Exposure to endogenous sex hormones has long been recognized as an important (albeit unavoidable) source of risk for cancer, particularly of reproductive organs. Studies addressing the breast cancer risk associated with endogenous hormone exposures have reported the increased breast cancer risk experienced by postmenopausal women who have higher than average serum levels of estradiol and its androgenic precursors. For example, in the European Prospective Investigation into Cancer and Nutrition cohort, the relative risk of breast cancer per doubling of serum estradiol in women sampled when postmenopausal was 1.31 (95% CI, 1.08-1.58).1 Of note, the European Prospective Investigation into Cancer and Nutrition investigators did not measure progesterone levels in postmenopausal women “as ovarian progesterone synthesis ceases after menopause.”1(p4183) The understudied possibility that progesterone exposure may be associated with breast cancer risk is highly relevant, particularly because efforts are under way to develop natural progesterone as a safe alternative to progestins in menopausal hormone therapy regimens.2
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Khan SA. Progesterone Exposure and Breast Cancer Risk—Addressing Barriers. JAMA Netw Open. 2020;3(4):e203608. doi:10.1001/jamanetworkopen.2020.3608
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