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Standards, Guidelines and Recommendationsof The International Society forThe Study of the Aging Male (ISSAM)Investigation, treatment and monitoring of late-onset hypogonadism in males Official Recommendations of ISSAM Department of Urology, Queen’s University Kingston, Ontario, Canada; *Faculty of Life Sciences Bar-Ilan
Key words: AGING, HYPOGONADISM, TESTOSTERONE REPLACEMENT
INTRODUCTION The field of hormonal alterations in the aging male
(PADAM), also widely known as andropause, is a
is attracting increasing interest in the medical com-
fast-developing field (since there is no consensus
munity and the public at large. Simultaneously,
on nomenclature, the terms late-onset hypo-
industry has realized the growing importance and
enormous potential of the impact of a rapidly
acceptable and used interchangeably). The under-
mounting population of males over the age of
standing of ADAM among large sections of the
50 years. This population will be positioned for
medical profession dealing with mature men (i.e.
special health needs in the first quarter of this
primary care, internists, urologists, etc.) has not
century and probably beyond. Among these needs,
kept pace with the developments in the field. The
hormone replacement therapy will find its proper
International Society for the Study of the Aging
place, as it has for postmenopausal women over
Male (ISSAM) believes that it is somewhat
premature to provide guidelines for the diagnosis,
It is fully recognized that the endocrinological
treatment and monitoring of men diagnosed with
changes associated with male aging are not limited
or suspected of suffering from ADAM. On the
to sex hormones. On the contrary, profound
other hand, a great deal of confusion and mis-
changes occur in other hormones such as growth
understanding exists surrounding the same three
issues (diagnosis, treatment and monitoring) of the
melatonin and, to a lesser extent, thyroxin. How-
condition. Therefore, ISSAM – in fulfilling its
ever, androgen decline in the aging male (ADAM),
mandate – considers that this is an opportune time
or partial androgen deficiency of the aging male
to provide factual information on the various
Correspondence: Professor A. Morales, Kingston General Hospital, Kingston, Ontario, Canada, K7L 2V7
STANDARDS, GUIDELINES AND RECOMMENDATIONS
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clinical aspects of the andropause in the form of
of early androgen preparations. The diagnostic cri-
a set of practical recommendations dealing
teria are presently better understood. For instance,
exclusively with ADAM and androgen replace-
recently, a couple of validated questionnaires4,5
ment therapy (ART). It is anticipated that further
have been proposed for either screening, diag-
recommendations and guidelines on other similar
nosing and/or assessing response to therapy5.
areas of competence for ISSAM will be produced
More sophisticated diagnostic and monitoring
questionnaires are in development. Although they
may prove useful for screening and diagnosis
hormone replacement in aging change frequently
of ADAM, all require further, wider experience,
and long-held views are now being vigorously
particularly in their transcultural applicability.
challenged. The material in these Recommenda-
tions represents recent information on the andro-
pause; however, it may require frequent updates as
Definition: A biochemical syndrome associated with
new and relevant data become available. At the
advancing age and characterized by a deficiency in serum
appropriate time, they may also be upgraded to
androgen levels with or without a decreased genomic
guidelines for the evaluation and treatment of
sensitivity to androgens. It may result in significantalterations in the quality of life and adversely affect the
A draft of Society’s Recommendations was
function of multiple organ systems.
previously published in this Journal1 to give the
opportunity for discussion at the 2002 biannual
DIAGNOSIS
meeting of ISSAM. The Recommendations were
reviewed by a panel of experts, a number of sugges-
Clinical
tions were submitted by well-informed physicians
The clinical picture is described in the definition
as well as representatives of industry and the docu-
below. It should be remembered that there is
ment was presented and discussed in Berlin during
significant interindividual variability in the onset,
velocity and depth of the androgen decline
approved in principle. Further opportunity was
associated with age, and no factors have emerged
given to the membership for criticisms. Some were
that predict the characteristics or effects of the
received and incorporated when deemed appro-
age-related hypogonadism. As a rule of thumb,
the mean serum testosterone level decreases after
the age of 50 years at a rate of approximately 1% per
DEFINITION
year. This is by no means a constant phenomenon:
biochemical hypogonadism is detected in only
In men, gonadal function is affected in a slow pro-
about 7% of the age group less than 60 years old but
gressive way as part of the normal aging process2.
