Abstract

To assess the effect of tibolone on mammary tissue of castrated rats over 3 different periods of time. Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days after surgery, with hypoestrogenism confirmed, the experimental rats were randomly assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days, tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for 23, 59 and 118 days, respectively. After treatment, all six pairs of mammary glands were removed and stained with hematoxylin and eosin (HE) for histological analysis after euthanasia. The histological parameters evaluated were: epithelial cell proliferation and secretory activity. The variables were analyzed statistically, with the level of significance set at 0.05. Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in 7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in 7/55, atypia without epithelial proliferation in 1/55, and no cases of severe epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats. The secretory activity was significantly higher in the tibolone groups compared to control at all the time points assessed (p=0,001). The histological changes were did not show significance when the control and tibolone groups were compared. The time of exposure to tibolone did not show significance when the three different periods of evaluation were compared. No relation between histological modification and tibolone treatment was verified after short-, medium- and long-term treatment.

Highlights

  • Ao final dos 118 dias de experimento, 20 ratas apresentaram alterações epiteliais focais em suas glândulas mamárias, sendo: HEB1 em 7 casos (35%), HEB2 em 5 casos (25%), hiperplasia alvéolo-nodular (HAN) em 7 casos (35%), atipia sem proliferação epitelial em 1 caso (5%)

  • Ao se comparar as alterações histológicas verificadas nos grupos C e T em cada período do experimento, não foram encontrados dados significantes que possam atribuir as alterações presentes no grupo T à terapêutica com a droga em nenhum dos períodos avaliados no estudo (Tabela 1)

  • Foram encontrados 1 caso de HEB 1 (25%), 2 casos de HAN (50%) e 1 caso enquadrado no padrão de atipia plana (25%)

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Summary

Tibolone Breast neoplasms Hormone replacement therapy

OBJETIVO: Avaliar o efeito da terapia hormonal com tibolona, em três períodos de tempo diferentes, sobre o tecido mamário de ratas castradas. As variáveis foram submetidas à análise estatística, adotando-se como significante p0,05) os grupos controle (C) e T. A variável tempo de exposição à droga não apresentou significância, quando comparados os três períodos avaliados. CONCLUSÃO: Não foi verificada relação entre as alterações histológicas e a terapêutica com tibolona em curto, médio e longo prazo

Risco de doença invasora Baixo risco
Findings
Tibolona Valor p
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