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Andropause,
the Male Menopause
Although most
people know that Menopause has generated a
large population of women who have
excessive rates of bone fracture and CHD,
men also suffer from these conditions. The
male menopause or Andropause,
is due to hypogonadism- low testosterone
levels. Andropause, the word, appeared in
the literature in 1952 and is defined at
the natural cessation of the sexual
function in older men. Andropause
also refers to sexual regression in men
over 40 due to dropping male hormone
levels.
Endocrinologically,
the difference between the irreversibly
hypogonadal man and the post-menopausal
hypogonadal woman is not very great. (1)
Neither has adequate levels of androgens
or estrogens and they both can be expected
to show similar tendencies; i.e.
hypogonadal men also tend to have frequent
MIs and bone fractures. There is recent
evidence of a protective effect of
testosterone against both heart attacks
and bone fractures. (2)
Low hormone levels
of testosterone in men, have detrimental
influences on both mood and mental
abilities , including decline of memory,
and loss of youthful sexual functioning.
Studies have shown that the sexual aging
process results in organic impotence,
erectile dysfunction, ejaculatory and
urinary problems, decreased sexual drive
or libido and deterioration of the general
physique.
About
Testosterone, The Male Sex
Hormone:
Testosterone is
the principal androgen of which 95% made
in testes, 5% in adrenals. It is
synthesized from cholesterol at
approximately 6mg/day and metabolized by
liver and excreted in urine. Testosterone
can be bioconverted into two other
steroids at target tissues:
- 1.
Dihydrotestosterone (DHT)- binds more
readily to androgen receptors.
Conversion noted at prostate, seminal
vesicles, pubic skin.
- 2. DHT is 10x
more powerful than testosterone, thus
conversion amplifies the action of
testosterone.
- 3. Estradiol-
an estrogen, 25% made by testes ,75%
bioconverted in liver and brain from
testosterone.
Testosterone is
the hormone which regulates the structure
of all body proteins and assures the
development and integrity of the genitals
in males. The adult testicles normally
produce about 7-10 mg of testosterone
daily. A deficiency below this level
causes only modest changes initially such
as an increase in weight, progressive
aging of the face, muscular weakening and
weakening of bone tissue. Lowered
testosterone secretion causes low
functioning of the body organs resulting
in the eventual failing of memory and
resulting irritability associated with
general fatigue. The development of
arteriosclerosis, varicose veins,
hemorrhoids, increase in body fat, atrophy
of the skin, systolic hypertension and
increased cholesterol are aging associated
changes of males that are reversible with
testosterone supplementation.
(3)
About
Androgens and
estrogens:
Androgens and
estrogens have similar metabolic effects
in the liver where testosterone is
enzymically converted into estradiol or
E2. Estrogen, which a combination of three
estrogen subtypes; E1-estrone,
E2-Estradiol , the active "female hormone"
and E3-estriol. Estriol is protective
against breast cancer and its deficiency
directly causes the hot flashes and
nervousness associated with "the change".
Estradiol causes breast enlargement in men
as well as the female changes that occur
in women at adolescence. During menopause,
women typically experience hot flashes,
but no similar consistent signal seems to
appear in aging men as they develop
hypogonadism. However, most men do
experience hot flashes when hypogonadism
is abruptly induced by pharmacological
agents that rapidly abolish lutenizing
hormone (LH). The absence of obvious
symptoms and the slow course and
unpredictability of the development of low
testosterone or hypogonadism, may
contribute to its lack of recognition and
its attribution to “normal aging.
Erectile
dysfunction=
Impotence:
Impotence, or the
inability to achieve an erection is due to
inadequate blood volume filling up the
spongy penile tissue. A non erect penis
contains about 8cc. of blood compared to a
fully erect penis engorged with 64 cc. of
blood. EIGHT TIMES the normal volume of
blood is required for an erection!
Therefore it is easy to see that any
process which decreases blood volume to
the penis or does not keep the blood
within the penis, will result in
unsatisfactory erections.
Erectile
dysfunction is due to these "inadequate"
erections. Erectile function is dependent
on the penis receiving its full dose of
blood on a daily basis. If for some
reason, erections do not occur during the
night in REM (deep) sleep, then eventually
these tissues will scar and atrophy. If we
do not use it, we lose it!!!
The loss of sexual
drive is one of the first changes most
notice of "aging". This decreased libido
and failure to awaken with erections is
the foreboding of the " impotence
experienced by hypogonadal men".
