| Your personal background. |
|---|
The use of androgenic anabolizing steroids as a vehicle to increase the athletic performance and physical
attractiveness of males has been known for decades, as well as their prominence in the sporting world, having
been classified among the doping substances.
But these synthetic derivatives of testosterone
have diverse therapeutic indications.
Androgenic anabolizing steroids (ASA) are synthetic derivatives of testosterone that were initially developed in the 1930s.
These compounds preferably promote the development of the skeletal muscle (anabolic effects) and,
to a lesser extent, the development of male sexual characters (androgenic
effects). Anabolizing action can be differentiated from virilizing
action, and with some compounds some dissociation has been achieved, although there is no androgen that is completely lacking a certain virilizing activity.
That is, through various modifications of the testosterone molecule, androgenic activity has been reduced and anabolizing activity has been maintained.
Anabolizing actions are fundamentally metabolic.
EAAs are legally available only by medical prescription. Anabolic therapy with these compounds
is indicated in the functional limitations associated
with aging and chronic diseases, in fragility, in cachexia for cancer and osteoporosis.
BETWEEN THE BEST WARNING EFFECTS OF THE USE OF STEROIDS DESTACAN:
DOLORES OF CABEZA, RETENTION OF LIQUIDS (specially in the
EXTREMITIES), GASTROINTESTINAL IRRITATION, DIARREA, DOLORES OF ESTÓMAGE AND BRAZINE PIES
However, the EAAs have been used since the 1950s of the last century to
improve athletic performance and male physical attractiveness as they increase body weight, muscle mass and strength when combined with training.
In the absence of training, muscle mass can be increased with increased dosage
of EAA. Therefore, its use has been widely extended as doping agents, using this
purpose dose that sometimes exceed the therapeutic interval.
The oral administration of 3-5 g of EAA per week can reach levels of up to 100
times the physiological rank in an adult male. This
unbridled abuse has led all professional sports organizations to ban the use
of EAA. Its use has not been limited to high-level
sport, and has continuously and increasingly reached adolescents, both athletes and non-sporters.
In the extra-sport environment, adolescents find in the EAA a strategy for gaining musculature, strength and power, which can be useful,
in their view, to improve their self-esteem and social acceptance.
The adverse side effects as a result of EAA consumption include sexual dysfunction, cardiovascular system alterations, and psychological behavior and
liver toxicity. However, severe side effects only occur after prolonged use at high
doses.
At times, the abuse of EAA may be related to negative life experiences
or certain social and psychological traits of the user such as low self-esteem and self-confidence, suffering
hostility, childhood behavior disorders and a tendency to high-risk behaviors.
EAA abuse is 2-3 times greater in males than in females.
However, the risk of dependence on EAA is very low and the
effects of withdrawal are relatively mild.
CLASIFICATION AND FARMACOCINÉTICS OF EAA
Testosterone is not active by mouth because it has presystemic liver
inactivation. Sterification originates more soluble compounds,
not active by mouth, but with a slow absorption by intramuscular path, associated with the length of the sterified chain. Once absorbed, these drugs are hydrolysed to testosterone.
More than a thousand testosterone derivatives have been synthesized and can be grouped into two classes:
• Class A: they are esters of the 17-beta-hydroxy-testosterone of high liposolubility, so they
require intramuscular dosing. Examples include oleous solutions of ownborn, enantato or cypionate of testosterone and oleous solutions of deanate or phenpropionate of nandrolone.
• Class B: are compounds rented in position 17-alpha-hydroxy
that can be given by mouth. They stand out in this class: danazol, fluoximesterone, metandrostenolone, methyltestosterone, oxandrolone,
oximetolone, stanozolol.
Alkylated derivatives are compounds that are more resistant to liver metabolism, so they resist the first hepatic step
and can be given by mouth. Sexual hormones
circulate in plasma together with plasma proteins.
