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Copyright : Georges Debled |
ANDROPAUSE CAUSE CONSEQUENCES and TREATMENT
TESTOSTERONE AND SEXUAL INVOLUTION IN MEN
THE FOUNDATION OF THE LIFE MAINTENANCE SYSTEM
TESTOSTERONE AND AGEING ILLNESSES
ARTERIOSCLEROSIS, ATHEROSCLEROSIS AND HYPERTENSION
VARIX, HEMORROIDS AND THROMBOSIS
LOSS OF PULMONARY ELASTICITY AND REPIRATORY IMPAIRMENT
TRANSFORMATION OF THE SILHOUETTE
The life maintenance
system is made up of all the biological factors produced by each organism to
ensure its normal working.
The production of
biological factors indispensable to the maintenance of a normal physiology
decreases with age.
Ageing illnesses
basically represent the consequences of the failure of the life maintenance
system.
The organism's
glandular system is an essential part of the maintenance system both for men and
for women. The glands progressively stop functioning.
The main hormones
are secreted by
These secretions
diminish year to year after forty (and sometimes even before).
The cells
manufacture other hormones.
The kidney secretes
a hormone, erythropoietin, that causes the manufacture of red cells by the
bone marrow.
In the United States
of America, the biotechnological industry already produces harmless somatotropic
hormones through genetic engineering.
Today specific
hormones also manufactured through genetic engineering allow for the manufacture
of red corpuscules, white cells and platelets. These products will be given intravenously in vain to people who have not looked after their life
maintenance system, especially from the age of forty on.
No one can today say
what the length of life will be for men and women who have looked after the life
maintenance system.
THE
FOUNDATION OF THE LIFE MAINTENANCE SYSTEM
In 1992, at an
international congress on ageing in Dallas, Dr Georges DEBLED presented his
theory, based on twenty year's clinical experience, according to which the fall
in testosterone secretion is responsible for male climacteric and ageing
illnesses (1-2).
These works have
brought to attention the consequences caused by the diminution in testosterone
secretion with age (4).
TESTOSTERONE AND
SEXUAL INVOLUTION IN MEN
This fact demonstrated by numerous studies leads to sexual involution in men characterized
by weak libido, poor frequency of sexual intercourse, impotency, ejaculation's
problems, sclerosis of the penis and sometimes gynecomastia.
The deregulation of
the biological androgens chain induce or aggravate prostate illnesses: atrophy,
adenoma and cancer.
Testosterone
is implicated in the metabolism of all proteins of the body. It regulates the
sugar metabolism and through this pathway it influences the fat metabolism.
The
main phenomenon of the male climacteric is a lack of male hormone and the
"sexual concept" is too restrictive because, in fact, when
testosterone is missing, all structures of the body involve progressively
through different biochemical and pathological mechanisms.
Universality
of the androgen receptor
The
androgen receptor is identified in a variety of organs : the
seminal vesicles, the hair follicle, the sebaceous glands, the foreskin
glands and more generally all secondary sexual organs, the testicles and the
epididymis, the uterus and the ovary, the kidney, the submaxillary glands,
definite cerebral areas as the hypothalamus, the pituitary gland and the
cerebral cortex, the elevator ani muscle and the skeletal muscle, and the bone
marrow. In reality small quantities of androgens' receptors have been observed
in numerous organs (10).
Protein metabolism
The
trophic action of androgens upon the skeletal muscle is well known for many
years. It is spectacular with body-builders taking androgens.
According
to several authors, experimental studies have proved the effects of androgens on
the incorporation of amino acids into muscle proteins (11-12-13-14-15).
Research
on rats treated with testosterone have shown a significant incorporation of
marked leucine in the proteins and of marked uridine into ribonucleic acid in
some muscles of those animals.
Sugar metabolism
The
regulation power of testosterone on sugar metabolism acts for a long time : after an androgenic treatment the
glycemy of diabetics is reduced during a few days and rises after to the initial
levels.
