Background Evidence that aspirin and other non-steroidal anti-inflammatory drugs reduce risk for colorectal cancer has prompted interest in their ability to prevent other cancers. We aimed to find out what effect over-the-counter analgesics have on risk of ovarian cancer. Methods In a case-control study we compared use of over-the-counter analgesics by 563 women from eastern Massachusetts and New Hampshire, USA, who had epithelial ovarian cancer with 523 women from the general population. We calculated exposure odds ratios to estimate the effect of over-the-counter analgesics on ovarian cancer risk. Use of over-the-counter analgesics was assessed through interviews and defined as use al least once a week continuously for at least 6 months. Findings The odds ratio for risk of ovarian cancer for aspirin use was 0.75 (95% CI 0.52-1.10), that for ibuprofen was 1.03 (0.64-1.64), and that for paracetamol was 0.52 (0.31-0.86), after adjusting for age, study centre, education, religion, parity, oral contraceptive use, and menstrual, arthritic, or headache pain. Relative to no use, the lower risk of ovarian cancer associated with paracetamol was more apparent for use on a daily basis, 0.39 (0.21-0.74), for more than 10 years of use, 0.40 (0.19-0.88), or for more than 20 tablet years defined as (tablets per dayXyears of use), 0.45 (0.20-0.99). Interpretation In our data, there was a statistically significant inverse association between paracetamol use and ovarian cancer risk. There was a modest but nonsignificant inverse association with aspirin use and ovarian cancer and no association with ibuprofen use. Experimental studies in rodents demonstrating uterine and ovarian atrophy at high doses of paracetamol and decreased ovarian-cyst formation at lower doses suggest a biological basis for our observations.
