The Safe and Effective Use of Estrogen for Women Part 1

Many menopausal and postmenopausal inquire about the use of estrogen therapy at the Stengler Center for Integrative Medicine. There are many factors that Dr. Angela and I consider when prescribing estrogen. However, it is true that low estrogen levels can mean troublesome menopause with severe hot flashes, night sweats, vaginal dryness, depression, cognitive problems, and other symptoms. a reduced quality of life, and increased risk of serious diseases.
The Estrogen and Aging Link!
One mainstream medical journal noted that estrogen deficiency, as observed with menopausal women, accelerates aging! The same study notes that dropping estrogen levels with menopause is associated with cardiovascular disease, osteoporosis, urogenital atrophy [breakdown of the urinary tract and genitals], dermal[skin]aging, increased risk of colon cancer, more malignant breast cancer forms, loss of neurons from the brain that results in cognitive decline and earlier expression of Alzheimer’s disease, macular degeneration, and cataract formation.
Also, a study published in the American Journal of Public Health estimated that the avoidance of estrogen therapy in women ages 50 to 59 years who had a hysterectomy died prematurely! It is estimated that 91,610 postmenopausal women died prematurely over a ten-year span due to avoiding estrogen therapy.
And if you are a woman who experiences premature menopause, say under the age of 40, the impact of low estrogen is so significant that you are at higher risk of “of premature death, neurological diseases, psychosexual dysfunction, mood disorders, osteoporosis, ischemic heart disease, and infertility.”
There are roles for estrogen in postmenopausal women too. For example, low estrogen production in postmenopausal women increases the risk of bone fracture, cardiovascular disease, and Alzheimer’s disease.
A Much Needed Hormone
Amazingly, estrogen has approximately 400 functions in the body! Since many body cells have estrogen receptors, you can see why it has so many functions. Here is a summary of some of the highlights:
Increases metabolic rate
Improves insulin sensitivity
Improves sleep
Stimulates an enzyme in the brain that produces acetylcholine (memory and Alzheimer’s prevention)
Maintains muscle mass
Reduces cataract and glaucoma risk
Increases blood flow
Decreases plaque accumulation in arteries
Maintains collagen in the skin and increases the water content of skin for softness and thickness
Reduces wrinkles
Decreases blood pressure
Decreases LDL cholesterol levels and LDL oxidation
Protects against muscle damage
Acts as an antioxidant
Regulates carbohydrate and fat metabolism
Normal sexual and reproductive function
Regulates bone mass and strength
Decreases risk of colon cancer
Prevents tooth loss
Relieves hot flashes
Treats vulvo-vaginal atrophy
Treats vaginal dryness and pain with sexual intercourse related to vaginal atrophy
Treats urinary symptoms such as urgency, pain, and recurrent urinary tract infections
Reduces joint pain
Used in the formation of neurotransmitters in the brain such as serotonin to lessen depression, irritability, anxiety, and sensitivity to pain
It All Starts With Cholesterol
The initial building block of estrogen is cholesterol! So, you can imagine what happens to your estrogen production if you are on a cholesterol-lowering drug. The ovaries produce most estrogen in premenopausal women. However, it is also produced by peripheral tissues (fat tissue), especially in postmenopausal women, from steroid precursors such as pregnenolone and dehydroepiandrosterone (DHEA), conversion from testosterone into estrogen. Estrogen is also produced in the brain, bone tissues, vascular endothelium (inside lining of blood vessels).
Types of Estrogen
It is essential to realize that the term estrogen is a plural term. There are many different types of naturally produced estrogen in females. There are three main natural estrogens. The first is known as estrone (E1). E1is the primary estrogen made by the body after menopause. Next is estradiol (E2). E2 is the main form of estrogen during childbearing and premenopausal years. It is also the most potent form of estrogen. The third is estriol (E3). E3 is the primary estrogen made during pregnancy but is also present in all women. Estriol is much weaker than estradiol and may have protective effects against breast cancer by blocking breast estrogen receptors. Therefore, holistic doctors include it in natural estrogen formulations combined with estradiol, whereas conventional doctors generally prescribe estradiol without estriol.
After estrogen has interacted with cell receptors throughout the body, they are metabolized by enzymes in cells, especially in the liver. There are several known estrogen metabolites. These estrogen metabolites appear to be important in terms of breast cancer risk. For example, estradiol and estrone are inactivated by an enzyme in cells known as catechol-o-methyltransferase (COMT). Estrogen is acted upon in the liver by a process known as conjugation, where they are made more soluble to be eliminated mainly in the urine.
Research is demonstrating that one of the good estrogen metabolites is 2-hydroxyestrone (2 -OHE1). This metabolite of estrone is considered to be protective against cancer. The formation of the good 2-OHE1 is dependent on a process known as methylation. Some people have genetic problems with methylation activity in their cells. This methylation activity can be tested indirectly with blood homocysteine levels. An elevated level suggests you have problems with methylation. However, you can have your genes tested directly with genetic testing, such as the MTHFR and COMT genes. If you inherited problems with these genes, you could improve methylation with supplementation such as methylated B vitamins, especially B2, folate, B6, and B12, as well as magnesium. You can also increase the good 2-OHE1 with exercise, cruciferous vegetables, flaxseeds, and supplements such as indole-3-carbinol (I3C) and diindolylmethane (DIM), omega 3 fatty acids, rosemary, turmeric, and by losing weight.
An estrogen metabolite that is carcinogenic is 4-hydroxyestrone (4-OHE1). It can damage cell DNA and is one of the metabolites of the synthetic estrogen replacement that used to be popular with conventional doctors known as Premarin.
Estrogen Metabolite Testing Available
I often test these estrogen metabolites with a urine test to see if a woman has high levels of harmful estrogens. This test can be done whether a woman is on hormone replacement or not.
Look for part two of this article in the future, where I discuss the safest method for using estrogen replacement therapy.
Selected References
Birge S. 2003. The use of estrogen in older women. Clin Geriatr Med. 19.
Cui J, Shen Y, Li R. 2013. Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends in Molecular Medicine 19:197-209. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595330/
Okeke T, Anyaehie U, Ezenyeaku C. 2013. Premature Menopause. Annals of Medical and Health Sciences Research 3:90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634232/
Sarrel P, Njike V, Vinante V, Katz D. 2013. The Mortality Toll of Estrogen Avoidance: An Analysis of Excess Deaths Among Hysterectomized Women Aged 50 to 59 Years. American Journal of Public Health 103:1583-1588. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780684/