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Thread: interesting read
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12-22-2003, 11:01 PM #1
interesting read
this is a good read, kinda long but not too bias.
Anabolic Steroids
A Review for the Clinician
Eric C. Kutscher,1,2 Brian C. Lund2 and Paul J. Perry2,3
1 Western Missouri Mental Health Center, Kansas City, Missouri, USA
2 Clinical and Administrative Pharmacy Division, College of Pharmacy, University of Iowa,
Iowa City, Iowa, USA
3 Department of Psychiatry, College of Medicine, University of Iowa, Iowa City, Iowa, USA
The number of athletes self-administering ergogenic pharmacological agents
to increase their competitive edge continues to be a problem.Most athletes using
anabolic steroids (AS) have acquired a crude pharmacological database regarding
these drugs. Their opinions regarding steroids have been derived from their subjective
experiences and anecdotal information. For this reason, traditional warnings
regarding the lack of efficacy and potential dangers of steroid misuse are
disregarded. A common widely held opinion among bodybuilders is that the anabolic
steroid experts are the athletic guruswho for years have utilised themselves
as the experimental participants and then dispensed their empirical findings. This
review will address the common anabolic steroid misconceptions held by many
of today’s athletes by providing an evaluation of the scientific literature related
to AS in athletic performance.
As athletic competition continues to intensify,
athletes strive for higher levels of performance to
achieve success. Many of these athletes, as well as
their coaches, believe that one must do whatever is
required to win. If this formula requires the use of
performance enhancing substances, such as anabolic
steroids (AS), this is an acceptable gamble. Thus,
the number of athletes administering performance
enhancing pharmacological agents to achieve their
goals is no longer limited to elite athletes, but to all
categories of athletes.[1]
Being actively involved with the bodybuilding
population, through various regional and national
bodybuilding competitions as well as interviewing
bodybuilders around the Midwest, the authors are
aware of the use of various types of performance enhancing
agents. These athletes have varying attitudes
on the effects, mechanism of action, and adverse
effects that are related to the use of these substances.
AS are themost prevalent agents being used among
this population. AS are also the most studied of all
the performance enhancing agents. Although there
are many AS studies, there is no consensus among
researchers regarding their effectiveness as ergogenic
agents. In contrast, bodybuilders eagerly postulate
numerous potential mechanisms of action and
endorse AS efficacy because of their first-hand experience.[
2]
The AS using athletes of today have a ‘sophisticated’
steroid pharmacological knowledge, based
on both their subjective experiences and anecdotal
information, which in their minds surpasses the majority
of healthcare providers.[1,3] For this reason,
traditional warnings from healthcare providers regarding
the lack of efficacy and potential dangers
of steroid misuse are largely disregarded.[1] Today,
it appears that the AS experts in athletic competition
are not medical clinicians, but athletes and former
athletes who dispense their anecdotal AS experience
as dogma to anyone willing to listen. Healthcare
professionals caring for these athletes need to
have amore thorough understanding of theAS ergogenic
literature to have legitimate dialoguewith these
patients when caring for them. Clinicians run the
risk of losing their credibility with patients because
they are under-informed as to the efficacy and toxicity
of the AS.[1]
Unfortunately, based on the pattern of AS usage
currently being practised in the US, past efficacy
and toxicology studies are of limited value in delineating
the benefits and hazards of these drugs in
the common dosages used by today’s athletes. Due
to the limitations among current studies on the effects
of AS, and the lack of literature in athletic performance,
understanding the beliefs of the user by
the general practitioner may be difficult. The goal
of this article is to provide an unbiased summary
of the relevant literature relating to AS use, including
epidemiology, pharmacology, efficacy, adverse
effects and misconceptions common among bodybuilders.
This review will also incorporate the anecdotal
theories of bodybuilders relating to safety
and efficacy and the relevant literature that rebuts
or strengthens their arguments. The uses of nutritional
AS, such as androstenedione, are not included
in this review.
