Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice

Acta Cir Bras. 2016 Apr;31(4):286-93. doi: 10.1590/S0102-865020160040000010.

Abstract

Purpose: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia.

Methods: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test.

Results: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups.

Conclusion: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Publication types

  • Evaluation Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / etiology
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Aromatase Inhibitors / pharmacology*
  • Aromatase Inhibitors / therapeutic use
  • Carcinogenesis / drug effects*
  • Carcinogenesis / pathology
  • Endometrial Hyperplasia / chemically induced
  • Endometrial Hyperplasia / drug therapy*
  • Endometrial Hyperplasia / pathology
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / etiology
  • Endometrium / drug effects
  • Endometrium / pathology
  • Estradiol / blood
  • Ethylnitrosourea
  • Female
  • Letrozole
  • Medroxyprogesterone Acetate / pharmacology
  • Mice, Inbred BALB C
  • Nitriles / pharmacology*
  • Nitriles / therapeutic use
  • Progesterone / blood
  • Reproducibility of Results
  • Time Factors
  • Treatment Outcome
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Nitriles
  • Triazoles
  • Progesterone
  • Estradiol
  • Letrozole
  • Medroxyprogesterone Acetate
  • Ethylnitrosourea