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Two-thirds of the
citizens of this country are obese. By
now that’s not exactly exciting news.
What is news are the new ways of looking at this problem.
Obesity
brings with it a host of health issues.
Excess weight can have serious implications on health. Excess weight increases the risk of high
cholesterol, hypertension, and insulin resistance leading to Type II
diabetes. There are cardiovascular
problems, respiratory problems, musculoskeletal problems, gastroesophageal
reflux disease, urinary problems, venous stasis disease, and gallbladder
disease.
There is also
evidence that weight gain increases the risk of certain types of cancer. Women who gain 21 to 30 pounds after the age
of 18 are 40 percent more likely to experience breast cancer. Raise that weight gain to 70 pounds and the
risk doubles. Men who gain excessive
amounts of weight are more likely to get prostate cancer. The risk of colon cancer goes up.
Abdominal obesity, the most common kind, is
an independent predictor of type 2 diabetes, dyslipidemia, hypertension,
cancer, and cardiovascular disease.
There is also the
intangible factor of what has been termed “Quality of Life.” Because the obese are unable to move around
as freely and be as active as they might wish to be they are often aware of
their obesity as a social issue. There
is, in other words, a significant deterioration of quality of life.
ETIOLOGY OF OBESITY
Obviously there is no one cause of
obesity. Lifelong obesity is usually due
to poor eating habits, excessive calorie intake, and a low exercise level.
Genetic factors
may play a role in obesity occurring later in life. Also significant are changes in lifestyle
with advancing years such as a decrease in activities, a decrease in
exercising, and a tendency to eat more. For every 5 years we age after 30 we need to
eat 50 calories less per day. So by age 60, all things being equal, we need
about 300 fewer calories per day than at age 30. Overeating by 300 cal per day can result in a
weight gain per year of 30 pounds.
WHY HORMONES SHOULD BE
CONSIDERED
When you speak about hormone replacement the
usual assumption is you are speaking about the replacement of estrogen and
progesterone. Actually there is an
entire litany of hormones that decrease with age.
The human endocrine system is comprised of more
than a score of hormones including thyroid, dehydroepiandrosterone, or DHEA, insulin,
cortisol, parathyroid, melatonin, and of course, all of the hormones that are
secreted by the pituitary. Many of those hormones have fat regulatory
functions and should absolutely be considered when we speak about “hormone
replacement therapy for weight management.”
THYROID
One of the key hormones that should be
evaluated in older patients is thyroid.
Thyroid hormone has an effect on lipid metabolism, stimulating fat
mobilization. Thyroid hormones stimulate
almost all aspects of carbohydrate metabolism, including enhancement of
insulin-dependent entry of glucose into cells.
Thyroid hormone also has an effect on the Leydig cells in the testicles, the prime source of testosterone in men.
Thyroid begins to drop in the mid 30’s and
that drop is often seen as subclinical hypothyroidism.
DHEA
DHEA was the first of the anti-aging
hormones described about 30 years ago.
Produced by the adrenal glands, it is also one of the most abundant
steroids in the human body and is a precursor to estrogen and testosterone.
Some sources state it is the only substance that can lower fat in the
body without a change in diet and it has been shown to build muscle mass.
Beginning in the late 20’s, DHEA begins to
drop until in the 90’s it is almost at zero.
Recent research has begun to connect the dots and tie the loss of DHEA
to the adverse consequences of aging.
TESTOSTERONE
Testosterone in men plays a key role in
almost everything. Testosterone
builds emotional well-being and self-confidence. It affects fat, fitness, and
strength. It governs mood, and plays a
part in how aggressive a man feels.
Testosterone
levels begin to decline slowly but surely with the onset of middle age. The testes (the place where most
testosterone is made) are less responsive to hormones that control testosterone
production. To make matters worse, "free" testosterone - the kind
that's most biologically active - declines to an even greater extent.
Since
testosterone plays a vital role in muscle growth, most aging men find it increasingly
difficult just to maintain muscle mass, let alone increase it. Even worse, low testosterone levels make it
more likely that fat will accumulate. Research from the University of Washington,
for example, shows a link between low testosterone levels and abdominal fat.
Low
testosterone in men may lead to sleep disturbances, sweats, depression,
impaired thinking, lower bone mass, decreased bone strength, and fatigue. Some
signs are more subtle. Decreases in sex drive, energy, motivation, initiative,
aggressiveness and self-confidence are other signals.
