Many women do not realize that 'estrogen' is not an actual hormone, such as testosterone or progesterone, but is the term used to refer to a class of molecules that have estrogen like activity in the body. There are many molecules that are estrogens, but the principal estrogens in a woman are estradiol, estrone, and estriol. It is important to understand this when you are deciding what kind of estrogen replacement therapy you are going to take.
Estrogens circulate throughout the body, and become attached to cells that express the estrogen receptor (ER). Estrogens and the ER function in much the same way as a key and a lock. When the key is placed in a lock the door is opened; when an estrogen locks onto an ER, a series of events occur that mediate the effect that we see in the tissue, such as building up of the lining of the uterus, or keeping the bones from becoming thinner. The difference is that the many different estrogens can lock on to the ER, but each with a different degree of effectiveness and with different effects in different tissues.
For example, estradiol is the most potent of the estrogens produced by the ovary. A very small amount circulating in the blood can tightly lock onto the ER and cause potent changes in estrogen responsive tissues. Estrone, a metabolite of estradiol is considerably less potent, and estriol a further metabolite of estradiol, is quite weak.
This is a question often asked by women who are seeking a 'more natural' approach to HRT because they have heard that there are fewer side effects with a natural approach. Unfortunately, natural is equated with herbal or coming from a plant rather than being chemically synthesized. Thus, women choose to take things like yam extract or herbs that are said to have estrogen like activity. But yams have no molecules with any significant estrogen activity. What they contain is a precursor molecule, diosgenin, which can then be chemically converted into many different estrogens. We believe that the important distinction is not between natural and synthetic, but between hormones that are "naturally" found in the human body, which are called bioidentical hormones; and hormones that may have similar activity in some tissues but are not naturally found in the human body—exogenous or foreign hormones.
Estradiol, estrone, and estriol, and all of their metabolites are bioidentical hormones; which are "naturally" found in the body. In contrast, Premarin, the most commonly prescribed estrogen formulation for HRT, is mixture of two human estrogens, estradiol and estrone, and 10 or more horse estrogens, which are exogenous to humans. The problem with exogenous hormones is that while their activity in some tissues is well studied, we can't be sure of it in other tissues.
Premarin is very natural in that it is derived from pregnant mare urine and is not synthesized, but it is not natural in that it contains many estrogens that are not naturally found in a woman's body. Some of these hormones, such as equilenin, are very potent estrogens, even more so than estradiol. As such, the level of these potent hormones needs to be closely monitored. Unfortunately, there are no readily available blood or saliva tests for monitoring the levels of these foreign hormones (and that also goes for the estrogen substitutes such as raloxifene, known as Evista, and tamoxifen, known as Novaldex). This is particularly important because, as we will see in the next section, how one takes a hormone, especially an estrogen, under certain circumstances dramatically alters the blood level.
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