increases to 20% in those over 60 years of age6. It
This process, leading to hypogonadism is variously
may be argued, therefore, that only a minority of
known as male climacteric, andropause or, more
individuals develop ADAM. This may not be the
case. Associated with advancing age, there is also
andropause and male climacteric are biologically
an increase in the levels of sex hormone binding
wrong and clinically inappropriate, but they
globulin (SHBG) which translates into a further
adequately convey the concept of emotional and
decrease in bioavailable testosterone (free plus
physical changes that, although related to aging in
albumin-bound fractions). When the diagnosis
general, are also associated with significant hor-
is based on the measurement of bioavailable
monal alterations. The clinical manifestations of
testosterone, up to 70% of men over the age of 60
male secondary hypogonadism have been well
were found to be hypogonadal4. To compound the
defined over 50 years3 but ART was not widely
difficulties in establishing biochemical and clinical
accepted, in part due to unrealistic expectations
correlates, there are three important areas that
and adverse effects due to improper management
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(1) It is not yet known what level of serum
(These manifestations need not all be present to identify
testosterone defines deficiency in an older
the syndrome. In addition, the severity of one or more of
man, although it is generally accepted that
them does not necessarily match the severity of the others,
2 standard deviations below normal values
nor do we yet understand the uneven appearance of thesemanifestations. Moreover, the clinical picture may or may
(11 nmol/l total testosterone or 0.255 nmol/l
not be associated with low testosterone. Therefore, theclinical diagnosis should be supported by biochemical tests
described by Vermeulen and colleagues7. confirming the presence of hypogonadism).
For bioavailable testosterone the value of
3.8 nmol/l has been recommended. A tool for
calculating free and bioavailable testosterone
Biochemistry
Establishing the presence of slight hypogonadism
on a purely clinical basis is, in most cases, difficult
significantly from laboratory to laboratory, the
and unreliable. Only the more severe cases lead
results from each patient should be compared
to clinical suspicion. Despite this, there is some
with the normal ranges established by each
controversy as to the need for hormonal evaluation
of the aging man. For instance, hormonal evalua-
(2) In older men, there may be variable responses
tion in men with erectile dysfunction has been
by the target organs (brain, bone, prostate,
questioned on the basis that it is not cost-
muscle, etc.) to the levels of androgens.
effective14. Although this scepticism is not shared
by others15,16, there are several reasons to justify,
(3) The response by target organs may be influ-
at least, basic hormonal assessment of men with
enced by a variety of endocrine disruptors,
erectile dysfunction. It is commonly accepted that
the nature of which is only beginning to be
the combination of low sexual desire and erectile
difficulties may be the result of serious hormonal
The combination of these three uncertainties
abnormalities. The reality is not as simple or clear-
is important: deficiency may become clinically
cut as that. Not only may hypogonadal men be
apparent at different points within an individual
capable of adequate sexual erections but hormonal
or a population, depending on the marker used
supplementation resulting in normal testosterone
(e.g. androgen levels, bone mineral density).
values does not always result in restoration of
libido and improvement in the quality of erectile
ADAM or the andropause is a syndrome characterized
In men at risk, or suspected of having hypo-
gonadism, the ideal test would be the measurement
(1) The easily recognized features of diminished sexual
of free testosterone by the equilibrium dialysis
desire and erectile quality, particularly nocturnal
method. This method, however, is difficult to
perform, not automated and largely inaccessible
to most clinicians. Measurement of ‘free testoster-
(2) Changes in mood with concomitant decreases
one’ by radioimmunoassay is widely available but
in intellectual activity, spatial orientation ability,
should be discouraged due to its unreliability. fatigue, depressed mood and irritability9;
Determination of bioavailable testosterone is
(3) Decrease in lean body mass with associated
attainable in some parts of the world but it is
diminution in muscle volume and strength10,11;
expensive and not readily accessible. Measurement
of total testosterone is readily available but the
(4) Decrease in body hair and skin alterations12;
results need to be interpreted with caution,
(5) Decreased bone mineral density resulting in
particularly in the elderly and the obese in
factual hypogonadism that is not disclosed by
the results of a total testosterone determination.
