Your questions about bio-identical hormones, answered!

First, let’s briefly review what a hormone is in the first place. Hormones are produced by our endocrine organs, including our sexual organs (testes and ovaries), pituitary gland, adrenals and thyroid as well as other areas of our body like our fat and heart and GI tract. Hormones are messengers that carry vital communication between glands, organs and other hormones throughout the body. In many cases hormones work as antagonists to each other (meaning, one keeps the other one in check). When your body’s hormones are not communicating well, when they aren’t in balance, you will experience symptoms and a greater risk for disease.

Hormones are complicated (isn’t everything when it comes to women?), because they do indeed interact with each other and because they respond (fluctuate/increase/decline) in response to many external stimuli as well as to what is going on in the rest of the body. Stress is a big external stimulus (our stress hormone cortisol can significantly reduce production of other vital hormones). Toxins (environmental as well as those in our food) are another external influence on our hormones. . . I go into this  in more detail in my book The Hormone Fix. 

Within the body, the health state of different systems and organs can affect hormone balance. For example, if you have an unhealthy gut (perhaps from a poor diet or food intolerance issue) your ability to detox hormones such as estrogen could be affected, allowing toxic levels to build up.

The other thing that impacts all of our hormones is simply the process of aging. Hormones decline starting in our 20’s, as you can see from this graphic from my book.

I remember a few years ago I interviewed Dr. Edwin Lee, who I consider one of the best physicians – and experts in bio-identical hormones – that I know. In that interview he said that menopause itself is a dangerous disease that puts women at risk for a higher rate of Alzheimer’s or dementia, heart disease and osteoporosis. For that reason he felt all women should consider bio-identical hormones as a preventative strategy against these health concerns as well as to reduce risks for breast cancer. 

This expert’s thumbs-up was not just focused on symptom relief; it was about considering bio-identical hormones as a preventative women’s health strategy. 

This is so important and not well-known to a lot of women; that bio-identical hormone replacement therapy isn’t just about symptom relief  (although, yes…that’s significant, too, as any woman can tell you!)  but can support long-term health.

So let’s talk about why women may want to consider hormone replacement therapy in the first place. Then I’ll talk about the key differences between traditional (synthetic) hormone replacement therapy and bio-identical hormone replacement therapy.

While I won’t talk about other hormones beyond the master reproductive hormones we think of when we use the term “HRT” for hormone replacement therapy (estrogen, progesterone, and our androgens, testosterone and DHEA) in this article, follicle stimulating hormone (FSH) and  luteinizing hormone (LH) are other key hormones during our reproductive years, with higher levels signaling the start of perimenopause. Other important hormone fluctuations women may experience include thyroid hormones (and thyroid hormone replacement therapy!) and you can read more about supporting your thyroid in this previous article. Thyroid symptoms can often mimic symptoms of menopause. 

Growth hormone is important; cortisol  and insulin are other major hormones that we won’t really talk about too much today, but can significantly impact other hormone levels; you can read more about these at the linked pages. Again, hormones are interconnected, so what happens with one will impact the others…this is important to keep in mind.

If you’ve been experiencing perimenopausal or menopausal symptoms you may have already been prescribed estrogen hormone replacement therapy (HRT). It has been the traditional “go to” for hot flash relief, and is used to address weight gain, insomnia, night sweats, vaginal dryness, etc.  It also has been looked at to help prevent postmenopausal osteoporosis. (1)

Younger women are often given estrogen to address ovarian hormone insufficiency, infertility or signs of early menopause.

What you may not be aware of, however, is that estrogen is also vital for brain health and heart health.

Estrogen is a master regulating hormone that transports glucose to the brain; literally feeding the brain. There is a reason that as estrogen declines as women age we start to experience brain fog, mood and memory issues!  (while estrogen is necessary for gluconeogenesis in the brain, ketones can be an alternative energy source, which is why my Keto-Green approach can rapidly relieve brain fog). Estrogen is neuroprotective beyond just nourishing our brain; it supports healthy mitochondrial function. Mitochondria are the major source of energy in brain cells and deficiencies in energy metabolism have been shown to be an early player in the disease process associated with Alzheimer’s disease.(2) 

Many scientists now believe that estrogen HRT can actually exert a positive effect on brain function if a woman starts HRT prior to menopause. I consider this TRUTH! The timing aspect of this (referred to as the “window of opportunity” theory) is important information because the reality is that many women do not start estrogen hormone replacement therapy until after menopause – or perhaps even post-menopause – which is beyond their “window of opportunity.” You can read much more about estrogen, brain fog, memory and cognitive health in this earlier article. 

