Breast Cancer in Postmenopausal Women After Hormone Therapy—Reply

In Reply: Both Dr Baber and Dr Hermsmeyer and colleagues correctly note that only 1 hormone dose and schedule was evaluated in the WHI randomized clinical trial and that lower dosage and different estrogen and progestins are now in wider use. Hermsmeyer et al offer preclinical evidence and an observational study on endogenous progesterone levels to suggest exogenous progesterone may be safer than synthetic progestin. However, similar types of preclinical findings and observational studies offered to support overall safety for combined hormone therapy did not predict the adverse WHI randomized clinical trial findings. As a result, the Food and Drug Administration currently mandates the same black box prescription label warning for all estrogen and progestin products (including progesterone and estradiol), taking the position that, in the absence of product-specific clinical studies, similar risk should be assumed for all preparations.¹ Also, although results are mixed, large observational studies of preparations frequently used in Europe have found little variation in breast cancer risk according to hormone constituents, which included progesterone-like progestins and estradiol.^2- 3