Stress
can also cause men of any age to experience a drop in testosterone levels. The inability to handle stress, I might add,
is cited by Perricone, in his newest book, as being the single biggest negative
influence on health.
Not
only does it affect the way a man looks, testosterone also affects the way he
feels. Because the human brain is filled with testosterone receptors (the parts
of the brain that respond to testosterone), your is affected if testosterone
levels drop too low.
Termed
by some "irritable male
syndrome," low testosterone levels might explain why some men become
grumpy and irritable the older they get.
In women, testosterone effects libido,
muscle mass, bone strength, and mood.
And don’t overlook its effects on well-being.
HORMONES IN WOMEN
There is a large
body of evidence that, in women as well as men, much of the responsibility for
increased weight in women later in life can be attributed to hormone
imbalance.
THE MENSTRUAL CYCLE
During the so-called child-bearing years a
woman’s body produces estrogen, progesterone, and testosterone.
ESTROGEN
Estrogen is actually an inclusive name for
three estrogens produced in the body—E1, or Estrone, E2, or Estradiol, and E3,
or Estriol. We will speak more of
Estriol later.
For purposes of consistency we speak of a
menstrual cycle as going from the onset of menses to the onset of menses. The “average” length of a cycle is 28 days
but it can vary from 21 to 45 days.
The ovaries produce estrogen at a relatively
constant rate from the time of puberty until the ovaries stop functioning at
the menopause.
Estrogen has far-reaching effects on the
brain, bone, heart, liver, uterus, vagina, and skin.
PROGESTERONE
Progesterone only enters the picture after
ovulation when it is released from the corpus luteum. If ovulation does not occur, no progesterone
is formed.
Progesterone helps to balance blood sugar
levels, facilitates fat metabolism, stimulates osteoblast formation and bone
growth, potentiates estrogen by increasing the sensitivity of estrogen
receptors, assists in thyroid function, and helps to maintain normal cell
membrane function.
WHEN THE SYSTEM BREAKS DOWN
Ovulation is, at best, a hit or miss
proposition with women only ovulating about 10 or so months out of each
calendar year. The body, however,
behaves as if ovulation happened every month.
As the ovaries become older more ovulation opportunities are missed with
the result that progesterone is significantly depleted leading to many of the
symptoms of the perimenopause and of progesterone deprivation.
At menopause most, but not all of the
estrogen production falls. What remains
comes from fat cells, the adrenal gland, and a small amount from the
ovaries. Progesterone falls to zero.
More often than not menstrual periods do not
abruptly cease. Many women will
experience a variable period of time during which menses are irregular, a time
known as the perimenopause or more popularly now as the pre-menopause.
Perimenopause can begin
as early as the 30’s or as late as the 50’s and the irregular menses often do
not stop until menopause. The
perimenopause is the time that hormones are fluctuating, typically with a drop
of progesterone associated with irregular ovulation.
Most of the data indicate that the weight
gain actually begins in the perimenopause.
Some investigators have documented a weight gain of one pound per year
during this critical time. An article in
the Annals of Internal Medicine in 1995 concluded that women who have undergone
menopause have higher levels of body fat and more central fat distribution than
age-matched controls.
The thinking is
that with ovarian failure at the menopause, estrogen decreases. Because a specific estrogen, estrone, is
manufactured and can be stored in fat cells, the body responds to the decrease
in estrogen by increasing the number of fat cells in an attempt to punch up the
estrogen levels.
TESTOSTERONE
Testosterone is normally produced in a
woman’s body by the ovaries and the adrenal glands in about equal amounts. In women, testosterone helps maintain muscle
and bone mass and contributes to the libido.
When the ovaries stop functioning at the menopause, half of the
testosterone is gone. The half that is
produced by the adrenal glands decreases about one to two percent a year so by
the time a women is mid-fifties she has less than 25 percent of the
testosterone she had when she was younger.
In
the menopause, therefore, the patient is deficient in estrogen, progesterone,
and most likely, testosterone.
The
effects of dropping hormone levels with age are well-documented. If
you accept the premise that replacing thyroid in hypothyroidism is important,
that administering insulin to diabetics is critical, my position is that you
must accept the premise that replacing estrogen, progesterone, and testosterone
is a major key to improving quality of life.
Are you beginning to see
the rationale for replacing hormones?
ESTROGEN – PROGESTERONE REPLACEMENT
Articles
as far back as 1991 in the journal METABOLISM
concluded that postmenopausal hormone replacement prevents central
distribution of body fat after menopause.
