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February 2, 2011

Breast Cancer in Postmenopausal Women After Hormone Therapy

JAMA. 2011;305(5):466-467. doi:10.1001/jama.2011.75

To the Editor: The increase in risk for breast cancer incidence and mortality observed in the WHI1 is specific to the estrogen and progestin formulation used in the study (Prempro; Wyeth Ayerst, Collegeville, Pennsylvania), and therefore conclusions cannot be extrapolated to progesterone, alone or in combination with estrogen. Chemical and biological distinctions exist between synthetic progestin (medroxyprogesterone), a C24 androgenic vasoconstrictor, and endogenous progesterone, a C21 antiandrogenic vasodilator.2 Progesterone is the only steroid hormone that has been shown to be free of carcinogenicity in controlled clinical studies.3 Dr Chlebowski and colleagues state that “[r]eproductive hormones, especially progestin, are potent stimulators of angiogenesis.” However, low physiological levels of progesterone inhibit angiogenesis through binding to progesterone receptor A, while higher-dose synthetic progestin stimulates angiogenesis through binding to progesterone receptor B.4 Deficits of progesterone are associated with significantly increased medical risk in postmenopausal women.5 No prospective study that replaced the deficiency of progesterone, either alone or with estrogen, has been carried out. We believe such a study is critically needed.