article - estrogen metabolism

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::Articles - Estrogen Metabolism

Hormones are chemicals, which act as messangers within ourbodies. They can be slow or fast acting. Hormones are generated atall times and different bodily tissues are responsible for producingdifferent hormones. Their purpose is to maintain certain equilibriumwithin its host and make the body function optimally.

Estrogen is a hormone.It is produced by man and women. In man,if released in high enough quantities it will produce secondary femalesex characteristics such as breast development, female voice,absence of facial hair and many more. In females, it is produced inlarge amounts and it is responsible for female characteristics. Thefocus of this paper will be to look at the different types of estrogens,their metabolism and some dietary and nutritional factors thatinfluence estrogens biochemical pathways.

There are three forms of estrogen circulating in our bloodstream:estradiol, estrone and estriol. The normal ratios of these three typesof estrogens ideally should be: 10 - 20% : 10 20% : 60 80%respectively 1 . It is common however, to have this ratio disruptedthough number of ways, such as: synthetic estrogens, estrogens inanimal products, xenoestrogens (estrogens which are found in someenvironmental chemicals), phytoestrogens (estrogens found inplants) and production of estrogens in our body. In women of reproductive age, the primary source of circulating estrogens is theovaries. In postmenopausal women and pre-puberty girls the mainsource of estrogens comes from extraglandular sites 3 . Onceestrogen is produced and released into the bloodstream, it reachesits target tissues and the liver. The estrogen that accounts for mostof the tissue stimulation is called estradiol. Estrone is a little bit lesspotent with estriol being the weakest 1 . In general, the mostbiologically active estrogens are the unconjugated ones and asmentioned above estradiol type would be the most potent one. Thelevel of estrogenic activity becomes important when there is apathology present or if there is a genetic or environmentalsusceptibility towards certain hormone receptive diseases.

Metabolism of estrogens occurs in several areas of the body,however the main ones are liver and gastrointestinal tissues. Morethan 50% of the metabolism and conjugation of estrogens takesplace in the liver, therefore targeting the liver becomes central whenit comes to affecting the circulating estrogen ratio. Cholesterol is amolecule, which serves as a backbone for formation of a lot of hormones including estrogen. There are a lot of biochemicalpathways, which lead to the production of estrogen. Some of thesepathways are shown in appendix 1. The major pathway of estrogenmetabolism is from estradiol to estrone 6 . In turn, estrone (whichcan either come from androstenedione or estradiol) is metabolizedfurther to 2-hydroxyestrone or 16alfa-hydroxyestrone. Finally,16alfa-hydroxyestrone can be further metabolized into estriol (the
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weakest form of estrogen) 1 or to the catechol estrogens, which arethen conjugated primarily as glucuronides, sulfates andthioether 5,7 . The conjugated forms of estrogen are water-soluble aswell as they also do not bind to transport proteins. Therefore theconjugated forms of estrogen are readily excreted via bile, feces andurine 4 . The glucuronide conjugates are excreted in the urine morerapidly than are the sulfates. Because the estrogen sulfates are

excreted from the body at a slower rate, they have a higher chanceto be hydrolyzed in tissues and act as a source of biologically activeestrogens 8 .

Another way estrogen metabolism is accomplished is by thegastrointestinal system. Approximately 50% of the estrogenconjugates, which enter or are formed in the liver, are excreted inthe bile, pass into the intestine, and are hydrolyzed by intestinalbacteria 9 . Following this hydrolyzation reaction in the intestines theestrogens either are excreted in the feces or they are reabsorbedinto the portal circulation. After the reabsorbtion takes place, thehydrolyzed estrogens are metabolized by the liver again andreleased into the bile or they stay in the circulation and stimulatetheir target tissues 2 . The hydrolysis of estrogen-glucoronides isaccomplished by the bacterial enzyme called beta-glucuronidase.This enzyme is carried in some unfavorable intestinal bacteria.However, certain nutritional supplements, diet and antibiotics caninfluence the level of activity of this enzyme.

One study done by Adlercreutz and colleagues, examined the effectsof supplementation of oral ampicillin to pregnant women resulted ina 34% decrease in urinary estrogen excretion and a 6-fold increasein the excretion of fecal estrogen. The concentration of conjugated

forms of estrogen in the feces actually increased 60-fold10,11

.Another study done by Shultz looked at plasma estrogen levels invegetarian and nonvegetarian women. Fourteen premenopausalvegetarian women were compared with 9 premenopausalomnivores. 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 12 .Finally, study presented by Sherwood and colleagues, showed thatvegetarians excreted threefold more estrogen in their feces, hadlower urinary excretion, and had 15-20% lower plasma estrogenlevels. The above studies show a positive correlation between highplasma levels of estrogen and consumption of fat, as well as, anegative correlation with consumption of high fiber diet. The aboveresults indicate that diet can alter the route of excretion of estrogenby influencing the enterohepatic circulation and that this, in turn,influences plasma estrogen levels.

In summary, the breakdown and excretion of estrogens is anextremely complicated process and a wide range of factors caninfluence it. Research seems to suggest that certain components of diet either increase or decrease the metabolism as well as excretionof estrogens. Dietary factors can also shift the production of estrogen from the more potent to less potent ones.

1. Sat Dharam Kaur. A call to women. Kingston ON: Kingston Quarry PressInc.; 2000. p. 58-66.


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2. Sherwood L. Gorbach, Barry R. Goldin. Diet and the excretion andenterohepatic cycling of estrogens. Preventive Med 1987;16:525-31.

2. Longcope C, Kato T, Horton R. Conversion of blood androgens toestrogens in normal adult men and women. J Clin Invest 1969;48:2191-201.

3. Robert K. Murray et at. Harpers biochemistry. Connecticut: Lange MedicalPublications; 1993. p.547-50.

4. Eriksson H, Gustafsson JA. Excretion of steroid hormones in adults. Eur JBiochem 1971;18:146-50.

5. Fishman J, Bradlow HL, Gallagher TF. Oxidative metabolism of estradiol. J

Biol Chem 1960;235:3104-07.

6. Mustapha A. Beleh et al. Estrogen metabolism in microsomal, cell andtissue preparations of kidney and liver from Syrian hamsters. J SteroidBiochem Molec Biol 1995;52(5):479-89.

7. Tseng L, Stolee A, Gurpide E. Quantitative studies on the uptake andmetabolism of estrogens and progesterone by human endometrium.Endocrinology 1972;90:390-404.

8. Sandberg AA, Slaunwhite WR. Jr. studies on phenolic steroids in humansubjects. J Clin Invest 1957;36:1266-78.

9. Adlercreutz H et al. Intestinal metabolism of estrogens. J Clin EndocrinolMetab 1976;43:497-505.

10. Adlercerutz H et al. Effect of ampicillin administration of the excretion of twelve estrogens in pregnancy urine. Acta Endocrinol 1975;80:551-7.

11. Shultz TD,Ledlem JE. Nutrient intake and hormonal status of premenopausal vegetarian Seventh-Day Adventists and premenopausalnonvegetarians. Nutr Cancer 1983;4:247-59.

Margaret Balajewicz B.Sc, Naturopathic Doctor
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