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Fact
or fiction A discussion on the fors
and againsts of the Andropause.
Why is it that the 'male
menopause', otherwise known as the 'andropause', is
still neither recognised nor treated by the majority
of general practitioners, urologists or even andrologists?
I suggest that the main reasons can be grouped together
as historical, medical and image problems, and
illustrate how ideas come into fashion and go out of
style in a cyclical fashion.
Historical
Factors
One hundred and fifty years
ago, a German Professor called Berthold showed that
transplant of a cockerel's testis prevented atrophy
of the comb after castration. This first clearly documented
case of successful hormone replacement therapy inaugurated
a century of attempts to use testicular transplants
and extracts to rejuvenate the male, which has resulted
in the dubious "monkey-gland" image of testosterone
treatment which persists to this day.
It was only with the isolation
and synthesis of testosterone 60 years ago that effective
replacement therapy with this hormone became possible.
Testosterone was immediately introduced into clinical
medicine either as pellets of the crystals, which is
still the most effective and convenient form of treatment
available so far, or as the oral form methyl testosterone,
which unfortunately is toxic to the liver and heart,
and has adversely coloured the thinking of the two intervening
generations of physicians. It has only been recently
that tests have been made available to measure levels
of testosterone in samples of blood. Prior to this,
there was no way of diagnosing by analysis whether a
man was suffering from the Andropause. Such analytical
methods now make dignosing the Andropause a simple matter.
Within the English speaking
world there is not the eqyivalent of a gynaecologist
for mens' health issues. There are a number of "Andrologists"
who specifically deal in mens' health on the Continent
of Europe, where the diagnosis and management of the
Andropause is taken more seriously.
Furthermore, unlike the
situation for womens health, there has been a chronic
lack of interest and very little funding for mens' health.
The disparity remains as great as ever, even now.
Medical
Factors
In 1944 what is now described
as the male menopause, or andropause, was reported in
a key article in The Journal of the American Medical
Association by two American doctors, Carl Heller and
Gordon Myers. They compared the symptoms with those
of the female menopause, and undertook a blind controlled
trial showing the effectiveness of testosterone treatment.
Even after this excellent article, the condition and
treatment with testosterone in general, other than in
obvious cases of testicular insufficiency, failed to
achieve general acceptance.
400 men attending a private
clinic in London complaining of symptoms which they
or their GPs attributed to the male menopause, were
studied. The nature of the complaints and their frequency
were remarkably similar to those reported in the Heller
and Myers study.
These included fatigue
82%, depression 70%, irritability 61%, reduced libido
79%, awareness of premature ageing 43%, aching and stiff
joints in the hands and feet 63%, increased sweating
especially at night 53%, and classic hot flushes 22%.
Last but not least, 80% suffered erectile dysfunction,
reduced early morning erections often being an early
warning sign.
The age range of 31-80
(mean 54) was wider than that of the menopause in women
(45-55) reflecting the importance of the wide range
of factors influencing its onset. The overlapping associated
factors appeared to be psychosocial stress (59%), alcohol
(35%), injuries or operations, particularly vasectomy,
(32%), medication (31%), smoking (26%), obesity (22%),
infections (such as the orchitis caused by mumps
and glandular fever, and prostatitis) (11%) and impaired
descent of the testes (5%).
The hormonal picture clearly
demonstrated the reasons why this condition remains
undiagnosed. Total testosterone, which is all that is
usually measured in men complaining of these symptoms,
was only low in 13% of cases. However, more detailed
blood analyses showed that the Free Androgen Index (FAI)
obtained by dividing total plasma testosterone level
by that of the important carrier protein, Sex Hormone
Binding Globulin (SHBG), was decreased in 74%, mainly
because of high levels of the latter.
One obvious difference
between the female menopause and the andropause is the
contrast between the abrupt fall in oestrogen levels
in women, compared to the slow decline of total plasma
testosterone levels with age in healthy men. However,
there is a range of factors which can cause a relative
rather than absolute deficiency of testosterone in men
from mid-life onwards. Free, biologically active, testosterone
in the blood and tissues decreases markedly with age,
mainly because of the rising levels of the binding protein
SHBG in the blood, which stops the testosterone
getting into the cells to exert its many important functions.
There is also decreased production of testosterone by
the testes, because of stress, illness, low fat diets,
and altered hormonal balance in the body due to ageing
and other life events.
The findings in a cross-sectional
survey of 1,000 men in London, indicated that impairment
of the many actions of testosterone crucial to both
vitality and virility causes symptoms of the Andropause
to emerge when the FAI falls to a critical level of
around 50%, or the total testosterone level is subnormal.
There was a significant
dose related relief of the andropausal symptoms with
two oral forms of treatment (Restandol [Organon], Pro-Viron
[Schering]), and especially with testosterone implants.
The safety of the forms of testosterone treatment used
in this carefully monitored group of men, particularly
in relation to the heart, liver and prostate gland was
confirmed by detailed serial tests at periods of three
to six months for up to five years.
