Hormones and liver detoxification

Hormones. We can’t live without them, but fluctuations and imbalances make being a woman a love-hate relationship. Female sex hormones, progesterone and estrogen, feminize the female skeleton and add curves that define the female silhouette. Bones become strong and blood vessel are less susceptible to injury due to female hormones. Tweaking concentrations of estrogen or progesterone, however, can lead to a host of challenges. Insufficient progesterone can cause the embarrassment of adult acne, the disappointment of infertility, and the confusion of male pattern hair growth – hair loss and hair growth in areas that look undoubtedly better on men! Excess estrogen may elicit some health concerns, including gynaecological cancers (breast, cervical, vaginal, and endometrial), fibroids, endometriosis, and elevated PMS symptoms. On the other hand, low estrogen, such as during menopause, gives way to brittle bones, dry skin and dry vagina, impaired fertility, and low libido. Hormone imbalances spell frustration. Thankfully, there are solutions. Liver detoxification is key to managing estrogen imbalances, the first step in hormonal balance.

Detoxification, the liver, and estrogens

Estrogen is an umbrella term for estradiol, estrone, and estriol. Estrogens, along with other sex hormones, are produced on-demand; they are not stored. Estrogens circulate in blood and bind to estrogen receptors on target tissues, which include brain, bone, endometrium, skin, breast, and walls of arteries. Estrogens clear from circulation via detoxification pathways in the liver. Other organ cells are able to clear estrogens, although detoxification enzymes are most concentrated in the liver. These enzymes modify estrogen to make it readily eliminated from the body via urine and feces. Detoxification is a multi-step process requiring phase I and phase II detoxification enzymes. Estrogens that enter the liver interact with phase I detoxification enzymes, which modify estrogens into one of two main products (metabolites): 2-hydroxyestrone (2-hydroxyestradial) or 16α-hydroxyestrone (16α-hydroxyestradial). For estrogen balance and chemoprotection, increasing the ratio of 2-hydroxyestrone to 16α-hydroxyestrone is desired. This is due to 2-hydroxyestrone having weak estrogenic activity. It also can occupy estrogen receptors, thereby reducing binding sites for stronger estrogens. Conversely, 16α-hydroxyestrone has strong estrogenic activity. It is a “bad estrogen,” due to its association with rapid cell division, DNA damage, and carcinogensis (1,2).

Factors that favour “good estrogen” over “bad estrogen”

Numerous factors, including dietary modifications, enhance production of 2-hydroxyestrone over 16α-hydroxyestrone, thereby lowering estrogenic activity and offering protection against estrogen-sensitive cancers. For example, indole-3-carbinol(3)from cruciferous vegetables favours the production of 2-hydroxyestrone. Consider drinking raw cabbage or sauerkraut juice to increase the protective effect of indole-3-carbinol on breast cancer cells (4). In addition, lignin from flaxseed (5)improves the ratio of 2- to 16α-hydroxyestrone. Consider adding 10 grams (1 ½ tablespoons) of freshly ground flaxseeds into your diet daily. Add it to muffins, hot cereal, meatloaf, meatballs, or as a coating for “crispy” baked chicken. One tablespoon of ground flaxseed soaked in 3 tablespoons of water  of 5 minutes can replace an egg. Aside from dietary additions, moderate-intensity physical exercise (6)and genetics (7)increase estradiol metabolism via the 2-hydroxyestron pathway. On the flip side, there are other factors that lower the 2:16 ratio by either inhibiting the 2-hydroxyestron pathway or enhancing the 16α-hydroxyestrone pathway, thereby increasing estrogenic activity and possibly enhancing carcinogenesis in estrogen-sensitive organs. Its recommended to avoid endocrine (hormone) disrupting chemicals (8,9), especially those with estrogenic effects such as phthalates in scented products and fragrances, nail polish and removers, and soft plastics; parabens in lotion and sunscreens; and bisphenol A in the lining of food cans, till receipts and plastics marked PC or #7. Try to achieve a healthy body weight, since excess body fat is a well-known risk factor for breast cancer (10)due to its alteration of estrogen processing, specifically its inhibition of 2-hydroxyestron pathway (11).

Phase II liver detoxification

The fate of estrogen metabolites, 2-hydroxyestrone and 16α-hydroxyestrone, largely depends on phase II detoxification enzymes. These convert fat-loving (lipophilic) estrogen metabolites to water-loving (polar) forms, which can then be eliminated from the body via urine or feces. Fat-loving compounds, of which includes all sex hormones, are poorly eliminated from the body. Each detoxification enzyme is dependent on nutrients to function. Low levels of vitamin B12, B6, folate, and sulphur-rich foods (see table for examples) inhibit phase II enzymes needed to finish detoxification of estrogen metabolites. Prolonged circulation of these in the body causes stronger estrogenic effects suggestive of estrogen excess.

Take home

Effects from hormonal imbalances can be corrected; women need not endure embarrassment, disappointment, and confusion from the effects of hormonal imbalance. Hormonal therapy is not always required. Understanding the fate of estrogen in the body is a great start; modifying factors that promote or inhibit certain pathways is a necessary follow-through for balancing hormones indefinitely. Once again, dietary modifications are strong factors for balancing hormones as is being active and maintaining a healthy body weight. To learn more about how liver detoxification affects systems in the body, plan to attend Whole Foods Detox Class on May 9 from 7:00-9:00 pm at the St. Elias Ukrainian Orthodox Church (basement) in Bonnyville, AB. There is so much more to say! The focus of this article was not on progesterone, the other female sex hormone. Though imbalances in progesterone are also cause for concern, it will be addressed in a future article. References 1. Bolton JL, Pisha E, Zhang F, Qiu S. Role of Quinoids in Estrogen Carcinogenesis. Chem Res Toxicol. 1998;11:1113–27. 2. Cavalieri E, Rogan E. Catechol quinones of estrogens in the initiation of breast, prostate, and other human cancers: keynote lecture. Ann N Y Acad Sci. 2006;1089:286–301. 3. Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS, Crowell JA, Hurwitz A. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2005;14:1953–60. 4. Szaefer H, Licznerska B, Krajka-Kuźniak V, Bartoszek A, Baer-Dubowska W. Modulation of CYP1A1, CYP1A2 and CYP1B1 expression by cabbage juices and indoles in human breast cell lines. Nutr Cancer. 2012;64:879–88. 5. Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, Thompson LU. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr. 2004;79:318–25. 6. Bentz AT, Schneider CM, Westerlind KC. The relationship between physical activity and 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2/16 ratio in premenopausal women (United States). Cancer Causes Control CCC. 2005;16:455–61. 7. Taioli E, Bradlow HL, Garbers SV, Sepkovic DW, Osborne MP, Trachman J, Ganguly S, Garte SJ. Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev. 1999;23:232–7. 8. Colón I, Caro D, Bourdony CJ, Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect. 2000;108:895–900. 9. Sepkovic DW, Bradlow HL. Estrogen hydroxylation–the good and the bad. Ann N Y Acad Sci. 2009;1155:57–67. 10. Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev Off J Int Assoc Study Obes. 2003;4:157–73. 11. Bradlow HL, Sepkovic DW, Telang N, Tiwari R. Adipocyte-derived factor as a modulator of oxidative estrogen metabolism: implications for obesity and estrogen-dependent breast cancer. Vivo Athens Greece. 2011;25:585–8.
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