The Basics of BHRT for Menopausal Women
Bio-identical Hormone Replacement Therapy for Menopausal Women
What is it?
BHRT is the exogenous administration of human sex hormones; the most commonly prescribed are estrogen, progesterone, and testosterone. These hormones can be administered topically (transdermal), orally, intravenously, intra-vaginally, rectally, intramuscularly, sublingually, buccally, etc.
Why consider HRT?
When women begin menopause, their estrogen, progesterone, and testosterone levels drop. This can lead to a variety of frustrating symptoms such as weight gain, night sweats, irritability, sleep disturbances, brain fog, hair loss, dry skin, hot flashes, depression, and decreased libido. In the long term, low levels of estrogen can also increase the risk of Alzheimer’s, atherosclerosis, and osteoporosis by accelerating aging.
Why topical vs oral?
Although there are many possible forms of administration, topical and oral administration of estrogen, progesterone, and testosterone are the most common. Topical estrogen is often recommended because it avoids first-pass metabolism in the liver, rendering lower doses as effective as higher oral doses. Topical estrogen is absorbed into the skin to act both locally and systemically, and transdermal absorption may be safer than oral estrogen due to hepatic metabolism avoidance and potentially less estrogen being converted to estrone (an unfavorable estrogen linked to cancer).¹ However, further studies are needed.
Topical estrogen can be combined with topical progesterone in one convenient cream, but oral progesterone may more closely mimic the natural oscillations of progesterone in the body due to its longer half-life and circulation in the blood. It is important that women with a uterus are prescribed both estrogen and progesterone to prevent endometrial hyperplasia.
What can exogenous estrogen do?
Replacing the lack of estrogen in the body when it is no longer being released in normal quantities and restoring it to pre-menopausal levels can reduce menopausal symptoms and slow the rate of aging.
Some benefits that might result from taking estrogen during menopause:
- Increased skin elasticity⁴
- Increased vaginal lubrication
- Increased libido
- Weight loss
- Hair growth
- Improved wound healing⁴
- Menopausal symptom relief (i.e. hot flashes, night sweats, sleep disturbances)³
- Reduced risk of atherosclerosis (as long as HRT is started peri-menopausal and not years post)²
- Reduced risk of Alzheimer’s and dementia²
- Reduced risk of osteoporosis (which is the loss of bone tensile strength, NOT of bone density, which is why calcium is not beneficial)²
Because HRT is replacing hormones, when the HRT is stopped and estrogen levels return to menopausal levels (very low to nonexistent), the expected rate of aging will return. The cognitive and atherosclerotic protection will be negated.²
When should BHRT be started?
Ideally, hormone replacement therapy is begun when women are peri-menopausal, prior to the complete eradication of progesterone and estrogen (when levels are zero or near-zero). An indicator that a woman is nearing menopause is high levels of FSH, especially alongside lowering levels of estradiol. As the body loses its ability to synthesize estrogen and progesterone, FSH and LH production in the body will be ramped up to try and compensate for the lack of estrogen and progesterone (because estrogen and progesterone are not inhibiting FSH and LH production in a negative feedback loop). Blood tests can be used to measure FSH, LH, estrogen, and progesterone.
What are the three types of estrogen, and why are they administered in different percentages?
E1- estrone : this is an unfavorable form of estrogen, the “carcinogenic” estrogen also secreted by adipose tissue, as well as the only type naturally produced by the body after menopause.
E2- estradiol : this is the most potent and biologically active form of estrogen, especially during reproductive years.⁵
E3- estriol : this estrogen is least likely to be converted to estrone (because it first must be converted to E2 and thus would take two steps). It is less biologically active than estradiol and rises naturally during pregnancy.⁵
A typical prescription usually indicates a ratio of E3 to E2. Often, it is 50/50, 80/20, or 90/10. Although there may be a lower chance of conversion to estrone with a higher ratio of E3 to E2, a higher dose may be required to have an effect on the body, because E2 is the more biologically active, potent, and effective at mitigating menopausal symptoms.
How does estrogen improve my symptoms?
Estrogen is a hormone that acts systemically and binds to receptors all over the body. Hormones interact widely in various signaling pathways within the endocrine and neuroendocrine systems. Maintaining the hormone range correspondent with that of a younger female can slow the rapid increase in oxidative stress and aging associated with a drop in estrogen.⁶ For example, the loss of estrogen is linked to dementia, cardiovascular disease, and wrinkle formation. In regards to wrinkle formation, skin thickness declines, collagen content is reduced, and the skin wrinkles. Estrogen prevents this.⁷
How is estrogen broken down?
