Effect of Conjugated Estrogens and of Medroxyprogesterone on Breast Tissue: an Experimental Study - Revista Brasileira de Ginecologia e Obstetrícia

Purpose: to evaluate the effect of hormone replacement therapy on breast cell proliferation and on collagen and elastic fiber formation and to analyze the changes occurring in the breast parenchyma as a whole. Method: a total of 61 adult Wistar rats were divided into 5 groups. The standard group (12 rats) represented the normal hormonal ovarian status. The remaining 49 rats were oophorectomized and, starting on the 96th P.O. day, received the specific drug for 30 days. The CEE group received 50 mg/day conjugated equine estrogens (13 rats); the MPA group, 2.0 mg/day medroxyprogesterone acetate (12 rats); the CEE + MPA group, both drugs (12 rats), and the DW group, distilled water (12 rats). On the 31st day of medication, the animals were sacrificed and the inguinal mammary glands were removed for histological analysis. Cell proliferation was assessed at the ductal and acinar levels using anti-PCNA antibody. Mature collagen (type I) and immature collagen (type III) were quantified by Sirius-Red staining, and elastic fiber formation was quantified by Weigert staining. Anatomopathological analysis was performed by hematoxylin-eosin staining, with the determination of number of acini per terminal duct, number of ducts per field, presence of intraductal secretion, and intensity of intracytoplasmic vacuolization. Results: the CEE + MPA group presented a smaller percentage of proliferating ductal cells (46.1%) (p<0.0001) and a greater proliferation of acinar cells (66.3%), similar to those detected in the MPA group (p=0.075) but differing from those detected in the remaining groups (p<0.004). The CEE group showed the largest amount of immature collagen (33.6%) (p<0.01) and the MPA group showed the highest concentration of elastic fibers (11.7%) (p<0.0001). The CEE + MPA and MPA groups showed secretory acinar hyperplasia that was intense (91.7%) in the CEE + MPA group and mild (41.7%) or moderate (58.3%) in the MPA group, but differering in both cases from the remaining groups (p<0,097). Conclusions: conjugated equine estrogens in combination with medroxyprogesterone inhibit ductal cell proliferation and stimulate acinar cell proliferation causing secretory acinar hyperplasia; conjugated horse estrogens intensify the formation of immature (type III) collagen, and medroxyprogesterone acetate increases the formation of elastic fibers.