Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses' Health Studies

JAMA Oncol. 2018 Dec 1;4(12):1675-1682. doi: 10.1001/jamaoncol.2018.4149.


Importance: Ovarian cancer is a highly fatal malignant neoplasm with few modifiable risk factors. Case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin.

Objective: To evaluate whether regular aspirin or nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use and patterns of use are associated with lower ovarian cancer risk.

Design, setting, and participants: This cohort study analyzed NSAID use and ovarian cancer diagnosis data from 2 prospective cohorts, 93 664 women in the Nurses' Health Study (NHS), who were followed up from 1980 to 2014, and 111 834 in the Nurses' Health Study II (NHSII), who were followed up from 1989 to 2015. Follow-up was completed on June 30, 2014, for the NHS and June 30, 2015, for NHSII. Data were analyzed from June 13, 2016, to September 18, 2017.

Exposures: For each analgesic type (aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen), timing, duration, frequency, and number of tablets used were evaluated; exposure information was updated every 2 to 4 years.

Main outcomes and measures: Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of aspirin, nonaspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were 2-sided, with a significance level of .05.

Results: In the NHS, the mean (SD) age at baseline (1980) was 45.9 (7.2) years, and 93% of participants identified as non-Hispanic white. In the NHSII, the mean age at baseline (1989) was 34.2 (4.7) years, and 92% identified as non-Hispanic white. Among the 205 498 women in both cohorts, there were 1054 cases of incident epithelial ovarian cancer. Significant associations between aspirin and ovarian cancer risk were not observed when current vs nonuse of any aspirin was evaluated regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). However, when low-dose (≤100-mg) and standard-dose (325-mg) aspirin were evaluated separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96), but no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49) was observed. Current use of nonaspirin NSAIDs was positively associated with risk of ovarian cancer compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and significant positive trends for duration of use (P = .02 for trend) and cumulative average tablets per week (P = .03 for trend) were observed. There were no clear associations for the use of acetaminophen.

Conclusions and relevance: These results appear to be consistent with case-control studies that show a reduced risk of ovarian cancer among regular users of low-dose aspirin. An increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly nonaspirin NSAIDs, was observed, although this finding requires confirmation.

MeSH terms

  • Adult
  • Analgesics / administration & dosage
  • Analgesics / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / classification
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use
  • Carcinoma, Ovarian Epithelial / epidemiology*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Nurses / statistics & numerical data
  • Ovarian Neoplasms / epidemiology*
  • Risk Factors


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Aspirin