 | |
| Adult Patients with Anemia d | 1.42 | 0.102 | 1.42 | 0.109 | 0.55 | 0.340 | 1.37 | 0.015 | |
| Adolescent Patients with Anemia e | 0.79 | 0.073 | 0.59 | 0.210 | 0.65 | 0.085 | 0.77 | 0.053 | |
Note: Low-PTA, pure tone average at low frequencies; High-PTA, pure tone average at high frequencies.a Model 1: Univariate regression; b Model 2: Multiple regression; c Adjusted covariates: sex, race, age, hypertension, diabetes, coronary heart disease, heart failure, stroke; d Adjusted covariates: sex, race, hypertension, diabetes, coronary heart disease, heart failure, stroke; e Adjusted covariates: sex and race.
4. Discussion
In this study, anemia was found to be associated with auditory threshold shifts, which can be used to explain the higher prevalence of LFHL in elderly participants with anemia. To date, the mechanism of anemia-associated HL remains unclear and non-conclusive, although some plausible mechanisms were proposed. In the cochlear, intricate vasculature provides oxygen and nutrients needed for the stria vascularis of the cochlear duct to maintain the ionic composition of the endolymph and the endocochlear potential [14,15]. As anemia could decrease oxygen delivery in the labyrinthine arterial blood due to reduced hemoglobin concentration, blood oxygen supply to the cochlear is highly sensitive to ischemic damage.
Previous studies indicated that IDA is a potential risk factor for ischemic stroke [16], and patients with vascular disease have a higher risk for developing sudden sensorineural HL [7,17,18,19,20]. Iron is not only an essential component of hemoglobin in the red blood cells for tissue oxygen delivery but also a cofactor in neurotransmitter metabolism, DNA synthesis, and nerve myelination [21,22,23,24]. Neurological disorders might be associated with sensorineural HL. A systematic review and meta-analysis showed that compared with individuals without IDA, the age-specific OR of sensorineural HL was higher for children (3.67, 95% CI 1.72–7.84) than for adults (1.36, 95% CI 1.15–1.61; p = 0.27) [5]. However, participants with anemia have higher values of low and high PTA than those without anemia in the elderly but not the adult or adolescent population in this study (Table 3). We found that adolescent population with anemia are not apparent with low PTA threshold shift of 0.42–0.54 dB and high PTA threshold shift of 0.35–0.76 dB; low PTA threshold shift of 0.69–1.34 dB but high PTA negative threshold shift of 0.38–1.19 dB in the adult population. Elderly participants with anemia have remarkably low PTA threshold shift of 2.94–4.24 dB and high PTA threshold shift of 2.98–3.54 dB. Therefore, it is speculated that the biological interaction of aging and anemia would be a chronic progressive contributing factor to HL in the elderly population. In contrast, it may be different from IDA that has been regarded as a deteriorating factor of sudden sensorineural HL among adults aged <44 years [7].
Presbycusis, or age-related HL, is a common disorder characterized by symmetrical progressive loss of high-frequency hearing over the years. The World Health Organization estimates that >500 million people aged >60 years worldwide will suffer significant impairment from presbycusis by 2025 [25]. In this study, although elderly people with anemia have higher high PTA threshold values, similar prevalence of HFHL was found between the elderly people with (99.35%) and without anemia (98.33%). It is noteworthy that anemia was associated with LFHL only in the elderly population. The prevalence of LFHL in elderly people with anemia is 87.30%, which is higher than 80.71% in those without anemia. Based on our study results, we should particularly check and correct the hemoglobin level of elderly patients in routine clinical care to prevent the chronic progressive development of LFHL.
Limitations
This study had several limitations. First, all data in NHANES are cross-sectional, and thus this study cannot establish the causal relationship between anemia and hearing threshold shift. Second, we cannot assess environmental, occupational, or recreational noises around the participants included in this study. Previous reports have highlighted the significance of noise-induced HL from both work and recreational activities [26,27]. Third, this study also could not evaluate the use of medications among these participants. Some drugs, such as gentamicin, sildenafil, and cisplatin chemotherapy, can damage the inner ear [28,29,30]. In addition, high doses of aspirin, other non-steroidal anti-inflammatory drugs, antimalarial drugs, or loop diuretics have also been reported to cause temporary tinnitus or HL [31]. Fourth, information about ear infection and abnormal bone growths or tumors in the outer or middle ear that can also result in HL was not available in the NHANES. Fifth, LFHL may be caused by Meniere’s disease, genetic conditions, central lesions, low spinal fluid pressure, and lithium use. These confounders cannot be adjusted in the multiple regression analysis of this study. Sixth, LFHL is also often related to conductive hearing loss, but bone thresholds are not available from the NHANES dataset. Therefore, we could not exclude conductive LFHL in this study. Seventh, previous evidence indicated that both anemia and hearing loss are sometimes partly explained by genetic deviations. Genetic components of anemia and HL were not available for this study. In addition, we did not consider some chronic diseases, like kidney diseases, rheumatism and cancer, which could be the comorbidity of both anemia and HL. Finally, the study findings should be cautiously generalized to other ethnicities because all patients included in this study were US residents.