1. Epidemiology
The prevalence of AS use has been reported in
several populations, but data on the exact prevalence
are limited to surveys of students and athletes
whomay be reluctant to admit actual usage of these
controlled substances. There have been estimates of
more than 1 to 3 million current or former AS users
in the US. Many of these may be young adults.[4,5]
The most recent estimates report that 4 to 12% of
US high school boys have used AS at sometime in
their life.[6] Arecent survey conducted by Blue Cross
and Blue Shield Association[7] reported that AS were
the second most common substances known to be
used for athletic performance among 12- to 17-yearold
people, second only to creatine (31 vs 57%,
respectively). Sullivan et al.[8] reported that 65 to
84% of adolescent AS users were participants in
organised athletics.[8] On the other hand, other reports
showed that 3.2% ofModesto, California 7th
grade girls and 2.8% of Massachusetts 6th and 7th
grade girls have reported using AS, respectively.[9,10]
These reports of AS use may be confounded by false
positive reports, consisting of over the counter AS
supplements or failure to accurately answer survey
questions correctly. Nonetheless, these numbers are
worrisome, especially when considering the adverse
growth suppressing effects of AS in young adults.[11]
A recent National Collegiate Athletic Association
survey[12] found that only 1.1% of college athletes
surveyed reported AS use, and Yesalis et al.[13] reported
29.3% of college football players and 20.6%
of male track-and-field athletes reported AS use.
Some of the highest estimates have come from Yesalis
and Bahrke,[10] reporting that 78% of trackand-
field athletes in 1972 had prior steroid use .
After Olympic athletes, the second most prevalent
group believed to misuse AS is the bodybuilding
and/or weightlifting population. Yesalis et al.[14]
reported that 55%of elite power lifters admit to AS
usage. Tricker et al.[15] reported the same percentage
among amateur competitive bodybuilders. These
high numbers relate to the fact that many bodybuilding
competitions do not actually test for AS
usage among competitors.Many of the ‘natural bodybuilding’
organisations provide the option of polygraph
or urinalysis tests if a competitor stands out
as an AS user. Most ‘major’ competitions such as
those held by the National Physique Committee,
state that athletes must be ‘drug free’but do not test
the competitors. Additionally, athletes have found
systems to work around the rules of competing ‘drug
free’ and have actually challenged the credibility
of drug testing in athletic competition.[16]
Although these reports of AS usage seem high,
our experience in surveying bodybuilders suggests
that these numbers may be under estimated. Indeed,
current methods of self-reporting and/or surveying
AS usage may yield inaccurate estimates in this
population. We have observed that since AS were
286 Kutscher et al.
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categorised by the US Congress as Schedule III
(non-narcotic) class drugs of misuse in 1990,[10]
AS users have become far less forthcoming about
their use of these drugs. This makes identification
of AS using athletes by the primary care practitioner
as well as in epidemiology studies problematic.
2. Physiology
In general, the physiological mechanisms of AS
are commonlymisunderstood and overstated in the
bodybuilding population. Many beliefs are anecdotal
at best, and not supported by the medical literature.
The two most common AS questions posed by
bodybuilders to physicians are, ‘How exactly do AS
cause muscle growth,’ and ‘Is this a dose-dependent
effect?’ AS have numerous proposed mechanisms
of action related to athletic performance. These include:
increased skeletal muscle protein synthesis
and skeletal muscle hypertrophy;[17,18] a decrease
in the rate of protein breakdown;[11] an increase in
the number of mononuclei;[19] activation of satellite
cells;[19] and an increase in the number of androgen
receptors containing mononuclei.[19] However, the
exact mechanism is not understood. Misconceptions
among athletes regarding the effects of AS on
physiology often occur, and may account for the
increase in serious adverse effects seen in this population.
The physiological function of satellite cells in
muscle growth is a source of considerable confusion.
The effects of AS on the satellite cells are
commonly misunderstood by bodybuilders. During
muscle growth, myoblasts (young muscle cells)
proliferate to eventually form mononuclei (mature
muscle cells) in skeletal muscle. There are a number
ofmyoblasts that do not mature into mononuclei;
these cells are labelled as satellite cells.[19] After
injury, such as that related to athletic training, satellite
cells are recruited as the primary vehicle in
muscle repair. These cells are eventually incorporated
into muscle fibres as mononuclei during the
repair and growth process.[19] Strength training increases
the number of satellite cells, thereby causing
muscle growth.[19] When the stress from exercise
or training does not inducemuscle injury there
does not seem to be growth in the muscle. The number
of satellite cells available for recruitment in AS
users versus non-users does not differ.[19] Thus,AS
do not affect muscular hypertrophy by increasing
the number of satellite cells in the muscle after injury.
Instead, training appears to be the dynamic parameter
that governs satellite cell number. This finding
contradicts the notion of most bodybuilders that
AS increase muscle recovery after intense training.
Themisconception of faster recovery during heavy
training may be psychological and related to the
AS-induced euphoria athletes experience during
training. This issue will be discussed inmore detail
in section 4.4.[20]
Some bodybuilders have reported that AS will
precipitate muscle growth without intense strength
training. Thus, AS are hoped to be an antidote for
the ‘ancient wisdom’ of ‘no pain no gain’. However,
the available data suggest the opposite. Bhasin et
al.[21] provided evidence that testosterone administration
could increase muscle strength and size in
males, but only in the presence of weight-training.
