Abstract

To evaluate the association of histologic changes in the breasts of female rats undergoing therapy with sex steroids. An experimental study was conducted of 40 castrated female non-pubertal rats, 20 had given birth (Group B) and 20 had no offspring (Group A). After four weeks, these rats were randomly allocated to subgroups: A1, A2, A3, A4, A5 and B1, B2, B3, B4, B5. Steroids were given to subgroups as follows: A1 and B1--estradiol benzoate; A2 and B2--medroxyprogesterone acetate; A3 and B3--estradiol benzoate and medroxyprogesterone acetate; A4 and B4--tibolone; A5 and B5--placebo. After 10 weeks of treatment, animals were sacrificed and their mammary glands were analyzed. Histologic parameters evaluated were: epithelial cell proliferation, epithelial cells with secretory activity; and cell atypia in terminal duct units and buds or terminal alveoli. The association between microscopic analysis and diverse therapeutic regimens were analyzed by calculating the odds ratio and its respective 95% confidence interval. Histologic changes were observed in 29 rats: moderate hyperplasia (52.5%), hyperplastic alveolar nodule (42.5%), epithelial atypia (35%), mild hyperplasia (32.5%), secretory activity (20%) and severe hyperplasia (5%). In rats with no offspring when compared to the control, 1.3 times more hyperplastic alveolar nodules were found in the group treated with estradiol, the same was true for moderate hyperplasia in the rats that received medroxyprogesterone acetate, hyperplastic alveolar nodules and epithelial atypia in the group treated with estradiol plus medroxyprogesterone acetate. In the rats with offspring 1.3 times more secretory activity was found with estradiol. Epithelial hyperplasia and epithelial atypia with no proliferation are strongly associated to combined therapy with estradiol plus medroxyprogesterone acetate, mainly in the rats without offspring.

Highlights

  • Epithelial hyperplasia and epithelial atypia with no proliferation are strongly associated to combined therapy with estradiol plus medroxyprogesterone acetate, mainly in the rats without offspring. [Rev Assoc Med Bras 2006; 52(5): 369-74]

  • Black LJ, Sato M, Rowley ER, Magee DE, Bekele A, Williams DC, et al Raloxifene (LY 139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats

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Summary

Alterações Histológicas

Figura 1 – Alterações histológicas observadas em mamas de ratas castradas e submetidas à terapêutica com esteróides sexuais e tibolona. Já no subgrupo tratado com associação de estrogênio com progestogênios, observaram-se índices de 100% para a HEB 2, HAN e atipia sem proliferação. Já as ratas tratadas com E2 + AMP tiveram aumento significativo, e de mesma magnitude, para o desenvolvimento de atipias sem proliferação epitelial e HAN. A mesma análise feita no grupo de ratas com prole (grupo B) demonstrou haver associação entre a terapêutica de estrogênio e progestogênios combinados com a presença de atividade secretora nas células epiteliais (Tabela 3). No presente estudo houve associação do uso de esteróides sexuais com proliferação e atipias epiteliais e, ainda, atividade secretora celular, alterações essas observadas em animais que receberam terapia isolada com estrogênios ou progestogênios, embora o maior efeito tenha sido observado com a combinação de ambos.

Alterações histológicas
METHODS
RESULTS
CONCLUSION
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