DR. JOHN R. LEE'S THREE RULES FOR HORMONE REPLACEMENT THERAPY
Use a sprinkle of common sense and a dash of logic.
by John R. Lee, M.D.
The recent Lancet publication of the Million Women Study (MWS)
removes any lingering doubt that theres something wrong with conventional
HRT (see Million Woman Study in the UK, Published in The Lancet, Gives New
Insight into HRT and Breast Cancer for details). Why
would supplemental estrogen and a progestin (e.g. not real progesterone)
increase a womans risk of breast cancer by 30 percent or more? Other
studies found that these same synthetic HRT hormones increase ones risk
of heart disease and blood clots (strokes), and do nothing to prevent
Alzheimers disease. When you pass through puberty and your sex hormones
surge, they dont make you sickthey cause your body to mature into
adulthood and be healthy. But, the hormones used in conventional HRT
are somehow not rightthey are killing women by the tens of thousands.
The question iswhere do we go from here? My answer iswe go
back to the basics and find out where our mistake is. I have some ideas on
Over the years I have adopted a simple set of three rules covering
hormone supplementation. When these rules are followed, women have a decreased
risk of breast cancer, heart attacks, or strokes. They are much less likely to
get fat, or have poor sleep, or short term memory loss, fibrocystic breasts,
mood disorders or libido problems. And the rules are not complicated.
Rule 1. Give hormones only to those who are truly deficient in them.
The first rule is common sense. We dont give insulin to someone
unless we have good evidence that they need it. The same is true of thyroid,
cortisol and all our hormones. Yet, conventional physicians routinely prescribe
estrogen or other sex hormones without ever testing for hormone deficiency.
Conventional medicine assumes that women after menopause are
estrogen-deficient. This assumption is false. Twenty-five years ago I reviewed
the literature on hormone levels before and after menopause, and all
authorities agreed that over two-thirds (66 percent) of women up to age 80
continue to make all the estrogen they need. Since then, the evidence has
become stronger. Even with ovaries removed, women make estrogen, primarily by
an aromatase enzyme in body fat and breasts that converts an adrenal hormone,
androstenedione, into estrone. Women with plenty of body fat may make more
estrogen after menopause than skinny women make before menopause.
Breast cancer specialists are so concerned about all the estrogen women
make after menopause that they now use drugs to block the aromatase enzyme.
Consider the irony: some conventional physicians are prescribing estrogens to
treat a presumed hormone deficiency in postmenopausal women, while others are
prescribing drugs that block estrogen production in postmenopausal women.
How does one determine if estrogen deficiency exists? Any woman still
having monthly periods has plenty of estrogen. Vaginal dryness and vaginal
mucosal atrophy, on the other hand, are clear signs of estrogen deficiency.
Lacking these signs, the best test is the saliva hormone assay. With new and
better technology, saliva hormone testing has become accurate and reliable. As
might be expected, we have learned that hormone levels differ between
individuals; what is normal for one person is not necessarily normal for
another. Further, one must be aware that hormones work within a complex network
of other hormones and metabolic mediators, something like different musicians
in an orchestra. To interpret a hormones level, one must consider not
only its absolute level but also its relative ratios with other hormones that
include not only estradiol, progesterone and testosterone, but cortisol and
thyroid as well.
For example, in healthy women without breast cancer, we find that the
saliva progesterone level routinely is 200 to 300 times greater than the saliva
estradiol level. In women with breast cancer, the saliva progesterone/estradiol
ratio is considerably less than 200 to 1. As more investigators become more
familiar with saliva hormone tests, I believe these various ratios will become
more and more useful in monitoring hormone supplements.
Serum or plasma blood tests for steroid hormones should be
abandonedthe results so obtained are essentially irrelevant. Steroid
hormones are extremely lipophilic (fat-loving) and are not soluble in serum.
Steroid hormones carry their message to cells by leaving the blood flow at
capillaries to enter cells where they bond with specific hormone receptors in
order to convey their message to the cells. These are called free
hormones. When eventually they circulate through the liver, they become
protein-bound (enveloped by specific globulins or albumin), a process that not
only seriously impedes their bioavailability but also makes them water soluble,
thus facilitating their excretion in urine. Measuring the concentration of
these non-bioavailable forms in urine or serum is irrelevant since it provides
no clue as to the concentration of the more clinically significant
free (bioavailable) hormone in the blood stream.
When circulating through saliva glands, the free
nonprotein-bound steroid hormone diffuses easily from blood capillaries
into the saliva gland and then into saliva. Protein-bound, non-bioavailable
hormones do not pass into or through the saliva gland. Thus, saliva testing is
far superior to serum or urine testing in measuring bioavailable hormone
Serum testing is fine for glucose and proteins but not for measuring
free steroid hormones. Fifty years of blood tests have
led to the great confusion that now befuddles conventional medicine in regard
to steroid hormone supplementation.
