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S. Ivanova, K. Ivanov, S. Pankova, L. Peikova
CONSEQUENCES OF ANABOLIC STEROIDS ABUSE
S. Ivanova1, K. Ivanov1, S. Pankova2, L. Peikova2
Medical University Plovdiv, Faculty of Pharmacy, Department Pharmacognosy
and Pharmaceutical Chemistry, Plovdiv, Bulgaria
2
Medical University Sofia, Faculty of Pharmacy, Department Pharmaceutical Chemistry, Sofia, Bulgaria
1
Abstract. Many cases of anabolic steroid abuse are reported nowadays. Anabolic androgenic
steroids are used to enhance athletic performance and appearance. Not only athletes take anabols
but also young people who practice fitness and want to look like a bodybuilder. Anabolic steroid
abuse can be associated with a wide range of adverse side effects ranging from some that are
physically unattractive, such as acne and breast development in men, to others that are life threatening, such as heart attacks and liver cancer. Most are reversible if the abuser stops taking the
drugs, but some are permanent, such as voice deepening in females. Most data on the long-term
effects of anabolic steroids in humans come from case reports rather than formal epidemiological
studies. Steroid abuse disrupts the normal production of hormones in the body, causing both reversible and irreversible changes. Changes that can be reversed include reduced sperm production
and shrinking of the testicles (testicular atrophy). Irreversible changes include male-pattern baldness and breast development (gynecomastia) in men. In one study of male bodybuilders, more
than half had testicular atrophy and/or gynecomastia.In this study we make review of the most
important side effects of use of steroids.
Key words: anabolic androgenic steroid; androstenedione; dehydroepiandrosterone; steroids;
side effects, sport medicine
Abbreviation: anabolic-androgenic steroids (AAS); low-density lipoprotein (LDL); cardiovascular diseases (CVD); high-density lipoprotein (HDL); anabolic androgenic steroids (AASs)
Introduction
The roots of bodybuilding go all the way back to
ancient Greece. It was the athletes of ancient Greece
who used to train in the gymnasiums. They did not
use resistance training as a form of body modification but rather a means to improve at the sport they
participated in. It was in 11th century India that bodybuilding as we know it first arrived on the scene. It
was back then the Indians would use primitive dumbbell weights carved from stone for the sole purpose of
getting bigger and stronger, it is also reported that by
the 16th century weight lifting had become a national
past time in India. By the mid-19th century weight
training as a means of improving health and increasing strength was becoming increasingly popular. Born
1867 in Prussia by the name Friedrich Muller, Eugene Sandow later became referred to as “The Father
of Modern Bodybuilding”. In 1970 Schwarzenegger
won the competition Mr. Olympia, making him the
youngest ever Mr. Olympia at the age of 23, a record he still holds to this day. Bodybuilding had a
new star and the bodybuilding became the new star
of the 20-th century. The 80’s ushered in a new era
of massive bodybuilders. The reports of abuse with
steroids begins at the time when bodybuilding gane
more and more popularity. Sociocultural standards of
beauty for males emphasize strength and muscularity. The broad-shouldered, narrow hipped male body
is idealized in the modern society. Weight machines
and performance enhancing supplements are widely
advertised in health and fitness centers [17]. Nowadays there is a big demand of food supplements with
androgenic effects or product with steroids, however
the steroids are forbidden substances in food additives. Most athletes use anabolic-androgenicsteroids
(AAS) to obtain a well-trained, athletic, and healthy
looking body [19]. Users of anabolic steroids can be
divided into two groups: first who use these products
Consequences of anabolic steroids abuse
for medical purposes (anabolic steroids are prescribed
for a small number of legitimate medical purposes)
and the second group include those who use them
to enhance their strength and athletic ability, and/or
enhance their physical appearance by adding muscle
mass. There are different groups that use performance
enhancing drugs and abuse with steroids [22]. The
first group - elite athletes who have a definite plan
to achieve their goal, the second - people who practice fitness and want to look good. Very often these
people have only a crude knowledge about the pharmacological databases and the serious side effects
regarding these drugs. Proponents of their use claim
that the drugs increase muscle strength and mass, endurance, decrease recovery time between workouts
and improve physique. Critics claim that these beneficial effects are due primarily to expectancy and
other factors associated with training; many doctors
also claim that their use is actually quite dangerous.
Regardless of their efficacy, the use and abuse of anabolic-androgenic steroids has escalated such that in
1990 the US Congress enacted the Anabolic Steroids
Control Act requiring that anabolic steroids be added to Schedule III of the Controlled Substances Act.