Image
Factors
There are a variety of
what can best be described as image problems connected
with the male menopause and the use of testosterone
to treat it. Firstly the name of the condition, even
if dignified with the medical title of Andropause, appears
an unacceptable threat to masculinity, the "macho"
self-image. It is seen as their end of life as potent
males, as leaders and as lovers. While women are willing
to discuss with each other, and with their medical advisers,
their menopausal symptoms and HRT to mitigate them,
men are remarkably reluctant to turn to either unless
desperate.
Secondly, the condition
is often incorrectly confused with the psychological
traumas of the "Male Mid-life Crisis". Thirdly,
because of reports of the abuse of anabolic steroids
by athletes, testosterone has suffered a very bad press.
Together with deliberately exaggerated horror stories
of their physical and psychological dangers, which have
filled the newspapers at increasingly frequent intervals
over the last twenty years, this "pharmacological
arms race" has damaged testosterone's image.
Fourthly, there is the
public perception of testosterone as the hormone responsible
for undesirable male traits such as aggression and hypersexuality.
The unfounded fear that such treatment will "bring
out the beast in men", and turn them into rapacious
monsters as portrayed by Jack Nicholson in the recent
film "Wolf", holds many andropausal men, who
unlike him cannot claim to have "retained my testosterone
longer than most males", back from treatment.
Lastly, there is the same
argument that women had to overcome in relation to HRT,
that it was flying in the face of nature and they should
learn to grow old gracefully. Given the wide range of
benefits to psyche, soma and sexuality that oestrogens
are being shown to offer postmenopausal women in adding
life to years as well as years to life, increasing numbers
see it more as modern science giving nature a helping
hand. It seems likely that men will come to the same
view of living their lives like alkaline batteries,
going full charge to the end.
Key
Points on TRT in the treatment of the Andropause
Reduced Testosterone
activity is common in men from the age of 40 onwards.
This causes the loss
of energy, libido and potency which make up the
"Male Menopause" or "Andropause".
The Condition can
usually be helped by carefully monitored Testosterone
Replacement Therapy (TRT).
TRT is as safe and
effective as Hormone Replacement Therapy (HRT) for
women.
In addition to TRT,
a wide range of other treatments to restore potency
are available, especially Viagra.
TRT is an important
form of preventive medicine, probably slowing the
ageing process in men.
Testosterone
Replacement Therapy for Men (TRT)
TRT - HRT
for men using Testosterone, has been shown to be dramatically
effective in relieving symptoms and restoring drive,
health, potency, and a sense of renewed vitality and
virility when the right preparations are given to the
right patients in the right doses at the right
time.
To ensure its safety and
effectiveness however it is essential that a full assessment
or "work-up" of each patient is carried out
before hormone replacement is started, and that the
results of treatment are carefully monitored. For this
purpose careful history-taking and examination and blood
tests need to be carried out.
Both to establish the diagnosis
and to monitor the treatment properly, laboratory measurements
of the sex hormones and the complex range of factors
regulating their action, together with tests of blood
fat, liver, kidney, and prostate function and haematology
profile, all need to be checked before treatment and
at each follow-up assessment.
TRT is
usually given in tablet or capsule form for the first
three to six months. It can then be continued if necessary
by mouth, transdermally, by injection, or by implantation
of pellets of fused testosterone crystals into the buttock,
under a local anaesthetic, at six monthly intervals.
Availability
of Testosterone Preparations
In
many parts of the world, the two main safe oral preparations,
Testosterone Undecanoate (Andriol or
Restandol made by Organon) and Mesterelone
(Pro-Viron made by Scherring) are available, as well
as Testosterone Pellet Implants, also
made by Organon. Transdermal Testosterone
in the form of body or scrotal patches or creams is
also available in most countries. In the USA, Testosterone
is mainly available either by patches,
or injectable forms such as Testosterone
Enanthate, though it is hoped that Andriol
may soon also be available there.
Availability
of treatment
The
availability of testosterone treatment is rapidly increasing
world-wide, as more doctors become convinced of the
benefits and safety of TRT for men. One of the aims
of the Andropause Society is to accelerate this process
by making doctors more aware of the problems associated
with the Male Menopause, or andropause, and informing
them of the latest research in its favour and providing
training for them via the Web using the latest video
conferencing technology.
This is the commonest presenting
problem in male sexual dysfunction clinics and peaks
at the time when the andropause appears, that is the
mid-forties onwards. It is a major health problem which
is seldom adequately investigated or treated.
The
Mechanics of Erection
Man's ability to have an
erection, which has been worshipped from the earliest
of times, is actually a recurring miracle of hydraulic
engineering. It is brought about by a complex series
of chemical changes and nerve reflexes, which work together
to increase the amount of blood flowing into the penis
and temporarily decrease the amount going out. Two elongated
blood sacks, the corpora cavernosa, become engorged
and create the erection. This event, which is achieved
with effortless and sometimes embarrassing ease in the
teens and twenties, usually becomes a more difficult
feat in the thirties and forties, can be variable in
the fifties and sixties, and is often a disappointingly
brief and infrequent wonder in the seventies and beyond,
especially in the 'hormonally challenged' andropausal
male.