Use of AS and exercising theoretically increases
the number of mononuclei in the muscle that can
be used to increase protein synthesis and hence repair
injured muscle and increase muscle size and
strength.[19] For muscle growth to occur, stress on
the muscle is required. Thus, the idea of using AS
without increased weight-training to increasemuscle
size and strength is erroneous.
Most bodybuilders believe that a high protein
diet enhances muscle growth during training. This
observation is true since athletic training causes the
catabolic effects of the glucocorticoids to generate
a negative nitrogen balance. The body responds to
this negative nitrogen balance by utilising the protein
stores of the body to revert to a positive balance.[
20] AS are extremely anticatabolic and convert
a negative nitrogen balance to a positive balance
by improving the utilisation of dietary protein and
increasing protein synthesis.[17,20] AS use in normal
and catabolic (training) individuals precipitates
protein synthesis within the muscle cell, which in
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turn results in a positive nitrogen balance. Since
normal individuals are not in a negative nitrogen
balance (catabolic state), the effects of ASwill only
be short-lived.[20] This fact explains why AS users
report that the more they train and ingest protein
while using AS, the more they ‘grow’.
AS oppose the effects of glucocorticoids, not only
through a positive nitrogen balance, but also through
competition for glucocorticoid binding sites.[18,22]
This effect decreases the amount of cortisol and
other glucocorticoids available in the body. Studies[
22] show that testosterone and other AS compete
with cortisol, dexamethasone and triamcinolone for
glucocorticoid binding sites. This competition may
help reverse the negative nitrogen balance induced
by training. Hence, the belief of some athletes that
AS have an anticatabolic effect that results in a
positive nitrogen balance is correct.
Most bodybuilders assume that there is a dosedependent
effect of AS on androgen receptor formation
and muscle mass increase (unpublished observations).
This notion is not absolutely correct in the
absence of strength training. Kadi[19] showed that
androgen-receptor–containing muscle fibres ormononuclei
are highly selective. Androgen receptor content
of the muscle fibres is a function of the type of
muscle. There can either be a receptor up-regulation
(increase in receptors) or a down-regulation (decrease
in receptors) depending on the type of skeletal
muscle involved. This could explain the distinguishing
features of most bodybuilders, such as large
trapezius and deltoid muscles, which may result
from greater AS receptor up-regulation in these two
areas.[19]
The significance of the AS-androgen receptor
complex interaction is commonly misunderstood.
When an androgen binds to the androgen receptor
on the nucleus of a muscle cell, a receptor-androgen
complex is formed that is then transferred into the
nucleus of themuscle cell. Once in the nucleus, this
complex binds to complementary regions on DNA
to activate the transport-RNAand producemessenger
RNAthat encode a variety of enzymes and proteins.[
17,23] The action that eventually occurs is the
up- or down-regulation of the androgen receptors,
increased protein synthesis and possibly an increase in
the number of mononuclei in a muscle fibre.[17,23]
Hence, the effect of AS on muscle fibre androgen
receptors is dependent on themuscle type and number
of receptors present.
Muscle fibres replicate after strenuous activity,
which in turn increases the total number of androgen
receptors in that muscle group. An increased
number of androgen receptors provide additional
functional binding sites for androgens, which in turn
leads to an enlargement of that muscle group.[17]
An opinion that transcends all the AS medical literature
is that AS do not provide much benefit in
the absence of strength training.[19,24-26] This opposes
bodybuilders’ anecdotal observations that higher
doses of AS are more effective for muscle growth
in the absence of increased strength training. The
only means by which excessive supraphysiological
doses of AS can benefit an athlete is by there being
a surplus of uninnervated AS receptors. However,
the only means to achieve a surplus of AS receptors
is by heavy training.[19]
The final performance-enhancing effect of AS,
which is less commonly known among bodybuilders,
but well known by runners, is the resultant increase
in erythropoietin synthesis. This increase in erythropoietin
subsequently increases hematocrit and blood
oxygen carrying capacity.[24] Because of these effects,
AS have been used in the treatment of anaemia.[
27] However, this indication has been largely
forgotten after recombinant human erythropoietin
(epoetin alfa) became commercially available. Although
the increase in oxygen carrying capacity
would be expected to increase athletic performance,
it is partially offset by sodium retention and blood
volume increase. This can result in potentially fatal
sludging of blood should the hematocrit increase
too much.[24] These haemodynamic alterations may
contribute to some of the bodyweight gain observed
byASusers.[24] Currently erythropoietin has replaced
the use ofAS for ‘blood doping’where athletes transfused
themselves with blood having a greater than
normal content of red blood cells.
