Are the progestins responsible for breast cancer risk during hormone therapy in the postmenopause? Experimental vs. clinical data.

Evidence is increasing suggesting that adding progestins to estrogen replacement therapy may be more harmful then beneficial, however it is debatable whether all progestins act equally on breast epithelial cells. Experimental data with the comparison of various progestins in the same in vitro model present a rather high evidence that there may be differences between the various progestins regarding breast cancer risk. Especially of concern may be to differentiate between primary and secondary risk i.e. between benign and malignant breast epithelial cells. The epidemiological studies and especially the Women's Health Initiative (WHI) trial, so far the only prospective placebo-controlled interventional study, demonstrate an increased risk under combined estrogen/progestin therapy, but they have the limitations that they up to now cannot discriminate between the various progestins mostly due to too small or not comparable patient numbers in the subgroups with the various progestins. However, there is evidence that the natural progesterone, possibly also the transdermal usage of synthetic progestins, may avoid an increased risk, but this must be proven in further clinical trials.