Testosterone
and Erectile Function
Though it is difficult
to say precisely what part testosterone plays in helping
to produce erections, it certainly both primes the penis
and triggers the chain of events which bring an erection
about. It is surprising, but gratifying, how often when
adequate testosterone therapy is given, all the symptoms
of the andropause disappear within a few weeks or months,
including erectile difficulties, particularly when other
factors contributing to its onset or continuation are
dealt with.
A statistically highly
significant improvement in erectile function occurred
in over 70 per cent of 1000 cases treated with a variety
of different forms of testosterone. This was particularly
marked with the more powerful oral preparation, Restandol
(Andriol), which sometimes needed to be given in high
but safe doses, and with the testosterone pellet implants.
Though this use of testosterone
to help erection problems is controversial and not acknowledged
by some authorities, which say it only increases frustration
without giving back the means to perform, this is certainly
not the experience in this large group of patients.
The efficiency of testosterone in restoring potency
is a common experience with doctors prepared to give
it an adequate trial.
It was even recognised
over 50 years ago in the article on the 'male climacteric'
by Drs Heller and Myers in an article on"The Male
Climacteric" in JAMA in 1944. They found that erectile
function returned in nearly all of their testosterone
deficient patients when they gave the hormone and went
away again when they stopped.
Even though it is more
difficult to restore function than desire, unless the
source of the problems is obviously psychological or
mechanical, it seems logical to investigate the testosterone
balance of the patient, and restore it to normal as
the first stage of treatment. Even if erections are
not greatly improved by this alone, libido and confidence
usually are. The most commonly used methods such as
penile injections of prostaglandins, as in Caverject,
then seem to work much better. Recent experience at
in London has shown this to be particularly true when
Viagra and Testosterone are combined to cure over 98%
of impotence problems.
THE ADDITION OF
TESTOSTERONE REPLACEMENT THERAPY TO TREAT ERECTILE DYSFUNCTION
AFTER FAILURE OF SILDENAFIL ALONE IN MEN WITH ACQUIRED
ANDROGEN DEFICIENCY SYNDROME
Brian Rosenthal, Phillip C. Ginsberg, Michael
Metro, Richard C. Harkaway, Philadelphia PA
(The Journal of Urology, Vol. 169, No 4, Supplement,
Tuesday, April 29, 2003)
INTRODUCTION AND OBJECTIVE: While Viagra
(sildenafil citrate) is an affective treatment for erectile
dysfunction, it does not always result in adequate potency.
We evaluated whether combination therapy with Viagra
and testosterone replacement theapy is effective in
achieving adequate potency in patients who have failed
with Viagra alone and were subsequently found to have
low serum testosterone levels.
METHODS: Between July 2000 and June
2001, we evaluated 80 men who failed 3 months of Viagra
therapy at maximum dosage with at least three attempts
at intercourse during the three month period. 24 of
the 80 men were found to have testosterone between 90
and 400mg/ml. Each of the 24 men was then started on
testosterone replacement (Androgel 5mg daily) for 4
weeks, Viagra was subsequently restarted in combination
therapy with the Androgel after 4 weeks of androgen
replacement therapy. Potency was defined as the ability
to have at least one episode of satisfactory intercourse
during the treatment period.
RESULTS: At 4 weeks follow up, after
the start of Hormone Replacement Therapy (HRT) alone,
none of the men had regained potency. At 3 months follow
up after combination therapy was started, 22 of the
24 men (92%) reported improved potency.
CONCLUSIONS: We recognize that this
study lacks an adequate control group of men with prolonged
use of HRT alone to determine the success of potency.
However, our data shows promising results for the use
of combination therapy with testosterone replacement
therapy and Viagra in patients who have failed Viagra
and were found to have low normal serum levels of testosterone.
In addition, it underscores the number of men with low
or low-normal testosterone levels who would benefit
from testosterone screening when being evaluated for
erectile dysfunction.
In
the treatment of erectile dysfunction (E.D.) Viagra
is‘a giant leap for mankind’.
Probably more men care about putting the manhood back
in the man than putting a man on the moon. In fact,
this drug can put a man and woman over the moon by ending
the dreaded ED and the misery this causes.
In
terms of media attention, it seems to have caught the
public imagination just as much, and not even NASA’s
triumph made the cover of the two American magazines
Time and Business week simultaneously, as Viagra did
in 1998.
Does
it deserve this degree of hype? It seems to do so, both
as a major advance in a long neglected area of men’s
health, and as the official dawn of a ‘New Era
of Lifestyle Drugs’.
How
Good is Viagra?
In over 4,000 patients in more than twenty different research
studies World-wide, Viagra has been shown to be highly
effective in ED of many different types, whether due
to psychosocial problems, diabetes, or prostate cancer
operations. The benefits are dose related, just over
60% responding to the 25mg dose, over 70% to 50mg, and
80% to 100mg.
How
Bad is Viagra?
The
side effects of Viagra are also dosage related, and
the figures shown are on the strongest dose of 100mg.
Fortunately, they are usually mild and short-lived,
and with experience, its usually possible to adjust
the dose for maximum action and minimum side effects.
