• Bisphenol A (BPA) found in can liners, receipt paper, and plastics


• Polybrominated diphenyl ethers (PBDE’s) found in flame retardants and house dust


• Dioxins formed as an unintentional by- product of many industrial processes involving chlorine such as waste incineration, chemical and pesticide manufacturing and pulp and paper bleaching


• Perfluorinated chemicals (PFC’s) found in nonstick cookware and water-resis- tant coatings


• Polychlorinated biphenyls (PCB’s) found in coolants and lubricants


• Diethylstilbestrol (DES) given to preg- nant women from 1941 to 1971 to prevent pregnancy complications and pregnancy loss, now known to cause increased risk for gynecologic prob- lems including vaginal cancer in the daughters of women exposed to DES in utero. (DES exposure can also cause significant medical problems in “DES sons” as well.)


Increased Production of Estrogen Estrogen (specifically estradiol) is made from testosterone in the body via an enzyme called aromatase. The activity of aromatase is stimulated by:


• High levels of inflammation • Excess body fat • High insulin levels (insulin resistance) • Alcohol


The aromatase enzyme is found in


many tissues throughout the body: ovary, brain, fat, blood vessels, skin, and bone, as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer. After menopause, most estrogen is produced in areas outside of the ovary, most notably in excess body fat. Drugs which block the activity of aromatase are used to treat breast cancer. Inappropriately increased aromatase activity leads to excess circulating estrogen in the body.


Free (active) estrogen levels in the


body can also result from decreased levels of binding to a carrier protein in the blood called SHBG (sex-hormone binding globu- lin). Decreased SHBG levels are associated with obesity, elevated insulin levels, steroid use, hypothyroidism, and elevated testoster- one levels.


Decreased Balancing Effects from Progesterone


Progesterone is another sex steroid


which balances the effects of estrogen in the body. Progesterone levels rise in the second half of the menstrual cycle after ovulation to decrease estrogen levels and stabilize the lining of the uterus to prevent irregular or ex- cessive bleeding. If pregnancy occurs during that cycle, progesterone rises dramatically to support the growth of the fetus. Progesterone is primarily produced by the ovary, in smaller amounts by the adrenal glands, and in large amounts by the placenta during pregnancy. It has multiple physiologic effects including decreasing estrogen receptor activity and blocking the production of estrogen at the DNA level. Thus, conditions that decrease progesterone relative to estrogen or block the activity of progesterone at its cellular recep- tor can contribute to estrogen imbalance. These include:


• Inflammation • Polycystic ovarian syndrome (PCOS) • Excess cortisol levels (from excess stress)


• Decrease in ovulatory cycles in the years approaching menopause (i.e., “perimenopause” which on average occurs at age 46)


• Hypothyroidism


• Inappropriately elevated levels of the hormone prolactin, responsible for breast milk production after childbirth


Decreased Elimination of Estrogen and Xenoestrogens Detoxification and elimination of hormone and toxins occurs primarily in the liver and in the gut, through a process called biotransformation. Biotransforma- tion is the conversion of toxic substances into non-toxic substances by making them water-soluble to be excreted in stool and urine. The capacity of the body to detoxify is dependent on many different enzymes, nutrient cofactors needed for function of those enzymes, and healthy gut bacteria.


In the liver, the transformation of estrogens has 2 phases:


Phase One detoxification involves three primary “highways” down which estrogen can travel. The most favorable route converts estrogen to a metabolite called 2-hydroxy estrone. The less favorable routes lead to products called 4- and 16- hydroxyestrone. Higher 4-hydroxy estrone levels are associated with direct DNA dam- age and progression to cancer.


Phase Two detoxification involves a process called methylation, which essential- ly neutralizes the 2- and 4- hydroxy estrone products.


Thus, anything we can to do increase 2-OH estrone, decrease 4-OH estrone, and enhance balanced methylation will lead to proper estrogen balance. These estrogen metabolites can be measured in the urine.


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