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The calculated free testosterone is an adequate
DHEA and DHEA-S
compromise when only determinations of total
testosterone and SHBG are available7. The
formula for calculated free testosterone is avail-
DHEA-S is a more constant feature of advancing
able from the Society’s web page. Calculated free
age than hypogonadism. By the fifth decade, the
testosterone is an indirect but reliable method.
levels of DHEA decrease to less than 30% of those
‘The evaluation of aged men’s androgenicity
in men under the age of 30 years19. There is a
should rely on at least one of these assessments’
widespread belief that declining levels of DHEA
(bioavailable testosterone or calculated free
run in parallel with a decrease in well-being and
that supplemental exogenous DHEA results in an
It should be remembered, however, that the
improvement in quality-of-life parameters20. More
methodology for assessment of SHBG is not
recently, a study in healthy aging men found no
standardized and that the results of calculated free
beneficial effect of DHEA over placebo21.
testosterone may vary among different areas of the
secreted primarily by the adrenal glands. Their role
in the maintenance of an adequate androgen milieu
is not known with certainty but appears to be
In patients at risk or suspected of hypogonadism the
limited. Limited trials22 have shown that exo-
following biochemical investigations should be done:
genous DHEA does not have a detrimental effect
(1) Serum sample for testosterone determination
on prostate-specific antigen (PSA) values; how-
between 08.00 and 11.00. The most reliable and
ever, only properly controlled long-term studies
widely acceptable parameter to establish the presence
will provide a clear picture on the effectiveness
of hypogonadism is the measurement of bioavailable
and safety of adrenal androgens in the treatment
testosterone or, alternatively a calculated free testos-
of global androgen deficiency states. Behavioral
correlates of DHEA and DHEA-S in the male are
inconsistent23 and consensus on their usefulness
(2) If testosterone levels are below or at the lower limit ofthe accepted normal values, it is prudent to confirmthe results with a second determination together withassessment of follicle stimulating hormone (FSH),Growth hormone luteinizing hormone (LH) and prolactin.
The production of growth hormone (GH), after
puberty, also decreases with age, about 14% per
decade25,26. Since the production of circulating
OTHER ENDOCRINOLOGICAL
insulin-like growth factor-I (IGF-I) is controlled
ALTERATIONS ASSOCIATED WITH
by GH levels, both decline together. This reduc-
ADVANCING AGE
tion is associated with changes in lean muscle mass,
bone density, hair distribution and the pattern of
It is important to dispel the concept that endo-
obesity also described in hypogonadal states27,28.
crinopathies of elderly men are narrowly focused
Administration of GH can reverse these altera-
on testosterone. Although hypotestosteronemia is
tions29 and does so more efficiently in eugonadal
the most widely recognized and investigated
men than in their hypogonadal counterparts30.
hormonal alteration associated with the aging
Whether the possible clinical improvement after
process, the production of several other hormones
GH administration will be outweighed by undesir-
is also profoundly affected by age. Increasing atten-
able side-effects and whether the improvements
tion is being paid to these hormones because
would be sufficient to justify the financial burden,
changes in their levels can be responsible for
deserve further inquiry. The same applies to the use
some of the manifestations previously attributed
of the newer, orally active GH-releasing peptides
exclusively to testosterone deficiency.
and related non-peptide secretagogues.
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Melatonin
contrast, leptin, a relatively recently described
Melatonin secretion by the pineal gland in
hormone from adipocytes, is altered in hypo-
response to hypoglycemia and darkness also
gonadism which explains, in part, some the
decreases with age regardless of these stimuli31. The
changes in fat distribution observed in these men38.
physiological role of the pineal gland is not com-
Levels of leptin can be brought down by androgen
pletely understood but it is involved in gonadal
supplementation39 that usually results in a decrease
function and regulation of biorhythms32. Other
physiological effects ranging from analgesic and
The following recommendation is put forward
antioxidative33 to immunomodulating34 properties
regarding other endocrine alterations associated
have been attributed to melatonin. Olcese
presented evidence indicating that administration
of melatonin slows the growth of cancer cells in
It is recognized that significant alterations in other
rodents35. However, the large popular enthusiasm
endocrine systems occur in association with aging but
around the hormone has a precarious scientific
the significance of these changes is not well understood.