This action placed compounds such as testosterone
cipionate and nandrolone decanoate in the company
of various opioid drugs, amphetamines and barbiturates. As chair of the American Society for Pharmacology and Experimental Therapeutics’ Committee
on Substance Abuse, Scott Lukas advocates continued research on the effectiveness, toxicity and natural
PHARMACIA, vol. 61, No. 4/2014
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Fig. 1. Basic structure of steroid hormones and the possibilities of chemical derivatization.
history of anabolic-androgenic steroid abuse [2]. All
androgens posses the cyclopentanophenanthrene nucleus, typical of steroid hormones.
The structures of testosterone and some selected
derivatives used as anabolics are shown in Figure 2.
These compounds have been synthesized and used to
maximize the bioavailability, and to prolong the androgenic effects.
Clinical studies about side effects of AAS
Anabolic androgenic steroids are synthetic derivatives of testosterone, which is the primary male sex
hormone. Anabolic androgenic steroids are used to
enhance athletic performance and appearance. Adverse effects include those on the liver, serum lipids,
psyche/behavior and reproductive system. Androstenedione is an anabolic androgenic steroid used to
increase blood testosterone levels for the purposes of
Fig.2. Structures of testosterone and some of the most common synthetic derivatives used as anabolics
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increasing strength, lean body mass and sexual performance. However, there is no research indicating
that androstenedione, or its related compounds, significantly increases strength and/or lean body mass in
humans by increasing testosterone levels. The longterm health effects of prolonged androstenedione
supplementation are unknown. Dehydroepiandrosterone (DHEA) is a weak androgen also used to elevate
testosterone levels, and is advertised as an anti-obesity and anti-aging supplement capable of improving
libido, vitality and immunity levels [1]. The health
consequences of steroid abuse are very serious. Rising levels of testosterone and other sex hormones
normally trigger the growth spurt that occurs during
puberty and adolescence and provide the signals to
stop growth as well.
Cardiovascular side effects
Adverse cardiovascular effects induced by anabolic steroids include hypertension, left ventricular hypertrophy, impaired diastolic filling, polycythaemia,
and thrombosis.[13]Steroid abuse has been associated with cardiovascular diseases (CVD), including
heart attacks and strokes, even in athletes younger
than 30. Steroids contribute to the development of
CVD, partly by changing the levels of lipoproteins
that carry cholesterol in the blood. Steroids, particularly oral steroids, increase the level of low-density
lipoprotein (LDL) and decrease the level of high-density lipoprotein (HDL). High LDL and low HDL levels increase the risk of atherosclerosis, a condition in
which fatty substances are deposited inside arteries
and disrupt blood flow. If blood is prevented from
reaching the heart, the result can be a heart attack. If
blood is prevented from reaching the brain, the result can be a stroke .Steroids also increase the risk
that blood clots will form in blood vessels, potentially disrupting blood flow and damaging the heart
muscle so that it does not pump blood effectively
.Steroid abuse has been associated with liver tumors
and a rare condition called peliosis hepatis, in which
blood-filled cysts form in the liver. Both the tumors
and the cysts can rupture, causing internal bleeding
.Steroid abuse can cause acne, cysts, and oily hair and
skin .Many abusers who inject anabolic steroids may
use nonsterile injection techniques or share contaminated needles with other abusers. In addition, some
steroid preparations are manufactured illegally under nonsterile conditions. These factors put abusers
at risk for acquiring lifethreatening viral infections,
such as HIV and hepatitis B and C. Abusers also can
develop endocarditis, a bacterial infection that caus-
S. Ivanova, K. Ivanov, S. Pankova, L. Peikova
es a potentially fatal inflammation of the inner lining
of the heart. Bacterial infections also can cause pain
and abscess formation at injection sites. Since the
Bodybuilding became also and a female sport many
female bodybuilders began to use steroids. In the female body, anabolic steroids cause masculinization.
Breast size and body fat decrease, the skin becomes
coarse, the clitoris enlarges, and the voice deepens.
Women may experience excessive growth of body
hair but lose scalp hair. With continued administration of steroids, some of these effects become irreversible.Bonetti et all from the University of Parma
Italy have made a 2 year study for the side effects of
steroids. Long-term side effects of high doses of anabolic androgenic steroids self-administration were
evaluated in this study. Twenty male bodybuilders,
voluntarily starting steroid self-administration, were
followed every 6 months over 2 years. Physical examination, haematological, metabolic and endocrine
variables, semen analysis, hepatic and prostate ultrasound and echocardiographic evaluations were performed. LH values (baseline 3.43 ± 1.75) were suppressed at 18 (1.98 ± 1.99) (p = 0.026) and 24 (2.43
± 2.17) (p = 0.026), and FSH (3.95 ± 2.01) at 6 (3.01
± 2.16) (p = 0.031), 12 (2.45 ± 2.54) (p = 0.029), 18
(2.02 ± 2.29) (p = 0.032) and 24 (3.42 ± 2.64) (p =
0.032) months and SHBG (34.11 ± 10.88) values significantly lowered at 12 (24.81 ± 12.49) (p < 0.05),
18 (21.28 ± 11.15) (p < 0.01), 24 months (25.42 ±
11.16) (p < 0.01). A significant decrease in spermatozoa count (p < 0.01), and fertility index (p = 0.01)
occurred. HDL-cholesterol (baseline 56.94 ± 13.54)
was reduced at 18 (41.86 ± 14.17) (p < 0.01) and 24
(43.82 ± 18.67) (p < 0.05) months and Apo A-1 at 12
(p < 0.001), 18 (p = 0.05) and 24 (p = 0.05) months.
