Could long-term analgesic use increase risk of deafness?
A large epidemiological study from the US found an increased risk of hearing loss associated with long-term use of analgesics (aspirin, NSAID, and paracetamol). The increases in risk are small, however, and should be taken with caution.
There is some experimental evidence that various analgesics (salicylates, NSAID, paracetamol) may be ototoxic, however there is also evidence that low-dose aspirin may protect hearing. The authors of this study used data from a pre-existing large cohort, the Health Professionals Follow-up Study. Participants are US male health professionals who were aged between 40 to 75 years in 1986 when the study started: at this point, they provided details on diet, health and medication history by mailed questionnaire. Health and mediation history is updated every two years and the 2004 questionnaire included a question asking whether the respondent had ever been professionally diagnosed with hearing loss and if so when. For this analysis, the authors used the data from this question plus preceding medication history to examine whether there was any association between hearing loss and regular (twice weekly or more) use of aspirin, NSAID, or paracetamol. Outcome measure was incident new-onset hearing loss, were defined as cases diagnosed after 1986. The potential confounding factors included in the analysis were age, race, body mass index (BMI), alcohol intake, folate intake, physical activity, smoking, hypertension, diabetes, cardiovascular disease, elevated cholesterol, and use of frusemide.
HPFS originally enrolled 51,529 men, of whom 31,496 provided data on hearing loss in 2004, and 26,917 were eligible for this analysis (main exclusions age >75, hearing loss onset before 1986, and history of cancer). In the study group, there were 369,079 person-years of follow-up and 3,488 reported cases of hearing loss. After adjustment for the most significant confounding factors, compared to less frequent users, those who were regular users of all three drug classes were at increased risk of hearing loss with hazard ratios (HR) between 1.12 and 1.22 (aspirin HR 1.12; 95% CI, 1.04 to 1.20; NSAID HR 1.21; 95% CI, 1.11 to 1.33; and paracetamol HR 1.22; 95% CI, 1.07 to 1.39).
Risk increased with longer duration of regular use, and younger men were at higher risk than older for all three drug groups.
The authors conclude that regular use of analgesics is associated with increased risk of hearing loss. They note a number of limitations with their study, including lack of data on noise exposure and reasons for analgesic use. They suggest that such use might increase risk of hearing loss, and that given the widespread use of these drugs this may be a significant public health issue.
[Editor’s comment: the authors’ conclusion given in the abstract is misleading, as it asserts that regular analgesic use ‘increases the risk of hearing loss’ – a confident implication of causality that is not present in the full conclusion. The increases in risk are mostly small, and it is important to note that small differences in risk found in observational studies – even large good quality ones like HPFS – are not robust. Despite the authors’ considerable efforts to reduce the effects of confounding factors, the differences have to be treated with care due to the inherent limitations of the study design. Further studies on different datasets are essential before any causal effects can be confirmed. Bandolier has commented on the problems with limitations - they conclude in Bandolier 2007; 14(7): 1-3 that relative risks below 2, and certainly below 1.5, should be treated with caution, especially outside a randomised controlled trial.]
Am J Med 2010; 123: 231-7 (link to abstract)