Fat metabolism
Through the pathway
of sugar metabolism testosterone influences the fat metabolism . When you have
too much glucose in the blood, it can't be burned enough through the Krebs'
cycle (the capacity of burning is limited) and you have an overproduction of
acetyl-coenzyme A which is the initial compound for making cholesterol and
lipids.
Because every man,
some time or other, will have a lack of testosterone production after forty, the
values for triglycerides and of cholesterol will increase in the blood with age.
TESTOSTERONE AND
AGEING ILLNESSES
The most noticeable
phenomenon in the field of health concerns the massive and deteriorating
ageing of the entire population. One French person in four dies before the
age of 65. Average life for men is about 73 years. Women live on average for 81
years.
After fifty,
mortality is mainly caused by :
1. Cardiovascular
illnesses.
2. Senility.
3. Cancers.
These illnesses are
characterized by cellular deterioration.
Deterioration of the
arteries and the heart muscle,
deterioration of the
cerebral nervous fibres,
deterioration of
immunity cells encouraging cancers.
Death generally occurs after a 20 year period of deterioration. The consequences of deteriorating illnesses provoke recurrent disability.
Deregulation of
sugar, fat and proteins' metabolisms have a devastating effect on the organism
They are actually
200 millions cases of diabetes in the world. This number will be multiplied
by two in the beginning of the third millenary.
The decrease of male
hormone with age lead to a chronic intolerance to glucose and to diabetes.
Chronic lack of
testosterone with ageing is a leading cause of the maturity-onset diabetes after
forty years (17-18-19-20-21-22).
Accumulation of fat
leads to overweigth and obesity .
Glass and coll. from the department of medicine from the UCLA School of Medicine in California reported, in 1976, that plasmatic testosterone levels are decreased in obese men (23-24-25-26-27).
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LOW
PLASMA TESTOSTERONE IN MASSIVELY OBESE MEN |
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|
|
Plasma
Testosterone in nanograms/100 ml. |
|
Obese
group (200 to 280 % of the ideal body weight) |
223 |
|
Control
group (85 to 135 % of the
ideal body weight) |
599 |
Table
1.
According to Glass
and coll.
In 1990, Zumoff and
coll. from the division of Endocrinology and
Metabolism from the Beth Israel Medical Centre in New York, reported that free and total testosterone levels are clearly subnormal
in obese men. The degree of subnormality is proportional to the degree of
obesity and the authors conclude : "Hormonally speaking, the distinction
between morbid obesity and lesser degrees of obesity would seem to have no
validity; the decline of free, non-SHBG-bound, and total testosterone levels in
obese men represents a continuum, observable at any degree of obesity"
(28).
Because the decrease
of testosterone secretion with age is seems logical to believe that this
phenomenon is a leading cause of fat deposits everywhere in the body and that
overweight is a clinical sign of andropause.
The metabolism of
the muscle is influenced by testosterone which increases the quantity of
specific contractile proteins as seen above. Testosterone increases also the
input of glycogen into the muscle cells. Glycogen constitutes fuel or energy for
the muscle's contraction. The link between glycogen and testosterone during
exercise is reported by F. Plas from the University Hospital Pitié-Salpêtrière
in Paris, in 1978 (29).
During andropause
the muscles are weak and exercise aggravates the loss of testosterone. In this
situation any intensive sport is dangerous even the jogging. The heart which is
also a muscle is deprived of its fuel and heart attacks and even sudden death
may occur at any moment!
ARTERIOSCLEROSIS,
ATHEROSCLEROSIS AND HYPERTENSION
According to the
"Vital Statistics Report" of the National Centre for Health
Statistics, the cardiovascular diseases are the first cause of death in the
world and in the United States (30).
The arteries are
involved by two different phenomenons, arteriosclerosis and atherosclerosis,
which occur often simultaneously.
The pathology of
arteriosclerosis is characterized by the replacement of the muscular fibres of
the artery by collagen tissue which is inelastic. Muscular fibres need
testosterone to maintain their
activity. With the loss of testosterone the muscular fibres became weak and are
replaced by fibrous tissue.