It is intuitively obvious that to the extent hormones increase
well-being and improve quality of life, patients would respond with an increase
in physical activity which would, of itself, help to stabilize weight.
Resting energy expenditure or REE is the
number of calories the body burns during periods of rest. Researchers enrolled a group of young women,
not menopausal, blocked estrogen production, and made no other changes. REE was measured and showed a decrease of
nearly 100 calories per day. One hundred
calories per day can add up to 10 pounds per year.
A
5-year clinical trial performed for the Danish osteoporosis prevention study showed
hormone replacement therapy dissociates fat mass and bone mass and tends to
reduce weight gain in early postmenopausal women.
The
aim of this was to study the influence of hormone replacement therapy (HRT) on
weight changes, body composition, and bone mass in early postmenopausal women
in a partly randomized comprehensive cohort study design. A total of 2016 women
ages 45-58 years from three months to 2 years past last menstrual bleeding were
included. One thousand were randomly assigned to HRT or no HRT in an open
trial, whereas the others were allocated according to their preferences.
All
were followed for 5 years for body weight, bone mass, and body composition
measurements. Body weight increased less
over the 5 years in women randomized to HRT (1.94±4.86 kg) than in women
randomized to no HRT (2.57±4.63, p=0.046). A similar pattern was seen in the
group receiving HRT or not by their own choice. The smaller weight gain in women
on HRT was almost entirely caused by a lesser gain in fat. The main determinant
of the weight gain was a decline in physical fitness.
The
researchers concluded (1) that body weight increases after
the menopause. (2)The gain in weight
is related to a decrease in working capacity. (3) HRT is associated with a smaller increase in fat mass after
menopause. (4) Fat gain protects
against bone loss in untreated women but not in HRT-treated women.
In addition to
prevention of abdominal obesity, estrogen replacement therapy has been shown to
prevent subsequent progressive insulin resistance consistent with metabolic
syndrome and reduce the risk of developing diabetes.
TESTOSTERONE REPLACEMENT
Benefits
of testosterone supplementation in women with “low testosterone” include increased bone mass; increased muscle
mass; increased strength; increased libido; and improved quality of life.
When you restore
testosterone levels, men
universally report they feel like their old selves again. Boosting testosterone can boost muscle
strength, mood, bone density, sexual function, and general quality of
life.
Even
though 18 recent studies in the Journal of the National Cancer Institue
conclude there is no correlation between prostate
cancer and testosterone, this remains a lingering concern.
There
is evidence that men with low testosterone have a higher all-cause mortality
regardless of other risk factors.
THYROID
REPLACEMENT
Thyroid
hormone replacement often results in increased energy, improved fat metabolism,
and improved testosterone levels.
DHEA REPLACEMENT
Because it is metabolized into other
hormones, supplementing with DHEA may allow the body to choose which hormone is
needed, then synthesize that hormone from the available DHEA. This may account
for the astonishing range of benefits that many researchers attribute to this
hormone. DHEA's separate metabolites, including 7-Keto DHEA, have also been
shown to have individual benefits, including lowering cholesterol, burning fat,
and boosting the immune system.
DHEA has also been shown to
improve cognitive decline and fight depression.
HOW I GO ABOUT WORKING UP A CANDIDATE
The
workup for a patient you feel is a candidate for hormone replacement begins
with a good history in which you inquire about, among other things, energy
levels, sleep habits, libido, cognitive loss, weight loss or gain, and general
health issues.
It
is always important to be sure the candidate has a primary care physician and
is up to date on colonoscopies, mammograms, and PSA’s.
LAB WORK
We
always request laboratory tests of hormone levels (a so-called “hormone
panel”). Testing can be useful but it is
critical to remember we are treating the patient, not the lab test.
DHEA levels are measured by a straightforward
blood test. Monitoring the blood levels
of DHEA is necessary since the best results should occur when DHEA levels are
brought back into the "normal" range. The "normal" range,
however, will vary by age, by individual, and by laboratory. Therefore, before
being able to determine if one individual value is "normal" or
"low", there has to be an established standard to measure that value
against.
One
of the most complete studies to date was published by Orentrich in 1984.(4) His
recorded values shows that there exists a statistically restricted range of
normal values based on the individuals' age and sex. In order to
reconfirm this narrow range of blood values, Dr. Lichten focused his attention
on a group of senior Olympic athletes. Since these elderly individuals maintain
excellent health, their blood values are expected to be a more uniform measure
of "normal" for their age groups. In a preliminary review of men and
women over 65, the healthiest individuals had as expected, what would be
considered elevated blood levels.
