Posts: 588
Threads: 21
Joined: Feb 2013
...Pondering the statement about the liver playing a critical role in the conversion of estrogen. I did a search to see exactly where a liver sits in a body. It's located mostly on the RIGHT side and just below the shoulder blade. Hummm, that more accurately describes where my pain was. I always thought it was a little strange that the pain was concentrated on my right side and if PM was affecting my kidneys, why only my right kidney? Perhaps it was my liver instead.
Anyway, I found this article that puts the process in layman's terms. I Thought it might be useful for instruction or banter.
Articles - Estrogen Metabolism
Hormones are chemicals, which act as messengers within our bodies. They can be slow or fast acting. Hormones are generated at all times and different bodily tissues are responsible for producing different hormones. Their purpose is to maintain certain equilibrium within 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 female sex characteristics such as breast development, female voice, absence of facial hair and many more. In females, it is produced in large amounts and it is responsible for female characteristics. The focus of this paper will be to look at the different types of estrogens, their metabolism and some dietary and nutritional factors that influence estrogen’s biochemical pathways.
There are three forms of estrogen circulating in our bloodstream: estradiol, estrone and estriol. The normal ratios of these three types of estrogens ideally should be: 10 - 20% : 10 – 20% : 60 – 80% respectively 1. It is common however, to have this ratio disrupted though number of ways, such as: synthetic estrogens, estrogens in animal products, xenoestrogens (estrogens which are found in some environmental chemicals), phytoestrogens (estrogens found in plants) and production of estrogens in our body. In women of reproductive age, the primary source of circulating estrogens is the ovaries. In postmenopausal women and pre-puberty girls the main source of estrogens comes from extraglandular sites 3. Once estrogen is produced and released into the bloodstream, it reaches its target tissues and the liver. The estrogen that accounts for most of the tissue stimulation is called estradiol. Estrone is a little bit less potent with estriol being the weakest 1. In general, the most biologically active estrogens are the unconjugated ones and as mentioned above estradiol type would be the most potent one. The level of estrogenic activity becomes important when there is a pathology present or if there is a genetic or environmental susceptibility towards certain hormone receptive diseases.
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-fold10,11.
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 vegetarians12. 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.
1. Sat Dharam Kaur. A call to women. Kingston ON: Kingston Quarry Press Inc.; 2000. p. 58-66.
2. Sherwood L. Gorbach, Barry R. Goldin. Diet and the excretion and enterohepatic cycling of estrogens. Preventive Med 1987;16:525-31.
2. Longcope C, Kato T, Horton R. Conversion of blood androgens to estrogens in normal adult men and women. J Clin Invest 1969;48:2191-201.
3. Robert K. Murray et at. Harper’s biochemistry. Connecticut: Lange Medical Publications; 1993. p.547-50.
4. Eriksson H, Gustafsson JA. Excretion of steroid hormones in adults. Eur J Biochem 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 and tissue preparations of kidney and liver from Syrian hamsters. J Steroid Biochem Molec Biol 1995;52(5):479-89.
7. Tseng L, Stolee A, Gurpide E. Quantitative studies on the uptake and metabolism of estrogens and progesterone by human endometrium. Endocrinology 1972;90:390-404.
8. Sandberg AA, Slaunwhite WR. Jr. studies on phenolic steroids in human subjects. J Clin Invest 1957;36:1266-78.
9. Adlercreutz H et al. Intestinal metabolism of estrogens. J Clin Endocrinol Metab 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 premenopausal nonvegetarians. Nutr Cancer 1983;4:247-59.
Margaret Balajewicz B.Sc, Naturopathic Doctor