The pathology of
atherosclerosis is characterized by fat and cholesterol involvement of the
arterial wall. This phenomenon is the consequence of cholesterol and lipid
accumulation in the body through the impaired sugar and fat metabolism when
testosterone is missing.
Arteriosclerosis and
atherosclerosis are two general involution phenomenons increasing with the
decrease of testosterone secretion. It is probably the reason for the elevation
of blood pressure with age.
The main question
about blood is not " how it coagulates" but "how it remains
fluid". Thrombosis and embolism are common complications of cardiovascular
diseases usually treated by
anticoagulant agents
as heparin or dicoumarin. The use of those substances can produce haemorrhages.
The dissolution of
the blood clot is under the influence of fibrinolytic agents.
On the other hand, a normal blood level of antithrombine III guarantees a good
blood fluidity without risk of bleeding.
Fibrinolitic agents
of the blood are under the influence of testosterone as reported in the Lancet
of the 21 July 1962 by Fearnley and coll. (31).
Claire Bonithon-Kopp
and coll. from the Broussais hospital in Paris, who demonstrated in 1988 that low
plasmatic levels of male hormone contributes to hypercoagulability and to
ischemic heart disease (32).
VARIX, HEMORROIDS
AND THROMBOSIS
Veins like arteries
are constituted by muscular fibres. Loss of testosterone produces always an
involution of their muscular tissue.
The number of red
blood cells is decreased from 10% in
castrated men. This is often so in men with low testosterone plasmatic levels.
The ischemic heart disease is of course aggravated by this phenomenon.
In 1981, Najean and
coll. reported in the American Journal of Medicine the improvement of anemia in
a serial of 137 patients when treated by male hormones. Anemia recurs when the
therapy is stopped and improve again with androgens (33).
On the other hand,
patients with polyglobulia may constitute a problem for therapy with androgens. The
normal account of red blood cells varies normally (5,4 + 0,9 millions/millilitre) (34). So patients with 6,3 millions red blood
cells/millilitre and presenting a failure in the life maintenance system can be
carefully treated with an appropriate monitoring of the androgens without
increasing of the number of their red blood cells. Those cases are rare.
The muscle cells of
the rat heart contain a specific receptor to androgens as demonstrated in 1978
by Michael Krieg from the Department
of Clinical Chemistry from the University of Hamburg in Germany (35-36). In
1956, Ruth Blasius, from the Medicine Department
of the University of Munich in Germany, demonstrated the increase of contractile
proteins in the heart of animals under the influence of testosterone (37).
Angina pectoris
Ch. Breier, from the
Department of Internal Medicine from the University of Innsbruck in Austria, and
his collaborators reported the 1 June 1985 in the Lancet the positive
correlation between coronary heart disease and the increase of plasma levels of
total cholesterol, low density lipoproteins (LDL) and triglycerides and the
decrease of testosterone plasma levels. HDL-cholesterol is correlated negatively
with coronary heart disease (38).
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High
level of |
Correlation
with coronary heart disease |
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Total
cholesterol |
+ |
|
LDL-
Cholesterol |
+ |
|
Triglycerides |
+ |
|
HDL-
Cholestérol |
- |
Table
2.
According several
authors the coronary heart disease is correlated
positively with a decrease of total testosterone, free testosterone and
dihydrotestosterone plasma levels
and with an increase of estradiol plasma levels (39-40-41-42-43).
|
Hormone |
Plasma
level |
Correlation
with coronary heart disease |
|
Total
testosterone |
Low |
+ |
|
Free
testosterone |
Low |
+ |
|
Dihydrotestosterone |
Low |
+ |
|
E |
Elevated |
+ |
Table
3.
In 1946, Lesser
demonstrated the benefit of testosterone therapy
in one hundred cases of angina pectoris (44).
In 1984, Jens
Moeller, President of the European Organization for the Control of Circulatory
Diseases and Helge Einfeldt published a book Testosterone Treatment of
Cardiovascular Diseases, edited by Springer Verlag, according an experience of
more than thirty years in Copenhagen (45).