In the trials, only 2-3% withdrew because of unwanted
reactions to Viagra, and generally it is considered
a very safe drug.
Viagra
and the Andropause
Viagra
only treats one symptom of the male menopause or andropause,
that of E.D. The others of low sex drive, reduced mental
and physical energy, irritability and night sweats would
all go untreated by Viagra alone. Also, all the research
studies agree that it is not an aphrodisiac, and will
not work if the desire is not there.
Testosterone
is the hormonal basis of desire in both men and women,
and if it is low, so is the libido. It is the desire
and sexual excitement that generates the nitric oxide
that increases genital blood flow and lubrication in
both sexes, producing erections in the male, and by
slowing its breakdown, Viagra prolongs these responses.
This is why both in theory and in practice the two work
better together.
Also,
as was recorded in two key articles in the Journal of
the American Medical Association over fifty years ago
(Werner, A.A., JAMA, 1939 and Heller, C.G. and Myers,G.B.
JAMA, 1944: 126:472), testosterone treatment on its
own can restore potency in the majority of andropausal
men.
In
over a thousand such men studied in London over the
last ten years, in 65% erectile function improved with
the male HRT treatment alone to the point where intercourse
was satisfactory. Only in the remainder, the group now
most likely to receive additional benefit from Viagra,
was treatment needed with methods such as the now thankfully
largely superseded penile injections.
Also
the initial findings of work on the combined treatment
suggests not only a higher response rate (up to 98%),
but that Viagra works at lower doses, and longer and
stronger with additional testosterone.
Also
of course Viagra has none of the preventive medical
benefits of male HRT with testosterone, especially to
the heart and circulation, muscles and bones. Like oestrogen,
testosterone has recently been shown to increase nitric
oxide production in blood vessels all over the body,
which as in the penis relaxes them and improves blood
flow. This is likely to be important in slowing aging
changes in both heart and brain as papers presented
at The First World Congress on the Aging Male held
in Geneva February (1999) confirmed.
Viagra
Plus Testosterone is the logical answer to the commonest
cause of E.D., the andropause.
Testosterone
replacement therapy has been widely available for over
60 years and has been used extensively to treat men
with low levels of the hormone.The aim of treatment is to return the
level of testosterone in the blood to normal that is
from a state of deficiency to sufficiency.Such a concept is true for diabetes and
other hormonal deficiency states such as an underactive
thyroid gland as well of course as hormone replacement
therapy for menopausal women.
There
has been concern in the past that testosterone replacement
therapy can cause prostate cancer, principally because
prostate cancer, when it exists, is often made worse
by testosterone.Although clearly the presence of prostate cancer
is a contra-indication to testosterone treatment, there
is no evidence that testosterone treatment causes prostate
cancer. Prostate
cancer appears to arise because of genetic and environmental
factors and it is believed that a high fat diet may
also be implicated.In a review of over 1,000 patients at a London
clinic, the chance of getting prostate cancer whilst
on testosterone therapy appears no greater than in the
normal population.Other studies have also failed
to show that testosterone precipitates prostate cancer1,2.In order to make sure that patients do not have
prostate cancer before testosterone replacement therapy
is initiated, all patients have a blood sample taken
to measure the level of prostate specific antigen a
marker for prostate cancer.The PSA level should be checked
6 monthly thereafter in line with World Health Organisation
guidelines.
Testosterone
can increase the amount of red blood cells and the pigment
haemaglobin however it is common to find that men with
low levels of testosterone have low levels red cells
and haemaglobin before treatment is started, infact
some are clearly anaemic.In such cases testosterone replacement
therapy merely normalises their blood picture.
There
has been great interest recently about the benefits
of testosterone on the cardiovascular system.It has been reported that men with abnormally
low levels of testosterone may be at greater risk of
cardiovascular disease3,4,5.Such men with heart disease when
given TRT to normalise their testosterone levels gain
cardiovascular benefit and one study has shown that
blood flow in the coronary arteries is improved4,5.Other studies have shown that men with low levels of testosterone
have an adverse cholesterol, blood sugar and blood clotting
factor profile and therefore may be at greater risk
of cardiac problems6.Testosterone replacement therapy
reverses these adverse profiles when they are present.
It
has also been shown that men with abnormally low levels
of testosterone are at greater risk of osteoporosis
and fracture of the hip and that replacement may benefit
the bones7,8.
Depression
and lack of well-being are also common associations
with low testosterone levels and that treatment with
testosterone improves symptoms9
Testosterone
deficiency, like thyroid deficiency or diabetes is an
abnormal state of affairs with physiological and psychological
consequences.As it is an abnormality it should be treated.
References
1.Atkinson LE, Chang YL, Snyder P.Long-term experience with testosterone replacement
through scrotal skin.In: Nieschlag E, Behre HM (eds)Testosterone.Action deficiency substitution.
Springer-Verlag, Germany. 1998, 364-88.
2.Schroder FH.The prostate and androgens: the risk of supplementation.In: Oddens B, Vermeulen A(eds)Androgens and the aging male. Parthenon publishing
Group., New York, 1996, pp223-6.
