Harm Kuipers, M.D., Ph.D.
Department of Physiology
University of Limburg
P.O. Box 616
Kuipers, H. (1998). Anabolic steroids: side effects. In: Encyclopedia of Sports Medicine and Science, T.D.Fahey (Editor). Internet Society for Sport Science: http://sportsci.org. 7 March 1998.
Anabolic steroids (AS) are effective in enhancing athletic performance. The trade off, however, is the occurrence of adverse side effects which can jeopardize health. Since AS have effects on several organ systems, a myriad of side effects can be found. In general, the orally administered AS have more adverse effects than parenterally administered AS. In addition, the type of AS is not only important for the advantageous effects, but also for the adverse effects. Especially the AS containing a 17-alkyl group have potentially more adverse affects, in particular to the liver. One of the problems with athletes, in particular strength athletes and bodybuilders, is the use of oral and parenteral AS at the same time (“stacking”), and in dosages which may be several (up to 40 times) the recommended therapeutical dosage. The frequency and severity of side effects is quite variable. It depends on several factors such as type of drug, dosage, duration of use and the individual sensitivity and response.
AS may exert a profound adverse effect on the liver. This is particularly true for orally administered AS. The parenterally administered AS seem to have less serious effects on the liver. Testosterone cypionate, testosterone enanthate and other injectable anabolic steroids seem to have little adverse effects on the liver. However, lesions of the liver have been reported after parenteral nortestosterone administration, and also occasionally after injection of testosterone esters. The influence of AS on liver function has been studied extensively. The majority of the studies involve hospitalized patients who are treated for prolonged periods for various diseases, such as anemia, renal insufficiency, impotence, and dysfunction of the pituitary gland. In clinical trials, treatment with anabolic steroids resulted in a decreased hepatic excretory function. In addition, intra hepatic cholestasis, reflected by itch and jaundice, and hepatic peliosis were observed. Hepatic peliosis is a hemorrhagic cystic degeneration of the liver, which may lead to fibrosis and portal hypertension. Rupture of a cyst may lead to fatal bleeding.
Benign (adenoma’s) and malign tumors (hepatocellular carcinoma) have been reported. There are rather strong indications that tumors of the liver are caused when the anabolic steroids contain a 17-alpha-alkyl group. Usually, the tumors are benign adenoma’s, that reverse after stopping with steroid administration. However, there are some indications that administration of anabolic steroids in athletes may lead to hepatic carcinoma. Often these abnormalities remain asymptomatic, since peliosis hepatis and liver tumors do not always result in abnormalities in the blood variables that are generally used to measure liver function.
AS use is often associated with an increase in plasma activity of liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (GGT). These enzymes are present in hepatocytes in relatively high concentrations, and an increase in plasma levels of these enzymes reflect hepatocellular damage or at least increased permeability of the hepatocellular membrane.
In longitudinal studies of athletes treated with anabolic steroids, contradictory results were obtained on the plasma activity of liver enzymes (AST, AST, LDH, GGT, AP). In some studies, enzymes were increased, whereas in others no changes were found. When increases were found, the values were moderately increased and normalized within weeks after abstinence. There are some suggestions that the occurrence of hepatic enzyme leakage, is partly determined by the pre-treatment condition of the liver. Therefore, individuals with abnormal liver function appear to be at risk.
Anabolic Steroids and the Male Reproductive System
AS are derivatives of testosterone, which has strong genitotropic effects. For this reason, it will not be surprising that side effects include the reproductive system. Application of anabolic steroids leads to supra-physiological concentrations of testosterone or testosterone derivatives. Via the feed back loop, the production and release of luteinizing hormone (LH) and follicle stimulation hormone (FSH) is decreased.
Prolonged use of anabolic steroids in relatively high doses will lead to hypogonadotrophic hypogonadism, with decreased serum concentrations of LH, FSH, and testosterone.
There are strong indications that the duration, dosage, and chemical structure of the anabolic steroids are important for the serum concentrations of gonadotropins. A moderate decrease of gonadotropin secretion causes atrophy of the testes, as well as a decrease of sperm cell production. Oligo, azoospermia and an increased number of abnormal sperm cells have been reported in athletes using AS, resulting in a decreased fertility. After stopping AS use, the gonadal functions will restore within some months. There are indications, however, that it may take several months.