Thyroid is best measured by measuring TSH, or
thyroid stimulating hormone. This is the
hormone released by the pituitary that stimulates the thyroid to release
thyroid hormone. If TSH goes up, the
body is signaling that thyroid hormone is low.
The
confusion arises because the normal range of TSH is 0.5 to 5.5 mlU/L. By the time you get to 5.5 you are seeing
overt hypothyroidism. Most physicians
who work with hormone replacement agree that if TSH exceeds 2.0 you are dealing
with subclinical or early hypothyroidism which should be treated by thyroid
replacement.
Testosterone can be measured by a blood test.
The
normal range of testosterone is reported as 350- 1200ng/dl. Studies in the
1940's showed the average testosterone level to be at 700 ng/dl, 300 ng/dl
higher than for men today. In the past, a drop in testosterone levels to 250
ng/dl was rarely reported before men were 80 years of age. Yet today, it is not
an uncommon value for middle aged men!
Testosterone
levels are highest in the early twenties. The decrease in serum levels is now
occurring at an even earlier age. Up to 50% of all men at 40 now have
testosterone levels below what was considered the normal range of 450 ng/dl.
Recent studies imply that the pesticides and preservatives in foods and the
hormone pellets to fatten up cattle, pork and chicken act as "hormonal disruptors." Based
on the low sperm counts, infertility, obesity, and low serum testosterone I see
in younger men, I fear this is true.
Married
men have lower testosterone levels than single guys. A recent study among the
Ariaal people in Kenya
showed that unmarried men had higher testosterone levels than men with a single
wife. And men with two or more wives had even lower testosterone than those
with one.
Therapeutic
levels should approach 800 ng/dl. This
is the level at which you begin to see a decline in all-cause mortality.
Estrogen
levels can be measured by a blood test.
The problem is that the normals for post-menopausal women published by
labs are woefully inadequate.
You
will read about normal for post-menopausal women being between 25 and 75
picograms/milliliter. The problems is
when you get into the low 20’s you usually see patients with symptoms.
In
the post-menopause, progesterone is close to zero.
Let
me repeat: Certain tests are mandatory before hormone replacement can
begin. Even with their limitations, it
is important to get an annual mammogram in women and a PSA in men. It is important the patient be current on
things like colonoscopies, general physical exams, etc.
TREATMENT
When
indicated, we then proceed to prescribe a precise dosage of bio-identical estrogen, progesterone,
or testosterone hormones, along with DHEA and thyroid. Bio-identical hormones are hormones that are
molecularly identical to the hormones the body is missing. Synthetic hormones, the kind made by large
pharmaceutical companies such as Wyeth, are designed to be different for the
simple reason that pharmaceutical companies cannot patent a naturally occurring
product. They therefore invent synthetic hormones that are patentable (Premarin
and Provera being the most widely used examples). They can patent Provera, for
example, but not natural progesterone.
The
great appeal of bioidentical hormones is that they are exactly the same as the
hormones our bodies are missing. Out
bodies can metabolize them as it was designed to do since we already have the
enzymes necessary to break the hormones down when we need to do that.
Synthetic
hormones are close to the actual hormone that is missing and being replaced,
but the match is not exact and there are often unwanted side effects.
For
example: The drug most often used to replace progesterone is Provera,
medroxyprogesterone acetate. The problem
with Provera is that it has some masculinizing effects. The classic hormone of pregnancy is
progesterone but if you have a patient on progesterone who becomes pregnant the
drug should be stopped immediately because of those masculinizing effects.
Synthetic
estrogen is 17 beta estradiol. Again
close, but not an exact match.
Premarin
is the ultimate bad example of estrogen replacement. Derived from the urine of pregnant mares,
Premarin contains up to 40 percent equine-specific estrogen for which our body
has absolutely no neutralizing enzymes. The
result is a buildup in the body of estrogenic substances that are, in most
cases, more potent than our bodies can handle and that may be responsible for
increased cancer.
There is a lot of interest recently about
Estriol. Estriol, or E3, is the weakest
of the three estrogen subgroups. It
appears to have a protective effect on the breasts. Unlike conjugated
estrogens, when you take estriol, it isn’t converted into estrone --
which means you aren’t exposing yourself to the estrogens that have been linked
to cancer.