3.English KM, Mandour O,Steeds RP et al. Men with coronary artery diseas have lower levels of androgens
than men with normal coronary angiograms.Eur Heart J. 2000; 21: 890-4.
4.Rosanno GMC, Leonardo F, Pagnotta P et
al.Acute anti-ischaemic effect of
testosterone in men with coronary artery disease.Circulation.1999; 99: 1666-70.
5.Webb CM, McNeill DCRR, Hayward CS et
al.Effect of testosterone on coronary
vasomotor regulation in men with coronary heart disease.Circulation.1999, 100, 1690-6.
6.Phillips GB, Pinkernell BH, Jing TY.The association of hypotestosteronaemia with
coronary artery disease in men.Arterioscler Thromb.1994; 14: 701-6.
7.Jackson JA, Riggs MW, Spiekerman M.Testosterone deficiency as a risk factor for
hip fracture in men; a case control study.Am J Med Sci.1992; 304: 4-8.
8.Finkelstein JS.Androgens and bone metabolism.In: Nieschlag E, Behre HM (eds).
Testosterone.Action deficiency substitution.
Springer-Verlag, Germany. 1998, 187-207.
9.Wang C, Alexander G, Berman N et
al.Testosterone replacement therapy
improves mood in hypogonadal men -a clinical research centre study.J Clin Endocrinol Metab.1996; 81: 3578-83.
There
is no such thing as estrogen! It is, instead, a name for
a diverse group of ubiquitous compounds that have the
capability to activate cellular activities in the many
life forms that depend on it. In fact, there are few if
any compounds more consistently present in nature than
estrogens, except, perhaps, DNA. These estrogenic compounds
are structurally interrelated by similarity in the dimensions
and shapes but differing greatly in chemical composition.
It is this similarity in conformation that allows different
estrogenic compounds from totally different sources to
activate estrogen receptors in different types of cells
from different genuses and species.
When we discuss estrogens as human hormones, we must
include the many environmental and dietary sources of
naturally occurring estrogenic compounds as well as
the steroid hormones produced within, since all can
activate receptors in human cells throughout the body.
Environmental estrogens that may be synthesized for
other purposes, such as DDT and other pesticides, are
called xeno-estrogens. Plant estrogenic compounds are
called phyto-estrogens. Many powerful herbal compounds
belong to this category and have their effects mediated
through activating estrogen receptors. All structurally
similar molecules from these groups have at least some
capability to occupy receptors and activate or block
the activity programmed for that receptor, some more
powerfully than the native hormone!
In humans, estrogen receptors
have been found in every tissue. Two different estrogen
receptors, ERa
and ERb, have
been identified, each switched on and controlled by
a different gene. Both may be active in the same cells
at different times of growth, development or "mature"
cell activities. They are associated with different
activating proteins which allow for great diversity
of effects at different times. They control our brains,
our immunity, our bones and our sexuality. In fact,
they participate in every major function in the body.
Why else would they be so widely distributed? It should
become obvious by now that estrogens are essential for
life and health.
So where does testosterone
the "king" of the powerful hormones fit in
to this schema. It is a "masculine" hormone
of higher species that has specific receptors and effects.
Testosterone can either activate androgen receptors,
AR, or be converted to estradiol to activate estrogen
receptors! This
occurs in both sexes. We tend to think in terms of "male"
or "female" when we discuss testosterone and
estrogen. But what is becoming obvious is that these
hormones are not sex specific, rather sex dominant,
both being present in both sexes.
Biblically, in Genesis,
the female is formed from the "marrow" or
essence of the male. The Yin and the Yang principle
also expresses a duality and an intertwined connection
between the essence of male and female, testosterone
and estrogen. What has not been recognized is the fact
that all human estrogens are derived from "male"
hormone precursors, particularly testosterone! This
conversion takes place inside cells and tissues all
around the body. In fact, many of the well known functions
of testosterone are mediated through conversion first
to estradiol, the primary estrogen. In particular, our
sexuality is governed almost ironically by this "male"
to "female" conversion! Both sexes seem to
have this "androgynous" switching to activate
the final receptors of sexuality, the ERa
and ERb estrogen
receptors. These may balance the classic androgen receptors,
AR, that have been until now thought to be the major
players in sexuality. So it comes as a shock to most
males that estrogen may be the most powerful of all
the "sex-hormones", the queen among kings!
Many of the popular herbs used to enhance sexuality,
such as Maca, Ginseng, Vitex and others, may contain
active phyto-estrogens that interact within our hypothalamus
and the diverse ER receptors located there, directly
firing up these receptors. This may account for the
stimulating effects that have been reported with use
in both men and women. Improvement in hormone activity
during the peri-menopause and menopause may be derived
from the ability to activate the receptors that are
getting variable messages from the failing ovaries.
Likewise, in men, improved libido or sexual performance
may be the result of activation of the ER receptors
that mediate these functions centrally or activation
of local receptors in the pelvic area directly as male
hormones decline in a somewhat similar fashion.