Rule 2. Use bioidentical hormones rather than synthetic hormones.
The second rule is also just common sense. The message of steroid
hormones to target tissue cells requires bonding of the hormone with specific
unique receptors in the cells. The bonding of a hormone to its receptor is
determined by its molecular configuration, like a key is for a lock. Synthetic
hormone molecules and molecules from different species (e.g. Premarin, which is
from horses) differ in molecular configuration from endogenous (made in the
body) hormones. From studies of petrochemical xenohormones, we learn that
substitute synthetic hormones differ in their activity at the receptor level.
In some cases, they will activate the receptor in a manner similar to the
natural hormone, but in other cases the synthetic hormone will have no effect
or will block the receptor completely. Thus, hormones that are not bioidentical
do not provide the same total physiologic activity as the hormones they are
intended to replace, and all will provoke undesirable side effects not found
with the human hormone. Human insulin, for example, is preferable to pig
insulin. Sex hormones identical to human (bioidentical) hormones have been
available for over 50 years.
Pharmaceutical companies, however, prefer synthetic hormones. Synthetic
hormones (not found in nature) can be patented, whereas real (natural,
bioidentical) hormones can not. Patented drugs are more profitable than
non-patented drugs. Sex hormone prescription sales have made billions of
dollars for pharmaceutical companies Thus is womens health sacrificed for
Rule 3. Use only in dosages that provide normal physiologic tissue
The third rule is a bit more complicated. Everyone would agree, I think,
that dosages of hormone supplements should restore normal physiologic levels.
The question ishow do you define normal physiologic levels? Hormones do
not work by just floating around in circulating blood; they work by slipping
out of blood capillaries to enter cells that have the proper receptors in them.
As explained above, protein-bound hormones are unable to leave blood vessels
and bond with intracellular receptors. They are non-bioavailable. But they are
water-soluble, and thus found in serum, whereas the free
bioavailable hormone is lipophilic and not water soluble, thus not likely to be
found in serum. Serum tests do not help you measure the free,
bioavailable form of the hormone. The answer is saliva testing.
It is quite simple to measure the change in saliva hormone levels when
hormone supplementation is given. If more physicians did that, they would find
that their usual estrogen dosages create estrogen levels 8 to 10 times greater
than found in normal healthy people, and that progesterone levels are not
raised by giving supplements of synthetic progestin such as medroxyprogesterone
Further, saliva levels (and not serum levels) of progesterone will
clearly demonstrate excellent absorption of progesterone from transdermal
creams. Transdermal progesterone enters the bloodstream fully bioavailable
(i.e., without being protein-bound). The progesterone increase is readily
apparent in saliva testing, whereas serum will show little or no change. In
fact, any rise of serum progesterone after transdermal progesterone dosing is
most often a sign of excessive progesterone dosage. Saliva testing helps
determine optimal dosages of supplemented steroid hormones, something that
serum testing cannot do.
It is important to note that conventional HRT violates all three of
these rules for rational use of supplemental steroid hormones.
A 10-year French study of HRT using a low-dose estradiol patch plus oral
progesterone shows no increased risk of breast cancer, strokes or heart
attacks. Hormone replacement therapy is a laudable goal, but it must be done
correctly. HRT based on correcting hormone deficiency and restoring proper
physiologic balanced tissue levels, is proposed as a more sane, successful and
Hormone imbalance is not the only cause of breast cancer, strokes, and
heart attacks. Other risk factors of importance include the following:
- Poor diet (excess sugar and refined starches, trans fatty acids, lack
of needed nutrients such as omega-3 fats, full range of essential amino acids,
vitamins, minerals, etc.)
- Environmental xenoestrogens and hormones not removed by water
treatment. (Be sure that your home water filter will remove hormones.).
- Insulin resistance.
- Lifestyle problems such as excess light at night (poor sleep,
melatonin deficiency), alcohol, cadmium (cigarette smoking), and birth control
pills during early teens.
Men share these risks equally with women. Hormone imbalance and exposure
to these risk factors in men leads to earlier heart attacks, lower sperm counts
and higher prostate cancer risk.
Conventional hormone replacement therapy (HRT) composed of either
estrone or estradiol, with or without progestins (excluding progesterone)
carries an unacceptable risk of breast cancer, heart attacks and strokes. I
propose a more rational HRT using bioidentical hormones in dosages based on
true needs as determined by saliva testing. In addition to proper hormone
balancing, other important risk factors are described, all of which are
potentially correctable. Combining hormone balancing with correction of other
environmental and lifestyle factors is our best hope for reducing the present
risks of breast cancer, strokes and heart attacks.
A much broader discussion of all these factors can be found in the updated and revised edition of
What Your Doctor May Not Tell
You About Menopause and
What Your Doctor May Not Tell
You About Breast Cancer.