Interestingly enough , this feeling tends
to be accompanied in most men, not by
frustrated sexual urges or complaints of
frustration but rather by "passivity
according to Dr. Swartz.(1)
More than half of
the healthy men over age 70 that he
surveyed showed morning serum testosterone
levels at or below 300ng/dl, the customary
threshold of hypogonadism. (5) One of the
earliest signs of impending impotence is
ejaculation without full erection. In this
type of early erectile dysfunction, men
who notice that they are able to
masturbate and ejaculate without full
erection should be seen by their physician
at once. The new drug, VIAGRA, prevents
impotence by causing nightly erections in
those men who took it .(6)
Impotence,
testosterone and
Alcohol:
One of the major
causes of impotence is heavy drinking.
This pattern of alcohol use is common in
25% of American men at some time during
their adulthood. The relationship between
alcohol consumption and testosterone
secretion has both reversible and
irreversible components.
Serum testosterone
abruptly rises to normal levels when high
alcohol intake is discontinued but
moderate alcohol intake does not
substantially affect its level. However,
the very low serum testosterone level
under 300ng. was found in 62% of long
abstinent ex-alcoholic men over the age of
60 and in only 15% of nonalcoholic men of
the same age, indicating that past heavy
drinking is associated with a reduction of
the current morning serum testosterone
level by an average of 122ng/dl.
The decreased
testosterone level prevents morning
erections from occurring. In an ongoing
study, I have found that replacing
testosterone to "younger level" restores
morning erection frequency to a daily
occurrence. There is also an associated
increase in sexual drive but this effect
varies with different age groups. (5) Men
who had used alcohol heavily in their
middle decades had much lover levels of
testosterone than their counterparts who
did not drink or drank moderately.
Therefore, alcohol
induced hypogonadism is common and may
affect many men over the age of 60. A
moderate amount of alcohol is the
equivalent of 1-2 ounces per day or 2-4
beers or glasses of wine or 2 shots of
hard liquor. Women are much more sensitive
to alcohols effects and no more than three
drinks a week are recommended in order to
prevent breast cancer.
Low
hormones and heart attacks:
The best-known
consequences of hypogonadism in men are
impotence and dwindling libido. However,
both melancholia and psychiatric
disturbances , from depression to
psychosis, can also occur in association
with testosterone deficiency. Perhaps the
most dangerous consequence of hypogonadism
in men is myocardial infarction (MI).
Serum testosterone levels were about 90
ng/dl lower in patients who had suffered
MI's than in those who had not. Results
also suggested that low testosterone
levels predispose to MI and are lower in
men with severe coronary artery
atherosclerotic disease than in controls.
Very high blood levels of testosterone
might protect against atherosclerosis
especially in men over age 60.
Testosterone is
not the only androgen that appears to
protect again MI. Estrogen exerts a
profound effect by both lowering the "bad"
cholesterols, raising the good
cholesterols and decreasing clotting of
blood and blood pressure in women.
DHEA-Dehydro-epiandrosterone, a precursor
of both testosterone and estrogen, has
digitalis-like effects and strengthens the
heart muscle. Together, testosterone and
DHEA prevent the death of CNS nerve cells.
This information suggest that there are
beneficial systemic effects in maintaining
blood levels of androgens similarly to the
benefits of maintaining normal thyroid
hormone levels.
Illegal
and legal use of Testosterone
replacement:
- Current polls
indicating use of testosterone
replacement, illegally by the
following:
- 96%
Professional Football
Players
- 80-99% Male
Body Builders
- 11% High
School Football Players
- 6.6% High
School Senior Males
The prescription
and use of steroids is legal in the United
States. The issue is clouded by the
Anabolic Steroid Control Act of 1990,
which criminalizes sale and possession of
any anabolic steroid intended for
non-medical use. Misuse of steroids in the
sports world has led to stigmatization of
their legitimate medical uses; however,
some care must nonetheless be exercised in
prescribing steroids. The best protection
for a physician is to carefully document
symptoms and test results and not to over
prescribe any replacement therapy.
Black market worth
$300-400 million annually. Half are
counterfeit. Most said to come from
Mexico. Labels often claim illegal
importation despite local manufacture.
Purity is questionable and users sharing
needles run risk of hepatitis, HIV
infection and subsequent AIDS, abscesses,
cellulitis and death. Potential steroid
users are further advised that buying a
known counterfeit steroid is a felony, as
is buying a non-FDA approved steroid.
Testosterone has
been found to inhibit clot formation by
decreasing fibrinogen and hardening of the
arteries by increasing HDL and decreasing
serum triglycerides. (4) It also
strengthens muscles beyond normal limits
and testosterone is the androgen of
greatest concentration in cardiac tissues.
Testosterone can make heart muscle more
resistant to death during ischemia through
improved maintenance of cardiac output as
well as decreasing the clotting mechanism.