288 Kutscher et al.
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3. Efficacy
Reviews of the effect of AS on athletic performance
suggest that there is only limited evidence
to support the efficacy of these drugs in athletic
performance.[10] Many studies[21,25,26,28] contain
significant methodological flaws in dosage and administration
strategies when compared with realworld
use. Athletes ‘stack’ AS. The drugs are administered
in cycles of gradually increasing doses
and increasing numbers of agents combined together
(stacked). The cycles used are generally between 7
to 14 weeks in length and involve a combination
of oral agents and long-acting injectable agents.[29]
In contrast, for ethical reasons, clinical investigations
have been restricted to single agent regimens.
Athletes tend to use oral agents in doses that are
similar to those of clinical studies, but typically use
injectable steroids at doses 3 to 8 times those utilised
in clinical trials.[29] Disconcerting to us are anecdotal
reports of supraphysiological doses of themore
hepatotoxic C-17 alkylated agents being used (table
I). Because higher dosages of AS tend to be
used by athletes, it is difficult to compare anecdotal
reports of efficacy with findings of clinical trials
evaluating AS as single agents administered at lower
dosages.
Currently available data suggest that AS cannot
produce a significant effect on muscle strength unless
they are combined with weight training. The
most recent demonstration of AS ergogenic potential
was documented by Bhasin et al.[21] Forty-three
men were randomised into four groups: placebo and
no exercise, testosterone and no exercise, placebo
plus exercise, and testosterone plus exercise. Testosterone
was administered as testosterone enanthate
(TE) 600 mg/wk, defined as a supraphysiological
AS dosage. The mean bodyweight in all participants
who received TE increased significantly (p <
0.001) greater than that noted in the placebo group.
The TE and exercise group increased the most, with
an average bodyweight gain of 6.1kg. Additionally,
both TE groups had significant increases (p <
0.001) in cross-sectional areas of the triceps and
the quadriceps verses the placebo group, with the
largest increase once again occurring in the TE plus
exercise group. The greatest increases in bench press
were observed in the TE plus exercise group (p <
0.001), although the placebo and exercise group
did increase to a lesser degree (p = 0.005). There
were no significant muscle increases observed in
the placebo and no exercise group.[21]
Two additional studies[26,30] also observed increased
strength with metandienone administration
plus exercise over placebo groups, which supports
the Bhasin et al.[21] findings. Hervey et al.[31] noted
that high dosages (25 mg/day) did not produce obvious
differences in strength over low dosages (10
mg/day). Thus, these data suggest that AS augment
exercise to produce muscle growth. Additionally,
the larger dosages used did not produce obvious
muscle gains over the lower dosages. Unfortunately,
no conclusions can be drawn regarding the megadoses
commonly utilised by today’s AS users, because
of a lack of controlled clinical studies.
There are many anecdotal and case reports of
largemuscle and strength gains by the use of supraphysiological
doses of AS. Perry et al.[29] reported
bodyweight gains of an average of 19.9kg after AS
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12-22-2003, 11:04 PM #2
sorry, heres the rest of it.
Currently available data suggest that AS cannot
produce a significant effect on muscle strength unless
they are combined with weight training. The
most recent demonstration of AS ergogenic potential
was documented by Bhasin et al.[21] Forty-three
men were randomised into four groups: placebo and
no exercise, testosterone and no exercise, placebo
plus exercise, and testosterone plus exercise. Testosterone
was administered as testosterone enanthate
(TE) 600 mg/wk, defined as a supraphysiological
AS dosage. The mean bodyweight in all participants
who received TE increased significantly (p <
0.001) greater than that noted in the placebo group.
The TE and exercise group increased the most, with
an average bodyweight gain of 6.1kg. Additionally,
both TE groups had significant increases (p <
0.001) in cross-sectional areas of the triceps and
the quadriceps verses the placebo group, with the
largest increase once again occurring in the TE plus
the placebo and no exercise group.[21]
Two additional studies[26,30] also observed increased
strength with metandienone administration
plus exercise over placebo groups, which supports
the Bhasin et al.[21] findings. Hervey et al.[31] noted
that high dosages (25 mg/day) did not produce obvious
differences in strength over low dosages (10
mg/day). Thus, these data suggest that AS augment
exercise to produce muscle growth. Additionally,
the larger dosages used did not produce obvious
muscle gains over the lower dosages. Unfortunately,
no conclusions can be drawn regarding the megadoses
commonly utilised by today’s AS users, because
of a lack of controlled clinical studies.