Myocardial infarct
Jaffe(46), Geisthövel
(47), Conrad Swartz (48), demonstrated a link between low testosterone levels in
the blood, angina pectoris and myocardial infarct.
In 1997, Unit U-21
of INSERM of France confirmed the
"Association between plasma total testosterone and cardiovascular risk factors in healthy adult men" in a study published in the U.S.A in the Journal of Clinical Endocrinology and Metabolism (Vol 82, N° 2, p. : 682- 685). The study known as the Telecom study, was conducted during 8 years comparing two groups of men.
The first group had a well balanced blood testosterone during the 8 years and did not showed any increase of the cardiovascular risk during this period.
The second group had a decrease in blood testosterone during the 8 years and showed a significant increase of the cardiovascular risk (49).
Gangrene
The spectacular
effects of testosterone on gangrene are shown by pictures in the Moeller's book
Testosterone Treatment of Cardiovascular diseases (45). The testimonies of
numerous doctors having visited the clinic of Moeller in Copenhagen are
unanimous to certify the efficacy of testosterone treatment upon gangrene
(50-51-52-53).
STIFNESS, LIMITATION
OF THE MOVEMENTS AND ARTHROSIS
With aging the
connective tissue loss its elasticity and its constitution is changed in a worse
structure.
According to
Ladislas Robert, Research Director at the CNRS and Director of the Laboratory of
biochemistry of the connective tissue from the Medicine Faculty of Paris-XII,
the elementary fibres of collagen are linked by chemical bridges. The increase
of the resistance of collagen with aging is the consequence of an increase of
the quantity of bridges or from an alteration of their structure. This phenomenon is increased
by the chemical affinity of glucose for the collagen tissue (54). The loss of
male hormone lead to hyperglycemia as we have seen above. There is why the
sweetened
middle aged man
becomes stiff.
At the same time the
ground substance of the connective tissue is altered and the oxygenation of the
connective cells is compromised. The rarefaction of the normal ground substance
is the consequence of the loss of male hormones as demonstrated, in 1958, by
Harry Sobel and Jessie Marmorston, from the University of Southern California in
Los Angeles (55).
Those phenomenons
added with overweight lead to arthrosis.
In France,
occupational doctors diagnosed an explosion of bone diseases between 1991 and
1994, with growth of 160 % compared to preceding years.
Back trouble, which
is a major cause of disability, accounts for six million consultations a year, a
third of rehabilitation prescriptions, 13 % of occupational accidents, 7% of
work stoppages due to illness and 2,5% of non-hospital prescriptions. The
deterioration of the muscular-bone-articulary system is continually ignored.
In 1978, Daniel
Baran and his collaborators, from the department of Medicine and Pathology,
Division of Bone and Mineral Metabolism from the Washington University School of
Medicine, reported the positive effect of testosterone therapy on bone formation
in a hypogonadic male with osteoporosis (56).
In 1981, Delmas and
Meunier from the Research Laboratory on histodynamics of the bones and the
Alexis Carrel Faculty of Lyon in France, reported eight cases of osteoporosis in
eight men with low levels of male hormones (57).
In 1983, Gérard
Milhaud from the University hospital Saint Antoine in Paris, has reported the
fragility of the bones in climacteric women but also in climacteric man accordig
studies on the mineral constitution of their bones (58). The rapidity of the
mineral loss in man is slower than in women.
The same year,
Doctor Foresta and his collaborators reported in the scientific revue Hormone
Metabolic Research the linear relation between testosterone plasmatic levels and
bones' density (59).
LOSS OF PULMONARY
ELASTICITY AND REPIRATORY IMPAIRMENT.
Normal breathing is
the result of a good elasticity of the connective tissue of the lungs.
Respiratory muscles in good condition are also necessary for a good respiration.
Connective tissue deterioration and amyotrophy of respiratory muscles in low
testosterone conditions leads to breathing problems.
The altered
connective tissue is also responsible for skin aging and phimosis. This
condition leads to chronic skin infection.
Testosterone
stimulates immunity (60-61-62). A decrease of androgens' secretion induces a
lack of production of lymphocytes leading to chronic infections and cancer.