Estrogen is also important to heart health, as estrogen receptors are found throughout the vasculature in the body where they support positive effects on the ability of blood vessels to dilate and respond well to changes in blood pressure. Estrogen has also been found to be lipid-lowering as well as have antithrombotic (clot-preventing) effects. 

Much like with estrogen’s neuroprotective benefits there may be a window of time when estrogen therapy is good or bad relating to heart health as well. Studies show that early in menopause (during the initial 6-10 years) estrogen decreases the risk for strokes and heart attacks, but that 10-12 years after menopause estrogen use results in an increase in cardiovascular events. (3)  

I know this can all get confusing, which is why having a good functional medicine practitioner – and in particular someone who works with bio-identical hormones – is so important. 

We’ll talk more about this in the next section but the type of hormone (synthetic or bio-identical; oral or transdermal, etc.) is key to achieving optimal protective benefits! For example, oral synthetic estrogen has actually been tied to worsening heart health.

There is also an issue relating to taking estrogen HRT by itself (without also taking estrogen’s “counter-balancing antagonist” progesterone). Research has shown that estrogen has a stimulating effect on endometrial cells in the uterus which can increase the risk for endometrial cancer. For this reason, women having a uterus should always pair estrogen HRT with progesterone.

Estrogen HRT without taking progesterone can also result in estrogen dominance. Estrogen dominance is when our bodies have too much estrogen compared to the amount of progesterone. It is a common issue, usually caused by the steep decline in progesterone that occurs as we age (think back on the earlier graphic), but magnified by our exposure to estrogen mimickers (also called endocrine disruptors, these are toxins we are exposed to in our meat, environment and even our skincare!)  Estrogen dominance can occur even when estrogen levels are low if progesterone levels are lower. Having a poor detox/elimination system (due to poor diet, being a poor methylator, dehydration, etc.) can cause hormones such as estrogen to be recycled versus eliminated, which can become very toxic. (I discuss this in more detail in Chapter 7 of my book, The Hormone Fix). We’ll talk more about how important these types of other factors are relating to the effectiveness and health risks of taking HRT. Simple lifestyle interventions can help.

I always say, “What doesn’t progesterone do for us?”

It is good for our brain, our heart, our breasts and our bones. It is anti-inflammatory and a natural diuretic (which can help flush out all of that harmful recycling estrogen). It is helpful for our moods (it makes more GABA available, which is our calming neurotransmitter). It can help us get more sleep. Research has shown it can help with anxiety and hot flashes. 

We have progesterone receptors all over our body. Progesterone is my favorite hormone…well, except maybe for oxytocin. 

If we still have a uterus progesterone can help stabilize the endometrium (uterine lining). In this way, progesterone suppresses the direct cell stimulating action of estrogen in the uterus, helping to maintain a healthy balance and offering protection against the development of endometrial cancer of the uterus in women undergoing estrogen HRT.

But progesterone is important even for women who no longer have a uterus. There are just so many important health benefits associated with it.

Use of progesterone has been linked to:

• Lower rates of uterine and colon cancers 
• May be helpful in treating other cancers such as melanoma, ovarian, mesothelioma, and prostate
• Being preventative and protective of breast cancer. (4)  

Progesterone is also important as it provides neuroprotective effects.

It may be helpful in treating – and perhaps preventing - neurodegenerative conditions such as traumatic brain injury and stroke. We’ve got progesterone receptors within our brain. Lots of great research relating to the use of progesterone and improved memory. When I’ve had women, even those who have had their uterus removed and are only on estrogen, start using bio-identical progesterone they consistently report back to me, “I feel like the fog has lifted.” 

So you see, 

EVEN IF WE NO LONGER HAVE A UTERUS WE CAN STILL BENEFIT GREATLY FROM PROGESTERONE!!  

And while I am not focusing on fertility issues in this article, progesterone can be a major player in addressing a number of fertility challenges as well (the word progesterone actually comes from the word progestational, meaning proceeding pregnancy; it prepares the endometrium for implantation and helps maintain a healthy pregnancy). 

Androgens are muscle and bone-building hormones, and have been found to support a healthy libido as well. In my years of prescribing bio-identical hormones I often combined one of these important androgens into a patient’s prescription with beautiful results.

Though any hormone (thyroid, insulin, etc.) can be made to be “bio-identical,” the term is most often used to describe formulations containing estrogen, progesterone, and androgens.

Bio-identical hormones have a molecular structure identical to that of the same hormone found in the human body. Because they are the same they fit into receptor sites just as if they were hormones made in the body. Bio-identical hormones are made from plant chemicals extracted from yams and soy.