The key plus of estriol is its weakness: It
appears to offer the benefits of the stronger estrogens with fewer of the
risks. Tests have indicated that it relieves menopausal symptoms, and protects
against heart disease and osteoporosis, as the other estrogens do, but doesn’t appear
to increase the risk of breast cancer or endometrial cancer. In fact, many
studies indicate that is has an anti-cancer effect, and actually may work
better than Tamoxifen for women with breast cancer.
Because
they are not manufactured by pharmaceutical companies, these bio-identical hormones cannot be
purchased at your neighborhood Walgreen drug store but must be purchased at compounding
pharmacies. Compounding pharmacies
purchase the bulk bio-identical hormones from chemical companies. The bio-identical hormones are then made up
into a cream so that they may be applied to the skin and absorbed that
way.
Why creams?
Applying the hormones via a cream applied to the thin skin of the inside
of the arm gets the product directly into the blood stream. When you give synthetic hormones orally,
larger doses are required because of the gastric acid breakdown in the
stomach. The remaining hormone then
passes through the portal circulation into the liver where more hormone is lost
in the “first pass.”
The result of passing
estrogen through the liver is interesting:
There
is an increase in C-reactive protein, an independent cardiovascular risk
factor, an increase in triglycerides, and sometimes an increase in LDL. In addition, passing estrogen through the
liver results in an increase in Sex
Hormone Binding Globulin, or SHBG. SHBG
binds with estrogen, working at cross purposes, and binds with testosterone,
effectively lowering available testosterone.
This, by the way, explains many of the patients who experienced a drop
in libido when they took oral contraceptives.
Again…the first thing to remember when
evaluating a patient up for hormone replacement is that we’re after
balance. We’re not after the big hit,
we’re not after a huge turnaround in 24 hours, but we are after improvement in
the long haul.
It’s a good thing, too, because
improvement is typically seen after two to three weeks of therapy.
I will typically prescribe estrogen
and progesterone separately. I prescribe
a mixture of Estradiol and Estriol in the morning and Progesterone at
bedtime. The creams are applied to the
inside of the forearms.
If I prescribe testosterone I give
that in the morning as well.
Replacing DHEA is rather straightforward. There are many companies that manufacturer
what is essentially a direct replacement.
You can compound tablets or creams, but whichever route you choose, we
usually start patients on 25 mg per day and reevaluate the DHEA level in a
month or so.
Thyroid
hormone has two
components—T3 and T4. Most clinicians
will replace T4 on the grounds that T4 is converted to T3.  The T4 to T3 conversion process does
not function in hypothyroid patients as it does in euthyroid patients and for
them T3 supplementation is often necessary.
Thyroid is
available in compounded form as a combination of T3 and T4.
In
diabetes, the gold standard for treatment is insulin, and the gold standard for
insulin in human insulin. Though bovine
and porcine insulin are similar to human insulin, their composition is slightly
different. Consequently, a number of patients' immune systems produce
antibodies against it, neutralizing its actions and resulting in inflammatory
responses at injection sites. Added to these adverse effects of bovine and
porcine insulin, are fears of long term complications ensuing from the regular
injection of a foreign substance.
These
factors led researchers to consider synthesizing Humulin by inserting the insulin gene into a
suitable vector, the E. coli bacterial cell, to produce an insulin that is
chemically identical to its naturally produced counterpart. This has been
achieved using Recombinant DNA technology.
LONG-TERM FOLLOW UP
Each
patient is then monitored carefully through regular follow-up visits and hormone
panels to ensure we get symptom relief at the lowest possible dosage. In the
initial stages every patient has access to my cell phone and I encourage them
to call me whenever. We ask for a
hormone panel and follow-up visit at three months, then six months, then at a
year.
It
is important to remember we are treating a patient, not a laboratory test.
CONCLUSIONS
It
is not my position that hormones are
a first-line treatment for obesity.
Rather hormone balance should be considered as part of a complete
approach to the problem.
In
my practice, we have had the greatest success with an individualized
approach. This is where the flexibility
of compounded creams is priceless.
Adjusting the dose in small increments is always possible.
It
is my strongly considered opinion that in hormone replacement, bio-identical
products are the only course to take. In
other words, the goal is to replace the missing hormone with the exact
molecular duplicate, a bio-identical product.
And
remember, please, the key word is: balance.
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