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Objective: Dienogest (DNG) 2 mg (Visanne) was launched for endometriosis treatment in Europe in 2010. The Visanne Post-approval Observational Study (VIPOS) was designed to assess the safety of DNG 2 mg/day compared to other hormonal endometriosis treatments, focusing especially on clinically relevant depression and anemia., Study Design: Large, prospective, non-interventional, active surveillance study in six European countries. Participants were recruited via gynecologists or specialized centers routinely prescribing endometriosis medication. Self-administered questionnaires during study entry and follow-up collected information on baseline characteristics, health status and endometriosis treatment. Patient-reported anemia and depression cases were validated by health care professionals. Inferential statistics were based on Cox proportional hazards models and crude and adjusted hazard ratios (HR) between cohorts were calculated (including 95% confidence intervals [CI]). Adjustment for potential confounding was performed by including predefined prognostic factors as covariates in the Cox models., Results: Out of 26,430 participants, 11.4% used DNG, 12.8% used other approved endometriosis medications (OAED) and 75.7% used hormonal treatments not approved but frequently used for endometriosis treatment (NAED). At baseline, DNG users more frequently reported a surgically confirmed endometriosis diagnosis, severe endometriosis-associated pain and a history of depression, compared to the other cohorts. Baseline characteristics showed large inter-country variability. Overall, the number of confirmed anemia and depression events were substantially lower than expected. The adjusted HRs for anemia were 1.1 (95% CI, 0.4-2.6) for DNG vs OAED and 1.3 (95% CI, 0.7-2.4) for DNG vs NAED. The adjusted HRs for new or worsening depression were 1.8 (95% CI, 0.3-9.4) for DNG vs OAED and 1.5 (95% CI, 0.8-2.8) for DNG vs NAED., Conclusion: The main limitations encountered (low number of confirmed events and considerable inter-country variability) made a robust statistical analysis and a solid interpretation of the results challenging. However, no safety signal regarding anemia for DNG users could be detected, whereas a slight increase in depression risk cannot be excluded but might be explained by baseline severity of endometriosis or unknown country-specific confounding variables. VIPOS reflected routine use of hormonal endometriosis medications and provided real-world insights into endometriosis management in Europe., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Endometriosis is a common gynecologic disease associated with a significant burden on women's health and healthcare systems. Currently approved hormonal treatments for endometriosis can be effective in controlling symptoms, but may have clinically relevant side effects that limit their long-term use. Dienogest 2 mg (Visanne; Bayer AG, Berlin, Germany) is a 19-nortestosterone derivative that significantly reduces menstrual bleeding, dysmenorrhea, premenstrual pain, dyspareunia, and pelvic pain in women with endometriosis. Although dienogest 2 mg has demonstrated efficacy in clinical trials, data regarding long-term and real-world use are limited., Methods: To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is the largest real-world, noninterventional study performed examining the safety of dienogest and other hormonal treatments for the management of endometriosis in routine clinical practice. Patients self-reported medical and gynecologic history and symptoms and treatment information. Primary clinical outcomes were clinically validated and subject to independent blinded adjudication. Loss to follow-up was minimized through active contact with participating women at 6 months post-enrollment and annually thereafter to ensure almost all clinically relevant outcomes were captured., Planned Outcomes: VIPOS planned to enroll approximately 25,000 women initiating a new treatment for endometriosis, including those prescribed dienogest 2 mg/day and other hormonal medications for endometriosis (approved or nonapproved), from approximately 1000 centers in six European countries. The main clinical outcomes of interest for follow-up are anemia requiring medical intervention, de novo or clinically worsening depression, and treatment-failure patterns that result in drug discontinuation. Additional analyses will characterize the baseline risk factors of medically managed patients with endometriosis and assess treatment utilization patterns. VIPOS was designed to provide real-world information on endometriosis treatment and associated clinical outcomes, while not affecting the prescribing physician's decisions or the classification of patient diagnoses., Trial Registration: European Union Electronic Register of Post-Authorisation Studies (EU PAS) no. 1613, Clinicaltrials.gov: NCT01266421.