basis. It is likely that administration of melatonin
In general terms, determinations of DHEA, DHEA-S,
may improve the significant sleep disorders
melatonin, GH and IGF-I are not indicated in the
frequently seen in the elderly. As mentioned
uncomplicated evaluation of ADAM. Under special
before, profound hypogonadism is associated
circumstances, or for well-defined clinical research,
with alterations in melatonin production11,
assessment of these and other hormones may be
therefore making difficult the attribution of some
symptoms (sleep disturbances) exclusively to
deficits of one or the other hormone. Evidence is
emerging of a wide range of direct and indirect
TREATMENT
activities of melatonin on many human organ
Indications
It is common clinical wisdom that a firm diagnosis
Thyroxin
is desirable prior to embarking on any therapeutic
plan. This also applies to the treatment of the
With aging, there is an increase in serum thyroid
hypogonadal man. The goals of treatment most
stimulating hormone (TSH) levels and a decrease
commonly include the restoration of sexual func-
in thyroxin, although TSH levels in the elderly
tioning as well as libido and sense of well-being.
who have hypothyroidism are lower than in
Equally important, androgen replacement can
younger patients with the same disease. Hypo-
prevent or improve already established osteo-
thyroidism should be suspected if there are occur-
porosis and optimize bone density, restore
rences of unexplained high levels of cholesterol
muscle strength and improve mental acuity and
and creatinine phosphokinase, severe constipation,
normalize GH levels, especially in elderly
congestive heart failure with cardiomyopathy and
males32,41. Testosterone replacement therapy
unexplained macrocytic anemia. In the elderly
should maintain not only physiological levels of
there may be overt and subclinical thyroid
serum testosterone but also the metabolites of
deficiency. The diagnosis may not be clinically
testosterone including estradiol, to optimize
evident, and only an index of suspicion supported
maintenance of bone and muscle mass, libido,
by biochemical evidence confirms the diagnosis.
virilization and sexual function. Since some of the
Symptoms of hypothyroidism may mask those of
manifestations of ADAM are shared with other
conditions independent of a man’s androgenic
status, appropriate biochemical confirmation of
The production of corticosteroids and estradiol in
This recommendation is considered mandatory
males, remains fairly constant throughout life. In
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of testosterone production by the testes. This is
A clear indication (a clinical picture together with bio-
accomplished best by the transdermal preparations,
chemical support) should exist prior to initiation of
although oral testosterone may also approximate
a circadian rhythm by dose adjustments. The
relevance of reproducing a circadian rythmicity
during ART remains unknown. Common testos-
terone preparations and their recommended doses
As mentioned previously, aging of the pituitary–
gonadal axis is progressive. Hence, age more
likely correlates with the severity of the bio-
chemical changes and clinical manifestations.
These aging men, however, because of associated
infirmities and other socioeconomic reasons, are
Oral androgen preparations have become popular
less likely to be considered for treatment.
because of their convenience aspects (such as dose
Therefore, the following recommendation applies:
flexibility, possibility of immediate discontinua-
tion, self-administration). However, they demand
special consideration because they undergo rapid
In the absence of defined contraindications, age is not
hepatic and intestinal metabolism. Therefore,
a limiting factor to initiate ART in aged men with
special precautions may be necessary in order to
achieve adequate serum androgen levels.
An oral preparation that is widely used through-
Preparations
out the world (and which is currently in clinical
Current, generally available treatment options
undecanoate. As the only effective and safe oral
include buccal and oral tablets and capsules, intra-
testosterone ester, it circumvents the first passage
muscular preparations, both long- and short-
through the liver, it is free of liver toxicity and
acting, implantable long-acting slow-release pellets
brings serum testosterone levels within the
and transdermal scrotal and non-scrotal patches
physiological range. It is liposoluble and for
and gels. Neither injectable preparations nor
this reason it must be taken with meals. Studies
slow-release pellets reproduce the circadian pattern
have shown that oral testosterone undecanoate
Table 1 Most frequently used testosterone preparations
*17α-alkylated testosterone preparations fluoxymesterone and methyltestosterone are both associated with serious liver
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improves libido, erectile function and general
The most widely used parenteral preparations
well-being, increases bone mineral density and
are the 17β-hydroxyl esters of testosterone
which include the short-acting propionate and
In order to prevent the rapid metabolic break-
the longer-acting enanthate and cypionate. The
down in the liver, some oral agents available in
propionate is rarely used because its short half-
some countries (particularly in the USA) are
life requires administration every other day. The
chemically modified. These alkylated androgens
enanthate and cypionate esters of testosterone, on
generally provide erratic androgenic activity and
the other hand, can be administered at the dose of
exhibit a potential for significant liver toxicity
200–400 mg every 10–21 days to maintain normal
which includes hepatocellular adenomas and
average testosterone levels46. Higher doses will not
carcinomas, cholestatic jaundice and hemorrhagic
maintain testosterone levels in the normal range
beyond the 3-week limit. Another option is a
Finally, the oral dihydrotestosterone (DHT)
preparation containing a mixture of four test-
derivative mesterolone is available in some
osterone esters (propionate, phenylpropionate,
countries. The compound is not aromatizable and
isocaproate and decanoate), each with a different
cannot therefore be biotransformed into estradiol.
