The effect of medroxyprogesterone acetate and norethisterone on the estradiol stimulated proliferation in MCF-7 cells: comparison of continuous combined versus sequential combined estradiol/progestin treatment

Objective: Little is known on the type of progestin and regimen type in rel ation to breast cancer risk. We have compared the effect of medroxyprogeste rone acetate (MPA) and norethisterone (NET) on the estradiol Stimulated pro liferation in MCF-7 cells with respect to different regimens used in combin ed hormone replacement therapy (HRT). Design: To approximate the in vivo conditions in HRT, MCF-7 cultures were p retreated with estradiol followed by estradiol/progestin treatment to repre sent the sequential combined model and compared with non pretreated culture s followed by estradiol/progestin treatment for the continuous combined mod el. Results: When using progestins in the continuous combined form with estradi ol (10(-10) M) both progestins showed a significant reduction in the estrad iol stimulated proliferation of the MCF-7 cells. In the sequential combined model the addition of MPA led to a stronger significant reduction of MCF-7 proliferation but in a narrower concentration range (from 10(-8) to 10(-6) M) compared to the continuous treatment. NET did not show any significant effect on proliferation in the SC model. Conclusion: Different regimen types and different progestins do lead to sig nificantly different effects on the proliferation of a breast cancer cell l ine. These findings might be useful in the elucidation of potential mechani sms involved in the clinical situation.