The most important long-term adverse effects were
lower fertility and the impairment of lipid profile associated with an increased cardiovascular risk.[3] It
has been consistently shown that anabolic steroid use
is associated with abnormal lipid profiles: a decrease
in high density lipoprotein cholesterol and a variable
increase in low density lipoprotein cholesterol and
total cholesterol [14,15].
Infertility side effect
Abuse of anabolic androgenic steroids (AASs)
may be an aetiological factor in male infertility
among recreational power athletes [5]. Large doses
of exogenous androgenic agents induce apituitary
hypogonadal state, associated with decreasedsecretion of follicular stimulating hormone and luteinizing
hormone [13].
Consequences of anabolic steroids abuse
Neuropsychiatric side effects
Thomas A. Pagonis et all have made a very important study for the Psychiatric side effects of anabolic steroids correlate to the severity of abuse.
The study includes a substantial group of AAS
abusing athletes and two more groups demographically similar to the first, one composed of athletes
not using any substance and a placebo group. All
athletes were stratified according to the severity of
AAS abuse. Psychometric instruments were applied
to all athletes in specific time intervals, dependent
to the AAS abusers’ regimens, providing us with a
final psychological profile that was to be compared
to the pre-study profile. All results were comparable
(within and between groups) for statistically significant differences and correlated to the severity of the
abuse. Homogeneity of all groups was safeguarded
by random doping controls, monitoring of drug levels and analysis of all self obtained drugs by method of liquid chromatography/mass spectrometry. All
athletes were provided with a common exercise and
dietary regime, so common training and nutritional
conditions were achieved. We studied a cohort of 320
body-building, amateur and recreational athletes,
of whom 160 were active users of AAS (group C),
80 users administering placebo drugs (group B) and
80 not abusing any substance (Group A). Group C
athletes were stratified according to AAS abuse parameters, thus providing us with three subgroups of
“light, medium and heavy abuse”. Athletes of groups
A and B were included in a “no abuse” subgroup. The
psychometric instruments used were the Symptoms
Check List-90 (SCL-90) and the Hostility and Direction of Hostility Questionnaire (HDHQ). The psychometric evaluations took place within a time interval of 13 months. Statistical analysis was performed
by using the Mann–Whitney/Wilcoxon two-sample
non-parametric test (Kruskal–Wallis test for two
groups) for data that were not normally distributed
and Linear regression analysis was used to ascertain
the correlation between severity of use and escalation of side effects. The study showed a statistically significant increase in all psychometric subscales
recorded in group C, and no statistically significant
difference in group C and A. There was a significant
increase in the scorings of group C for all subscales
of SCL-90 and HDHQ. Correlation of abuse severity
and side effects showed that there was a statistical
significant increase in Δ values of all SCL-90 and
HDHQ subscales that escalated from light abuse to
medium and heavy abuse/consumption patterns [4].
A 2005 review determined that some, but not all, ran-
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domized controlled studies have found that anabolic
steroid use correlates with hypomania and increased
aggressiveness, but pointed out that attempts to determine whether AAS use triggers violent behavior have
failed, primarily because of high rates of non-participation [6]. A 2008 study on a nationally representative sample of young adult males in the United States
found an association between lifetime and past-year
self-reported anabolic-androgenic steroid use and involvement in violent acts. Compared with individuals that did not use steroids, young adult males that
used anabolic-androgenic steroids reported greater
involvement in violent behaviors even after controlling for the effects of key demographic variables,
previous violent behavior, and polydrug use.[7] A
trial conducted in 2000 using testosterone cypionate
at 600 mg/week found that treatment significantly increased manic scores on the YMRS, and aggressive
responses on several scales. The drug response was
highly variable. However: 84% of subjects exhibited minimal psychiatric effects, 12% became mildly
hypomanic, and 4% (2 subjects) became markedly
hypomanic. The mechanism of these variable reactions could not be explained by demographic, psychological, laboratory, or physiological measures [9].