elimination half-life, which is claimed to prolong
As a consequence, it only exerts a partial andro-
genic effect, making it a suboptimal treatment
Appropriate treatment of hypogonadism with
injectable esters of testosterone has been shown to
None of the oral medications results in a
improve libido, sexual function, energy levels,
faithful reflection of the circadian level variations.
mood and bone density if they are caused by
an androgen deficiency47. Persistent supraphysio-
and amount of the dosing may ameliorate this
logical levels of serum testosterone may result in
infertility due to suppression of LH and FSH
production48. Although concern exists about the
psychosexual effects of markedly elevated levels of
testosterone in serum, evidence has been presented
Injectable esters of testosterone have been available
indicating that, even in eugonadal men, amounts
for the longest time and their effects are well recog-
up to five times the physiological replacement
nized. They are inexpensive and safe but their use
doses of testosterone cypionate have only minimal
carries several major drawbacks which include:
(1) The need for periodic (every 2–3 weeks) deep
(2) Wide swings in serum levels, initially (in
Transdermal testosterone therapy (TTT) offers
about 72 h), result in supraphysiological levels
a close reflection on the variable levels in test-
of serum testosterone followed by a steady
osterone production manifested in normal men
decline over the next 10–14 days45.
over the 24-h circadian cycle. TTT is available in
(3) The steady decline frequently results in a very
both scrotal and non-scrotal patches and in a gel
low nadir immediately before the next injec-
form. The scrotal TTT lost its appeal due to incon-
veniences such as the inability to remain in place
swings in mood and well-being – the roller-
and the need for frequent shaving of the scrotal
coaster effect – which is disconcerting and
skin. In addition, due to the high concentrations
upsetting to both patients and their partners.
of 5α-reductase in the scrotal skin, they produce
abnormally high levels of DHT50. Transdermal
(4) Parenteral androgens do not provide the
non-scrotal patches produce normal levels of
normal circadian patterns of serum testoster-
estradiol but, as opposed to the scrotal ones, result
one and the intermittent supraphysiological
in normal levels of DHT51. In addition, to pro-
ducing physiologically appropriate serum levels of
testosterone, they lower levels of SHBG, promote
virilization and increase bone mineral density52.
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Also, the testosterone patches, as compared
to injectable forms, minimize excessive erythro-
Liver function studies are advisable prior to onset of
poiesis and suppression of gonadotropins53. Most
therapy, quarterly during the first year and on a yearly
common side-effects of the body patches are
basis thereafter during treatment.
related to the need to use enhancers to facilitate
absorption; this frequently results in various
degrees of skin reactions, occasionally reaching
Lipid and cardiovascular safety
significant chemical burns. This may be prevented
The relationship between hypogonadism and
with the use of triamcinolone. The testosterone gel
alterations of the lipid profile remains to be com-
offers all the advantages of the patches54, without
pletely resolved. Evidence is emerging supporting
the frequent skin reactions. Its only drawbacks
the concept that hypogonadism is associated with
reside in the potential for contamination of others
potentially unfavorable changes in triglycerides
and the lack of long-term studies with its use. The
and high-density lipoprotein cholesterol and that
efficacy of transdermal DHT therapy has been
such abnormalities can be corrected by restoring
a physiological androgen milieu57. Other studies
support the view that low testosterone is a signifi-
therapy, the following two recommendations are
cant risk factor for coronary artery disease58–60.
Although most recent evidence continues to
support the concept of a beneficial effect of
Currently available preparations of testosterone (with the
androgens in coronary artery disease61, the rela-
exception of the alkylated ones) are safe and effective. The
tionships between androgens and cardiovascular
treating physician should have sufficient knowledge and
risk factors are complex and still understood only
adequate understanding of the advantages and drawbacks
imperfectly. Similarly, the relationships between
androgen levels in the serum and other lipoprotein
sub-fractions have not been fully investigated62.
