Getting the Most Out of BHRT
By Jonathan Wright, M.D.
It’s Simple Really: Just Follow Mother Nature’s Hormone Recipe
Many doctors and patients think they are using genuine BHRT just by taking pills containing bio-identical estradiol and progesterone. Although estradiol is the primary estrogen produced by the premenopausal ovary, normal metabolic processes eventually result in three primary circulating estrogens: estriol, estradiol, and estrone.
Estradiol is the most potent and most carcinogenic of these and also comprises less than 10% of the total circulating estrogen. When women “replace” deficient ovarian hormones with 100% estradiol, they can distort the natural balance of circulating estrogens, and there’s no guarantee that their natural metabolic processes will produce sufficient estriol to counteract the inherent carcinogenicity of estradiol and the estrone, which the body does form from estradiol.
In true BHRT, potentially carcinogenic estradiol – in its natural physiologic proportions (10% or less) – is balanced by relatively high doses of the more benign, anti-carcinogenic estriol, which inhibits its intrinsic carcinogenic actions. In order to best approximate the natural premenopausal hormonal environment, it’s best to take estradiol and estriol, and occasionally estrone.
Conventional HRT: At Odds with Nature
Contrary to most conventional doctors’ erroneous belief, safe and effective use of BHRT demands a philosophical approach to medicine that is probably alien to what they have been taught throughout their entire careers. The key misconception was clearly expressed by the author of a review of “hormone” replacement regimens: “The aim of any [conventional] hormonal treatment of postmenopausal women is not to restore the physiological serum levels occurring in ovulatory cycles of fertile women, but to prevent or improve complaints and symptoms caused by estrogen deficiency.” (Italics added)
That pretty much says it all. The conventional medical approach – see a symptom, suppress a symptom with a patented drug – is at odds with Nature and completely inappropriate for BHRT. In the conventional view, whatever might be causing those symptoms is typically of secondary concern; as long as the treatment works and is not too toxic, it is deemed acceptable. The way the FDA’s drug approval process is structured, the treatment need not be better or safer than a natural or bio-identical alternative; it only needs to be more efficacious at removing said complaints and symptoms and not significantly more toxic than an inactive dummy drug, or placebo, the proverbial “sugar pill” (although they’re usually not made of sugar any more).
Rather than merely suppressing hot flushes using any patent medicine or pseudo-hormone that seems to work, the primary goal of BHRT is to restore a hormonal environment as close to the natural, premenopausal state as possible.
BHRT requires that we follow the hormonal recipe Mother Nature has worked out over millions of years of evolution in the human female. The closer that recipe is followed, the happier and healthier you will be. If symptoms are caused by an imbalance in a complex, integrated physiologic system, like the one that controls sex steroid secretion and activity, rather than ignoring and/or overriding that control – as conventional treatments almost always do – natural medicine aims to restore the natural balance of hormones to which the body is accustomed.
Since menopausal complaints and symptoms are largely a result of a “hormone deficiency,” once that deficiency is resolved by replacing the deficient hormones with bio-identical copies, the complaints and symptoms generally go away of their own accord. There is no need to suppress them artificially. This may seem like a subtle distinction, but when it comes to the overall health of women using hormone replacement, it makes all the difference in the world.
Maximizing the value of BHRT requires that doctors have a real appreciation of the way these hormones are metabolized and how much the body actually needs and can safely handle at any one time. Using too little may yield unsatisfactory results, while using too much may carry unacceptable risks. In this regard, what often gets lost in the translation from conventional HRT to BHRT is any serious attention to the dose, timing, route of administration, and metabolic processing of the replacement hormones.
If BHRT has any disadvantages, it is that it asks women to do more than just pop a pill every morning. It also requires doctors to pay close attention to their patients’ doses and hormone levels, and to make sure those hormones are safely metabolized.
Thirty years of experience with BHRT have taught us that close attention to these and other factors is essential if women are to achieve the highest degrees of safety and effectiveness from BHRT. Proper use of BHRT demands:
- The correct mix of human bio-identical hormones
- The optimal amount of each hormone
- Taking hormones by the safest, most natural route
- Approximating the natural timing of hormone secretion
- Close monitoring levels of hormones and metabolites for safety
What’s the Best Way to Take Bio-Identical Hormones?
You can take bio-identical hormones via one of several routes:
- Oral capsules. Nothing unusual here. Like most patented medicines and nutritional supplements, just swallow compounded bio-identical hormone capsules and the body does the rest, although as we shall see, not always for the best. Oral administration of steroid hormones has distinct disadvantages, as discussed below.
