TESTOSTERONE, MALE MENOPAUSE AND HORMONE BALANCE IN MEN
by John R. Lee, M.D.
Commentary on an Article by Jerome Groopman, published in the New Yorker
magazine, July 29, 2002
Mr. Groopman discusses the commercialization of
“andropause,” a moniker that implies a fall in androgen hormones similar to the
menopausal fall of estrogen in women. The commercialization comes via Unimed, a division of
Solvay, a Belgian conglomerate that includes pharmaceuticals. Unimed hopes to broaden the
concept of andropause to include men with symptoms of fatigue, low sex drive, depressed
mood, or poor erections. Their product, AndroGel, is a 1% transdermal gel, i.e., containing
10 milligrams (mg) of testosterone per gram of gel. Their recommended dose, as listed by their three page
ad in this week's TIME magazine, is 5 grams of gel (50 mg of testosterone).
The author points out that FDA approval of AndroGel was given for treating rather
rare disorders such as Klinefelter s syndrome (a rare genetic disorder causing
underdeveloped testes), or testes damaged by viral inflammation or trauma, and pituitary
disorders that lead to loss of testicular function, and not for “andropause.”
Once a drug is approved for sale, however, physicians can legally prescribe it for any
clinical condition he thinks might benefit from it.
Mr. Groopman s article describes the dichotomy between physicians who find it
useful (and remunerative) for practically every man entering their offices, and medical
scientists who are still uneasy about the definition of andropause and question the use of
supplemental testosterone. Points of difference include the questionable value of blood
tests and the wide variability of testosterone levels in men without any sign of andropause
symptoms, the subjective nature of so-called benefits, as well as testosterone s
potential risk of heart attacks and prostate cancer, and the claims that testosterone
prevents aging. Unfortunately, Mr. Groopman does not seem to understand that risk of
hormone side effects is largely a matter of dosage.
In his conclusion, the author regards the present surge of testosterone replacement
therapy by approximately a quarter of a million American men to be a vast, uncontrolled
experiment, whose consequences remain uncertain. He feels that what is needed is large
scale study involving “many thousands of men” over a period of many years, such
as was done for women in the Women s Health Initiative (WHI) study of conventional
Medicine s Lack of Understanding about Male Hormone Balance
I find the article, written in the cool, cosmopolitan style so adored by the New
Yorker magazine, to be glib and mistaken in its underlying hypotheses. Yes, there is a
parallel with the problems uncovered by the recently stopped WHI study. The major problem
is conventional medicine s lack of understanding of the realities of hormone
balancing. Any single hormone does not work in isolation – it works something like a
member of a large orchestra with many different players. The question of
testosterone s role can not be determined, in most cases, by knowing merely its serum
concentration. What is the right level for one person may not be right for another person.
Absolute levels are deceptive. Far more relevant is the ratio between testosterone and
estradiol concentrations. Testosterone is an antagonist of estradiol; it acts to oppose
estradiol s actions. Thus, a given estradiol level will lead to breast growth in a man
with low testosterone, and not in a man with higher testosterone levels.
Testosterone and Estrogen in Men
It is well known that the estradiol level in 55-year old men, for example, is usually
a bit higher than that of a 55-year old woman. The man, however, does not develop breasts
because he has a higher testosterone level than women do. As men age, their estradiol
levels gradually rise, whereas their progesterone and testosterone levels gradually fall.
The hormone balance changes. These gradual changes lead to reduction in testosterone
benefits and eventually to estrogen dominance. That is, his estradiol effects emerge since
his testosterone level is not sufficient to block or balance them. Estrogen dominance
stimulates breast cell growth and endometrial cell proliferation in women. In men, estrogen
dominance stimulates breast cell growth and prostate hypertrophy. Estrogen dominance is
responsible for the majority of breast cancers and is the only known cause of endometrial
cancer in women. Since the male prostate is the embryonic equivalent of the uterus, is
should not be surprising that estrogen dominance is also a major cause of prostate cancer.
Testosterone Supplementation in Men
Testosterone supplementation is the obvious treatment for men with testosterone
deficiency relative to their estradiol levels. If the estradiol, progesterone, and
testosterone balance that prevails in younger men (when they do not get prostate cancer) is
a healthy one, why not restore the hormone levels in older men to that same healthy
To achieve this desired goal of a healthy balance between these major sex hormones,
one must learn how to accurately measure their levels. All steroid hormones are
fat-soluble. When they circulate through the liver they wrapped up, so-to-speak, by a
protein coating, a process known as protein binding. When protein-bound, the hormones are
water soluble but less bioavailable. Being water-soluble, the protein-bound hormones pass
through the kidneys and are excreted in the urine. The non-protein-bound hormone (referred
to a “free” hormone) on the other hand, is the bioavailable form of the hormone.
It is fat-soluble and is carried in blood by red blood cells rather than in the serum, that
is the watery, non-cellular portion of the blood. When the blood circulates through the
tissue of the salivary glands, the “free” hormone, whether in red blood cells or
in the serum, filters through into the saliva, whereas the protein-bound form does not. If
one wished to know the concentration of “free” bioavailable hormone in the blood,
it is obvious that saliva hormone levels are more accurate and more relevant than serum
Serum vs. Saliva Holds True for Men Too
For reasons that escape rational thinking, conventional medicine persists in using
serum tests rather than saliva tests. The results have been disastrous. When using hormone
creams or gels, the hormone is absorbed through the skin and into the blood without first
passing through the liver. Thus, they are essentially all absorbed in the “free”
form. When given orally, they pass first through the liver and 90% of them become
protein-bound. For this reason, transdermal dosing is at least 10 times more efficient than
oral dosing. If one uses serum testing to measure the blood levels achieved by transdermal
dosing, the test will fail to measure all the hormone carried by red blood cells. As a
consequence, physicians are apt to greatly over-dose their patients.
When using saliva testing, it is found that the transdermal dose of testosterone when
treating someone with testosterone deficiency is only 0.25-0.5 mg in women, and 1-2 mg in
men. As the New Yorker article indicated, the transdermal doses of testosterone
ranged from 5 mg to 100 mg a day. The same is observed in estrogen replacement therapy
– the doses are generally all greatly excessive. The same hormone that brought good
health without side effects when in normal endogenous levels will bring on very bad side
effects when given in grossly excessive doses.
The problem is not the hormone, per se, the problem is the dosing.
Some physicians have attempted to measure “free” hormones in serum.
Regardless of how well this is done, such tests fail to measure the “free”
hormone being carried by red blood cells.
Use Only Bio-identical, Natural Hormones
The final correction that must be made is equally obvious – when treating someone
with a hormone deficiency, use only bio-identical hormone. Altered, synthetic versions of
our natural hormones will not do – they are foreign to the body, do not convey the
same benefits as the real hormone, and all are fraught with undesirable side effects not
conveyed by the real hormone.
Our problems in using hormones can be solved by the four guidelines summarized below:
- Learn how to measure total “free” hormone.
physiologic doses rather than pharmacologic doses.
- Use only bio-identical
- Learn how to achieve hormone ratios that produce proper hormone
Failure to follow these three guidelines is the principal cause
of the problems exposed by the Women s Health Initiatives. The makers of AndroGel use
bio-identical testosterone but their dosing regulations are faulty and dangerous. Any good
compounding pharmacist can make up a testosterone cream that will more easily supply the
right dose of testosterone in men with estrogen dominance due to testosterone deficiency.
For more information on this topic, please read Hormone Balance for Men a booklet by John R. Lee, M.D.