Contrast this to the traditional HRT that is more apt to be prescribed today, which is a synthetic hormone. All synthetic hormones have a molecular structure that is different than that same type of hormone in the body. They may bind to receptor sites in a different way than the bio-identical hormone would.

Different molecular structure results in slightly different actions on the body.

Now you might wonder why pharmaceutical companies wouldn’t have just produced all bio-identical hormones to begin with, right? Well…that’s up to interpretation, but many of my peers feel it comes down to something as simple as their not being able to patent something that is basically found in nature/the body. Synthetic prescriptions are patentable.

The FDA hasn’t yet approved many of the bio-identical hormone preparations that are routinely prescribed. This is due to the fact that most functional medicine and regenerative medicine physicians (like me) don’t just prescribe off-the-shelf (referred to as “commercial”) bio-identical prescriptions for our patients or clients. We usually customize bio-identical prescription using compounding pharmacies.

In my experience there is literally an “art” to fine-tuning just the right “mix” of hormones for a given woman and her given set of symptoms and concerns; so most of us have compounding pharmacies prepare hormones just for a given individual according to our specifications. 

The underlying bio-identical hormones used by compounding pharmacies as well as what is available by routine prescriptions are identical to each of their respective hormones in the body, but we may change up the dose as well as mix multiple hormones together. There may also be different delivery mechanisms we choose to use for a particular woman, whether that be oral (tablet, capsule or troches), transdermal (gels, creams, patches), vaginal, etc.

So as an example, we might prescribe a certain dose of bio-identical progesterone along with bio-identical testosterone, in a transdermal cream or vaginal tablet. For two different women we may choose different dosages or delivery mechanisms.  We often won’t use the FDA approved product - even if a bio-identical product is available - as it may be “commercially” available only in specific doses, let’s say in a 5 or 10 mg tablent (and we might want 7 mg for our patient). Or it may only come in a tablet and we want it to be delivered via a cream..

The FDA doesn’t like compounded solutions. They say that they don’t have an easy way to monitor all of the thousands of compounding pharmacies in the country who are doing this type of customization. To me, however, each physician prescribing these types of medications is taking on the important role of monitoring quality themselves!  I, as an example, always worked with the same handful of compounding pharmacies that I knew to maintain the utmost quality and safety.

To tailor the ideal prescription for any given individual, practitioners will look carefully at multiple labs, but perhaps as important we will look at the individual patient’s clinical history, symptoms and our own clinical evaluations. I think the best way to think about prescribing compounded HRT is that it is not one-size-fits-all!

Did I say this was confusing? And we haven’t even gotten into the controversy yet!

It is hard to find numbers on this, but I’ve seen estimates that say that between 1 million to 2.5 million women in the US (aged 40 or older) use compounded bio-identical hormones, with this number representing between 28% to 68% of all HRT prescriptions filled annually. (5) The North American Menopause Society (NAMS) reports that about 1.4 million women are using compounded bio-identical treatment or approximately 40% of all prescriptions for hormone therapy in women who are in menopause. (6) 

So clearly synthetic hormones are still the most commonly used for HRT (at least in the US) although bio-identical usage has been growing given all of the research that has come out with negative health findings relating to synthetic HRT offerings.

Before I get into more details on those negative health findings, I thought it would be helpful to list at least some of the commonly used bio-identical preparations available as well as synthetic offerings. It is good for women to recognize the common names. Note that this is not an exhaustive list and you’ll want to discuss the best alternatives for your use with your doctor.

Remember these can be “commercial”/ off-the-shelf or compounded. **** means the specific examples are FDA approved as a “commercial” off-the-shelf product (with specific available dosages and delivery mechanisms, and not as a compounded prescription).

• 17-Beta estradiol, estradiol vaginal products (Estrace, Estring, Vagifem) **** all are FDA approved
• 17-Beta estradiol transdermal patches (Estraderm****, FemPatch, Vivelle)
• 17-Beta estradiol (Climara, Alora, Esclim) **** all are FDA approved
• Estradiol transdermal spray (Evamist) ****
• Estriol cream (Estriol)
• Estrone sulfate – Note that estrone is the major circulating estrogen in postmenopausal women and has been associated with promoting estrogen-receptor positive (ER+) breast tumor growth and proliferation. (7) 
• Progesterone (Prometrium) **** this is in a peanut oil capsule so some may have allergy
• Progesterone vaginal gel (Crinone) ****
• Micronized progesterone (Progesterone) available through compounding in various forms (transdermal creams, capsules, troches, and vaginal suppositories). Dr. Lee likes these and I use a transdermal progesterone myself, along with my Balance cream, which is a lovely formulation of bio-available progesterone and pregnenolone.
• Combinations of estradiol and progesterone in compounded formulations as above. The most popular and commonly prescribed compounded formulations in the US have been Bi-est and Tri-est. Bi-est is a 20% 17-Beta estradiol and 80% estriol combination, and Tri-est is similarly formed from 10% estrone, 10% 17-Beta estradiol, and 80% estriol. (I no longer recommend this due to estrone concerns).
• Testosterone (Testosterone)
• DHEA (DHEA is one of the synergistic ingredients I use in Julva®, the anti-aging cream for the vulva that I created to help women) 

