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Hormone Replacement Therapy and Breast Cancer Risk

Carlo Campagnoli, MD; Nicoletta Biglia, MD; Piero Sismondi, MD
JAMA. 1996;275(15):1159. doi:10.1001/jama.1996.03530390024023.
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To the Editor.  —Investigations of the effect of progestin added to ERT in relation to breast cancer risk have produced inconsistent results. Dr Stanford and colleagues1 point out that progestins usually prescribed in Northern Europe (levonorgestrel at a dose of 0.25 mg/d or norethisterone acetate at a dose of 5 to 10 mg/d) differ from those most commonly used in the United States (medroxyprogesterone acetate at a dose of 10 mg/d), and they suggest that the different androgenic action of these drugs could possibly account for the observed differences in study results.Oral conjugated estrogens, through hepatocellular action, cause biological modifications potentially protective against breast cancer such as an increase of sex hormone binding globulin (SHBG)2 and a reduction of insulinlike growth factor I (IGF-I) serum levels.3 SHBG is able to bind steroid hormones (estradiol and testosterone), thereby reducing their biological activity.4 IGF-I is a potent


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