It is human nature to try to push the dose forever
upward in attempts to find the maximum purported effect.
Is more better? Like all hormones there is a window
of optimal effect. All hormones are pulsatile in nature.
There are none that are steadily produced indefinitely.
Cellular effects vary with the changing bio-rhythms
of cell cycles and cell functions. Hormonal receptors
also are variable in activity, turned on either through
a gene switch or by activation of chemical messengers
to turn on or off hormonal functions. Without these
switches and variable hormonal controls there would
be chaos inside cells once a powerful hormone enters
to trigger a function. Overstimulation by hormones or
hormonal compounds from herbs may result in down-regulation
of the receptor through central genetic or secondary
mechanisms. In other words, more is not always better.
Balance is the key!
Particularly, treatment with testosterone in high doses
results in excessive conversion into estradiol essentially
nullifying the benfits initially seen or looked for.
Much of the confusion in the medical literature is the
result of mis-understanding of this concept when large
doses were tested for effects, particularly sexual function.
With aging there is a general increase in conversion
of androgens into estrogen. This problem may underlie
the deficiency of testosterone through down regulation
centrally or through down regulation of receptors at
the cell itself. Treatment failure may be frequently
reversed using aromatase inhibitors or non-aromatizable
androgens. The delicate balance is the key to successful
treatment with all hormone replacement strategies.
When
Testosterone drops, Alzheimers protein increases
Sam
Gandy et al
ANA 126th Annual Meeting, Chicago, 30.9.2001
When doctors suppress
testosterone levels in men with prostate cancer, they
may inadvertently be increasing the level of a substance
that appears to control the risk of Alzheimer's disease.
A recent
study indicates that when testosterone levels go down,
there is a dramatic increase in levels of a protein
known as beta amyloid, the prime suspect in the death
of nerve cells in Alzheimer's disease.
We believe this
phenomenon may explain why Alzheimer's disease occurs
in late life. People with a genetic predisposition to
Alzheimer's may have borderline amyloid levels until
menopause or the male equivalent. Andropause, reduces
gonadal hormone secretions. Brain amyloid levels may
then rise enough to cause amyloid accumulation to begin.
A number of studies
have found that women on hormone replacement therapy
in the menopause have half the risk for the
disease, leading Gandy and his colleagues to speculate
that gonadal hormones such as estrogen and testosterone
might help to break down amyloid.
Although it has
not been proven, a wealth of evidence suggests that
the accumulation of amyloid into clumps called 'senile
plaques' is toxic to nerve cells. On autopsy of Alzheimer's
patients, doctors find especially high numbers of senile
plaques in brain areas that underlie memory
and reasoning, brain functions that deteriorate dramatically
in the disease.
Previous studies
by Gandy and his colleagues showed that brain concentrations
of amyloid increased significantly in female
guinea pigs whose ovaries had been removed. When the
animals received hormone replacement therapy, their
levels of amyloid dropped again.
The researchers
realized that a natural experiment could be conducted
with men whose testosterone levels are suppressed as
part of their treatment for prostate cancer. In each
of six men, when testosterone levels were suppressed,
plasma amyloid rose two-fold over the six
months' duration of the trial.
Other researchers
have shown that people with higher levels of amyloid
circulating in the blood are more likely to get Alzheimer's.
For that reason, it will now be important to follow
these measures for several years, while also administering
serial cognitive function exams to determine whether
any of the men develop Alzheimer's disease.
As for the effectiveness
of hormone replacement therapy in preventing Alzheimer's,
a large, ten-year study currently underway will yield
five-year interim result in 2003.
If hormones are proven to be effective in this trial, then
prevention of Alzheimer's disease may become a consideration
in selecting candidates of both genders for hormone
replacement therapy.
The
Mid-life Crisis by
Jean Coleman, MSc Consultant
Clinical Psychologist
Midlife
crisis is a term frequently used, and often incorrectly.
The midlife crisis is not another way of describing
the ‘male menopause’, andropause, or androgen
deficiency in the aging male.
Emotional, not Hormonal
The
midlife crisis is concerned with emotional issues,
the andropause is a condition caused by imbalance
of hormones.
The
midlife crisis strikes in the thirties in most
cases. Recently, because of the way some young
people can achieve material goals more rapidly,
the onset may be earlier, early thirties or even
late twenties.
The
andropause is encountered later in life - in most
cases. Depending on predisposing events earlier
in life, patients can begin to suffer from the
typical symptoms much earlier than the usual late
fifties to sixties. This syndrome can occasionally
manifest in the thirties and even more rarely,
in the late twenties.
The
midlife crisis is not biased against either sex,
both men and women can suffer from it. The andropause
is rarely found in the female of the species.
Technically,
of course, it is possible for a man to suffer
from both conditions at once. Not a pleasant combination
with even more confusion arising for both the
patient and those trying to help him.
So, what is the Midlife Crisis
The
midlife crisis is characterized by low mood, dissatisfactionwith life, a feeling of pointlessness in life. It is not always
distinguishable from clinical depression. Patients
are often treated with antidepressants, and this
may be appropriate.
