Available online at www.sciencedirect.
com Current Opinion in
ScienceDirect
Review
Abuse of anabolic steroids: A dangerous indulgence
Thiago Gagliano-Jucá and Shehzad Basaria
Abstract
Anabolic androgenic drugs include testosterone and its syn-
thetic steroidal derivatives (also known as anabolic androgenic
steroids [AAS]), as well as nonsteroidal selective androgen
receptor modulators, which exert tissue-specific androgenic
effects by binding to the androgen receptor. As these agents
increase muscle mass and strength, they have been widely
abused by professional athletes to seek competitive advan-
tage. Recently the use of these compounds has also increased
among amateur athletes and also among men who are not
athletes but want to enhance their body image. The use of AAS
is associated with many adverse effects, some of which are
serious and difficult to manage. In this article, we briefly review
the types of AAS, the mechanism behind their ergogenic ef-
fects, and finally discuss their adverse effects in some detail.
Addresses
Research Program in Men’s Health, Aging and Metabolism, Brigham
and Women’s Hospital, Harvard Medical School, Boston MA, USA
Corresponding author: Basaria, Shehzad (sbasaria@bwh.harvard.
edu)
Current Opinion in Endocrine and Metabolic Research 2019,
9:96–101
This review comes from a themed issue on Sports Endocrinology
Edited by Fabio Lanfranco
For a complete overview see the Issue and the Editorial
Available online 28 October 2019
https://doi.org/10.1016/j.coemr.2019.10.002
2451-9650/© 2019 Elsevier Ltd. All rights reserved.
Keywords
Anabolic steroids, Bodybuilding, SARMs, Androgens.
Introduction
The use of anabolic androgenic steroids (AASs), which
include testosterone and its synthetic derivatives and
nonsteroidal selective androgen receptor modulators
(SARMs), has increased significantly over the past de-
cades. The use of AAS is not only common among pro-
fessional and amateur athletes who take these agents for
their ergogenic effects but also by non-athlete men who
wish to enhance their body image. Recent data suggest
that approximately 80% of AAS users take these drugs to
enhance their appearance [1]; their desire to become
lean and muscular might be the result of exposure to
images of muscular men in media and/or they may suffer
Current Opinion in Endocrine and Metabolic Research 2019, 9:96–101
Endocrine and Metabolic Research
from muscle dysmorphia, a body image disorder that
manifests as an obsessive preoccupation with a muscular
appearance [2].
Starting in the late 1980s, surveys demonstrated that
between 3 and 11% of male high school students in the
United States admitted to having used AAS at some
time [3,4]. These observations have been corroborated
by recent studies conducted in the United States [5,6],
Europe [7,8], and Brazil [9]. These studies have pro-
duced a wide range of prevalence estimates, but in
general, the reports suggest that w3% of young men in
most Western countries have used AAS at some time in
their lives [10]. Interestingly, AAS use begins later than
most other drugs of abuse, with only 22% of men starting
their use before age 20 years [11]. A recent study esti-
mated that 2.9 to 4.0 million Americans aged 13e50
years have used AAS [11], with 1 million experiencing
AAS dependence [11]. AAS use and dependence may
result in serious adverse effects, particularly cardiovas-
cular, neuroendocrine, and neuropsychiatric disorders,
which may contribute to premature mortality in some
cases [12]. In this review, we highlight various types of
AAS, the mechanism behind their performance-
enhancing effects and their adverse effects.
Types of AAS
Steroids
AAS are a group of steroids that include testosterone and
its synthetic derivatives. These steroids can be largely
divided into aromatizable and non-aromatizable AAS.
Androgens like nandrolone and boldenone are de-
rivatives of testosterone that can be aromatized to es-
trogens by the enzyme aromatase, which removes the
methyl group from the 19th position of the androgen
ring. Non-aromatizable AAS such as stanozolol, oxan-
drolone, and trenbolone are modified such that the
enzymatic activity of aromatase on the 19th carbon is
impaired, precluding their conversion to estrogens [13].
Men who use AAS for the purposes of image-
enhancement usually prefer non-aromatizable AAS to
avoid development of gynecomastia [14]. Some AAS
undergo 5a-reduction by the enzyme 5a-reductase, as
occurs with conversion of testosterone to dihy-
drotestosterone. Some AAS are 17a-alkylated to
decrease first-pass metabolism, which improves their
oral bioavailability [13]. However, the major adverse
effect of oral 17a-alkylated AAS is hepatotoxicity.
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SARMs
A class of drugs known as SARMs have emerged as a new
group of frequently used androgens by individuals
looking for performance- and appearance-enhancing ef-
fects. These agents are ligands at the androgen receptor
and exert tissue-selective effects such as increasing
bone and muscle mass [15]. Many oral nonsteroidal
SARMs are currently being developed aiming to treat
functional limitations associated with muscle wasting
conditions [16], but none has yet been approved by the
US Food and Drug Administration. Nonetheless, these
agents can be purchased over the internet [17], making
it difficult to estimate the extent of their use [18].