Therefore, caution is advisable when supplement-
The purpose of ART is to bring and maintain serum
ing androgens in men with significant risk factors
testosterone levels within the physiological range. Supra-
for cardiovascular disease. The picture is further
physiological levels are to be avoided.
blurred by the fluid retention associated with
androgen administration; this may add to any
possible adverse effect of androgen therapy to the
ADVERSE EFFECTS
Like most medications, androgens have a potential
for undesirable side-effects. These concerns are,
primarily in regard to the liver, the prostate, lipid
profile and cardiovascular system, hematological
A fasting lipid profile prior to initiation of treatment
changes, sleep patterns and social behavior and
and at regular intervals (no longer than 1 year) duringProstate safety
Reports of liver toxicity manifested by jaundice
It is well established that, in the absence of suffi-
and alteration of liver function, as well as the
cient androgens the prostate gland fails to develop.
development of hepatic tumors, have been limited
Most studies, however, have shown no significant
almost exclusively to cases in which the alkylated
increases in PSA or prostate volume following
forms of testosterone have been used. Invariably,
administration of androgens to hypogonadal
inserts of commercial preparations mention the
men63. Evidence from placebo-controlled studies
potential for liver toxicity. Therefore, regardless of
of men receiving androgen supplementation
the form of ART employed, this recommendation
indicate that the differences between the men on
hormones and those on placebo were insignificant
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in regard to prostate volume, PSA or obstructive
obstruction has been successfully treated, these men are
symptoms64,65. Although testosterone has not been
candidates for androgen supplementation.
implicated in the development of benign prostate
hypertrophy (BPH), nevertheless, in the presence
of severe lower urinary tract obstructive symptoms
Mood and behavior
(LUTOS), the administration of testosterone may
The consequences of testosterone deficiency
result in the development of urinary retention.
in mood regulation are widely accepted69,70 to
Whether testosterone promotes the development
the point that, recently, a hypothesis has been
of prostate cancer remains to be elucidated.
advanced suggesting that perinatal androgen
Current evidence indicates that serum levels of
deficiency promotes deficient cognitive develop-
sex hormones bear no relation to the development
ment71. However, concerns exist regarding the
of prostate cancer and there is either no
promotion of sexually aggressive behavior
change or only a modest increase in PSA levels
following testosterone administration. Significant
after testosterone administration66. The suspicion
behavioral changes can be observed with supra-
of prostate cancer is, however, an absolute contra-
physiological levels of androgens. Proper treatment,
indication for androgen therapy. On the other
aimed at maintenance of physiological plasma
hand, prostatic biopsies prior to onset of ART
levels, makes this a rare occurrence and certainly
in the absence of an abnormal digital rectal
not a sufficient cause to withhold treatment72.
indicated. However, a rapid increase in PSA or
the appearance of abnormalities in the DRE are
ART normally results in improvements in mood
clear indications for a thorough evaluation of the
and well-being. The development of negative behavioral
prostate to rule out the presence of carcinoma. In
patterns during treatment calls for dose modifications or
this situation the administration of testosterone
may have served as an early warning to the
presence of an occult prostatic malignancy67.
The issue of prostate safety and exogenous
Hematology
androgens is, perhaps, the gravest concern. The
The stimulatory effect of testosterone administra-
topic was recently reviewed68. The following three
tion on bone marrow has long been recognized
separate recommendations were considered and
even in the presence of advanced malignant
disease73. Testosterone therapy in older men often
can result in a significant increase in red blood cell
Digital rectal examination (DRE) and determination of
mass and hemoglobin levels74. In younger,
serum prostate-specific antigen (PSA) are mandatory in
healthier individuals, such as those receiving
men over the age of 40 years as baseline measurements of
androgens for sexual dysfunction, the effects can
prostate health prior to therapy with androgens, at quar-
also be marked75. Therefore, dose adjustments or
terly intervals for the first 12 months and yearly thereaf-
phlebotomies may be necessary. Rarely, ART has
ter. Transrectal ultrasound-guided biopsies of the prostate
to be discontinued due to polycythemia. are indicated only if the DRE or the PSA are abnormal.Polycythemia occasionally develops during ART.Androgen administration is absolutely contraindicated inPeriodic hematological assessment is indicated. Dosemen suspected of having carcinoma of the prostate or breastSleep apnea Androgen supplementation is contraindicated in men
Other possible effects of testosterone treatment
with severe bladder outlet obstruction due to an enlarged,
include exacerbation of sleep apnea76 although
clinically benign prostate. Moderate obstruction represents
hypotestosteronemia has been cited as a cause of
a partial contraindication to ART. Once the urinary
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CONCLUSIONS There is insufficient evidence for a recommendationregarding safety of ART in men with sleep apnea. It is
There is clear evidence that advancing age is
suggested, therefore, that good clinical judgement and
associated with a decline in the production of
caution be employed in this situation.
