Longitudinal Study of Analgesic Use and Risk of Incident Persistent Tinnitus.

Background: Persistent tinnitus is common, disabling, and difficult to treat. High-dose aspirin may precipitate tinnitus, but longitudinal data on typical dose aspirin and other analgesics are scarce.

Objective: To investigate independent associations of aspirin, NSAIDs, and acetaminophen and risk of incident persistent tinnitus.

Design: Longitudinal cohort study.

Setting: Nurses' Health Study II (1995-2017).

Participants: A total of 69,455 women, age 31-48 years, without tinnitus at baseline.

Main Measures: Information on analgesic use and tinnitus obtained by biennial questionnaires.

Key Results: After 1,120,936 person-years of follow-up, 10,452 cases of incident persistent tinnitus were reported. For low-dose aspirin, the risk of developing persistent tinnitus was not elevated among frequent low-dose aspirin users. For moderate dose aspirin, frequent use was associated with higher risk of tinnitus among women aged < 60 years, but not among older women (p-interaction = 0.003). Compared with women aged < 60 using moderate-dose aspirin < 1 day/week, the multivariable-adjusted hazard ratio (MVHR, 95% CI) among women using moderate-dose aspirin 6-7 days per week was 1.16 (1.03, 1.32). Among all women, frequent non-aspirin non-steroidal anti-inflammatory drug (NSAID) or acetaminophen use was associated with higher risk. Compared with women using NSAIDs <1 day/week, the MVHR for use 4-5days/week was 1.17 (1.08, 1.28) and for 6-7days/week was 1.07 (1.00, 1.16) (p-trend=0.001). For acetaminophen, compared with use <1 day/week, the MVHR for use 6-7days/week was 1.18 (1.07, 1.29) (p-trend=0.002).

Limitations: Information on tinnitus and analgesic use was self-reported. Information on indications for analgesic use was not available. Studies in non-White women and men are needed.

Conclusion: The risk of developing persistent tinnitus was not elevated among frequent low-dose aspirin users. Among younger women, frequent moderate-dose aspirin use was associated with higher risk. Frequent NSAID use and frequent acetaminophen use were associated with higher risk of incident persistent tinnitus among all women, and the magnitude of the risks tended to be greater with increasing frequency of use. Our results suggest analgesic users are at higher risk for developing tinnitus and may provide insight into the precipitants of this challenging disorder, but additional investigation to determine whether there is a causal association is needed.