Terazosin as a Non-Hormonal Treatment for Endometriosis

Endometriosis is a chronic, estrogen-dependent inflammatory disease including aberrant local steroidogenesis, inflammation, angiogenesis, oxidative stress, and prostaglandin-mediated pain. Given the elevated adrenergic receptor expression in endometriotic lesions and the potential of terazosin to downregulate Steroidogenic Factor-1 (SF-1), this study aimed to evaluate terazosin as a non-hormonal therapy in a surgically induced rat endometriosis model. Forty female Wistar rats were randomized to sham, untreated endometriosis, leuprolide acetate or terazosin; two postoperative deaths yielded final group sizes of 10/9/10/9. Blinded histopathology verified successful lesion establishment. ELISA quantified SF-1, IL-6, IL-8, TNF-α, NF-κB, VEGF, HIF-1α, and PGE2 in lesion tissue, serum, and peritoneal lavage; oxidative status was assessed by TAS, TOS, and OSI. Compared with untreated endometriosis, terazosin significantly reduced SF-1, PGE2, IL-6, IL-8, TNF-α, VEGF and HIF-1α across compartments (all p < 0.001), comparable to leuprolide (p = 1.000). Terazosin also normalized oxidative stress by decreasing TOS/OSI and restoring TAS in tissue, serum, and peritoneal fluid (p < 0.001). NF-κB decreased in tissue and serum (p < 0.001) but not in peritoneal fluid (p = 0.206). Overall, terazosin produced leuprolide-like molecular benefits without hormonal suppression, supporting repurposing as a candidate non-hormonal therapy, while highlighting the need for longer-duration studies and randomized clinical trials given model and pain-assessment limitations.