Estrogen gets broken down in the liver into three metabolites: 2-hydroxyestrone, 4-hydroxyestrone, and 16-hydroxyestrone. 4-hydroxyesteone is largely a metabolite of conjugated estrogens. The ratio of 2-hydroxyestrone to 16-hydroxyestrone is ideally high, although some 16-hydroxyestrone is necessary. 2-hydroxyestrone is considered to be a more favorable estrogen metabolite, while the other two metabolites can lead to abnormal cell growth (cancer) when in high quantities.⁸ There are a variety of foods and lifestyle changes that can increase 2-hydroxyestrone (i.e. lignans in flaxseed, cruciferous vegetables, omega-3 supplementation, lowering body fat percentage).⁸
Do I need to take progesterone if I am also taking estrogen?
If you have a uterus, yes. Taking progesterone with estrogen lowers the risk of endometrial cancer by lowering the risk of the uterine lining growing too thick (hyperplasia). If you do not have a uterus, progesterone is often still recommended due to its calming effects.
What can exogenous progesterone do?
Progesterone is known to increase GABA synthesis and promote deep sleep. It is often considered a relaxing hormone. It can reduce anxiety and help menopausal symptoms (i.e. hot flashes, night sweats, vasomotor symptoms), alongside exogenous estrogen. Similar to estrogen, it can also improve cardiovascular endothelial function.⁹
What about DHEA?
DHEA is a hormone produced by the adrenal glands. It is a precursor to estrogen and testosterone, and it does not require a prescription. It is often touted as a more “natural” means to increase sex steroid levels and optimize their ratios (because under different conditions and enzymes, it can be converted to either estrogen or testosterone). It has been shown to improve skin, treat osteoporosis, reduce erectile dysfunction, and increase libido, likely due to its ability to increase estrogen and testosterone levels.¹¹ Its production is drastically reduced as we age.
Why BHRT vs synthetic hormones?
Bio-identical hormone replacement therapy, as the name implies, uses chemicals that are molecularly identical to human hormones. They are extracted from plant sources and then modified in a lab.¹² BHRT requires a compounding pharmacy that can personalize the dose for each patient’s unique needs and hormonal profile.
Synthetic hormones, on the other hand, come in standard doses. They may be metabolized differently in the liver and/or lead to different ratios of metabolites.
Why are people against HRT?
Lots of misinformation exists on HRT. Some studies report slight increases in breast cancer risk; however, most of these are not statistically significant. The commonly reported Women’s Health Initiative study had many design flaws, including using Premarin (conjugated pregnant horse urine) rather than bioidentical estrogen and micronized (bioidentical) progesterone, as well as testing asymptomatic post-menopausal women.² Despite reporting a moderately high relative increase in breast cancer risk, the absolute increase in breast cancer risk in the WHI study was less than 0.1%.
What are the other risks?
HRT may increase the risk of blood clots (coagulation); however, this may only be relevant for oral estrogen and not pertinent when administering estrogen transdermally. Additionally, the risk of cardiovascular disease may increase if a patient begins HRT when she already has advanced atherosclerotic plaques and calcification.
What is DIM?
DIM is a dietary supplement often used to assist liver detoxification, especially increasing the detoxification of estrogen into favorable metabolites (i.e. 2OHE) to be cleared from the body.
What are other naturopathic ways to improve menopausal symptoms or increase my hormone levels?
There are a variety of over-the-counter plant extracts and supplements that have been shown to improve menopausal symptoms and/or increase hormone levels, such as black cohosh, vitex, maca, Pueraria mirifica, and other phytoestrogens. Lowering cortisol can also be beneficial, in addition to maintaining adequate levels of vitamin D, magnesium, and zinc. Resveratrol, another phytoestrogen, may also offer cognitive and oxidative protection for post-menopausal women.
How is HRT different from birth control?
Oral contraceptives contain ethinyl estradiol, which impacts and is impacted by liver metabolism differently than natural estradiol; hence why ethinyl estradiol/oral contraceptives have been linked to liver complications and changes in hepatic function.
Birth control and HRT also typically have different doses of estrogen and progesterone, with birth control pills usually containing more estrogen than HRT. Additonally, hormone replacement therapy is prescribed to women with low to non-existent concentrations of estrogen, whereas oral contraceptives are often prescribed to women during their reproductive years when they are actively secreting estradiol. This may account for the different side effects and risks between birth control and HRT.
Is it unnatural to take HRT? Is menopause a natural part of aging?
In a way, BHRT could be argued to be the most natural means possible of addressing menopausal symptoms to improve quality of life. Rather than take a cascade of pharmaceuticals to relieve a variety of symptoms that stem from the same root cause, HRT can address that root cause and offer increased vitality.
As science advances and clinical trials continue, the best practice in medicine rapidly changes. It is important to form your own opinions on hormones by reading medical literature and taking note of how YOUR body responds to various hormones and dosages. Intuition in medicine should never be neglected.
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