Rented androgens show little affinity for the globulin of gonadal hormones (testosterone and estrogens) and are joined,
preferably, to albumin. The average life of the leased
compounds is longer and allows for longer administration intervals by mouth.
EAA consumers usually take an aromatase inhibitor, such
as anastrazole, to inhibit the aromatization of anabolizing steroids that results in estrogen production.
ANABOLIZING ACTIONS
Testosterone acts in other organs not related to reproductive activity, such
as kidney, liver, and muscle, prior interaction with androgenic receptors.
The interaction of different synthesis compounds (selective
grinders) with the androgenic receptor contributes to their unique
pharmacological actions. The ligand union induces specific conformal changes in the ligand
binding domain, which could modulate the surface topology and protein-protein interactions
between the androgenic receptor and the corregulators, resulting in the specific gene regulation of tissue.
Preclinical studies have demonstrated the ability of selective androgenic receptor modulators to increase muscle mass and bone mass
in preclinical models of rodents with different
degree of prostate preservation.
The most remarkable anabolic effect is the development of
muscle mass by increasing protein and hypertrophy synthesis of skeletal muscle fiber,
accompanied by increased strength. At high doses, plasma lipoproteins are
modified: HDLs are decreased, by activation of liver lipoproteinlipase and LDL and apolipoproteins (apo)
B are increased, and apo-A1 and apo-CIII are reduced,
giving them an aterogeneous profile. They also cause potassium retention, sodium, chlorine,
phosphate, calcium and sulphur, contributing to the weight
gain due to the water retention they condition. Anabolizing steroids also favor bone mineralization with the contribution of
estradiol produced locally by aromatization of testosterone.
They also stimulate the production of renal erythropoietin and the hepatic synthesis of the supplement factor C.
They stimulate the growth and secretion of the sebaceous
glands in which tapes may be formed that favor the infection and the appearance of acne.
The anabolizing capacity of the different synthesis compounds is expressed as the
androgenic activity/anabolizing activity relation. For example, for the testosterone cypionate this ratio is 1:
1, while for the stanozole is 1:30. Therefore, the capacity of the
stanozole to promote anabolizing action without the appreciation of signs of virilization is greater than that of the testosterone cypionate.
TERAPETIC INDICATIONS
EAAs are mainly used as replacement therapy in hypogonadism and in the treatment of some conditions for their anabolizing effects:
• Male hypogonadism. It can be due to testicular insufficiency or a
deficit of gonadotropins due to hypopituitarism. Treatment with androgens leads to normal sexual development.
• Muscle development. When administered in hypogonadism situations,
androgens cause significant nitrogen retention, increased muscle mass and increased weight.
This is why derivatives are used with anabolizing effect and with low
androgenic activity.
• Hematological disorders. EAAs stimulate the production of erythropoietin at renal and extrarenal levels,
so they can be used in the treatment of refractory anemias to other treatments.
The effects are less important in patients with kidney failure.
• Hereditary angioneurotic eema. Alkylated
derivatives (methyltestosterone and fluoximesterone) are used, although
oral AAAs (danazol) are also effective. Rented derivatives favor the hepatic synthesis of different proteins, such as coagulation factors and supplement inhibitor.
• Low height. The EAA stimulates linear growth if
they are administered prior to the closure of the epiphysis.
They are administered for short periods (up to 6 months).
• Breast carcinoma. The effect can be palliative, perhaps by acting as antiestrogens.
The most effective compound is testosterone,
which seems to induce greater remissions than conventional chemotherapy.
• Osteoporosis. It is treated with EAA if it is due to
androgen deficiency.
• Catabolic States. Its efficacy in stimulation of anabolism in acute and chronic diseases is
scarce or void and does not go beyond what androgen can do with increased appetite.
WARNING EAA EFFECTS
Steroid abuse interferes with the normal production of hormones in the body, causing both
reversible and irreversible changes. The side
effects of the EAA, however, are developed almost only during prolonged use.
