Probing Premarin

[The author responds:]

Premarin is a complex natural product comprised of multiple components. It has been the subject of more than 3500 citations and over 57 years of clinical use in Canada, the US and around the world. All of the estrogenic components that have been tested for biological activity have been found to be biologically active. As Theodor Lippert and Alfred Mueck state, different estrogens can produce different effects. An estrogen can be an agonist in one tissue and an antagonist in another; we know that these effects are tissue and cell dependent. Furthermore, we know that the effect of an estrogen can be different when administered acutely versus chronically and, perhaps most important, that its effect can be different, in fact opposite, when administered in conjunction with other estrogens.[1–4] Thus, the effects of Premarin cannot be ascribed to an individual metabolite or component or group of components. Effects are all too frequently ascribed to estrogens as a class by individuals whose knowledge in the area is limited; in any event the data are more often than not based on studies with Premarin. On the basis of current scientific and clinical knowledge of the mechanisms of estrogen action, an assumption that Premarin's effects apply or can be extrapolated to all estrogens is inappropriate.