There are many anecdotal and case reports of
largemuscle and strength gains by the use of supraphysiological
doses of AS. Perry et al.[29] reported
bodyweight gains of an average of 19.9kg after AS
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use, and an increase in the mean maximal bench press
of 47% (p < 0.0001). The authors hypothesised that
the obvious individual benefits of the AS makes
these drugs psychologically addictive in many users.
Additionally, the expected doses used may not
actually be the actual doses, because of the diluting
of the AS by black-market retailers. This blackmarket
quality control problem emphasises the importance
of obtaining serum testosterone profiles
(total, free and weakly bound serum testosterone
concentrations) in determining the effects ofmegadoses
of AS.
Contrary to beliefs of athletes using AS, some
investigators believe that AS induce their beneficial
effects as a result of psychological rather than
physiologic effects. Ariel and Saville[25] showed that
an athlete’s expectation of strength gains from AS
could causemuscle growth, independent ofAS use.
Fifteen male participants were informed that some
of them would be selected to receive AS; instead, all
participants received placebo. The apparent psychological
effects of AS on strength were observed
in several participants who experienced significant
strength gains due to the belief that they were receiving
AS. This study emphasised the psychological
aspect of human performance, and the potential
benefits of placebo supplementation on psychological
enhancement. This motivational effect may help
athletes produce significant athletic improvements
even in the absence of AS administration.
In light of the quality of AS literature, there remain
a number of issues that need to be resolved to
completely discern the efficacy of AS. All of the
studies reviewed used single agents, contrary to the
commonly used ‘stacks’ among athletes. Typically
the doses administered were much lower than the
mega-doses used by present day athletes. Despite the
unknown efficacy of stacking, many researchers
have suggested that stacking is a non-issue formuscle
growth.[19,24] This is logical because regardless
of the number ofAS being used, the endpoint is still
the same, that is an increase in the free,weakly bound,
and total testosterone concentrations in the body.
Thus, all future studies of AS ought to have in common
these three clinical chemistry parameters. Additionally,
if these parameters are routinely measured,
clinical correlations between AS dose and
strength gain, muscle mass increases and adverse
effects can be made. This monitoring strategy is
beneficial to the athlete in that it will probably result
in the use of smaller doses of AS. It also benefits
the healthcare practitioners who are attempting
to monitor and treat these athletes as patients.
Lack of a patient-physician relationship has lead
athletes to following guidelines in lay publications
such as those contained in theUnderground Steroid
handbook.[1,32]
4. Adverse Effects
The adverse drug effects of AS can be divided
into 5 general categories: hepatic, cardiovascular,
reproductive/endocrine, dermatological and psychiatric
(table II).
4.1 Hepatic Effects
The association between liver function tests
(LFT) elevations and AS has been documented in
the literature.[20,28,33] Bodybuilders are well versed
and quite concerned about this adverse drug effect.
Elevations in aspartate transaminase, alanine transaminase,
lactate dehydrogenase and alkaline phosphatase
have been reportedwithAS use.[20]Although
weightlifting alone can elevate LFT, individuals usingAS
are at a greater risk of having elevated LFT.[20]
However, hepatic enzymes usually return to normal
onceAS are discontinued. The reversible course of
the LFT elevations explains why athletes administer
AS in a cyclic pattern.[34] Consequently, if AS
are administered continually for at least 1 month,
but generally for greater than 2 to 5 months at supraphysiological
doses, dose-dependent jaundice and
hepatic dysfunction are likely to develop.[34] Death
caused by AS hepatotoxicity is extremely rare.[34]
Of the AS, the C-17 alkylated AS aremore often
associated with liver toxicity.[34] The most common
C-17 alkylated AS used by athletes are the oral
agents such as methyltestosterone , metandienone,
oxymetholone, oxandrolone and stanozolol . Nonalkylated
intramuscular agents such as testosterone
and nortestosterone aremuch less likely to produce
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liver problems.[20,34] However,many AS usersmisuse
other substances including alcohol, which could
possibly compound hepatic adverse drug effects.
There have been cases of carcinoma of the liver
associated with either high dose AS, long periods
of administration of AS or in AS users with predisposing
medical conditions.[20,34] Cyclic administration
of AS reverses the risk of liver toxicity.[3]
Additionally, avoiding C-17 alkylated agents (oral
agents) is another practice that decreases hepatotoxicity.
The ultimate means of preventing liver
toxicity are AS abstention and the avoidance of other
potentially hepatotoxic agents, such as alcohol. Although
accepting of these facts, athletes are not
usually concerned since the benefits of increased
muscle mass and strength overshadow the known
risks.
