Evidence is increasing suggesting that adding
progestogens to
estrogens can increase the risk of
breast cancer. However, our experimental data as a result of scientific collaboration between university of Tuebingen, Germany, and university of Beijing, China, comparing all available
progestogens used in
hormone therapy and
hormonal contraception present high evidence that there may be differences regarding
breast cancer risk. Especially of concern may be to differentiate between primary and secondary risk i.e. between the effect of on benign and malignant breast epithelial cells suggesting differences in primary risk and risk in patients after
breast cancer. Of importance also is that in contrast to natural
progesterone the apocrine impact of stromal
growth factors and also certain cell components of breast epithelial cells can strongly increase proliferation rates of some (but not all.
synthetic progestogens which can lead to clinical
cancer before (in contrast to
estrogen-only
therapy. carcinoprotective mechanisms can work. Regarding clinical data, epidemiological studies and especially the Women's Health Initiative, so far the only prospective placebo-controlled study, demonstrate an increased risk under combined
estrogen/
progestogen-, but not under
estrogen-only
therapy. However, up to now the clinical studies cannot discriminate between the various
progestogens mostly due to too small patient numbers in the subgroups, and in most studies either
medroxyprogesterone acetate or
norethisterone have been used. However, there is evidence that the natural
progesterone and
dydrogesterone, possibly also the transdermal usage of
synthetic progestogens, may have less risks, but this must be proven in further clinical trials.