These advantages of testosterone
replacement are also associated with a
general feeling of well-being, greater
strength and return of libido.
The anabolic
effects of steroids are those that have a
direct effect on the production of muscle
mass. There is an increase in muscular
strength and recovery from injury or
stress. Androgenic effects of steroids
include the development or increase of
facial hair, the deepening of the voice,
stimulation of sebaceous glands and some
as yet ill-defined effects on brain
tissue.
Anabolic/androgenic
steroids, in the presence of an adequate
diet, can contribute to increases in body
weight in the lean mass compartment
through the activation of protein
metabolism. The gains in muscular strength
achieved through high intensity exercise
and proper diet can be increased by the
use of anabolic/androgenic steroids in
some individuals.
Dangers of
anabolic-androgenic steroid
use:
- 1.Kidney
Disease
- 2.Serum LDLC
Increase, HDLC Decrease
- 3.Hypertension
- 4.Cardiovascular
Disease
- 5.Stunted
Growth
- 6.Depression
- 7.Aggression
- 8.Acne
- 9.Male Pattern
Baldness
- 10.Gallstones
- 11.In Male-
Testicular Atrophy, Decreased Sperm
Production, Gynecomastia- hypertrophy
of breast
- 12.In Female-
Hypertrophy of Clitoris, Facial Hair,
Deepening of Voice
- 13.Peliosis
Hepatitis- blood-filled cysts in liver
- 14.Cholestatic
Jaundice
There are health
problems in aging men associated with
testosterone administration. Enlargement
of the prostate, accelerated progression
of undiagnosed prostate cancer, increased
hematocrit and a variety of liver lesions
can occur. Administering testosterone by
intramuscular injection tends to avoid the
liver toxicity seen with oral
preparations. Administration of
testosterone cypionate reduced HDL and
synthetic androgen also increase total
serum cholesterol. Synthetic androgens are
not preferable to preparations of
testosterone itself.
Natural
vs. synthetic testosterone:
Natural
testosterone has been available since
1938. Most of the anabolic (tissue
building) steroids are synthetic analogs
of natural Testosterone, the male hormone.
Usually they are taken orally in large
quantities which are dangerous and can
cause serious liver diseases as well as
organ failure. Examples of "roids" such as
stanazolol, Winstrol or Android(
methyltestosterone), are used by
bodybuilders. Injections of nandrolone
deconate, or Durabolin, have been
available in the gyms of America for over
ten years.
These anabolic
(tissue building) hormones cause increased
incorporation of new amino acids into
tissue. This increased protein synthesis,
results in growth or hypertrophy of the
muscle. Injectable synthetic steroids both
androgenic:
Testosterone
Esters for medical
use:
Because
testosterone is rapidly metabolized by
liver if taken orally or by IM injection,
esters, which are more lipid soluble, are
produced and injected in a peanut oil
base.
- A)
Testosterone Propionate, is short
acting, half-life of
3-6hrs.
- B)
Testosterone Cypionate
(Depo-Testosterone, Virilon
IM)
- C)
Testosterone Enanthate (Delatestryl,
Testaval)
One injection can
maintain normal serum levels of
testosterone for 10-14 days. When used as
a replacement, no apparent side effects.
Nandrolone deconate is a synthetic
testosterone , which transforms to produce
both high levels of testosterone and more
anabolic steroids. This results in
transformation to excess estradiol which
can cause gynecomastia (breast
enlargement) in men. Testosterones action
on the muscles has been observed by young
male athletes who try to bulk up and
recover faster.
Medical uses of
anabolic include CRF patients to stimulate
red blood cell production. Prevention of
angioneurotic edema. Stimulation of
protein synthesis (burns, trauma, cancer,
AIDS) Men: Congenital Micropenis,
Hypogonadism, Impotence, Sexual
Libido; Women:
Osteoporosis and Endometriosis,
Fibrocystic Breast Disease and Breast
Cancer. Children: Stimulate linear bone
growth and speeds up growth of secondary
sexual characteristics, eg. penile growth
and pubic and axillary hair.
Oral
androgens:
Oral androgens are
not metabolized into testosterone but act
directly on androgen receptors. Because
they cannot be bioconverted into DHT or
estradiol, they are not as biologically
active. All androgens appear to act on
same receptors, but tissue sites vary in
absorption and metabolism. Oral androgens
are used medically for those patients with
bleeding disorders or intolerant of
injections.
