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

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.

Cystic endometrial hyperplasia and endometritis in a dog following prolonged treatment of medroxyprogesterone acetate

An 8-year-old female Yorkshire Terrier was presented for investigation of reduced appetite, and occasional vomiting. She has been treated with medroxyprogesterone acetate (MPA) from past 3 year-old age for contraception. Abdominal sonography showed abnormal enlargement of uterus, and ovariohysterectomy was performed. Main gross findings of uterus were enlarged lesions in two areas of the left horn, which had thickened wall and yellowish sticky material in the lumen. Histopathologically, cystic endometrial hyperplasia (CEH) and endometritis were present in the thickened area. In this case, CEH and endometritis may be attributed to prolonged treatment of MPA. It was concluded that further study is needed to clarify the association of MPA treatment with age, its pathogenesis and abnormal uterine changes in dogs.

Increased risk of endometrial abnormalities in breast cancer patients taking tamoxifen: the need for gynaecologic surveillance.

OBJECTIVE: To evaluate the risk of abnormally thickened endometrium associated with tamoxifen treatment in postmenopausal breast cancer patients. METHODS: Two groups of asymptomatic postmenopausal breast cancer patients were recruited in the study. The first consisted of 70 patients taking 20mg/day of tamoxifen for at least 6 months. The second group included 140 patients without tamoxifen treatment. Endometrial evaluation using transvaginal ultrasonography (TVS) was conducted for all patients. Fractional curettage was carried out for patients whose endometrial thickness was greater than 5 mm on TVS. RESULTS: The prevalence of abnormally thickened endometrium (greater than 5 mm on TVS) was significantly higher in patients receiving tamoxifen (58.57% VS 10.71 %, P = 0.0001). Patients undergoing tamoxifen treatment had a 5.61 relative risk of developing abnormally thickened endometrium (95% CI= 2.65 -11.86). CONCLUSION: Tamoxifen significantly increases the risk of developing abnormally thickened endometrium in postmenopausal breast cancer patients. There is, thus, a true need for gynaecologic surveillance in such patients to early detect neoplastic change of endometrium that may arise as a result of tamoxifen use.

Tamoxifen increases the proliferation of human endometrial stromal cells in in vitro. A model for evaluation of endometrial hyperplasia.

Tamoxifen given for breast cancer therapy, has a complex and an unclear action on the endometrium. A large number of literatures has attributed the proliferous changes in the endometrium caused by tamoxifen (Tam). No report has appeared on the endometrial cellular changes induced by Tam. The present study shows a significant (P < 0.001) increase in the proliferative activity due to Tam in endometrial stromal cells over control and estradiol (E2). This in vitro model is useful for the study of the hyperplasic effect of Tam at the cellular level.