In bodybuilding, where usually high dosages are uses, after stopping steroid use, often choriogonadotropins are administered to stimulate testicular function. The effectiveness of this therapy is unknown.
The various studies suggest that using more than one type of anabolic steroid at the same time (“stacking”) causes a stronger inhibition of the gonadal functions than using one single anabolic steroid. After abstention from anabolic steroids these changes in fertility usually reverse within some months. However, several cases of have been reported in which the situation of hypogonadism lasted for more than 12 weeks.
A well known side effect of AS in males is breast formation (gynecomastia). Gynecomastia is caused by increased levels of circulating estrogens, which are typical female sex hormones. The estrogens estradiol and estrone are formed in males by peripheral aromatization and conversion of AS. The increased levels of circulation estrogens in males stimulate breast growth. In general, gynecomastia is irreversible.
AS may affect sexual desire. Although few investigations on this issue have been published, it appears that during AS use sexual desire is increased, although the frequency of erectile dysfunction is increased. This may seem contradictory, but sexual appetite is androgen dependent, while erectile function is not. Since sexual desire and aggressiveness are increased during AS use, the risk of getting involved in sexual assault may be increased.
Anabolic Steroids and the Female Reproductive System
In the normal female body small amounts of testosterone are produced, and as in males, artificially increasing levels by administration of AS will affect the hypothalamic-pituitary-gonadal axis. An increase in circulating androgens will inhibit the production and release of LH and FSH, resulting in a decline in serum levels of LH, FSH, estrogens and progesterone. This may result in inhibition of follicle formation, ovulation, and irregularities of the menstrual cycle. The irregularities of the menstrual cycle are characterized by a prolongation of the follicular phase, shortening of the luteal phase or amenorrhea. Although these changes are generally more pronounced in younger women, large inter-individual responsiveness to anabolic steroids exists. The effects of AS dosages as generally used in sport, on the hypothalamic-pituitary-gonadal axis in females are hardly studied.
Other side effects of anabolic steroid use in females are increased sexual desire and hypertrophy of the clitoris. The few systematic studies that have been conducted suggest that the effects are similar to the effects in patients, treated with anabolic steroids.
Anabolic steroid use by pregnant women may lead to pseudohermaphroditism or to growth retardation of the female fetus. Anabolic steroid use may even lead to fetal death. However, these side effects have not been studied systematically. It is likely that the severity of the side effects is related to the dosage, duration of use and the type of the drug.
Additional side effects of anabolic steroids specifically in women are acne, hair loss, withdrawal of the frontal hair line, male pattern boldness, lowering of the voice, increased facial hair growth, and breast atrophy. The lowering of the voice, decreased breast size, clitoris hypertrophy and hair loss are generally irreversible. Females using AS may develop masculine facial traits, male muscularity, and coarsening of the skin.
When anabolic steroids are administered in growing children side effects include virilization, gynecomastia, and premature closure of the epiphysis, resulting in cessation of longitudinal growth.
Serum Lipoproteins and the Cardiovascular System
AS also affect the cardiovascular system and the serum lipid profile. Relatively few studies have been done to investigate the effect of anabolic steroids on the cardiovascular system. No longitudinal studies have been conducted on the effect of anabolic steroids on cardiovascular morbidity and mortality.
Most of the investigations have been focused on risk factors for cardiovascular diseases, and in particular the effect of anabolic steroids on blood pressure and on plasma lipoproteins. In most cross-sectional studies serum cholesterol and triglycerides between drug-free users and non-users is not different. However, during anabolic steroid use total cholesterol tends to increase, while HDL-cholesterol demonstrates a marked decline, well below the normal range. Serum LDL-cholesterol shows a variable response: a slight increase or no change. The response of total cholesterol seems to be influenced by the type of training that is done by the athlete. When a great deal of the exercise consists of aerobic exercise, the increasing effect of AS is counterbalanced by an exercise-induced increasing effect, which may result in a net decline in total cholesterol. Aerobic training does not seem to be able to offset the steroid-induced decline in HDL-cholesterol and its subfractions HDL-2, and HDL-3.
