According to new research, women who take ibuprofen or acetaminophen as seldom as 2 days per week may have an increased risk of hearing loss, and taking these pain relievers more often increases the risk still further. Similar effects had been found in men taking NSAIDs, including aspirin, for pain on a regular basis; however, cause-effect relationships are difficult to determine from the research evidence.
According to background information reported by ScienceDaily [here], more than half of American adults suffer from high-frequency hearing loss by the time they reach age 60, with a third of women in their 50s and nearly two-thirds in their 60s having some hearing loss. Adult-onset hearing loss is the 6th most common disease burden in high-income countries, according to the World Health Organization. At the same time, over-the-counter analgesics are the most frequently used medications to treat a variety of medical conditions.
Writing in the upcoming September 15th issue of the American Journal of Epidemiology, a research team led by Sharon G. Curhan, MD, of Brigham and Women's Hospital in Boston, reports on a prospective study examining the relation between frequency of aspirin, ibuprofen, and acetaminophen (parcetamol) use and risk of hearing loss among more than 62,000 women [Curhan et al. 2012]. These subjects, aged 31–48 years at baseline in 1995 were participants in the Nurses' Health Study II. The follow-up period was from 1995–2009 and the outcome of interest in this study was self-reported hearing loss, which was found in roughly 10,000 participants.
After excluding women whose hearing problems had begun before 1995, as well as those with a history of cancer or tinnitus, results indicated that, during 764,247 person-years of follow-up, ibuprofen and/or acetaminophen use were independently and significantly associated with increased risk of hearing loss. Here are the data…
- For ibuprofen, compared with use less than once per week on average, the Relative Risk (RR) of hearing loss was 1.13 (95% Confidence Interval [CI], 1.06 - 1.19) for use 2–3 days/week; RR=1.21 (95% CI, 1.11 - 1.32) for use 4–5 days/week; and RR=1.24 (95% CI, 1.14 - 1.35) for use ≥6 days/week (P-trend < 0.0001).
- For acetaminophen, the corresponding RRs were 1.11 (95% CI, 1.02 - 1.19) for 2-3 days/week, 1.21 (95% CI, 1.07 - 1.37) for 4-5 days/week, and 1.08 (95% CI, 0.95 - 1.22) for ≥6 days/week (P-trend = 0.0007).
- Aspirin use was not found to be significantly associated with hearing loss in this study; although, far fewer women were taking aspirin than the other two agents.
In sum, compared with infrequent use, ibuprofen was associated with a 13% increased risk of hearing loss if used 2 to 3 days per week by the women studied, and this increased to 24% if used roughly every day each week. For acetaminophen, the comparable risk was 11% if used 2 to 3 days each week and 21% if used 4 to 5 days; however, for unexplained reasons, the risk declined to 8% if acetaminophen was taken every day (which was not statistically significant since the CI included 1.0, the point of no effect). Aspirin did not appear to affect hearing loss.
Finally, the association of hearing loss and ibuprofen or acetaminophen tended to be greater among women younger than 50 years of age. This was particularly significant in those who took ibuprofen on a daily basis.
COMMENTARY: In an earlier study by this same research team — Curhan et al. 2010, in the American Journal of Medicine and discussed in an UPDATE [here] — a survey of nearly 27,000 men, repeated every 2 years from 1986 to 2004, found that about one-fourth had been clinically diagnosed with hearing loss. Those who used non-opioid pain relievers at least twice weekly were more susceptible than nonusers.
In this study, male aspirin users were 12% more likely to have hearing loss, those taking other NSAIDs were up to 21% more likely, and users of acetaminophen were 22% more likely. Compared with nonusers, men younger than 50 years old at the start of the study faced an even greater likelihood of hearing loss, and regular combined use of more than one type of non-opioid analgesic as well as longer duration of such use had a further negative impact on hearing.
While these data from both studies are somewhat similar, and add to concerns about the safety of OTC analgesics, direct cause-effect relationships cannot be concluded from longitudinal epidemiological investigations of this sort. Although the researchers in the most recent study  tried to control for the influence of potential confounders — including age, race, BMI, alcohol consumption, intake of various vitamins and nutrients, physical activity, smoking, hypertension, diabetes, and menopausal status — there is always a chance that unknown factors might have affected outcomes.
For example, the authors were unable to account for lifetime noise exposure, large amounts of which would likely cause hearing loss. Nor were they able to obtain information about analgesic dosage for all participants, and hearing loss was self-reported by the women rather than being clinically evaluated.
Only long-term prospective, randomized controlled trials might provide more definitive answers regarding the influence of these analgesics on hearing. However, such trials, of necessity spanning many years, would be very difficult, if not impossible, to conduct.
It is curious that aspirin was found to influence hearing loss in men but not in women, and this might portend some sort of weakness in one or both studies. It also is peculiar that the risk of hearing loss declined to nonsignificant levels with daily acetaminophen use in the women. Perhaps, this was an uncontrolled artifact of data collection and/or analysis, and it was a small but important finding that went unmentioned in almost every news report on this study.
In any event, a specific biological mechanism to explain how these analgesics might affect hearing has yet to be confirmed. Therefore, the results of both studies, in women and men, might be considered as rather tentative until they are confirmed by additional research.
> Curhan SG, Eavey R, Shargorodsky J, Curhan GC. Analgesic use and risk of hearing loss in men. Amer J Med. 2010;123(3):231-237 [article here].
> Curhan SG, Shargorodsky J, Eavey R, Curhan GC. Analgesic Use and the Risk of Hearing Loss in Women. American Journal of Epidemiology, 2012(Sep); online ahead of print [abstract here].
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