Class B anabolizers cause liver toxicity in the form of jaundice that is usually developed after 2-5 months.
Hepatotoxicity has not been described with the parenteral use of testosterone esters.
Serious side effects on the liver and in the lipoprotein pattern result mainly
from the EAAs rented at high doses.
The parenteral administration ASAs seem to damage the heart muscle, which can become clinically important after several
years. Fortunately, most of the serious effects that threaten life seem to be relatively rare.
THE POSITIVE EFFECTS OF TESTERONA IN THE HUMOR ARE BIEN ESTABLISHED AND VARIOUS STUDIES HAN DEMOSPHERE REPLACE THE STERAPY WITH THIS HORMONY CAN SUBSTANCET NEGATIVE STATES OF HUMOR ASSOCIATE TO FATIME, DEPRESION AND BASICAL
WARNING EFFECTS
The minor adverse effects of steroid use include headaches,
fluid retention (especially in the limbs), gastrointestinal irritation, diarrhea, stomach aches and fat skin. Acute effects
with increased clinical impact are jaundice, menstruation and hypertension alterations.
Infections can be developed at the injection site,
causing pain and abscess. In both sexes acne
is developed in puberty (not in adults) during androgen treatment due to the growth of the sebaceous glands and sebaceous secretion.
The aromatization is the process by which steroid hormones are interconvertible.
Testosterone and other aromatizable anabolizing steroids are partially metabolized to estradiol and other estrogenic agonists.
For this reason, males who consume high doses of EAA may present typical circulating
estrogen levels of women during a normal menstrual cycle.
This can lead to pain in the breasts and gynecomastia, often irreversible.
Observational studies suggest that the majority (88-96%) of anabolizing steroid users experience at least
one objective side effect: acne (40-54%), testicular
atrophy (40-51%), gyneecomastia (10-34%), cutaneous stretches (34%) and pain in the injection site (36%).
CRÓNIC WARNING EFFECTS
In this group we can distinguish:
Somatic effects
Anabolizing steroid abuse is associated with urogenital problems, acne and
cardiovascular and liver disease. Among the reversible changes experienced by men are a
decrease in the production of semen, impotence, difficulty
or pain when urinating and testicular atrophy.
In women, the high levels of EAA result in menstrual irregularities and the development of male characteristics such as decreased body and chest
fat, excessive hair growth and irreversible hair loss of the scalp,
as well as greater clitoris size. With the continued administration of steroids, some of these effects
become irreversible. In addition, steroids
have been associated with prostate cancer. The premature welding of the epiphysis in the child/adolescent by the
prolonged administration of EAA can stop growth and lead to a decrease in the height of the adult.
In some cases, however, the EAAs are indicated to limit the length of the abnormal body.
The use of EAA poses a growing risk for liver fatal cysts and liver cancer.
With the administration of rented EAA, there has also been an increase in liver lipase activity between 21 and 123%, as well as LDL by 29%.
On the other hand, the hepatic pathology induced by EAA is often reversible with the discontinued consumption. The predominance of adverse liver effects
on chronic EAA consumers is probably low.
The physiological and pharmacological mechanisms of the action of the
AE in vascular structure and function are well known. The EAAs
join the androgenic receptors in the heart and in the main arteries, and physiological levels (e.g.
testosterone) may have a beneficial effect on the coronary arteries through endothelial release of nitric oxide and inhibition of the tone of
the vascular smooth muscle. On the contrary, animal studies show
that the abuse of EAA can reverse this vasodilating response and
lead to growth-promoting effects in the heart tissue, as has been shown in hypertrophic cardiomyopathy followed by cell death by apoptosis.
These effects are probably mid by a cascade of second messengers that add to the Ca2+ intracellular and its mobilization from the sarcolasmic reticle.
