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


Bekdemir S., Yenigül N. N., Aksan A., GÜLER S.

F and S Science, 2026 (ESCI, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.xfss.2026.03.004
  • Dergi Adı: F and S Science
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus
  • Anahtar Kelimeler: Endometriosis, folliculogenesis, gonadotropin-releasing hormone agonist, inflammatory cytokines, letrozole
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

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.