4.2 Cardiovascular Effects
Use of AS can lead to detrimental changes in
serum lipid profiles. Potential changes include increases
in low-density lipoprotein (LDL) and decreases
in high-density lipoprotein (HDL).[27,33,35]
Bodybuilders are generally of the opinion that since
steroids are chemically similar to cholesterol, they
will affect lipids in the same way as eating too much
cholesterol. For bodybuilders this effect is not harmful
since many of them are on ketogenic diets, which
emphasises moderate to high fat, and low to moderate
complex carbohydrate foods, while consuming
extremely high amounts of protein.[32] Lipid
changes are typically unpredictable and are unrelated
to dosage and agents administered. A metaanalysis[
35] conducted in 1991 reported decreases
in HDL of 39 to 70% (mean 52%). These changes
generally occur within the first week of administration
and normalise within 3 to 5 weeks after AS
discontinuation. Conversely, reports of LDLelevations
between 11 to 100% have been reported (mean
36%).[35] Since HDL levels decrease and LDL levels
increase, total cholesterol levels generally do not
reflect these changes and the atherogenic potential
of AS can often be overlooked.[35]
Unfortunately, many bodybuilders seem to believe
that cholesterol monitoring is all that it required
to monitor their lipid status. Triglyceride
levels are also decreased by the exogenous androgen
administration.[3] The long-term impact on morbidity
and mortality of labile lipid profiles is unknown.
However, an increase in LDL levels might
directly contribute to arteriosclerosis especially if
Table II. Most common adverse effects of anabolic steroids
Hepatic
LFT elevations (hepatotoxicity)
Liver cancer
Cardiovascular
Decreased HDL
Increased LDL
Increased total cholesterol
Decreased triglycerides
Fluid retention (elevated blood pressure)
Cardiac hypertrophy
Reproductive and endocrine
Decreased LH
Decreased FSH
Decreased thyroid functioning
Adverse effects in males
decreased spermatogenesis
abnormal sperm morphology
feminisation in males
decreased size of testes
Adverse effects in females
hirsuitism
voice deepening
clitoral hypertrophy
decreased breast mass
amenorrhoea
male pattern baldness
Dermatologic
Oily hair
Oily skin
Alopecia
Sebaceous cysts
Increased incidence of acne
Psychiatric
Mood changes
Possible aggression
Possible hostility
Dependence and/or addiction
FSH = follicle-stimulating hormone; HDL = high-density lipoprotein;
LDL = low-density lipoprotein; LFT = liver function tests; LH =
luteinising hormone.
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these agents are used over long periods of time.[8]
With an increased risk of cholesterol plaques in the
coronary vessels, a subsequent thrombus may occur
in athletes using AS.[8] AS also stimulate platelet
aggregation, increase coagulation enzyme activity,
and cause coronary artery vasospasm.[8] Thus,AS
have the potential to predispose users to thrombus
formation by reductions of HDL, increases in LDL,
increased platelet aggregation, coronary artery vasospasm
and enhanced coagulation enzyme activity.
Elevations in blood pressure in AS users have
been reported and most likely result from blood
volume increases and fluid retention.[8,27] This effect
has not been well studied in humans, although
is well-documented in animal studies.[8,27] Anecdotally,
bodybuilders will complain of feeling an
increase of pressure in their head and body resulting
from what they believe is elevated blood pressure.
AS also increase heart rate, which may lead
to hypertrophy of the left ventricle.[8,36] Case studies
of AS users at autopsies have found cardiac hypertrophy
in these patients.[8] The consequences of
cardiac hypertrophy can lead to decreasedmaximal
oxygen uptake, remodelling of the heart, myocardial
ischaemia and cardiomyopathy.[8] These effects
are serious and can lead to sudden cardiac arrest,
and will persist well after cessation of AS.[8] Unfortunately,
it is difficult to ascertain whether the
effects of AS on the heart are independent of the
other agents present in the polypharmacy regimens
of many AS users such as amphetamines as weight
loss agents, as well as alcohol and tobacco cigarettes.
4.3 Reproductive/Endocrine Effects
In men, AS administration produces a predictable,
dose-dependent depression of luteinising hormone
(LH), and follicle-stimulating hormone (FSH)
via the negative feedback loop of the hypothalamicpituitary-
gonadal (HPG) axis.[30,37,38] As both LH
and FSH are required for spermatogenesis, AS administration
can lead to hypogonadotropic hypogonadism.
