Aim: To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of proliferation and apoptosis markers in normal breast tissue.
Methods: Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analyzed by quantitative immunohistochemistry in the breast tissue, and proliferation and apoptosis were analyzed semiquantitatively by microscopic imaging.
Results: There was a statistically significant difference among the groups for PCNA, caspase-3 and the caspase-3 : PCNA ratio. Tibolone was associated with the lowest proliferative activity, followed by estradiol benzoate + dydrogesterone; however, estradiol benzoate + dydrogesterone showed the greatest rate of apoptosis.
Conclusions: The various progestogens can have more or less proliferative and pro-apoptotic effects than estradiol alone. Among the treatment schemes analyzed, the estradiol + dydrogesterone combination resulted in a higher apoptosis rate in relation to the proliferation rate and tibolone was associated with the lowest proliferation.
Keywords: APOPTOSIS; BREAST CANCER; ESTROGEN; PROGESTOGENS; PROLIFERATION.