The FDA has also approved a number of combination (estrogen/progestin) products but as these contain synthetic progestin I do not recommend them.

In 1978 the idea of adding progestin (remember, this is synthetic) along with estrogen, to deal with estrogen related uterine cancer risks, was proposed as a safe solution.

But in the early 80’s and 90’s questions started surfacing relating to the safety and side effects associated with synthetic progestin (including breast tissue changes, cardiovascular risks, and other adverse metabolism effects). Bio-identical progesterone was proposed as an alternative.

There were more and more studies comparing synthetics to bio-identical by this time. One in particular compared synthetic estrogen (from pregnant horse urine) and progestin to bio-identical estrogen (estradiol) and progesterone. This study by Foidart and team found that use of the bio-identical hormones had less negative effects on breast tissue relating to cancer cell growth. There were many more studies as well, all pointing to less health risks being associated with bio-identical hormones, as well as their having the ability to resolve symptoms of menopause.

During this time large-scale studies were conducted in Europe focused on the use of bio-identical hormones (bio-identical hormone replacement is the primary therapy used by menopausal women in Europe) that also repeatedly showed both the elimination of menopausal symptoms as well as a lack of any long-term negative side effects.

In 1994 the infamous Women’s Health Initiative (WHI) began. This was conducted by the National Institutes of Health and was a controlled, large-scale study involving some 161,809 postmenopausal women aged 50 to 79 years. They were enrolled in a set of clinical trials designed to investigate the use of HRT, low-fat diet, and calcium plus vitamin D supplementation to prevent stokes, heart disease, breast cancer, colorectal cancer, and fractures in postmenopausal women (osteoporosis).Physicians had observed positive effects relating to all of these while prescribing HRT to their patients, but there was no specific data from an actual randomized clinical study to validate these observations.

In the WHI study there were no bio-identical hormones tested. This is important to understand, along with the fact that it was focused on an older population of women.

The study looked solely at Premarin (synthetic estrogen using pregnant horse urine estrogen) and Provera (synthetic progestin), sold under the brand name Prempro.

The WHI study was halted in 2002 because interim findings were showing an increased risk of stroke, myocardial infarction, and breast cancer with the use of Prempro.

Results of the WHI study showed that women who had received the synthetic estrogen/progestin combination were found to have:

•  A 26% increased risk of breast cancer
• A 29% increased risk of myocardial infarction or death from cardiovascular disease
• A 200% increased risk of venous thrombotic disease/embolism, deep vein thrombosis, and pulmonary embolism!
• But…also a 33% decreased risk of hip fracture
• A 37% decreased risk of colorectal cancer
• A reduction in menopausal symptoms

There was no increased risk of breast cancer found in those receiving estrogen alone.

Additionally in a secondary study, the results of which were published in 2003, the Women's Health Initiative Memory Study, or WHIMS, revealed that women aged 65 years or older who received the same combination of Prempro (synthetic estrogen and synthetic progestins) were at double the risk of dementia compared with their non–hormone-taking peers. (11) 

Women and doctors everywhere jumped off the hormone replacement therapy bandwagon at the time.

But the risks seen with the use of synthetic (pregnant horse urine estrogen) estrogen and progestin, such as increased risk of breast cancer and cardiovascular issues have not been seen with the use of bio-identical hormones in other studies.

Many studies have confirmed the safety and effectiveness of bio-identical hormones. One example is a large French study (Fournier) which looked at breast cancer risk factors in over 80,000 women. That study’s conclusion was that micronized progesterone, compared to synthetic progestin treatment, was associated with significantly lower breast cancer risks. (12) 

Much of the above can be found in a comprehensive 2009 summary review of published studies  on the topic.This review concluded with the recommendation that “bio-identical hormones remain the preferred method of HRT.” (13) There have been other more recent reviews as well.