Effects of letrozole alone or combined with a gonadotropin-releasing hormone agonist on inflammation, folliculogenesis, and estrogen levels in a rat model of peritoneal endometriosis

OBJECTIVE: To evaluate the effects of letrozole alone and in combination with a gonadotropin-releasing hormone agonist on inflammatory cytokines, folliculogenesis, and hormonal profiles in a rat model of surgically induced peritoneal endometriosis. DESIGN: Prospective, controlled experimental laboratory study. SUBJECTS: Twenty-eight adult female Wistar albino rats randomly assigned to four groups (n = 7 each): sham, untreated endometriosis, letrozole, and letrozole plus gonadotropin-releasing hormone agonist. EXPOSURE: Endometriosis was induced by autologous uterine tissue transplantation onto the pelvic peritoneum. After a 28-day lesion development period, intraperitoneal letrozole or combined letrozole plus gonadotropin-releasing hormone agonist therapy was administered for 30 days. MAIN OUTCOME MEASURES: Peritoneal interleukin-6, vascular endothelial growth factor, and tumor necrosis factor-α concentrations; serum estradiol, CA-125, and antimüllerian hormone levels; and histological counts of ovarian follicle subtypes. RESULTS: Untreated endometriosis increased peritoneal interleukin-6, vascular endothelial growth factor, and tumor necrosis factor-α levels, as well as serum estradiol and CA-125 levels, reduced antimüllerian hormone concentrations, and disrupted folliculogenesis with higher atretic follicle counts compared with controls. Letrozole alone and combination therapy significantly reduced inflammatory cytokines, estradiol, and CA-125, and decreased atretic follicle numbers. Antimüllerian hormone levels and most follicular subtypes did not differ among treatment groups. No significant advantage of combination therapy over letrozole monotherapy was observed. CONCLUSION: Letrozole alone and combined therapy effectively attenuate inflammatory activity and reduce follicular atresia in experimental peritoneal endometriosis. No significant advantage of combination therapy over letrozole monotherapy was observed. However, direct comparisons between regimens should be interpreted with caution because of the different letrozole doses used across treatment arms and the inherent limitations of the experimental animal model.