Introduction: Dienogest is a synthetic fourth-generation progestin that has been approved for the medical treatment of endometriosis, and its efficacy on pain symptoms and quality of life is well established even in the long term. Nowadays, only a few controlled trials evaluating the safety of dienogest compared with other hormonal therapies have been published. This systematic review and meta-analysis aims to compare efficacy and tolerability data between dienogest and combined oral contraceptives (COC) in patients taking hormonal therapy for endometriosis treatment in order to inform evidence-based guidelines.
Material and methods: PubMed (Medline), Web of Science, and Google Scholar were systematically searched from the inception of each database until October 2024. Selection criteria included any articles comparing efficacy outcomes and at least one tolerability data between dienogest and COC in patients diagnosed with endometriosis. Studies comparing COC containing Dienogest or another type of hormonal treatment were excluded. A random-effects meta-analysis was conducted if adequate data were available from at least three studies, reporting pooled mean differences and odds ratios between groups using Review Manager V.7.9.0. PROSPERO registration number: CRD42024598455.
Results: A total of four randomized control trials and one observational study were included, showing moderate risk at bias assessment. Meta-analysis did not show any statistical difference in improving pelvic pain after treatment [CI 95% (-1.45-1.17); I2 = 86%; p = 0.84]. In contrast, dyspareunia after treatment was significantly lower in the COC group [CI 95% (0.64-1.33); I2 = 0%; p < 0.00001]. No statistical difference was found in terms of vaginal bleeding [OR = 0.88; CI 95% (0.39-1.96); I2 = 41%; p = 0.75], nausea and vomiting [OR = 0.51; CI 95% (0.16-1.63); I2 = 67%; p = 0.26], headache [OR = 0.91; CI 95% (0.38-2.21); I2 = 59%; p = 0.84], hot flushes [OR = 1.16; CI 95% (0.54-2.48); I2 = 0%; p = 0.71], and hair loss [OR = 1.69; CI 95% (0.52-5.53); I2 = 46%; p = 0.39]. Treatment discontinuation rate was similar between groups.
Conclusions: Dienogest is comparable to COC in terms of efficacy and tolerability. The therapeutic choice should be based on the patient's preference, clinical history, and experience.
Keywords: combined oral contraceptives; dienogest; dyspareunia; efficacy; endometriosis; hormonal treatment; pelvic pain; safety; tolerability.
© 2025 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).