Dienogest use and the risk of breast and gynecologic cancers: A nationwide population-based study.

Objective: To evaluate whether dienogest exposure is associated with the risk of breast, endometrial, or tubo-ovarian cancer in women with endometriosis.

Methods: In this nationwide retrospective cohort study (January 2012 to December 2023), we used the Korean National Health Insurance Review & Assessment Service database. Women aged 20-49 years with endometriosis who received dienogest for at least 6 months were compared with an active control group treated with gonadotropin-releasing hormone (GnRH) agonists, with cohorts balanced by inverse probability of treatment weighting. Incident breast, endometrial, and tubo-ovarian cancers were ascertained, and adjusted hazard ratios (aHR) were estimated using Cox proportional hazards models.

Results: Among 1 887 957 women with endometriosis, 14 647 dienogest users and 181 587 GnRH agonist users met the eligibility criteria for the breast cancer cohort; sample sizes were similar for endometrial and tubo-ovarian analyses. Compared with GnRH agonists, dienogest use was not associated with increased risk of breast cancer (aHR 1.01, 95% confidence interval [CI] 0.75-1.37), endometrial cancer (aHR 0.84, 95% CI 0.40-1.77), or tubo-ovarian cancer (aHR 0.92, 95% CI 0.30-2.80). Use of dienogest for 0.5-1.5 years was associated with a reduced breast cancer risk (aHR 0.72, 95% CI 0.53-0.99), whereas associations for longer durations were inconsistent.

Conclusion: Dienogest use in women with endometriosis was not associated with higher or lower risks of breast, endometrial, or tubo-ovarian cancer compared with GnRH agonists, supporting its oncologic safety. Further longer-term studies are warranted to clarify duration-specific effects.