Clinical research study
Analgesic Use and the Risk of Hearing Loss in Men

https://doi.org/10.1016/j.amjmed.2009.08.006Get rights and content

Abstract

Background

Hearing loss is a common sensory disorder, yet prospective data on potentially modifiable risk factors are limited. Regularly used analgesics, the most commonly used drugs in the US, may be ototoxic and contribute to hearing loss.

Methods

We examined the independent association between self-reported professionally diagnosed hearing loss and regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen in 26,917 men aged 40-74 years at baseline in 1986. Study participants completed detailed questionnaires at baseline and every 2 years thereafter. Incident cases of new-onset hearing loss were defined as those diagnosed after 1986. Cox proportional hazards multivariate regression was used to adjust for potential confounding factors.

Results

During 369,079 person-years of follow-up, 3488 incident cases of hearing loss were reported. Regular use of each analgesic was independently associated with an increased risk of hearing loss. Multivariate-adjusted hazard ratios of hearing loss in regular users (2+ times/week) compared with men who used the specified analgesic <2 times/week were 1.12 (95% confidence interval [CI], 1.04-1.20) for aspirin, 1.21 (95% CI, 1.11-1.33) for NSAIDs, and 1.22 (95% CI, 1.07-1.39) for acetaminophen. For NSAIDs and acetaminophen, the risk increased with longer duration of regular use. The magnitude of the association was substantially higher in younger men. For men younger than age 50 years, the hazard ratio for hearing loss was 1.33 for regular aspirin use, 1.61 for NSAIDs, and 1.99 for acetaminophen.

Conclusions

Regular use of aspirin, NSAIDs, or acetaminophen increases the risk of hearing loss in men, and the impact is larger on younger individuals.

Section snippets

Participants

The Health Professionals Follow-up Study originally enrolled 51,529 male dentists, optometrists, osteopaths, pharmacists, podiatrists, and veterinarians who were 40-75 years of age at baseline in 1986. Study participants filled out detailed questionnaires about diet, medical history, and medication use. These questionnaires have been administered every other year, and the 20-year follow-up exceeds 90%. The 2004 long-form questionnaire included a question about whether the participant had been

Results

Characteristics of participants at baseline according to analgesic use are shown in Table 1. Although updated information was used for the analysis, characteristics are presented from baseline to provide representative values. Regular aspirin and NSAID users were older and acetaminophen users were younger than nonregular users. Hypertension was more common among regular analgesic users. It was common for an individual to use more than one type of analgesic regularly.

During 369,079 person-years

Discussion

Regular analgesic use was independently associated with an increased risk of hearing loss. The increased risk of hearing loss seen with regular analgesic use was greatest among younger men, particularly those below age 60 years. In men aged 60 years and above, there was no relation observed between the risk of hearing loss and regular aspirin use, and the relation between regular use of NSAIDs and acetaminophen was attenuated. The risk of hearing loss increased with longer duration of analgesic

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      Recently, several groups have reported evidence that long-term therapeutic use of analgesics, including APAP and NSAIDs, is associated with hearing problems. Data from numerous epidemiological studies indicate that use of those drugs modestly but significantly increases risk of premature hearing loss (Curhan et al., 2010, 2012; Kyle et al., 2015; Lin et al., 2017). Furthermore, there have been nearly 30 reports of serious ototoxicity resulting in deafness after therapeutic use or abuse of APAP/opioid combination products (McGill et al., 2016), and both in vitro and in vivo studies have provided a possible mechanistic basis (Yorgason et al., 2010; Kalinec et al., 2014; McGill et al., 2016).

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      Other external factors, including occupational noise, certain drugs, and exposure to heavy metals, are also considered ototoxic agents (Choi and Kim, 2014). Epidemiological studies have shown that regular use of some drugs is associated with an increased risk of auditory cell damage, including nonsteroidal anti-inflammatory drugs, loop diuretics, chemotherapeutic agents, antimalarics, macrolides, glycopeptides, and aminoglycosides (Curhan et al., 2010; Eiamprapai et al., 2012; Javadi et al., 2011). Metabolic disorders, such as diabetes and hypertension, are also associated with a reduction in cochlear microcirculation and with damage to neural structures.

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    Funding: This work was supported by National Institutes of Health grant P01 CA055075 and the Massachusetts Eye and Ear Infirmary Foundation, Boston, Mass.

    The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

    Conflict of Interest: The authors have no conflicts of interest to report.

    Authorship: All authors had access to the data and a role in writing the manuscript.

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