Revisiting the role of danazol in the contemporary management of endometriosis-related pain: a systematic review

Abstract

INTRODUCTION: Danazol is a synthetic steroid approved in 1976 for the treatment of endometriosis-associated pain. Despite its established efficacy, its clinical use has markedly declined due to androgenic and metabolic adverse effects, prompting reconsideration of its role in current practice. METHODS: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. Six electronic databases were searched up to June 2025 for studies evaluating oral danazol in women with endometriosis. Thirty studies (1,486 patients), including 22 randomized trials, were included. RESULTS: Danazol was evaluated across a wide range of dosing regimens, although most studies used 600 mg/day for 6 months. Consistent reductions in dysmenorrhea, dyspareunia, and chronic pelvic pain were reported across the majority of studies. Amenorrhea rates generally increased with higher doses, whereas treatment discontinuation due to adverse events ranged from 0 to approximately 14%. Symptom recurrence after treatment discontinuation was frequently observed. Overall risk of bias was low to moderate. CONCLUSIONS: Danazol demonstrates consistent efficacy in reducing endometriosis-associated pain. Although high-dose regimens are limited by adverse effects, limited evidence suggests that lower-dose regimens may offer a more favorable balance between efficacy and tolerability. These findings support a reappraisal of danazol as a therapeutic option for carefully selected patients within contemporary management strategies. PROTOCOL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO), CRD420251088044. Available at: https://www.crd.york.ac.uk/prospero.