Effects of oral contraceptives on breast epithelial proliferation

The association between oral contraceptive (OC) use and breast cancer is no t fully understood. Estrogen is a known mitogen to breast epithelial cells, but there is still a controversy about the effect of added progestogens. F ine needle aspiration (FNA) biopsies were used to assess epithelial prolife ration in normal breast tissue from 106 healthy premenopausal women with an d without oral contraceptives. In 26 women biopsies were performed before a nd after 2 months of OC use. Proliferation, expressed as percentage of Ki-6 7/MIB-1 positive cells, was correlated to endogenous progesterone, androgen ic/anabolic compounds and exogenous progestogen. We found a higher prolifer ation (p = 0.03) in OC users compared to non users, with mean values of 4.8 % and 2.2%, respectively. There was a positive correlation between prolifer ation and progesterone levels in non-users and with serum levonorgestrel co ncentrations in women using OCs containing this progestogen (rs = 0.43, p = 0.02). Women using OCs had significantly lower serum androgen levels compa red to naturally cycling women and free testosterone levels displayed an in verse relation to breast epithelial proliferation. There was a marked varia tion in the response to exogenous sex steroids. In certain women after 2 mo nths of OC use, the percentage of MIB-1 positive cells was as high as 40-50 %. The results add to the growing evidence that progestogens may be mitogen ic in breast tissue. Increased proliferation during hormonal contraception should be regarded as an unwanted and potentially hazardous side effect. Ef forts should be made to define hormonal contraceptive regimens which minimi ze breast epithelial proliferation and to identify those women with the mos t pronounced proliferative response.