Abuse of SARMs may have a similar adverse effect
profile as other androgens, including suppression of the
hypothalamic-pituitary-gonadal (HPG) axis and reduc-
tion in high-density lipoprotein (HDL) concentrations.
However, as these drugs are relatively new, long-term
health impact of abuse of SARMs remain unclear.
Performance-enhancing effects
The ergogenic effects of AAS on athletic performance
include an increase in skeletal muscle mass and strength
[19,20], and these effects are further increased by
concomitant resistance training [20] Androgens also
Figure 1
Adverse health effects of abuse of anabolic androgenic steroids.
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Abuse of anabolic steroids Gagliano-Jucá and Basaria 97
stimulate erythropoiesis [21], increase erythrocyte 2,3-
bisphosphoglycerate concentration [22], and promote
muscle fiber capillarity and mitochondrial biogenesis
[23], all of which enhance O2 delivery and uptake by
skeletal muscles. These adaptations translate to a higher
level of exercise performance.
Adverse effects
Considering that the use of SARMs is relatively recent
and information regarding their adverse effects is
limited, in this section, we will review adverse effects of
testosterone and their steroidal derivatives (Figure 1).
Musculoskeletal
Compared with bodybuilders who have not used AAS,
abusers of these compounds have been shown to have a
9-fold increase in the risk of tendon ruptures, mainly
upper-body tendons [24]. Although the exact mecha-
nism by which AAS affect the integrity and function of
the tendons remains largely unknown, the relatively
rapid increase in skeletal muscle mass and strength and
slower pace of adaptation by connective tissues has been
posited as the main reason for this increased risk. The
combination of long-term AAS use with resistance
training has been associated with higher patellar tendon
Current Opinion in Endocrine and Metabolic Research
Current Opinion in Endocrine and Metabolic Research 2019, 9:96–101
98 Sports endocrinology
stiffness compared with individuals who do resistance
training but have never used AAS [25]. These changes,
at least in part, have been posited to be because of
changes in the metabolism of type-1 and type-3 collagen
fibers [26]. Premature closure of the epiphyses in the
teenagers may occur with the use aromatizable AAS
[27], which may result in reduced final height.
Cardiovascular
Androgen receptors are expressed in human myocar-
dium [28], vascular smooth muscle [29], and endothe-
lium [30]; thus, use of AAS may have an influence on all
aspects of cardiovascular physiology. Although cardio-
vascular safety of physiologic testosterone replacement
in men with androgen deficiency remains controversial
[31], there is some consensus that supraphysiological
doses of AAS are deleterious to various aspects of car-
diovascular health, including an increased risk of ar-
rhythmias, incident (or exacerbation of) hypertension
[1], and myocardial dysfunction [32,33]. Additionally,
androgens may predispose to thrombosis and can cause
dyslipidemia. Indeed, there have been case reports of
stroke and myocardial infarctions even in young men
abusing AAS [34e36].
Androgens may affect blood pressure through multiple
mechanisms, including inhibition of extraneuronal
uptake of catecholamines [37] and inhibition of 11b-
hydroxylase [38], resulting in cortisol-induced activa-
tion of the mineralocorticoid receptor with salt and
water retention [39]. Many small studies have shown an
association between AAS use and hypertension [40,41];
this association becomes stronger with prolonged
exposure [41]. However, other studies have not found
such an association [42,43]. The lack of agreement
among these studies might be because of small sample
sizes and their observational design.
Arrhythmias in AAS abusers often occur during physical
activity and include atrial fibrillation, supraventricular or
ventricular tachycardia, and ventricular fibrillation
[44,45]. Some reports have suggested arrhythmias as the
cause of sudden death in some young athletes as no
thrombus or atheroma was seen on autopsies [46,47].
Long-term use of AAS may alter cardiac electrophysi-
ology [48,49] by stimulating myocardial fibrosis that can
predispose to lethal arrhythmias [50], and AAS abuse
also potentially affects cardiac size and function; how-
ever, as left ventricular hypertrophy is considered a
physiologic adaptation to endurance and resistance ex-
ercise [51,52], it is difficult to differentiate between the
impact of exercise training versus any direct effect of
AAS on cardiac remodeling. However, a recent report on
86 men (aged 34e54 years) with at least 2 years of cu-
mulative exposure to supraphysiologic doses of andro-
gens showed that these men had significantly impaired
systolic and diastolic function on echocardiography
Current Opinion in Endocrine and Metabolic Research 2019, 9:96–101
compared with 54 experienced weightlifters reporting
no androgen abuse [32]. Furthermore, cardiac dysfunc-
tion was worse in men who continued to use androgens
at the time of evaluation compared with previous users,
suggesting that discontinuation of androgens partially
restored cardiac function [32]. Additional studies have
shown distinct anatomical changes in the myocardium in
AAS users that are subtle and occur before the onset of
overt ventricular hypertrophy [53]. Androgen users also
display significantly greater coronary artery plaque
volume than nonusers on computed tomography coro-
nary angiography, with the degree of plaque volume
being associated with cumulative androgen exposure
[32].