The increase in Ca2+ affects mitochondrial permeability leading to the release of apoptogenic factors such as cytochrome c,
the inducing factor of apoptosis and caspasa-9. These
findings could explain the clinical observations that AAAs may lead
to the death of coronary thrombosis or atherosclerosis.
Steroids contribute to the development of cardiovascular disease, partly by modifying the levels of lipoproteins that carry cholesterol in the blood.
Steroids, particularly oral administration, increase LDL cholesterol levels and decrease
HDL cholesterol levels. In general, serum levels are normalized after several weeks or months after the cessation of consumption. High LDL and low
HDL levels increase the risk of atherosclerosis.
In addition, steroids induce blood clotting due to an increase in platelet counting and, therefore, plaquelet aggregation.
Some of the cardiovascular effects of AAAs, such as hypertension,
dyslipidemia, and clotting abnormalities, refer after discontinued
use, however, atherosclerosis and cardiomyopathy appear to be irreversible.
Since there are few empirical studies, it is difficult to estimate the prevalence or severity
of cardiovascular disease in EAA consumers. There is, however, no epidemiological evidence of cardiovascular disease due to the use
of EAA, so causality has not yet been established.
The risk of cardiovascular complications may also be due to the use of other
doping substances, such as growth hormone or erytropoyetin (EPO).
Neuropsychiatric effects
EAA abuse is associated with behavioral effects and psychiatric
effects, ranging from moderate, socially acceptable irritation to uncontrollable aggression, hostility and
even depression and mania. The frequency of these effects is usually low and depends
on much of the doses used. On the other hand, it is often difficult to judge whether the effects on the behavior and psychiatric effects are attributable to the use of EAA per
se, to the underlying features of the consumer personality
of EAA, or to the psychosocial factors that favor the use.
In this regard it should be mentioned that chronic EAA consumers
often present antisocial, narcissistic and histrionic traits.
In addition, several studies have suggested that the supraphysiological doses of EAA can directly cause hypomanic or manic symptoms, sometimes associated with aggression and violence.
However, not all studies have documented such prominent mood and mood
changes, indicating a great variability in the presentation of symptoms
due to differences in the dose consumed, the compound used, the duration of use, the
type of consumer personality and the current or previous use of other recreational drugs.
EAAs clearly cause psychiatric effects on individuals who consume excessive
doses (more than 1 g/week). The most prominent psychiatric characteristics are manic manifestations defined as irritability, aggression, euphoria, delusions of grandeur,
hyperactivity, imprudence or dangerous behavior.
For example, many consumers declare a good feeling about themselves, but extreme mood swings can also occur, such as manic-type symptoms
that could lead to violence. EAA consumers can present paranoid jealousy,
extreme irritability and impaired judgment. Other manifestations that may arise are acute psychosis, tics exacerbations and the
development of confusional acute states. Hypomania or manic episodes,
depression or suicide and psychopathic episodes have also been described.
ABUSE AND DEPENDANCE
EAAs are often used in combinations. Consumers can exercise "accumulation",
that is, they often take two or more EAA together, combining one of oral administration with another
of intramuscular administration. Another practice
is the cyclical dosing regime called "piramide".
At the beginning of a cycle, low doses of "accumtable"
substances are given and the dose is gradually increased for
6-12 weeks. In the second half of the first cycle, the doses are
gradually reduced to zero. Consumers believe that the pyramid allows the organism to adapt to the high doses, and the second "free" cycle of EAA allows the hormonal
system to recover.
Compared to other abuse drugs, the AAs are not strongly euphoric, i.e., they do not
trigger rapid increases in the release of dopamine in the mesolicimbic
system. However, the well-being effect derived from the use of
EAA and the dysphoric effects after withdrawal can contribute to ASA dependency syndrome in some individuals.
Prolonged use of EAA may have an impact on some brain paths (dopamine, serotonin and
opioid system) that are affected by abuse drugs.
