Effects of menopausal hormone therapy-based on the role of estrogens, progestogens, and their metabolites in proliferation of breast cancer cells

Menopausal hormone therapy (MHT) has been widely used for the clinical treatment of symptoms associated with menopause in women. However, the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated. The results of the Women's Health Initiative's randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy, with an elevated risk of breast cancer. The evidence currently available from randomized trials and observational studies is based on data from different populations, drug formulations, and routes of administration. Even though the risks of MHT and breast cancer have received a great deal of attention, information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed. Furthermore, the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied. Therefore, this review aimed to describe the biological effects of estrogen, progesterone, and their metabolites on the proliferation of breast cancer cells, based on relevant basic research and clinical trials, to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.