Testosterone therapy can be of the most importance in HIV viral illnesses (AIDS)
when the patient is weak, stressed and deprived of lymphocytes.
TRANSFORMATION OF
THE SILHOUETTE
The silhouette of
the climacteric men is often typical, with overweight and abdominal ballooning,
consequence of the weakness of the bowel's muscles. An increase of male hormones
is also responsible for breast enlargement which is very common in old men
(fig.1).
The regressive man's silhouette
The progressive man's silhouette
The kidney
insufficiency is the consequence of three great
mechanisms. The first is the lack of trophic influence on the renal
parenchyma. The second is the impairment of the kidney function by hypertension
in the ureteral cavities secondary to the hypertrophy of the uretero-trigonal
musculature which is the consequence of the bladder outlet obstruction created
by prostate diseases.
The third is the
arteriosclerosis of the renal arteries. All those phenomenons are aggravated by
loss of testosterone.
The small bones of
the ear and their ligaments, the connective tissue of the eye, its vascularization and its metabolism are damaged by the loss of testosterone. This
phenomenons lead
to troubles of
audition and vision.
It accounts for 100
million consultations a year worldwide. Aggravated by stress, it can announce
future deterioration in the nervous system.
The influence of
testosterone on the nervous system are numerous.
In 1971, Harold
Persky, a researcher from the National Institute of Mental Health of the US
Public Health Service, reported in the revue Psychosomatic Medicine the relation
of psychological measures of aggression and hostility to testosterone production in
man (63).
The plasma levels of
testosterone were studied in young men and in older men. In young man there is a
correlation between testosterone plasma levels and measures of aggression and
hostility. This equation was not valid for older men.
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RELATION OF PSYCHOLOGIC MEASURES OF
AGGRESSION AND HOSTILITY TO TESTOSTERONE PRODUCTION IN MAN |
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Age |
Plasma
testosterone in nanograms/ 100 ml. |
Reactions |
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22
( range 17-28) |
685 |
+ |
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45,1
( range 31-66) |
404 |
- |
Table 4.
According to Persky
H., Smith K.D. et Basu G.K.
In 1974, Joel
Ehrenkrantz, from the Department of Psychiatry from the Yale University School
of Medicine, New Haven, Connecticut, and his collaborators reported the
correlation between testosterone plasma levels with aggressive behaviour and
social dominance in man (64).
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PLASMA
TESTOSTERONE : CORRELATION WITH AGGRESSIVE BEHAVIOUR AND SOCIAL DOMINANCE
IN MAN |
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Behaviour |
Plasma
testosterone in nanograms / 100 ml |
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non
aggressive |
599
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socialy
dominant |
836 |
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aggressive
|
1 010 |
Table 5.
According to
Ehrenkrantz J, Bliss E. et Sheard M.H.
When you consider
the statistics of deaths by accident of the National Centre for Health
Statistics, you see immediately that, under 65 year, men are dying threefold
more than women, after 65 years the death rate is the same for women and men who
have lost their male hormones and their aggressivity.
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NUMBER
OF DEATH BY ACCIDENT REGISTRATED IN U.S.A. IN 1982 |
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Under
65 years |
More than 65 years |
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Men |
Women |
Men |
Women |
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54 000 |
17 000 |
12 000 |
11 000 |
Table 6.
According to the
National Centre for Health Statistics, Vital Statistics Report, Final Mortality
Statistics, 1982.
According to the
World Health Organisation 100.000.000 persons are suffering each year from
nervous breakdown.
Nervous breakdown is
a great symptom of the middle age crisis. In 1979, Mauvais-Jarvis and Bruno de
Lignières, from the Necker Hospital in Paris, reported
the correlation between nervous breakdown and low plasma testosterone
levels (65).
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LOW
PLASMA TESTOSTERONE AND NERVOUS BREAKDOWN |
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Men
consulting for impotency |
Number
of patients |
Plasma
testosterone at 9 a.m. in
nanograms/100 ml. |
Depressed |
8 |
205
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Non depressed |
9 |
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