The resulting effects of these physiologic
changes include declines in sperm density and
sperm count, decreased sperm motility, abnormal
spermmorphology, testicular atrophy, and no change
in libido.[10,27,39,40] However, the observed effect
on libido was based on testosterone doses not exceeding
500 mg/wk. These effects generally worsen
with increased use of AS, and severe oligospermia
can lead to infertility.[41] Bodybuilders are usually
aware of these effects and often use agents such as
chorionic gonadotropin (hCG ) to stimulate LH production
and testicular testosterone production.[32]
Turek et al.[41] described a case report of an AS user
who was administered hCG 2000 to 3000 units three
times a week. Following 3 months of treatment, the
patient’s wife became pregnant, reportedly due to
LH and sperm normalisation. FSH activity is required
for completion of spermatogenesis. However,
FSH activity is not precipitated by hCG. This
leads to the belief that sperm counts are increased
by hCG, but they may not be 100% viable. Many
athletes who discontinue AS have their sperm morphology
normalise within 4 months. However, this
is not necessarily always the case since normalisation
is a function of both the magnitude and duration
of AS exposure.[38] Some individuals required
up to 1 year for normalisation of morphology and
motility.[37,38]
AS can also lead to feminisation in males from
the conversion of testosterone to estrogen metabolites
(aromatisation).[27] As a result,many AS users
report increased voice pitch and gynaecomastia, although
these effects are unpredictable. Our experience
notes that many users of AS self-administer the
antiestrogenic agent tamoxifen to antagonise these
effects. Unsurprisingly, the efficacy and safety of
this practice remains to be confirmed. Our experiences
with AS-using bodybuilders indicate that hair
loss is minimal with testosterone ester doses of less
than 600mg/wk. The adverse effect is reversible on
discontinuation of the AS.
AS use in women can lead to hirsutism, acne,
deepening of the voice, clitoral hypertrophy, decreased
breastmass, decreased menstruation or amenorrhoea,
increased appetite and male pattern baldness.
Even after discontinuation of the causative
agents, these effects are sometimes irreversible.[42]
292 Kutscher et al.
Adis International Limited. All rights reserved. Sports Med 2002; 32 (5)
The willingness to tolerate any physical and/or reproductive
adverse drug effect to achieve an athletic
goal is unique among AS administrating athletes.
Other endocrine effects include decreased thyroid
function and decreased serum T-4 binding globulin
concentrations.[3]AS is known to cause acne
and other skin changes including, but not limited
to, oily hair and skin, alopecia, sebaceous cysts and
hypertrophy of sebacious glands.High doses ofAS
increase the amounts of Propionibacteria acnes,
free fatty acids and cholesterol in the skin, which
lead to these dermatological changes.[3]
4.4 Psychiatric Effects
Aggressive behaviour and mood changes have
been linked to use of AS in case reports, animal
studies and controlled clinical trials.[43,44] Although
these reports describe increases in aggression and
violent behaviour with AS use, there are relatively
few controlled studies relating aggressive behaviour
and mood changes to AS use among a bodybuilding
and/or weightlifting population. Despite the nature
of various reports on mood changes with AS administration,
many bodybuilders report that they
feel AS elicit an antidepressant-like feeling. This
observation was recently challenged when Seidman
et al.[45] reported no antidepressant effects of testosterone
replacement in men with major depressive
disorder. Conclusions of this study are limited and
future studies of AS use in depression are needed.
Six randomised controlled studies have administered
supraphysiologic doses of testosterone to
healthy male participants and observed them for
changes in their mental status.[40,46-50] In general,
these studies indicate little risk of mood changes
or aggressive behaviour with doses of up to 300
mg/week. However, with larger doses, changes in
various mood and aggression subscales have been
observed.
Pope et al.[48] described significant increases in
the Point Subtraction Aggression Paradigm (PSAP),
and theYoungMania Rating Scale (YMRS) among
recipients of higher testosterone doses (600 mg/wk)
compared with placebo.[48] While between-group
differences were observed, the distribution of individual
scores was also important. On average, the
endpoint YMRS scores were 3 points higher in recipients
of testosterone. However, this difference
does not indicate that all participants had a 3-point
increase, but rather that most participants experienced
no change, while a few individuals experienced
marked changes. While Pope et al.[48] was
able to demonstrate significant alterations in aggression
and mood endpoints, the majority of controlled
studies have not. This may be because psychiatric
adverse drug effects are dose-dependent and
all of the negative studies did not expose the participants
to large enough doses to induce a change
in the participants’mental status. Additionally, the
negative studies indicate that individuals with a positive
psychiatric history including personality disorder
may be more susceptible to changes in mood
and aggression.[40,46,47,49,50]
Although AS use promotes aggression and mood
changes, there are several limitations to the data.