several hormones. The most prominent alterations
are related to the sex steroids but other hormones
MONITORING PATIENTS ON ART
also profoundly affected. The clinical syndrome of
Hormonal replacement may be initiated for a
ADAM or andropause has been described but a
variety of indications but treatment is normally for
direct causality between its manifestations and the
life. Monitoring of these patients is also a lifetime
alterations in a specific hormone are not yet fully
commitment that cannot be taken lightly.
established. There is, however, a growing body
Monitoring, of course requires to be tailored to the
of literature supporting the concept of a clinical
indications and the individual needs of the patient.
picture associated with hypogonadism in aging
For instance, if the indication is osteoporosis,
men that impacts significantly on the quality of life.
serial bone mineral density determinations are the
Equally, there is sufficient evidence to support the
method for monitoring therapeutic response. In
concept that appropriate treatment of these men
this regard, the studies by Behre and colleagues78
results in alleviation of some of the manifestations
provide an elegant and graphic illustration on the
of the andropause. It behoves a variety of medical
effectiveness of chronic testosterone supplemen-
specialties to be familiar with the consequences
tation in increasing bone mineral density and in
of this condition, its investigation, treatment and
moving older men out of the range of high fracture
risk. Another common indication for testosterone
Our understanding of ADAM is still incomplete
administration is for treatment of sexual dysfunc-
and there exist a number of controversial issues in
tion. In this situation, a simple and effective rule
regard to hormonal replacement in elderly men.
of monitoring is that, frequently, the patient’s
Standards or guidelines on the subject are, there-
report is the most reliable indicator of treatment
fore, premature. Recommendations, however, are
effectiveness59. In addition to the specific areas of
justified with the present state of knowledge.
interest, long-term monitoring of these patients
Recommendations79 and guidelines80–82 in the
centers on six domains in which concerns have
area of ART require frequent updates as further
existed for possible serious adverse events: the liver,
information emerges. We provide this set of
lipid profile and cardiovascular disease, erytho-
Recommendations for physicians interested in the
poiesis, the prostate, sleep disorders and social
diagnosis and treatment of aging men with
symptoms of hypogonadism. Recommendations,
guidelines and standards are, normally, work
in progress. They will be discussed again at the
Monitoring during ART is a shared responsibility. The
biannual meeting of ISSAM in Prague, February
physician must emphasize to the patient the need forperiodic evaluations and the patient must agree to complywith these requirements. Since ART is normally for life,monitoring is also a lifetime mutual duty.References
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Sex differences in ‚climacteric symptoms™ with increasing age? A hypothesis-generating analysis of cross-sectional population surveys 124
Sex differences in ‚climacteric symptoms™ with increasing age? A hypothesis-generating analysis of cross-sectional population surveys
L. A. J. Heinemann, C. Thiel, A. Assmann, T. Zimmermann, W. Hummel and A. Vermeulen
S. Kudlacek, R. Willvonseder, P. Stohlawetz, P. Hahn and P. Pietschmann
Continence, incontinence and the aging male 143
Continence, incontinence and the aging male
A paradigm shift: from disease to health orientation 171
A paradigm shift: from disease to health orientation
Quality-of-life issues in the aging male 185
Quality-of-life issues in the aging male
Androgens and the risk of cardiovascular disease 190
Androgens and the risk of cardiovascular disease
Testosterone therapy Œ effects on prostate and bone 196
Testosterone therapy Œ effects on prostate and bone
Management of male aging: which testosterone replacement therapy should be used? 203
Management of male aging: which testosterone replacement therapy should be used?