Oral androgens are known to cause dyslipidemia [31], in
particular, reduction in HDL cholesterol and an increase
in low-density lipoprotein cholesterol and triglycerides
[54]; this adverse lipid profile may develop within a few
weeks of AAS use and may take several months to
resolve after their discontinuation [55].
Androgens also have prothrombotic effects that occur via
multiple mechanisms [31]. Erythrocytosis is a common
adverse effect of androgen therapy [56] and contributes
to increased blood viscosity [57] and blood-flow resis-
tance [58]. Furthermore, in vitro studies have shown a
direct correlation between hematocrit and platelet ag-
gregation [59]. Testosterone treatment has also been
shown to augment ex vivo platelet aggregability by
increasing thromboxane A2 receptor density on human
platelets [60]. Androgens also decrease production of
prostacyclins [61], an inhibitor of platelet aggregation.
Hepatic
Hepatic adverse effects of AAS use are generally limited
to oral 17a-alkylated agents, although data on SARMs
(oral agents) are limited. However, the frequency of
AAS-induced hepatotoxicity may be overestimated, as
rhabdomyolysis from high-intensity exercise can in-
crease transaminases and may mislead clinicians who
might consider these elevations of hepatic origin [1].
Nonetheless, prolonged administration of 17a-alkylated
agents have been shown to reduce the activity of hepatic
microsomal drug metabolizing enzyme system and the
mitochondrial respiratory chain complex and increases
hepatic lysosomal hydrolases [62]. These hepatotoxic
effects can occur even in the absence of elevated liver
function tests [62]. Macroscopic signs of AAS-induced
hepatotoxicity are related to the cumulative dose and
duration of 17a-alkylated AAS use and include chole-
static jaundice and hepatic peliosis (proliferation of si-
nusoidal capillaries that result in blood-filled cysts)
[62]. Some data suggest that peliosis and hepatic ade-
nomas are rare and occult, with most cases being found
incidentally or on autopsies; there have been rare re-
ports of spontaneous hepatic rupture in AAS users [63].
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Neuroendocrine/reproductive
Androgens are key regulators of the HPG axis [64];
administration of exogenous androgens, including
SARMs [65], suppress gonadotropin secretion via
negative feedback on the hypothalamus and the pitui-
tary, thereby reducing testicular steroidogenesis and
spermatogenesis, which may contribute to diminished
fertility [66]. Symptoms of androgen deficiency such as
sexual dysfunction may also occur [1]. Long-term AAS
abuse may result in prolonged hypogonadism even after
discontinuation of AAS [67]. Abuse of aromatizable AAS
may result in gynecomastia [68]. In women, AAS use
may result in virilization.
Neuropsychiatric
Although there is a widespread notion that AAS abuse
increases aggressive behavior, only a small number of
individuals display this change [69]. Recent studies
have shown that androgens enhance behaviors involved
in obtaining and maintaining a high social status (which
may translate into some aggressiveness), while some
men display generous behavior [70]. In addition to
experiencing neuropsychiatric symptoms during AAS
use, androgen withdrawal has been associated with
major depressive episodes, including suicidal ideation
[67]. Recent functional magnetic resonance imaging
data comparing AAS users versus non-users suggest that
these mood changes might be related to a decrease in
functional connectivity between the amygdala and the
default mode network, as well as with other central
nervous system foci involved in emotional and cognitive
regulation [71]. Moreover, neural structural changes
such as widespread thinning of the cerebral cortex and
smaller volumes of putamen have been demonstrated in
weightlifters with cumulative exposure to AAS of at
least 1 year compared with weightlifters who never used
AAS [72]. Although these studies do not establish cau-
sality, there is a concern that long-term use of AAS might
result in cerebral atrophy [14]. Indeed, preclinical
studies have shown that AAS can induce neuronal
apoptosis [73,74] and altered expression of nerve growth
factor, a key factor for neuronal differentiation and sur-
vival [75].
Dermatologic
Androgen receptors are present in the skin [28], and
testosterone has been shown to dose-dependently in-
crease sebum production [76]. Acne vulgaris and
folliculitis are frequently seen in AAS users [77]; they
generally resolve upon cessation of these drugs. Andro-
gens can also cause male-pattern alopecia [77], which
may be irreversible.
Conclusion
The use of AAS has increased among both professional
and amateur athletes seeking to improve physical
performance and among young men who take AAS to
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Abuse of anabolic steroids Gagliano-Jucá and Basaria 99
enhance their image and appearance. Use of these drugs
have potentially serious health consequences. A
tremendous amount of work needs to be done to make
sophisticated doping tests available to practicing clini-
cians; creation of a steroid hormone user registry, clinical
trials to assess the efficacy of selective estrogen receptor
modulators and aromatase inhibitors in hastening the
recovery of the gonadal axis, and an education campaign
to raise public awareness regarding the risks of AAS use.
Conflict of interest statement
Nothing declared.
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