First, many of the studies did not enrol bodybuilders
and/or weightlifters as participants.[40,46,47,49,50] The
inclusion of healthymale participants does not represent
individuals who are likely to use AS such as
weightlifters, bodybuilders and other athletes. The
second limitation is the exclusion of individuals
with psychiatric disorders, particularly personality
disorders. Such individuals may be more susceptible
to AS-induced psychiatric changes than normal
control participants. Finally, AS regimens were limited
to a single agent administered weekly at doses
less than 600 mg/week.[40,46-50] These regimens do
not represent the multidrug combinations (stacks)
and/or mega-doses of AS used by bodybuilders. Furthermore,
the maximum dose given in clinical trials
was 600 mg/week for 2 weeks, which is far below
the doses commonly used by bodybuilders.[46,48]
Data regarding AS use in bodybuilders and/or
weightlifters and associated psychiatric changes are
limited. Yates et al.[6] compared weightlifters that
were either AS users (n = 20) or non-AS users (n =
20) to alcoholics (n = 20) and non-weightlifting
community controls (n = 20). Personality disorders
were assessed using the Diagnostic and Statistical
Anabolic Steroids 293
Adis International Limited. All rights reserved. Sports Med 2002; 32 (5)
Manual of Mental Disorders (3rd edition, revised)
[DSM-III-R] criteria for cluster A, B and C personality
traits, and the self-report personality diagnostic
questionnaire. Forty-five percent ofAS users demonstrated
antisocial personality traits compared with
0% of community controls (p < 0.001).[6] In a later
study, Yates et al.[51] examined the Buss-Durkee
Hostility Inventory (BDHI) scores for eight AS users,
four previous AS users to 25 non-AS using
weightlifters. There were no significant differences
among AS users, non-AS users and previous users
on overall BDHI scores, but there were significant
elevations on the BDHI subscores of assault, indirect
aggression and verbal aggression among AS
users.[51]
A more recent study by Pope and Katz[52] conducted
interviews with weightlifters using AS (n =
88) and non-users (n = 68). DSM-III-R criteria
were applied to identify psychiatric syndromes.
Twenty-three percent of AS users experienced major
mood changes of mania, hypomania or major
depression. In contrast, the rate of major mood
changes was only 6% among non-AS users (p <
0.07). Aggressive behaviour, including fights, domestic
disrupts, assaults and arrests, was common
among AS users. All participants denied previous
behaviour of this type before AS use.[52]
Our experienceswithAS users indicate that psychiatric
effects are unique to each individual and
overall conclusions are difficult tomake.However,
there are data suggesting that AS administration
may be addictive. In interviews with 49 AS users,
at least one DSM-III-R symptom of dependence
was reported by 94% of the sample, while three or
more symptoms were reported by 57% of the sample.[
53] Three symptoms are required for a diagnosis
of drug dependence. Arecent article[54] reported
that 23% of AS using participants met DSM-IV
criteria dependence, while 25% met DSM-IV criteria
for abuse. The authors concluded thatASwere
addictive and suggested that dissatisfaction with
body sizemight lead to dependent patterns of use.[33]
Our experience with many athletes using AS suggests
that dissatisfaction with their body size and
increases in strength and size obtained from AS are
the primary stimuli for continued usage of these
agents. Although these observationsmay be related
to an underlying body dysmorphic disorder diagnosis,
and unrelated to AS usage, no studies have
been conducted addressing this issue in this population.
Clinicians should not discount the addictive
potential of these agents, as competitive athletes are
often willing to use any substance to obtain their
goals.
5. Conclusion
Understanding how AS are used in the bodybuilding
community merits more study. The desire
among competitive athletes to succeed is a powerful
stimulus and using legal substances for illegal
purposes to obtain these goals has become an increasingly
large concern for healthcare professionals.
Healthcare professionals should be able to educate
their patients regarding the risks of using these
agents. Aclinician’s warnings will gain credibility
if they have a sound understanding of the issues
related to AS use so that they can have an informed
conversation with the patient/user. Clinicians should
impress upon their patients that, despite the cavalier
use of AS among athletes, the long-termeffects
are not well established and they ought to be cautious.
This requires the clinician to obtain as much
knowledge about AS as possible by reviewing not
only the medical literature, but mass-media literature
as well. Physicians must warn their patients
who use AS that the effects of these agents on overall
health have not been extensively studied, and
encourage them to avoid these agents to prevent
any future health risks.
Acknowledgements
The authors had no funding for this article and have no
conflicts of interest that could affect its content.
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