A 1996 review examining the blind studies available
at that time also found that these had demonstrated a
link between aggression and steroid use, but pointed out that with estimates of over one million past
or current steroid users in the United States at that
time, an extremely small percentage of those using
steroids appear to have experienced mental disturbance severe enough to result in clinical treatments
or medical case reports.[8] Anabolic-androgenic steroids may both relieve and cause depression, and that
cessation or diminished use of anabolic-androgenic
steroids may also result in depression[11].
Fig.3 Stanozol (Winstrol)
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Hepatotoxicity
There are numerous reports of liver dysfunction
associated with anabolic steroid use. These include
asymptomatic elevations in serum aminotransferases, cholestasis, peliosis hepatitis (an uncommon
condition characterized by small blood filled cystic
spaces distributed throughout the liver parenchyma),
hepatocellular carcinoma, hepatic adenomas, and hepatic haematomas.[13] Hepatotoxicity is usually associated with the C17 alkylated compounds [20,21].
Good example for this is stanozolol, commonly sold
under the name Winstrol (oral) and Winstrol Depot
(intramuscular), is a synthetic anaboli steroid derived
from dihydrotestosterone. It was developed by Winthrop Laboratories (Sterling Drug) in 1962, and has
been approved by the FDA for human use.
Feminization
There are also sex-specific side effects of anabolic steroids. Development of breast tissue in males,
a condition called gynecomastia (which is usually
caused by high levels of circulating estradiol), may
arise because of increased conversion of testosterone
to estradiol by the enzyme aromatase (fig.4)
Fig.4. Conversion of testosterone to estradiol
Gynaecomastia occurs in about 40% of male
users of anabolic steroids [17]. Another male-specific side-effect that can occur is testicular atrophy,
caused by the suppression of natural testosterone
levels, which inhibits production of sperm (most
of the mass of the testes is developing sperm). This
side-effect is temporary: The size of the testicles
usually returns to normal within a few weeks of discontinuing anabolic steroid use as normal production of sperm resumes [10].
Masculinization
Just like the males atlets all professional female
bodybuilders are taking anabolic steroids. We don’t
recommend anabolic drugs to females. AAS destroy woman femininity and helth. Anabolic steroids
are designed to copy the muscle-building effects of
testosterone but with fewer of the accompanying
S. Ivanova, K. Ivanov, S. Pankova, L. Peikova
“masculinization” effects. Masculinization occurs in
females, leading to menstrual irregularities, clitoral
enlargement, hirsutism, deepening of voice, oily skin
and breast atrophy, increased hair growth on face,
legs and arms. Of these, clitoral enlargement and
voice changes are usually permanent [23].
Endocrine aspects of anabolic steroids
The unwanted consequences of AAS abuse are
most damaging in females and adolescents: irreversible virilization and stunting of linear growth, respectively. Suppression of the hypothalamic–pituitary–
gonadal axis that results in disturbances in menstrual function and infertility is, in contrast, reversible.
Stimulation of the sebaceous glands appears to be
dose-related: Increasing testosterone beyond the
physiological range in normal men results in further
increases in the sebum excretion rate. Consequently
AAS users tend to suffer from severe acne [12].
Fig.5. Dose – response relation of biological responses
to increasing concentrations of circulating testosterone
charavteristic of various clinical situations and therapeutic indications [12].
Testosterone concentrations encountered in AAS
abuse are typically orders of magnitude higher than
physiological concentrations [12]. The discontinuation of long-term anabolic steroid use can cause
unexpected withdrawal symptoms in addition to the
endocrine hypofunction [18].
An important side effect to mention for high
school athletes because steroids can cause the
premature closure of the growth plate, leading to
stunted growth. When a child or adolescent takes
anabolic steroids, the resulting artificially high sex
hormone levels can prematurely signal the bones to
stop growing.
Conclusion
For the past 50 years anabolic-androgenic steroids
have been used by a wide variety of people with the
Consequences of anabolic steroids abuse
hope of improving their performance and their body
shape. The wide use of AAS continues to be a problem because of the large number of side effects of
these products. The long-term consequences result
from the abuse of anabolic androgenic steroids are
side effects on the cardiovascular system, mental
health, endocrine system. Infertility, growth defects,
feminization and masculanization are very often irreversible side effects. The proportion benefit – risk
shows that any kind of abuse with AAS drugs is extremely dangerous.
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Corresponding author:
Stanislava Ivanova
Department Pharmagognosy and Pharmaceutical Chemistry
Faculty of Pharmacy,
Medical University – Plovdiv,
Plovdiv, Bulgaria
Mobile: +359 (0)879 061053
e-mail: [email protected]