Those
in crisis may show their distress by reacting
in several different ways: by denial (by escape
or overcompensation), by decompensation (with
anxiety, depression or rage), or by regression.
An individual may become discontented at work,
resort to alcohol or risk taking behaviour.
The
range of feelings experienced have been variously
described as hollowness and lack of genuine enjoyment,
emptiness and uncertainty, a mixture of strain
and boredom, floating unfocussed melancholy and
depression. This is the time when people are believed
to be vulnerable to hypochondria, accidents, illness,
alcoholism and suicide.
Midlife
crisis is described as an existential crisis,
that is to say, it is centred about issues of
meaning and purpose in life. This is why it arises
at the time it does, because by the mid thirties,
young people have often achieved their initial
goals in life (or realized they are not attainable).
The
hormone productionlevels are dropping, the head
is balding, then sexual vigour is diminishing,
the stress is unending, the children are leaving,
the parents are dying, the job horizons are narrowing,
the friends are having their first heart attacks;
the past floats by in a fog of hopes not realized,
opportunities not grasped, women not bedded, potentials
not fulfilled and the future is a confrontation
with one’s own mortality.’ (M.W.Lear,
1973).This
brings the person to appoint in life where they
need to review their life. Is this what I want
to be doing? Do I want to do this job forever?
Is this really the person I want to be with for
the rest of my life?
Crisis,Transition or Life Review?
For
most people, this period of review is not really
that critical. It is a transition period to the
second half of adult life may not be experienced
as a major problem. Where it does become a problem
is with individuals who have significant unresolved
issues from earlier in life, usually from childhood.
Becoming your own Person
For
example, Tony spent his childhood trying always
to be the person his controlling parents wanted
him to be. He was given the responsibility for
his younger siblings at the age of 6, and woe
betide him if anything untoward happened! At only
17, he escaped to live with, and then marry, a
lady who was ten years his senior and very happily
spent the next 17 years looking after by her,
but in a much less unpleasant way, still trying
to be the person she and her children needed.
Suddenly he became very depressed, fled the marital
home on a number of occasions and was found to
be sleeping rough in his car. He felt he could
not go on in this way and needed to change his
life and be on his own.
He
was overwhelmed with guilt at the way he felt
he was letting down this gentle lady who unbeknownst
to her, had been re-parenting him for all these
years. Fond of her still, he felt a strong need
at last, to go out into the world and live his
own life, to be his own person. Often in similar
cases, another woman is involved. In this case,
it was not.
He
never returned to his wife, and she had a difficult
time coming to terms with his leaving, but the
divorce was amicable and they continue to be friends.
He couldn’t continue to be a family man because
this involved continuing to be what other people
needed him to be. He needed to live for himself
for a while and learn to find his true identity.
Choosing the Right Goals
Young
people set out in life as adults with a series
of goals they wish to achieve. This is what they
believe will make them happy. To marry well, to
have this many children, to achieve this in my
career, to buy my own mansion; these are examples
of life goals. When these have been achieved,
what do you do next?
Sometimes
the goals set are inappropriate, as in the case
of Peter. Peter was a highly intelligent child,
but he got in with the wrong set where brawn rather
than brains was the thing to aspire to. He became
leader of the gang , the school bully and learned
to use coercion to get what he wanted.
Soon
after the birth of his first daughter, he found
he had no interest in his job as a storeman. He
could do this standing on his head. He was paid
well and already had his own, small, house. His
main interest suddenly was in nature and wildlife.
There was no one to share this with. He no longer
loved his wife and felt she’d be better off
without him and his aggressive outbursts. His
friends didn’t understand him and wanted
nothing more than to drink to oblivion or get
into a fight.
He
became depressed and thought of ending it all.
Eventually, he gave up his job and left his wife
and child in the family home to escape off round
the world where at least he could find interest
in plants and animals.Peter had ended up in the wrong life altogether
as a result of his poor choices earlier in life.
A Sense of one’s own Mortality
Completing
one’s initial life goals may be one precipitant.
Another is said to be a sudden clear awareness
of ones own mortality. Midlife crisis is often
preceded by the death of a parent or other close
family member; or even worse, the death of a friend
close to one’s own age.
It’s
as if the person suddenly feels vulnerable, ‘my
parents generation is old, we children are now
the grown ups in this society. We are the next
generation who will die. What’s the point
of all this if we are going to die anyway!’
A Purpose in Life
It’s
answering this last question that resolves the
midlife crisis. The person needs to find something
which gives them a purpose in life or which makes
life worth living. What this might be is different
for everyone. For some it may be grandchildren,
for others it might be a new wife, a new job,
revisiting an interest from the past or becoming
involved in spiritual matters.
If
the question is successfully answered, the person
can move on into a potentially more productive
or creative phase of life. If it has not been
dealt with, then the person may continue to be
depressed or unhappy indefinitely. Some writers
maintain that the one in continuing crisis may
go on repeating unhelpful patterns of behavior
or be subject to physical health problems. Some
may decide to end it all.