- Creams or gels. You can rub hormone-containing creams or gels into your skin (transdermal), or preferably your vaginal mucosa or labia (transmucosal or transvaginal). Based on more than 25 years of personal experience at the Tahoma Clinic, we have found these topical methods (especially transmucosal) to be the preferred ways of using bio-identical hormones, especially if they are personally formulated by a compounding pharmacist.
- You insert the hormone, formed into a suppository by a compounding pharmacist, either in the vagina or the rectum for rapid transmucosal absorption.
- Lozenges (troches). You allow the hormone-containing lozenge to dissolve in your mouth, but try not to swallow, so that a large portion of the hormones get absorbed directly into your blood stream through the mucous membranes that line your mouth. This method, which is technically considered to be a transmucosal method of administration, is designed to avoid having the hormones pass through the gastrointestinal (GI) tract. The problem is that, due to normal saliva formation, it can be hard not to swallow and usually 50% or more of the hormone winds up getting into your GI tract anyway.
- Sublingual (under-the-tongue) drops. The same logic as lozenges.
Oral administration works reasonably well for some drugs and nutritional supplements, but for replacement of sex steroids, oral administration can seriously detract from their optimal use. In fact, oral administration of steroid hormones is Exhibit A when it comes to demonstrating how profitability trumps safety and efficacy. To prove our point that taking sex steroids by mouth may not be the best idea, all we have to do is look again at the way the human body is designed.
Running the GI-Liver Gauntlet
Now, if Mother Nature had only thought to locate the ovaries in the stomach or some other part of the gastrointestinal (GI) tract, it might make sense for women to take their hormone replacements by mouth. With ovaries inside the GI tract, the body would certainly have evolved a way to process them safely and efficiently so that everything worked out the way it was supposed to.
Of course, the ovaries are not inside the GI tract; they’re located in the pelvic region of the lower abdomen, outside the GI tract, and connected to the uterus and vagina via the fallopian tubes. In this location, the ovaries have direct access to the circulatory system via a pelvic plexus of veins, which delivers their hormone secretions to estrogen-, progesterone-, and testosterone-sensitive cells all over the body.
Viewed from this perspective, taking hormones by mouth is just about the most unnatural way imaginable for sex steroids to gain entry to the body. In fact, simulating ovarian hormone secretion by delivering bio-identical hormones in physiologic amounts directly into the bloodstream is a lot simpler than we might imagine.
Hormones, carefully measured and formulated in an appropriate cream or gel, need only be rubbed once or twice a day into the skin, or preferably, mucous (epithelial) membranes, especially those that line the labia or vagina. The hormones diffuse through the skin or epithelial tissue and pass easily and directly into the bloodstream. With no destructive detours through the GI tract and liver, bio-identical estrogens and progesterone applied topically enter the blood stream metabolically unchanged. When you apply estrogen, progesterone, and testosterone topically it is estrogen, progesterone, and testosterone that go into your blood stream. Admittedly, this may take a little more effort than popping a pill in the morning, but the advantages are substantial!
Intravaginal Dosing Avoids “Dermal Absorption Fatigue”
Experience has shown us that intravaginal application offers more than merely theoretical advantages. At the Tahoma Clinic, we monitor the 24-hour urinary hormone levels of women using BHRT at regular intervals to make certain their levels are within their individual physiologic “target range.” Over several years, this monitoring has shown us that, in many women using transdermal estrogen preparations, urinary estrogen levels begin to decline progressively, suggesting that they are absorbing less and less estrogen through their skin as time goes by.
However, we have found that when we switch the route of administration from transdermal to transvaginal – without altering the dose – their urinary levels rise right back up to their target range, and any symptoms of low estrogen they might have been experiencing quickly disappear.
We attribute this loss of effect of transdermal administration to a factor we term “dermal absorption fatigue:” repeated transdermal applications over many months seem to cause the skin to lose some of its ability to transport the hormones into the blood stream. Why this happens remains a mystery, but we know it does, and we know that switching to intravaginal dosing avoids it.
Progesterone: Never Take Estrogen without It
Quantities of topical progesterone, can vary from 25 to 30 milligrams (after menopause) and up to 50 to 100 milligrams (during the menopausal transition), depending on each woman’s age and response. Progesterone is typically started on days 10 to 15 of the cycle and continued through day 25, as noted below.
DHEA: Help Restore Testosterone Levels
DHEA (dehydroepiandrosterone) is an androgen secreted by the adrenal glands. Like testosterone, DHEA levels decline with age, so most women of menopausal age (or even younger) would do well to replace this hormone, too. It is my observation that DHEA replacement is essential for maintaining optimum immune function and for helping to reduce the risk of cancer.
