Revista Brasileira de Ginecologia e Obstetrícia (Mar 2009)
Efeito da tibolona sobre o endométrio de ratas castradas Effect of tibolone on endometrium of castrated rats
Abstract
OBJETIVO: avaliar o efeito do uso prolongado de alta dose de tibolona na morfologia do endométrio em ratas castradas. MÉTODOS: foram utilizadas 15 ratas Wistar, fêmeas, com idade de oito semanas e peso médio de 250 g. Todas as ratas foram submetidas à ooforectomia bilateral e 30 dias depois foi coletada citologia vaginal, verificando-se o status de menopausa. As ratas foram divididas aleatoriamente em dois grupos: o tratado (n=9) recebeu via oral 1 mg tibolona/dia; o controle (n=6) recebeu apenas solução do veículo carboximetilcelulose. Após 20 semanas de tratamento, todos os animais foram sedados e sacrificados por deslocamento cervical. Os úteros foram retirados e fixados em formol 10% tamponado. Ambos os cornos uterinos foram clivados em três regiões (proximal, medial, distal) e processados para inclusão em parafina. Cortes histológicos corados com hematoxilina-eosina foram submetidos à análise morfológica e morfométrica. Foram avaliados os seguintes parâmetros: espessura do epitélio superficial endometrial, espessura do estroma endometrial, área endometrial, número absoluto de glândulas endometriais e número de glândulas/área endometrial. Os dados obtidos foram comparados mediante o teste t de Student. RESULTADOS: no Grupo Tibolona os úteros se apresentaram bem desenvolvidos e houve aumento significativo (pPURPOSE: to evaluate the effect of long-term use of a high dose of tibolone on the morphology of the endometrium of castrated female rats. METHODS: fifteen female Wistar rats, aged eight weeks and weighting about 250 g were used. All the female rats were submitted to bilateral oophorectomy and 30 days afterwards, vaginal cytology was collected, to verify the menopause status. The female rats were randomly divided in two groups. The Treatment Group (n=9) received 1 mg of tibolone/day orally; the Control Group (n=6) received a solution of carboxymethylcellulose vehicle. After 20 weeks of treatment, all the animals were sedated and sacrificed by cervical dislocation. The uterus was removed and fixated in 10% buffer formaldehyde. Both uterine horns were divided in three regions (proximal, medial and distal) and processed to be included in paraffin. Histological sections, stained with hematoxylin-eosin were submitted to morphological and morphometrical analysis. The following parameters have been analyzed: thickness of the endometrial superficial epithelium, thickness of the endometrium stroma, endometrial area, absolute number of endometrial glands and number of glands/endometrial area. The data obtained were compared by the t-Student test. RESULTS: in the Tibolone Group, the uteri were well developed and there was a significant increase (p<0.01) of all the histomorphometric parameters. In some cases, the cylindrical epithelium became stratified, pavimentous and covered the internal portions of the glands, as well as of the endometrium cavity. Rats from the Control Group presented uterine atrophy. There were few tubular-like glands and scarce intercellular substance. Glands were covered by cubic epithelium which extended itself to the endometrial cavity. CONCLUSIONS: high doses of tibolone, given for long periods of time to castrated female rats, have an estrogenic effect which can be dose-dependent, causing proliferation in the endometrium and causing changes in the cell differentiation (squamous metaplasia), but do not lead to hyperplasia.
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