The future of hormone replacement therapy in the aging male 210
The future of hormone replacement therapy in the aging male
Comparison of two health status measures and their associations with testosterone levels in older men 1
Comparison of two health status measures and their associations with testosterone levels in older men
N. Dunbar, C. Gruman, S. Reisine and A. Kenny
Practical consequences of the validation of a mathematical model in assessment of partial androgen deficiency in the aging male using bioavailable testosterone 23
Practical consequences of the validation of a mathematical model in assessment of partial androgen deficiency in the aging male using bioavailable testosterone
Visceral obesity, androgens and the risks of cardiovascular disease and diabetes mellitus 30
Visceral obesity, androgens and the risks of cardiovascular disease and diabetes mellitus
Sex steroids and brain functioning in the aging male 39
Sex steroids and brain functioning in the aging male
Anal ogies between laryngeal and pros tate cancers Œ fre quent malig nan cies of the elderly 57
Anal ogies between laryngeal and pros tate cancers Œ fre quent malig nan cies of the elderly
M. Medras, P. Jozkow, T. Krecicki and M. Zalesska-Krecicka
F. Montorsi, M. Zanoni, A. Salonia and P. Rigatti
H. Xiao, X.-H. Zhou, Y.-C. Xu and S.-Z. Qian
The sex-spe cific life expec tancy and the influ ence of tes tos ter one in a math e mat i cal aging sim u la tion model and its con se quences for pre ven tion 95
The sex-spe cific life expec tancy and the influ ence of tes tos ter one in a math e mat i cal aging sim u la tion model and its con se quences for pre ven tion
The aging pop u la tion in Aus tra lia 101
The aging pop u la tion in Aus tra lia
The influ ence of exer cise on the func tioning of the pitu itaryŒgonadal axis in physically active older and younger men 145
The influ ence of exer cise on the func tioning of the pitu itaryŒgonadal axis in physically active older and younger men
M. Slowinska-Lisowska and K. Witkowski
Andro gen replace ment therapy in aging men with sec ond ary hypogonadism Draft of Recommendations for endorsement by ISSAM 151
Andro gen replace ment therapy in aging men with sec ond ary hypogonadism Draft of Recommendations for endorsement by ISSAM
History of herbal med i cines with an insight on the phar ma co log i cal prop er ties of Tribulus terrestris 163
History of herbal med i cines with an insight on the phar ma co log i cal prop er ties of Tribulus terrestris
P. G. Adaikan, K. Gauthaman and R. N. V. Prasad
The aging male in the lit er a ture 170
Report of the World Health Organization Active Ageing: A Policy Framework 1
Report of the World Health Organization Active Ageing: A Policy Framework
Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction 38
Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction
T. J. Bunch, D. Abraham, S. Wang and A. W. Meikle
Effects of andro gen supplementation therapy on partial andro gen defi ciency in the aging male: a pre lim i nary study 47
Effects of andro gen supplementation therapy on partial andro gen defi ciency in the aging male: a pre lim i nary study
J.-Y. Li, J.-C. Zhu, J.-T. Dou, W.-J. Bai, S.-M. Deng, M. Li, W. Huang and H. Jin
Oral testosterone replacement in Korean patients with PADAM 52
Oral testosterone replacement in Korean patients with PADAM
What Malaysian women believe about Viagra: a qualitative inquiry 57
What Malaysian women believe about Viagra: a qualitative inquiry
W. Y. Low, S. N. Zulkifli, Y. L. Wong and H. M. Tan
Standards, Guidelines and Recommendations of ISSAM
Investigation, treatment and monitoring of late-onset hypogonadism in males 74
Investigation, treatment and monitoring of late-onset hypogonadism in males Official Recommendations of ISSAM
A. Vermeulen, J. M. Kaufman, S. Goemaere and I. van Pottelberg
P. Marandola, S. Musitelli, R. Noseda, S. Stancati, D. Vitetta, H. Jallous, D. Porru, H. Zmerly, M. Mensi, P. Colombo, G. Orlando, T. Cebrelli, M. Gerardini, G. Giliberto, L. Pasini, B. Lillaz, F. Pietropaolo, C. Sali and B. Rovereto
S E G U N D O C U A T R I M E S T R E 2 0 0 7 Antibioterapia en m e d i c i n a e q u i n a Armengou, L. Existen a nuestra disposición una gran cantidad de fármacos con poder antibiótico. Enmedicina humana su uso es claramente popular y aunque en el pasado significó un saltocualitativo en el tratamiento y prevención de infecciones, hoy en día el uso a vecesirresponsable y popular
Chapitre 3 : Transmissions cholinergiques 1. L’acétylcholine, 1er médiateur identifié Produit s’opposant à la stimulation nerveuse Nicotine isolée en 1828 Atropine purifiée en 1883 Curares : bloque la stimulation des muscles squelettiques Muscarine et nicotine miment la stimulation des nerfs p∑ et des nerfs moteurs Agonistes Dale (1914) découvre les récepteurs canaux nicot