Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
J Gen Intern Med. 2022 Nov;37(14):3653-3662. doi: 10.1007/s11606-021-07349-5. Epub 2022 Feb 7.
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.
背景：持续性耳鸣很常见，且具有致残性，难以治疗。大剂量阿司匹林可能会引发耳鸣，但关于典型剂量阿司匹林和其他止痛药的纵向数据却很少。 目的：研究阿司匹林、非甾体抗炎药和对乙酰氨基酚与持续性耳鸣发病风险的独立相关性。 设计：纵向队列研究。 地点：护士健康研究 II（1995-2017 年）。 参与者：共 69455 名年龄在 31-48 岁、基线时无耳鸣的女性。 主要观察指标：通过每两年一次的问卷调查获取有关镇痛药使用和耳鸣的信息。 主要结果：经过 1120936 人年的随访，共报告了 10452 例持续性耳鸣新发病例。对于低剂量阿司匹林，频繁使用低剂量阿司匹林的女性并未增加持续性耳鸣的发病风险。对于中等剂量阿司匹林，在年龄<60 岁的女性中，频繁使用与较高的耳鸣风险相关，但在年龄较大的女性中则没有（p 交互作用=0.003）。与每周使用中等剂量阿司匹林<1 天的年龄<60 岁的女性相比，每周使用中等剂量阿司匹林 6-7 天的女性多变量调整后的危险比（MVHR，95%置信区间）为 1.16（1.03，1.32）。在所有女性中，频繁使用非阿司匹林非甾体抗炎药（NSAID）或对乙酰氨基酚与更高的风险相关。与每周使用 NSAID<1 天的女性相比，每周使用 4-5 天的 MVHR 为 1.17（1.08，1.28），每周使用 6-7 天的 MVHR 为 1.07（1.00，1.16）（p 趋势=0.001）。对于对乙酰氨基酚，与每周使用<1 天相比，每周使用 6-7 天的 MVHR 为 1.18（1.07，1.29）（p 趋势=0.002）。 局限性：耳鸣和镇痛药使用情况为自我报告。镇痛药使用的适应证信息不可用。需要在非白种女性和男性中开展研究。 结论：频繁使用低剂量阿司匹林的女性发生持续性耳鸣的风险并未升高。在年轻女性中，频繁使用中等剂量阿司匹林与更高的风险相关。所有女性中，频繁使用 NSAID 和频繁使用对乙酰氨基酚与持续性耳鸣的发病风险增加相关，且随着使用频率的增加，风险幅度似乎更大。我们的研究结果表明，使用镇痛药的女性发生耳鸣的风险更高，这可能为这种具有挑战性的疾病的诱发因素提供了一些见解，但还需要进一步的研究来确定是否存在因果关系。
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