A daily schedule is recommended when replacing DHEA, because the adrenals secrete DHEA daily (not cyclically, like estrogen and progesterone). Since women’s bodies metabolize DHEA into testosterone, I frequently delay testosterone replacement until tests show whether DHEA is restoring their testosterone levels to normal. A reasonable, conservative starting dose of DHEA for most women is 15 milligrams per day, although for a few women, follow-up testing may indicate that the daily dose needs to be raised to 30 milligrams.
Like progesterone, OTC versions of DHEA are also available. However, these are presently all oral capsules. Continuing clinical observation is persuading me that the transdermal or transmucosal route is best for all steroid hormones, even DHEA. I write prescriptions for topical DHEA, both because I have a greater trust in the standard material available through compounding pharmacists, and because, at present no OTC topical DHEA products are available.
Testosterone: Women Need it too, but at Much Lower Doses
If testing shows that a woman’s DHEA is not getting metabolized to produce sufficient testosterone, she can also take testosterone (at an average dose of 5‑10 milligrams daily). It’s very important to remember that women require a fraction of the testosterone that men do. Thus, patented products containing bio-identical testosterone – patches or gels – designed for men are completely inappropriate – and dangerous – for women. The only option for women at the present time is testosterone formulated by a compounding pharmacist.
A good starting topical dose for women is 2.5 milligrams per day. A woman’s body will metabolize much of this testosterone into estrogens, so follow-up testing is mandatory to be sure that levels of both hormones are “just right” – neither too high nor too low.
Timing Hormone Replacement According to Nature’s Clock
Women who use conventional HRT are given all sorts of misinformation about the “hormones” they are taking, including when to take them. Here are a few examples that I’ve heard over the years:
- “My doctor told me to take Premarin® and Provera® on weekdays and not on weekends.”
- “I just take Premarin® every day, no pauses.”
- “I’ve used the ‘estrogen patch’ every few days for the last year or more.”
- “My doctor says my uterus is gone [surgically removed], so cycling hormones isn’t important anymore.”
We all know that Nature works in cycles. Ovaries don’t secrete estrogens, progesterone, and testosterone on weekdays, but take the weekends off; nor do they secrete hormones continuously for months or years without ever pausing.
When a woman starts BHRT, we try to mimic as closely as possible the timing of the full menstrual cycles she experienced during her earlier years. Of course, as every woman knows, “period” length varies from one woman to another; for some the typical period may be 26 days, for others 32. We ask her to think back to her early 30s, while her periods were still regular, and tell us approximately how long they were. We then use that number of days as a starting point to modify the schedule shown in Figure 9-6. However, many women find it simpler and more practical to work with a “regular” 30-day calendar.
Since she is no longer menstruating, the date she chooses to start her BHRT cycle is arbitrary. Her job is to keep track of the days she starts and stops each hormone. She can do this by crossing off days on a calendar or any other method she might find convenient. The exact pattern should always be specified by the pharmacist right on the prescription.
While estrogen cycling is pretty straightforward, the pattern for progesterone can be a bit more complicated. This is because progesterone’s functions (despite what conventional medicine preaches) go beyond merely “opposing” estrogen activities. In addition to its role in the menstrual cycle, the body uses some progesterone as the basis for making a whole other class of steroids that include cortisone, aldosterone, and many others. So when progesterone production drops, so does the production of these other important hormones.
Although our basic schedule calls for adding progesterone midway through the “cycle,” some women find they feel much better with continuous progesterone. For these women, we have found that we can modify their regimen by adding a small amount of progesterone (e.g., 10-20 milligrams per day), depending on whether she is having a “bleeding cycle” or not. The highest daily dose of progesterone – about 25 to 50 milligrams – should be used during the “luteal phase” (Days 12-25 in Fig. 9-6). If she needs to use it the rest of the month, a “step-down” dose of about 10 milligrams per day should be adequate.
Are Monthly Menstrual Periods Really Necessary? Are They Desirable?
An important principle of natural medicine is to prescribe the least amount of a substance necessary to do the job. Following this principle, many practitioners of natural medicine (including myself) recommend sufficient hormones to eliminate menopausal symptoms and to provide protection against osteoporosis, heart and blood vessel disease, senile dementia and Alzheimer’s disease, but not enough to induce a monthly menstrual period.
