Hormone replacement therapy and risk of breast cancer: the role of progestins

Epidemiological studies have shown an increased risk of breast cancer associated with the use of hormone replacement therapy (HRT). This notion is mostly based on studies from the USA. During the last decades unopposed estrogen treatment has been used to a lesser extent, whereas the combined estrogen-progestin treatment regimen is now prescribed worldwide. In the USA the predominant compounds are conjugated estrogens and medroxyprogesterone-acetate, whereas oestradiol combined with testosterone-like progestins is commonly used in Europe. These differences are mainly the result of traditions. Recent studies originating from both the USA and Europe suggest that the combined treatment regimens with estrogen and progestin increase the risk of breast cancer beyond the risk following the use of unopposed estrogen. At present it is not known if progestins with different androgenecity influence the risk of breast cancer to a varying degree. This review focuses on studies published after the latest meta-analysis in 1997, with special attention given to the type of progestin used and the treatment mode, i.e. cyclical or continuous regimen.