Metabolism of estrogens occurs in several areas of the body, however the main ones are liver and gastrointestinal tissues. More than 50% of the metabolism and conjugation of estrogens takes place in the liver, therefore targeting the liver becomes central when it comes to affecting the circulating estrogen ratio. Cholesterol is a molecule, which serves as a backbone for formation of a lot of hormones including estrogen. There are a lot of biochemical pathways, which lead to the production of estrogen. Some of these pathways are shown in appendix 1. The major pathway of estrogen metabolism is from estradiol to estrone 6. In turn, estrone (which can either come from androstenedione or estradiol) is metabolized further to 2-hydroxyestrone or 16alfa-hydroxyestrone. Finally, 16alfa-hydroxyestrone can be further metabolized into estriol (the weakest form of estrogen) 1 or to the catechol estrogens, which are then conjugated primarily as glucuronides, sulfates and thioether5,7. The conjugated forms of estrogen are water-soluble as well as they also do not bind to transport proteins. Therefore the conjugated forms of estrogen are readily excreted via bile, feces and urine4. The glucuronide conjugates are excreted in the urine more rapidly than are the sulfates. Because the estrogen sulfates are excreted from the body at a slower rate, they have a higher chance to be hydrolyzed in tissues and act as a source of biologically active estrogens8.
Another way estrogen metabolism is accomplished is by the gastrointestinal system. Approximately 50% of the estrogen conjugates, which enter or are formed in the liver, are excreted in the bile, pass into the intestine, and are hydrolyzed by intestinal bacteria9. Following this hydrolyzation reaction in the intestines the estrogens either are excreted in the feces or they are reabsorbed into the portal circulation. After the reabsorbtion takes place, the hydrolyzed estrogens are metabolized by the liver again and released into the bile or they stay in the circulation and stimulate their target tissues2. The hydrolysis of estrogen-glucoronides is accomplished by the bacterial enzyme called beta-glucuronidase. This enzyme is carried in some unfavorable intestinal bacteria. However, certain nutritional supplements, diet and antibiotics can influence the level of activity of this enzyme.
One study done by Adlercreutz and colleagues, examined the effects of supplementation of oral ampicillin to pregnant women resulted in a 34% decrease in urinary estrogen excretion and a 6-fold increase in the excretion of fecal estrogen. The concentration of conjugated forms of estrogen in the feces actually increased 60-fold.
Another study done by Shultz looked at plasma estrogen levels in vegetarian and nonvegetarian women. Fourteen premenopausal vegetarian women were compared with 9 premenopausal omnivores. The vegetarian women consumed significantly less fat, especially saturated fat, than the omnivores. Plasma levels of estrone and estradiol were found to be lower in the vegetarians. Finally, study presented by Sherwood and colleagues, showed that vegetarians excreted threefold more estrogen in their feces, had lower urinary excretion, and had 15-20% lower plasma estrogen levels. The above studies show a positive correlation between high plasma levels of estrogen and consumption of fat, as well as, a negative correlation with consumption of high fiber diet. The above results indicate that diet can alter the route of excretion of estrogen by influencing the enterohepatic circulation and that this, in turn, influences plasma estrogen levels.
In summary, the breakdown and excretion of estrogens is an extremely complicated process and a wide range of factors can influence it. Research seems to suggest that certain components of diet either increase or decrease the metabolism as well as excretion of estrogens. Dietary factors can also shift the production of estrogen from the more potent to less potent ones.