Midlife Crisis and Creativity
Jaques
(1965) maintained that the pattern of midlife
crisis is often seen in the lives of writers,
composers and artists. Their early work flows
easily from pen, brush, chisel or whatever. In
the second half of life, things progress more
slowly and with more of a struggle; but the results
are more meaningful, stronger, in many peoples
eyes, they are greater works of art.
Shakespeare’s
earlier works had a lighter, often more comedic
style; but it is his later works of tragedy that
have the deeper messages. So also with musicians
and other artists. Jaques would maintain that
the great work of Bach, Constable and Goya emerged
in mid-life.
Jaques
studied ‘some 310 painters, composers, poets,
writers and sculptors of undoubted greatness or
genius’. In this study, he found a tendency
for creativity either to cease, sometimes the
person actually died, or subsequent works were
changed in nature. The quality of work is no longer
a spontaneous expression but becomes a ‘sculpted
creativity’.
There
is no longer a need for obsessional attempts at
perfection, because inevitable imperfection is
no longer felt as bitter persecuting failure.
Out of this mature resignation comes the serenity
in the work of genius, true serenity, serenity
which transcends imperfection by accepting it.’
Levinson
(1976) also comments on the link between resolution
of the crisis and continuing effective creativity,
‘Men such as Freud, Jung, Eugene O’Neill,
Frank Lloyd Wright, Goya and Ghandi went through
a profound crisis at around 40 and made tremendous
creative gains through it. There are also men
like Dylan Thomas and F. Scott Fitzgerald who
could not manage this crisis and who destroyed
themselves in it.
Surviving the Midlife Crisis
Although
many writers describe the many possible negative
outcomes of this transitional period of life,
[‘psychological disturbance, depressive breakdown,
strengthening of manic defences’, Jaques,
‘under severe conditions many do not survive
it and commit suicide’ Rogers (1974), Levinson
(1976)] others are more positive in their conclusions.
Marmor
(1968) asserts that ‘the significance of
the crisis, psychotherapeutically, is that at
such periods of stress, properly presented interventions
can be of maximum efficacy’. Brim (1976)
concludes that ‘these changes, even when
they occur in crisis dimensions, bring for many
men more happiness than they had found in younger
days.
References
Jaques,
E., 1965: Death and the Midlife Crisis.
Int.J.Psycho-Analysis; 46: 502-514
Brim,
O.G., 1976: Theories of the Midlife Crisis.
Counselling Psychologist; 6 (1): 2-9
Levinson,
D. et al, 1976: Periods in the Adult
Development of Men: Ages 18-14. Counselling Psychologist;
6 (1): 21-25
Marmor,
J., 1968: The Crisis of Middle Age. Psychiatry
Digest; 29: 17-21
Rogers, K., 1974: Crisis at the Midpoint
of Life. New Society; 29 (619): 413-415
Differential
Diagnosis of andropause and male mid-life crisis
Probably
the best current definition of the term andropause is
that proposed by Tremblay and Morales as ‘when
men exhibit several of the symptoms and/or clinical
features of reduced testosterone availability to various
systems or organ functions’1. This key
article goes on to give a detailed list of symptoms,
which are strikingly similar both in content and frequency
to those originally listed by Werner2, and
several other authors over the past sixty years3;3;4;4-6;6.
This characteristic
"identikit" pattern of andropause symptoms
is the same as that seen in androgen deficient adult
males generally, whether caused by testicular damage,
suppression of testosterone by a prolactinoma, anti-androgens,
or increases in sex hormone binding globulin (SHBG)
caused by thyrotoxicosis or anticonvulsant drugs7.
It is also important
to distinguish the symptoms of the andropause from those
of male mid-life crisis. While the former most commonly
starts in the 45-55 age group, and is brought on by
androgen deficiency, the latter typically occurs age
35-45, and is a psychological, existential crisis. Though
they are often confused in both lay and professional
minds, to the detriment of the diagnosis and treatment
of both conditions, they have widely different clinical
pictures, which can and should be distinguished3.
Equally importantly
in relation to the differential diagnosis, the symptoms
are reversed by giving adequate doses of testosterone,
as reported consistently in the above studies and numerous
others over the last 50 years. Too often this group
of symptoms is written off as inevitable ageing, even
if it is occurring in forty or fifty year-olds, without
adequate clinical and laboratory investigation or a
therapeutic trial. This is in stark contrast to women
suffering similar symptoms who have far easier access
to their form of HRT.
Reference
List
1. Tremblay RR,.Morales
AJ. Canadian practice recommendations for screening,
monitoring and treating men affected by andropause or
partial androgen deficiency. The Aging Male 1998;
1:213-8.
2. Werner AA. The
male climacteric:Report of two hundred and seventy-three
cases. J.Am.Med.Ass. 1946;132:188-94.
3. Carruthers M.
Male menopause:Restoring vitality and virility. HarperCollins,
London, 1996.
4. Reiter T. Testosterone
implantation: A clinical study of 240 implantations
in ageing males. Journal of the American Geriatrics
Society 1963;11:540-50.
5. Heller CG,.Myers GB.
The male climacteric: Its symptomatology, diagnosis