Some proponents of BHRT advocate taking high doses of estradiol in order to induce a monthly “menstrual period” (with no ovulation, of course). They claim that this assures that the body is getting enough estrogen to provide its other benefits, that it is advantageous to “flush” the uterus on a regular basis, and that it may also help women feel more “youthful.”
The only research on this topic so far failed to support any health value of inducing a monthly period in postmenopausal women. A five-year study (during which routine endometrial biopsies were done to look for cancer cells) of women using estrogen and progesterone on a cyclic basis found no cancer cells in either the women who had monthly bleeding or those who did not .
Monitoring Hormone Levels for Safety Saliva, Blood, or Urine Testing?
Saliva Testing: Inexpensive, Convenient, and Highly Unreliable
Saliva tests are commonly available by mail order, through some compounding pharmacies, or some physicians. In the basic saliva test, you fill a small bottle with saliva, seal it and send it off to a laboratory for testing, and the results are sent to your doctor. The primary advantage of saliva tests for hormone levels is that they are relatively inexpensive, noninvasive, and convenient, because they can be done from home without having to go to a doctor’s office or lab.
On the other hand, you get what you pay for. Saliva testing may provide some useful information about sex steroid levels for younger women who are not using BHRT, but of the three major test modalities, it is certainly the least reliable.
Let’s get one important point about saliva testing out of the way right now. Saliva testing is not useful for women on BHRT, because it is very likely to indicate “sky high” hormone levels that bear no relation to their actual physiologic levels and may falsely suggest a hormone overdose.
Blood Testing: Sometimes Useful but Difficult to Interpret
We’ve all had blood tests, and the procedure for hormone blood tests is no different. Blood tests can measure levels of total estradiol, estrone, progesterone, testosterone, and DHEA in serum (the liquid portion of blood); they can be relatively accurate for women whether or not they are on BHRT. However, interpretation of hormone levels based on blood tests must be done carefully, because levels may vary depending on the timing of the test.
After menopause, women usually take their replacement hormones once or twice a day. Either way, the hormones do not circulate throughout your body at steady levels (unless you’re using a “patch”). Thus, the results of a blood test will depend on when you took your replacement hormones relative to the time your blood was drawn. Blood tests are also can’t even find the important anti-carcinogenic estriol, which is always present in urine in pre-menopausal women, and most frequently in amounts greater than estradiol or estrone. One researcher found that estriol gets “cleared” from the blood very rapidly, within a few minutes to slightly over an hour.
24-Hour Urine Testing: The “Gold Standard”
Because sex steroids are excreted in the urine, urine collection is without doubt the oldest and most reliable method of collecting steroid hormones, dating back thousands of years to Chinese emperors, not to mention still serving as the source for Premarin®. Although conventional doctors rarely use urine assays for measuring steroid hormones, they have known about their advantages for decades. According to one standard medical textbook, “Urinary assays are considered to reflect the secretory activity of the endocrine glands … [and] to provide clinical information that can reflect the production rates of these steroids.”
Unlike the small urine sample most of us are used to giving for a typical urinalysis, urine collected to measure hormone levels is collected over 24 consecutive hours in a large bottle. In other words, for one full day, you are asked to urinate into a bottle. Not only does this method even out all the peaks and valleys that complicate analysis of blood test results, it also facilitates the measurement of “unbound” (ie, “free”) levels of estradiol, estrone, estriol, progesterone, testosterone, and DHEA. Urine testing does not measure protein-bound hormones, which comprise the largest portion of “total” hormone production but are functionally irrelevant.
Without a doubt, 24-hour urinary collection is the preferred method of measuring sex steroid hormone levels, the “gold standard.” Moreover, this method is accurate for all women, whether or not they are on BHRT, unlike saliva testing. In women just starting BHRT, we usually recommend a 24-hour urine test every 3 to 6 months, until acceptable, stable levels of all hormones are achieved.
24-Hour urine collections are also preferable for two other reasons. First, they give the careful physician so much more information, including whether the hormones taken as BHRT are getting metabolized to mostly “safe” metabolites including estriol (anti-carcinogenic), 2-methoxyestradiol (very, very anti-carcinogenic), and 4-hydroxyestrone (pro-carcinogenic). Second, the expense for capturing a 24-hour urine “picture” of 25 to 30 metabolites of the hormones administered as BHRT is very much lower than checking for all these metabolites in blood. In fact, as noted above, many of these metabolites can’t even be measured with standard blood tests.
This article is edited and adapted from Chapter 9 of ‘Stay Young and Sexy with Bio-Identical Hormones” (2010)
by Jonathan V. Wright M.D. and Lane Lenard Ph.D.