- A)
Methyltestosterone (Android, Metandren,
Oreton methyl, Testred,
Virilon)
- B)
Fluoxymesterone
(Halotestin)
- C) Danazol
(Danacrine)
- D) Stanozolol
(Stromba, Winstal) Approved for
veterinary use only in US
Testosterone
Patches and a new
alternative:
Natural
Testosterone (T) can be used safely in
large doses by men who are deficient .
Physiologic doses present no apparent
health risks. A novel method of
administration through a skin delivery
system is now available pharmaceutically.
(2) Testoderm© /AndroDerm© are
patch delivery systems of natural
testosterone. They each deliver 4-6mg of
testosterone daily and can be applied to
the shaved scrotum or anywhere on the body
. Androderm is a very similar preparation
which releases 5 mg of T daily. To mimic
the normal pattern as much as possible,
the higher levels of testosterone occur
early in the morning. T patches are
applied each morning and result in a surge
of hormone within a few hours of
application.
Self-administration
by this technique is safe but awkward.
AndroGel™, a newly released
testosterone gel has been developed by
Unimed (7) and a natural testosterone
cream, TestoCreme® , has been
developed by Dr.
Kryger in Monterey,
California (5). Testosterone pellets (
TestoPel®) are also available for
hormone replacement in men. Even more
reliable than patches , Testopel pellets ,
contain 25 mg of a timed release
testosterone ; they can be inserted
beneath the skin to deliver testosterone
over 4-months in a simple office
procedure. (6). All testosterones are
prescription items which need to be
applied daily to maintain their long
duration of action. The hormone
testosterone is naturally derived from a
food source, soybeans or Mexican yams ,
and is identical to that T hormone
secreted by the testicles.
Why see
the doctor for a
cream?
Side effects of
any anabolic steroid depend on the extent
to which receptors on target cells are
stimulated. There are receptors on
sebaceous glands, hair follicles, and
muscle tissue and brain tissue. The side
effects would then be increased acne,
increased body hair growth and increased
male pattern baldness, and increased
muscle mass. Physicians are well advised
to monitor liver function, even if oral
steroids are not being used, and to
withdraw the hormone or decrease the
dosage in such cases.
It does not take
much hormone to exceed the recommended
physiologic dosage. Monitoring by a
physician and regular blood tests are
important to get the ideal level for each
man. The longer lasting injectable
preparations are synthetic steroid
supplements and should be delivered
intramuscularly by injection under
physician supervision. These synthetic
products do have various potentially
dangerous side effects. Most of the
effects are related to liver toxicity from
excessive doses. Testosterone has a very
large safety margin. Direct toxicity is
unknown in men, however in women
testosterone does cause masculinization
and facial hair growth. Due to the fact
that testosterone can be made from
progesterone in the female, it has been
used successfully as a female sexual
stimulant in tiny doses, for women with
decreased sex drive due to menopause.
A study is now
underway by The
Preventive Medicine Clinic of
Monterey
using the testosterone 10% rapidly
absorbing cream. The testosterone cream is
a prescription item and requires an early
morning blood test to check the serum
hormone levels before starting on the
hormone therapy. (5) It is also
recommended that the PSA (prostate surface
antigen) and a DRE ( digital rectal exam)
be done prior to hormone treatments of any
kind to rule out an occult or hidden
cancer.
References:
1. Low Serum
Testosterone: a Cardiovascular Risk in
Elderly Men. Conrad Swartz, Geriatric
Medicine today/Vol 7. No 12/Dec.
1988.
2. Transdermal
testosterone Substitution Therapy for male
hypogonadism. Bals-Pratsch,M, Yoo YD,
Knuth VA, Nieschlag E , 1986 . Lancet
4/943-946.
3. Transdermal
delivery of Testosterone. Findlay JC,
Place V, Snyder PJ, 1989. J. Clinical
Endocrinolology Metab. 64; 266-268.
4. Morning
erections and testosterone cream. A case
report , Abraham H. Kryger, DMD, MD.
6. Androgel.com
for information about the new
testosterone gel.
6. Barnhart,
Edward R., Publisher, Physicians' Desk
Reference, 45th Edition, Medical Economics
Data, Oradell, NJ 1991
7. Berkow, Robert,
MD, Editor, The Merck Manual of Diagnosis
and Therapy, Fifteenth Edition, Merck
Sharp & Dohme Research Laboratories,
Rahway, NJ 1987
8. Bower, Bruce,
"Pumped Up and Strung Out", Science News,
Vol.140, No. 2, July 13, 1991
9. Erinoff, Lynda,
Editor, and Lin, Geraline C., Editor,
National Institute on Drug Abuse Research
Monograph Series, Anabolic Steroid Abuse,
US Department of Health and Human
Services, Washington DC, 1990.
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