The results from the Women's Health Initiative study on enhanced
breast cancer risk in postmenopausal women using an
estrogen/
progestin combination clearly indicate the need for a comparison of different
progestins with regard to
cancer risk. To shed some light on this issue, we have investigated the influence of
progesterone and various synthetic C19- and C21-progestins on cell proliferation of a human
breast cancer cell line in vitro. Of special interested was the comparison of two different regimens commonly used in HRT, sequential and continuous combination with
estradiol. We used the human
breast cancer cell line MCF-7 as a model.
Progesterone (P),
chlormadinone acetate (CMA),
dienogest (DNG),
gestodene (GSD),
3-ketodesogestrel (KDG),
levonorgestrel (LNG),
medroxyprogesterone acetate (MPA), and
norethisterone (NET) were investigated in the range of 0.01nm to 10 micro M alone and in combination with 10 nM
estradiol. Cell proliferation was measured after 7 days using the
ATP chemosensitivity test. Tested alone, CMA, DNG, GSD, KDG, MPA and NET significantly stimulated cell proliferation, but only at high dosages. Sequentially combined with
estradiol, only CMA inhibited cell proliferation over the whole concentration range. Slight effects were found for DNG, GSD and KDG, whereas P and MPA only showed an effect at the highest concentration. NET had no significant effect on cell proliferation. Continuously combined, all
progestins exhibited an inhibitory effect over the whole concentration range. The most prominent effects were found for P, CMA, GSD, and KDG. Only slight effects were found for DNG, MPA and NET. Our in vitro results indicate that the influence on
breast cancer risk using HRT in postmenopausal women might depend on the type of
progestin used as well as on the regimen applied. However, the net inhibitory in vitro effect of the
progestins at clinically relevant dosages is rather minimal, and whether
progestins in general can reduce
breast cancer risk in long-term treatment remains uncertain. Further clinical trials are urgently needed to clarify this issue.