“Estrogen dominance” is the term coined by the late Dr John Lee to describe the concept of unopposed estrogen having harmful and uncomfortable effects in the body.
Many women arrive at a functional medicine practice already supplementing with estrogen, either in the form of Premarin (HRT), or bioidentical hormone replacement therapy (BHRT).
What are the differences? Premarin is the brand name for a type of HRT which comes from the urine of pregnant mares. It consists of a combination of many estrogen sulfates, which are metabolites of estrogen, also referred to as “conjugated estrogens.” The estrogens in Premarin are not bioidentical to human hormones. Estrone sulfate makes up 50-70% of the estrogens in Premarin.
BHRT, on the other hand, is the term for laboratory derived compounds that are molecularly identical to endogenously produced hormones. Pharmaceuticals such as Estrace, Evamist, Vivelle, Climera, Alora, Estroderm, Vagifem, Estring and ethinyl estradiol in oral birth control are all examples of bioidentical estradiol. Compounding pharmacies can customize estradiol formulations based on the desired potency and mode of delivery.
Most women who use HRT are in an estrogen dominant state, as they are not likely to be using bioidentical progesterone to counterbalance the effects of conjugated estrogens. They may be using a synthetic progesterone, called “progestin” which is not bioidentical, and does not counterbalance the deleterious effects of Premarin. In fact, using a progestin with premarin puts one at greater risk. In 2002 the Conjugated Equine Estrogen + Medroxyprogesterone (PremPro) arm of the Women’s Health Initiative was discontinued after 5.2 years instead of the planned 8.5 years due to increased risk of invasive breast cancer; cardiovascular disease including heart attacks, stroke, coronary artery disease and pulmonary embolism; and Alzheimer’s disease.
Premarin is usually delivered in oral form, which poses its own set of problems as oral estrogen impairs the metabolic action of growth hormone (GH) in the liver, which results in a decrease in insulin-like growth factor (IGF-1) which leads to an increase in fat oxidation, a loss of lean tissue and gain of body fat in postmenopausal women. It also increases inflammatory markers and acute phase proteins including Serum Amyloid A and C Reactive Protein (CRP). These effects have not been found with transdermal bioidentical estradiol as it bypasses the liver.
Recently at the Wellness Wednesday webinar we discussed several natural treatments that will tip the scales away from estrogen dominance for all women, supplementing or not, in an estrogen dominant (progesterone deficient) state:
Progesterone is the hormone that counterbalances the proliferative effects of estradiol. If estrogen is the fertilizer that ensures growth, progesterone is the gardener that manages the growth. When the gardener isn’t present, everything, including weeds, grows unchecked. Topical progesterone supplementation is an easy way to counterbalance estrogen and provides many health benefits. In addition to opposing the effects of estrogen in breast, brain and endometrial tissue, progesterone supports sleep, is cardioprotective, helps balance blood sugar, a natural antidepressant, and promotes bone growth and normal cell death.
Estriol (E3) is the protective form of estrogen that binds to the same receptors as the more biologically active estradiol (E2), and the more harmful estrone (E1). Think of estriol as a friendly, competitive inhibitor tying up the estrogen receptors interfering with the formation of harmful metabolites. In this way Estriol can help with estrogen dominance as it helps to water down the effects of estrogen. E3 also offers many beneficial effects beyond its ability to compete with E1 and E2, it can improve hot flashes, vaginal atrophy, skin enhancement, and can be a treatment for autoimmune disease.
Aromatase inhibitors interfere with the ability for the enzyme aromatase, found in fatty tissues, to convert testosterone into estradiol. While some conversion is natural and healthy, an increase in conversion due to excess adipose tissue, belly fat in particular, will increase estrogen supplies in women and men, and decrease testosterone in men. As a result, aromatization tips the scales toward estrogen dominance in both women and men. Some natural aromatase inhibitors that have been shown to slow down or impede the conversion of testosterone into estradiol include the flavonoids chrysin and resveratrol, and zinc.
The lignans in flax have been shown to bind estrogen, facilitate its excretion and promote the favorable estrogen metabolic pathway (2-OH). In a research study, women consuming 10g of flaxseed per day experienced longer menstrual cycle length, increased progesterone to estrogen (Pg/ E2) ratios, and fewer anovulatory cycles. Other foods high in lignans include: sesame seeds, cruciferous vegetables, apricots and strawberries.
Calcium d-Glucarate is a calcium salt found in orange, apples, grapefruit and cruciferous vegetables. It inhibits beta-glucuronidase, an enzyme produced in gut microflora. An elevated level of beta-glucuronidase activity is associated with an increased risk for hormone-dependent cancers such as breast, prostate and colon. Oral calcium-d-glucarate has also been shown to regulate estrogen metabolism, inhibit carcinogenesis, promote cellular differentiation and enhance excretion of carcinogens.
Curcumin is a naturally occurring compound found in the spice Turmeric, a member of the ginger family. A combination of curcumin and the isoflavone genistein has shown synergy in reducing xenoestrogen-induced growth of breast cancer cells.
DIM and I3C - These are compounds found in cruciferous vegetables that shift estrogen metabolism toward the healthier 2-OH metabolic pathway which has the lowest cancer risk/affiliation. While similar in action, research suggests that DIM may be more biologically active and have fewer side effects. DIM can block estrogen receptors and inhibit the growth of estrogen responsive breast cancer, and has been shown to inhibit the growth of both estrogen-dependent and estrogen-independent cancer cells by approximately 60 percent.
150 minutes per week of vigorous aerobic exercise also increases the favorable estrogen metabolic pathway by increasing urinary levels of 2-OH.
Melatonin - Scientists have speculated that the lack of melatonin, due largely to our sleep-deprived modern society, puts women at higher risk for breast cancer because there is an inverse relationship between melatonin levels and breast cancer. Melatonin can modulate estrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity.
Wondering where your patients land? The Pg/E2 ratio and estrogen quotient (EQ) are helpful tools for gauging estrogen dominance and estrogen metabolism. The Pg/E2 ratio indicates whether one is in an estrogen dominant state, and the EQ offer insight into estrogen metabolism, and whether one is being protected by her distribution of estrogens, or at risk for estrogen driven cancers.
