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Center for Neuroendocrine Studies University of Massachusetts Amherst, Massachusetts 01003
Address all correspondence and requests for reprints to: Jeffrey D. Blaustein, Ph.D., Editor-in-Chief, Endocrinology, Center for Neuroendocrine Studies, 135 Hicks Way, University of Massachusetts, Amherst, Massachusetts 01003-9271. E-mail: endocrinology{at}cns.umass.edu.
As an editor, and now Editor-in-Chief of this journal, as well as a reader of papers in endocrinology, I continue to see a problem with nomenclature that I believe needs to be remedied. The term estrogen has taken on numerous meanings, and this has led to a confusing, imprecise literature, and it has confused our colleagues and the public. Some authors use it synonymously with estradiol-17β, whereas others use it to refer to any compound with estrogenic properties in a particular system. However, estrogen is not a particular hormone. Rather, it refers to a class of compounds with estrogenic activity, defined by a variety of criteria. A compound could be categorized as an estrogen based on its binding to a particular estrogen receptor, by its effects in classical in vivo assays such as the uterotrophic or vaginal cornification assays (1), by its performance in in vitro assays (2), or by other biological effects (e.g. influences on female secondary sex characteristics or on neuroendocrine responses). Some of the common endogenous hormones from the class, estrogens, are estradiol-17β (commonly referred to as estradiol), estrone, and estriol. There are also synthetic estrogens, such as those that are found in some oral contraceptives, as well as xenoestrogens, compounds that are not endogenous to animals. These include the phytoestrogens, like genistein, as well as synthetic compounds, such as the endocrine disruptor used in plastics and epoxy resins, bisphenol A. The class, estrogens, also includes the conjugated estrogens, such as 17β-estrone sulfate, many of which are purified from horse urine and are found in Premarin and Prempro (3).
The number, variety, and sources of compounds that belong by one criterion or another to the class of hormones, estrogens, is large. Referring to all of them as estrogen does a tremendous disservice to our field. It also confuses the public, which needs to understand the nuances of different estrogens to make informed decisions about medical treatments.
I suggest the following terminology for this journal, and I hope that a similar convention is adopted by others. The term estrogens, not estrogen, should be used when referring to the class of hormones, which includes estradiol (or usually more specifically estradiol-17β), estrone, and estriol. Using this nomenclature, it would be correct to say that "estrogens have been implicated in uterine growth," rather than using the term estrogen, so that it is clear when reference is not to a specific compound. In contrast, when a specific estrogen is used or assayed, the particular estrogen must be specified. For example, it would be correct to say "when estradiol (or even more correctly, estradiol-17β) was injected ..." or "estradiol (or estradiol-17β) was assayed during the proestrous stage of the estrous cycle" or "1 nm of estradiol-17β was added to the incubation medium."
This issue may sound like a trivial detail to some. However, the scope of the confusion among scientists and the interested public regarding the meaning of the term estrogen behooves us to refine our use of these terms to increase clarity. The imprecise use of terminology can be exemplified in the misunderstandings that followed publication of the Women’s Health Initiative (4) and Women’s Health Initiative Memory Study (5). When these authors, as well as many others, referred to the cocktail of conjugated equine estrogens and other compounds (3) in Premarin and Prempro as estrogen, they did not mean the same thing as when others refer to estradiol-17β as estrogen. When endocrinologists use the same word for more than one compound or treatment, this is a problem bound to create misunderstanding.
A similar problem is seen in the use of the terms progesterone and progestins. Progesterone is a specific hormone belonging to the class of hormones called progestins, also sometimes referred to as gestagens or progestagens. The class, progestins, includes endogenously produced hormones as well as synthesized pharmaceuticals. Medroxyprogesterone acetate, the synthetic progestin found in Prempro is sometimes incorrectly referred to as progesterone. Endocrinologists know that it is not. Medroxyprogesterone is a synthetic steroid with progesterone-like effects in some situations. Although it also has androgenic and glucocorticoid activity (6, 7), it can appropriately be considered a progestin. However, it is not progesterone. The New York Times was incorrect when, for example, Jane E. Brody wrote, "Prempro is a combination of Premarin and a progesterone ..." (8). It cannot be a progesterone; progesterone is a specific hormone. Either Prempro has progesterone in it, or it does not. It does not. Likewise, The New York Times (as well as numerous other sources) was incorrect when it stated in an article by Denise Grady that "Prempro, a widely used pill combining estrogen and progestin, a form of progesterone..." (9). Progestin is not a form of progesterone, and Prempro does not contain progesterone; Prempro contains the progestin, medroxyprogesterone acetate.
The burden is on us, as endocrinologists, to adopt a consistent and precise terminology in referring to some of our favorite hormones and classes of hormones. I am asking members of the Editorial Board of Endocrinology and our reviewers to watch carefully for incorrect usage of these terms and those relating to other classes of steroid hormones. Although this editorial may sound preachy, I believe that it is essential for each of us to make sure that we use precise terminology when referring to these important hormones and classes of hormones. If we do not do so, we will continue to perpetuate misunderstandings by the public trying to make sense of endocrinological information. In time, perhaps our more precise terminology will find its way into common usage and the nonscientific press, and endocrinologists and the public will have a clearer understanding of what estradiol, estrogens, progesterone, and progestins are.
Received March 20, 2008.
Accepted for publication March 20, 2008.
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