The positive effects of testosterone in the mood are
well established and several studies have shown that replacement therapy with testosterone can substantially reduce
negative mood states related to fatigue, depression and self-esteem.
A two-phase model of dependence on EAA has been proposed.
Consumers start using steroids for their anabolizing effects, but with
continued exposure, it develops dependency on the psychoactive effects of the EAA.
However, the risk of EAA abuse in the classic pharmacological sense is
very low, although some recent studies suggest that EAA dependence
becomes quite common.
Currently, some EAA consumers are looking for treatment
for abuse of these substances. But this image can soon change
substantially, since the illicit use of EAA was not generalized until the 1980s of the last century,
and consequently those who started consumption being young at that time may have developed dependence on EAA and being entering a risk age of heart and psychoneuroendocrine complications sufficient to motivate them to follow a
treatment of uninhabitation. It is suggested that this
treatment should respond to at least three etiological mechanisms by
which dependency on EAA can be developed. First, individuals with
body image disorders, such as muscle dysmorphia, may become dependent
on AAAs for their anabolic effects, and these emotional disorders may respond to psychological and pharmacological therapies.
Secondly, the EAA suppresses the male-hypophisary-gonadal hypothalamus axis
through its androgenic effects, causing hypogonadism during withdrawal.
Men who experience prolonged dysphoric effects or major depression may wish to resume
consumption of EAA, which contributes to dependency. Hypogonadism induced by EAA may require treatment with human chorionic gonadotropin or clomifene to reactivate neuroendocrine function, and antidepressant treatments in cases
of depression due to inadequate response
to endocrine therapies exclusively. Thirdly, human and animal
testing indicates that AAAs also have hedonic effects, which are likely
to encourage dependence through shared mechanisms with addictive drugs, especially
opioids. The low reinforcement of androgens is comparable to
that of moderate reinforcers, such as caffeine or benzodiazepines.
Individuals who use high doses of EAA are at risk of developing dependency on EAA because they
may develop depressive symptoms, anhedonia and fatigue when they stop consumption.
THE INCREMENT OF AGRESIVITY AND HOSTILITY FEATURES
ENVIRONMENTS THE NOCIVY EFFECTS MORE FRECUENTLY ASSOCIATED TO THE ABUSE OF AUTHORITY
The increase in aggressiveness and feelings of hostility is among the most frequently harmful effects associated with EAA abuse.
The use of EAA may occasionally trigger violent acts in individuals who
did not previously present such tendencies. The use of EAA may
precipitate violence with frequent symptoms at high doses (600-1,000 mg of testosterone/week) and
few symptoms at 300 mg/week. However, it has also been described that the supraphysiological
doses of testosterone enantate administered for several months do
not increase aggressive behavior or irritability. The association between the
use of EAA and violence often depends on other risk factors.
For example, the use of EAA is often associated with
the concomitant use of psychotropic substances, particularly opioids.
Finally, it seems that alcohol and ASAs are strongly synergistic in the precipitation of violent impulsive
behavior.
GENERAL BIBLIOGRAPHY
Bhasin S, Jasuja R. Selective androgen receptor
modulators as function promoting therapies.
Curr Opin Clin Nutr Metab Care. 2009;12(3):232-40.
Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG Jr.
Treatment of anabolic-androgenic steroid dependence:
Emerging evidence and its implications. Drug Alcohol Depends.
2010;109(1-3):6-13.
Thevis M, Schänzer W. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.
Handb Exp Pharmacol. 2010;195:99-126.
van Amsterdam J, Opperhuizen A, Hartgens F.
Adverse health effects of anabolic-androgenic steroids. Regul Toxicol Pharmacol.
2010;57(1):117-23.
Feel free to visit my web page; jbhnews.com |
| Your feedback on this profile |
|---|
| Recommend this profile for User of the Day: |
I like this profile |
| Alert administrators to an offensive profile: |
I do not like this profile |
|
| Account data |
View |
| Team |
None |
|