In conclusion, our study demonstrated that anemia was associated with LFHL in the elderly population. However, further larger epidemiologic studies need to be conducted to confirm the effects of anemia on auditory threshold shifts in different ethnic groups and countries.
Supplementary Materials
The following are available online at https://www.mdpi.com/1660-4601/17/11/3916/s1, Table S1: Regression analyses of relationships between pure tone average and anemia according to sex and ethnicities.
Author Contributions
L.-T.K. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: J.-H.S., I.-H.L., and L.-T.K. Acquisition, analysis, or interpretation of data: J.-H.S. and L.-T.K. Drafting of the manuscript: J.-H.S. and L.-T.K. Critical revision of the manuscript for important intellectual content: J.-H.S., L.-T.K., I.-H.L., C.-H.W., H.-C.C., L.-Y.F. and J.-H.T. Statistical analysis: K.-T.P. and L.-T.K. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by Tri-Service General Hospital, Taipei, Taiwan (TSGH-D-109145 and TSGH-E-109242) and Department of Health, Taipei City Government, Taipei, Taiwan (10801-62-072).
Conflicts of Interest
The authors declare no conflict of interest.
References
- 1.WHO . Addressing the Rising Prevalence of Hearing Loss. World Health Organization; Geneva, Switzerland: 2018. [Google Scholar]
- 2.WHO . Global Costs of Unaddressed Hearing Loss and Cost-Effectiveness of Interventions: A Who Report, 2017. World Health Organization; Geneva, Switzerland: 2017. [Google Scholar]
- 3.Goman A.M., Reed N.S., Lin F.R. Addressing estimated hearing loss in adults in 2060. JAMA Otolaryngol. Head Neck Surg. 2017;143:733–734. doi: 10.1001/jamaoto.2016.4642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Rizzo S., Bentivegna D., Thomas E., La Mattina E., Mucia M., Salvago P., Sireci F., Martines F. Sudden Sensorineural Hearing Loss, an Invisible Male: State of the Art. Nova Science Publishers, Inc.; New York, NY, USA: 2017. [Google Scholar]
- 5.Mohammed S.H., Shab-Bidar S., Abuzerr S., Habtewold T.D., Alizadeh S., Djafarian K. Association of anemia with sensorineural hearing loss: A systematic review and meta-analysis. BMC Res. Notes. 2019;12:283. doi: 10.1186/s13104-019-4323-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lago M.R.R., Fernandes L.D.C., Lyra I.M., Ramos R.T., Teixeira R., Salles C., Ladeia A.M.T. Sensorineural hearing loss in children with sickle cell anemia and its association with endothelial dysfunction. Hematology. 2018;23:849–855. doi: 10.1080/10245332.2018.1478494. [DOI] [PubMed] [Google Scholar]
- 7.Chung S.D., Chen P.Y., Lin H.C., Hung S.H. Sudden sensorineural hearing loss associated with iron-deficiency anemia: A population-based study. JAMA Otolaryngol. Head Neck Surg. 2014;140:417–422. doi: 10.1001/jamaoto.2014.75. [DOI] [PubMed] [Google Scholar]
- 8.Schieffer K.M., Chuang C.H., Connor J., Pawelczyk J.A., Sekhar D.L. Association of iron deficiency anemia with hearing loss in us adults. JAMA Otolaryngol. Head Neck Surg. 2017;143:350–354. doi: 10.1001/jamaoto.2016.3631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Schieffer K.M., Connor J.R., Pawelczyk J.A., Sekhar D.L. The relationship between iron deficiency anemia and sensorineural hearing loss in the pediatric and adolescent population. Am. J. Audiol. 2017;26:155–162. doi: 10.1044/2017_AJA-16-0093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Aderibigbe A., Ologe F.E., Oyejola B.A. Hearing thresholds in sickle cell anemia patients: Emerging new trends? J. Natl. Med. Assoc. 2005;97:1135–1142. [PMC free article] [PubMed] [Google Scholar]
- 11.Gates G.A., Mills J.H. Presbycusis. Lancet. 2005;366:1111–1120. doi: 10.1016/S0140-6736(05)67423-5. [DOI] [PubMed] [Google Scholar]
- 12.Beutler E., Waalen J. The definition of anemia: What is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107:1747–1750. doi: 10.1182/blood-2005-07-3046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Su B.M., Chan D.K. Prevalence of hearing loss in us children and adolescents: Findings from nhanes 1988–2010. JAMA Otolaryngol. Head Neck Surg. 2017;143:920–927. doi: 10.1001/jamaoto.2017.0953. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Lamm K., Arnold W. The effect of blood flow promoting drugs on cochlear blood flow, perilymphatic po(2) and auditory function in the normal and noise-damaged hypoxic and ischemic guinea pig inner ear. Hear Res. 2000;141:199–219. doi: 10.1016/S0378-5955(00)00005-8. [DOI] [PubMed] [Google Scholar]
