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Info Articles
Estrogen: the Queen of the Kingdom

By Eugene Shippen, MD

There is no such thing as estrogen! It is, instead, a name for a diverse group of ubiquitous compounds that have the capability to activate cellular activities in the many life forms that depend on it. In fact, there are few if any compounds more consistently present in nature than estrogens, except, perhaps, DNA. These estrogenic compounds are structurally interrelated by similarity in the dimensions and shapes but differing greatly in chemical composition. It is this similarity in conformation that allows different estrogenic compounds from totally different sources to activate estrogen receptors in different types of cells from different genuses and species.

When we discuss estrogens as human hormones, we must include the many environmental and dietary sources of naturally occurring estrogenic compounds as well as the steroid hormones produced within, since all can activate receptors in human cells throughout the body. Environmental estrogens that may be synthesized for other purposes, such as DDT and other pesticides, are called xeno-estrogens. Plant estrogenic compounds are called phyto-estrogens. Many powerful herbal compounds belong to this category and have their effects mediated through activating estrogen receptors. All structurally similar molecules from these groups have at least some capability to occupy receptors and activate or block the activity programmed for that receptor, some more powerfully than the native hormone!

In humans, estrogen receptors have been found in every tissue. Two different estrogen receptors, ERa and ERb, have been identified, each switched on and controlled by a different gene. Both may be active in the same cells at different times of growth, development or "mature" cell activities. They are associated with different activating proteins which allow for great diversity of effects at different times. They control our brains, our immunity, our bones and our sexuality. In fact, they participate in every major function in the body. Why else would they be so widely distributed? It should become obvious by now that estrogens are essential for life and health.

So where does testosterone the "king" of the powerful hormones fit in to this schema. It is a "masculine" hormone of higher species that has specific receptors and effects. Testosterone can either activate androgen receptors, AR, or be converted to estradiol to activate estrogen receptors! This occurs in both sexes. We tend to think in terms of "male" or "female" when we discuss testosterone and estrogen. But what is becoming obvious is that these hormones are not sex specific, rather sex dominant, both being present in both sexes.

Biblically, in Genesis, the female is formed from the "marrow" or essence of the male. The Yin and the Yang principle also expresses a duality and an intertwined connection between the essence of male and female, testosterone and estrogen. What has not been recognized is the fact that all human estrogens are derived from "male" hormone precursors, particularly testosterone! This conversion takes place inside cells and tissues all around the body. In fact, many of the well known functions of testosterone are mediated through conversion first to estradiol, the primary estrogen. In particular, our sexuality is governed almost ironically by this "male" to "female" conversion! Both sexes seem to have this "androgynous" switching to activate the final receptors of sexuality, the ERa and ERb estrogen receptors. These may balance the classic androgen receptors, AR, that have been until now thought to be the major players in sexuality. So it comes as a shock to most males that estrogen may be the most powerful of all the "sex-hormones", the queen among kings!

Many of the popular herbs used to enhance sexuality, such as Maca, Ginseng, Vitex and others, may contain active phyto-estrogens that interact within our hypothalamus and the diverse ER receptors located there, directly firing up these receptors. This may account for the stimulating effects that have been reported with use in both men and women. Improvement in hormone activity during the peri-menopause and menopause may be derived from the ability to activate the receptors that are getting variable messages from the failing ovaries. Likewise, in men, improved libido or sexual performance may be the result of activation of the ER receptors that mediate these functions centrally or activation of local receptors in the pelvic area directly as male hormones decline in a somewhat similar fashion.

It is human nature to try to push the dose forever upward in attempts to find the maximum purported effect. Is more better? Like all hormones there is a window of optimal effect. All hormones are pulsatile in nature. There are none that are steadily produced indefinitely. Cellular effects vary with the changing bio-rhythms of cell cycles and cell functions. Hormonal receptors also are variable in activity, turned on either through a gene switch or by activation of chemical messengers to turn on or off hormonal functions. Without these switches and variable hormonal controls there would be chaos inside cells once a powerful hormone enters to trigger a function. Overstimulation by hormones or hormonal compounds from herbs may result in down-regulation of the receptor through central genetic or secondary mechanisms. In other words, more is not always better. Balance is the key!

Particularly, treatment with testosterone in high doses results in excessive conversion into estradiol essentially nullifying the benfits initially seen or looked for. Much of the confusion in the medical literature is the result of mis-understanding of this concept when large doses were tested for effects, particularly sexual function. With aging there is a general increase in conversion of androgens into estrogen. This problem may underlie the deficiency of testosterone through down regulation centrally or through down regulation of receptors at the cell itself. Treatment failure may be frequently reversed using aromatase inhibitors or non-aromatizable androgens. The delicate balance is the key to successful treatment with all hormone replacement strategies.