Use of metformin and the risk of ovarian cancer: a case-control analysis

OBJECTIVE: To explore the association between use of metformin or other antidiabetic drugs and the risk of ovarian cancer. METHODS: Using the UK-based General Practice Research Database, we conducted a case-control analysis to evaluate whether users of metformin or other antidiabetic drugs had an altered risk of ovarian cancer. Cases had an incident diagnosis of ovarian cancer, and up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Results were further adjusted by multivariate logistic regression analyses for BMI, polycystic ovaries, endometriosis, use of estrogens or oral contraceptives, a history of hysterectomy, and smoking. RESULTS: We identified 1611 case patients with a recorded diagnosis of ovarian cancer. Mean age ± SD was 61.2 ± 13.1 years at the time of cancer diagnosis. Long-term use (≥ 30 prescriptions) of metformin, but not of sulfonylureas, was associated with a tendency towards a reduced risk of ovarian cancer (OR 0.61, 95% CI 0.30-1.25 for metformin and 1.26, 95% CI 0.65-2.44 for sulfonylureas). Long-term use of insulin (≥ 40 prescriptions) was associated with a slightly increased risk for ovarian cancer (OR 2.29, 95% CI 1.13-4.65). CONCLUSION: In this large epidemiological study long-term use of metformin, but not of sulfonylureas, was associated with a tendency towards a decreased risk of ovarian cancer. Long-term use of insulin was associated with an increased risk of ovarian cancer.