- 15.Shi X. Physiopathology of the cochlear microcirculation. Hear Res. 2011;282:10–24. doi: 10.1016/j.heares.2011.08.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Chang Y.L., Hung S.H., Ling W., Lin H.C., Li H.C., Chung S.D. Association between ischemic stroke and iron-deficiency anemia: A population-based study. PLoS ONE. 2013;8:e82952. doi: 10.1371/journal.pone.0082952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Capaccio P., Ottaviani F., Cuccarini V., Bottero A., Schindler A., Cesana B.M., Censuales S., Pignataro L. Genetic and acquired prothrombotic risk factors and sudden hearing loss. Laryngoscope. 2007;117:547–551. doi: 10.1097/MLG.0b013e31802f3c6a. [DOI] [PubMed] [Google Scholar]
- 18.Marcucci R., Alessandrello Liotta A., Cellai A.P., Rogolino A., Berloco P., Leprini E., Pagnini P., Abbate R., Prisco D. Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss. J. Thromb. Haemost. 2005;3:929–934. doi: 10.1111/j.1538-7836.2005.01310.x. [DOI] [PubMed] [Google Scholar]
- 19.Rudack C., Langer C., Stoll W., Rust S., Walter M. Vascular risk factors in sudden hearing loss. Thromb. Haemost. 2006;95:454–461. doi: 10.1160/TH05-08-0554. [DOI] [PubMed] [Google Scholar]
- 20.Chung J.H., Lee S.H., Park C.W., Kim C., Park J.K., Shin J.H. Clinical significance of arterial stiffness in idiopathic sudden sensorineural hearing loss. Laryngoscope. 2016;126:1918–1922. doi: 10.1002/lary.25853. [DOI] [PubMed] [Google Scholar]
- 21.Lopez A., Cacoub P., Macdougall I.C., Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2016;387:907–916. doi: 10.1016/S0140-6736(15)60865-0. [DOI] [PubMed] [Google Scholar]
- 22.Camaschella C. Iron-deficiency anemia. N. Engl. J. Med. 2015;372:1832–1843. doi: 10.1056/NEJMra1401038. [DOI] [PubMed] [Google Scholar]
- 23.Zhang C. Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein Cell. 2014;5:750–760. doi: 10.1007/s13238-014-0083-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Badaracco M.E., Ortiz E.H., Soto E.F., Connor J., Pasquini J.M. Effect of transferrin on hypomyelination induced by iron deficiency. J. Neurosci. Res. 2008;86:2663–2673. doi: 10.1002/jnr.21709. [DOI] [PubMed] [Google Scholar]
- 25.Sprinzl G.M., Riechelmann H. Current trends in treating hearing loss in elderly people: A review of the technology and treatment options—A mini-review. Gerontology. 2010;56:351–358. doi: 10.1159/000275062. [DOI] [PubMed] [Google Scholar]
- 26.Ivory R., Kane R., Diaz R.C. Noise-induced hearing loss: A recreational noise perspective. Curr. Opin. Otolaryngol. Head Neck Surg. 2014;22:394–398. doi: 10.1097/MOO.0000000000000085. [DOI] [PubMed] [Google Scholar]
- 27.Tikka C., Verbeek J.H., Kateman E., Morata T.C., Dreschler W.A., Ferrite S. Interventions to prevent occupational noise-induced hearing loss. Cochrane Database Syst. Rev. 2017;7:CD006396. doi: 10.1002/14651858.CD006396.pub4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Breglio A.M., Rusheen A.E., Shide E.D., Fernandez K.A., Spielbauer K.K., McLachlin K.M., Hall M.D., Amable L., Cunningham L.L. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat. Commun. 2017;8:1654. doi: 10.1038/s41467-017-01837-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Corbacella E., Lanzoni I., Ding D., Previati M., Salvi R. Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures. Hear Res. 2004;197:11–18. doi: 10.1016/j.heares.2004.03.012. [DOI] [PubMed] [Google Scholar]
- 30.Khan A.S., Sheikh Z., Khan S., Dwivedi R., Benjamin E. Viagra deafness--sensorineural hearing loss and phosphodiesterase-5 inhibitors. Laryngoscope. 2011;121:1049–1054. doi: 10.1002/lary.21450. [DOI] [PubMed] [Google Scholar]
- 31.Joo Y., Cruickshanks K.J., Klein B.E.K., Klein R., Hong O., Wallhagen M. The contribution of ototoxic medications to hearing loss among older adults. J. Gerontol. A Biol. Sci. Med. Sci. 2019;75:561–566. doi: 10.1093/gerona/glz166. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.