Astaxanthin Therapy in Women with Advanced Endometriosis: A Randomized Controlled Trial with Exploratory Analysis of Endometrial Wnt/β-Catenin Signaling

Background Endometriosis is a chronic gynecological disorder associated with pelvic pain and infertility, characterized by molecular and cellular dysregulation in the eutopic endometrium. Aberrant Wnt/β-catenin signaling has been implicated in disease pathophysiology. Astaxanthin (AST), a potent antioxidant, may influence cellular signaling pathways relevant to female reproductive health. This study investigated the effects of AST on Wnt/β-catenin signaling in the eutopic endometrium of women with advanced endometriosis. Methods In this randomized, triple-blind, placebo-controlled trial, 50 women with advanced-stage endometriosis received either AST (6 mg/day) or placebo for 12 weeks. Endometrial samples were collected during the mid-secretory phase before and after the intervention. Wnt/β-catenin pathway gene expression was quantified using real-time PCR, and protein levels were assessed by Western blotting. Results AST supplementation was associated with reduced β-catenin expression (P = 0.041) and increased GSK-3β (P = 0.009) and DKK-1 (P = 0.042) levels. CD44 expression was also lower post-intervention (P = 0.021). These findings suggest that AST may promote a shift toward normalization of Wnt/β-catenin signaling in the eutopic endometrium. Conclusions In women with advanced endometriosis, AST supplementation was associated with modulation of Wnt/β-catenin pathway components in the eutopic endometrium. While these results are exploratory, they highlight the potential of AST to influence endometrial signaling pathways, supporting further investigation of its role in reproductive health. Trial Registration Iranian Registry of Clinical Trials (IRCT) IRCT20220625055274N1. Registered on 03 September 2022.