The precise effect of anabolic steroids on LDL-cholesterol is unknown yet. It appears that anabolic steroids influence hepatic triglyceride lipase (HTL) and lipoprotein lipase (LPL). Males usually have higher levels of HTL, while females have higher LPL activity. HTL is primarily responsible for the clearance of HDL-cholesterol, while LPL takes care of cellular uptake of free fatty acids and glycerol. Androgens and anabolic steroids stimulate HTL, presumably resulting in decreased serum levels of HDL-cholesterol.
The effect of anabolic steroids on triglycerides is not well known. It is suggested that relatively low doses do not affect the serum triglyceride levels, while it cannot be excluded that higher doses elicit an increase.
No unanimity exists about the influence of anabolic steroids on arterial blood pressure. The response is most probably dose dependent. There is some data suggesting that high doses increase diastolic blood pressure, whereas low doses fail to have a significant effect on diastolic blood pressure. Increases in diastolic blood pressure normalize within 6-8 weeks after abstinence from anabolic steroids. It appears that repeated intermittent use of anabolic steroids does not affect diastolic blood pressure during drug free periods.
There is evidence that the use of anabolic steroids does elicit structural changes in the heart and that the ischemic tolerance is decreased after steroid use. Echocardiographic studies in bodybuilders, using anabolic steroids, reported a mild hypertrophy of the left ventricle, with a decreased diastolic relaxation, resulting in a decreased diastolic filling. Some investigators have associated cardiomyopathy, myocardial infarction, and cerebro-vascular accidents with abuse of anabolic steroids. However, a possible causal relationship could not been proved, because longitudinal studies that are necessary to prove such a relationship, have not been conducted yet. There is convincing evidence that oral administration of anabolic steroids has stronger adverse effects on the mentioned variables than parenteral administration.
Although the effects of anabolic steroids have an unfavorable influence on the risk factors for cardiovascular disease, no data are available about the long term effects. Most of the mentioned effects appear to reverse within 6-8 weeks after abstention. It is unknown, however, whether the structural changes as reported in the heart, are reversible as well.
Administration of AS may affect behavior. Increased testosterone levels in the blood are associated with masculine behavior, aggressiveness and increased sexual desire. Increased aggressiveness may be beneficial for athletic training, but may also lead to overt violence outside the gym or the track. There are reports of violent, criminal behavior in individuals taking AS. Other side effects of AS are euphoria, confusion, sleeping disorders, pathological anxiety, paranoia, and hallucinations.
Anabolic steroid users may become dependent on the drug, with symptoms of withdrawal after cessation of drug use. The withdrawal symptoms consist of aggressive and violent behavior, mental depression with suicidal behavior, mood changes, and in some cases acute psychosis. At present it is unknown which individuals are particularly at risk. It is likely that great individual differences in responsiveness may exist. Some individuals try to minimize the withdrawal affects by administration of human choriogonadotropins (hCG), in order to enhance endogenous testosterone production. However, it is unknown in how far the hCG administration is successful in ameliorating the withdrawal effects.
Additional Side Effects
In addition to the mentioned side effects several others have been reported. In both males and females acne are frequently reported, as well as hypertrophy of sebaceous glands, increased tallow excretion, hair loss, and alopecia. There is some evidence that anabolic steroid abuse may affect the immune system, leading to a decreased effectiveness of the defense system. Steroid use decreases the glucose tolerance, while there is an increase in insulin resistance. These changes mimic Type II diabetes. These changes seem to be reversible after abstention from the drugs.
There are some case reports suggesting a causal relationship between anabolic steroid use and the occurrence of Wilms tumor, and prostatic carcinoma. In the literature also sleep apnea has been reported, which has been associated with AS-induced increased in hematocrit, leading to blood stasis and thrombosis.
AS use may affect thyroid function. Administration of AS has been found to decrease thyroid stimulation hormone (TSH), and the products of the thyroid gland. In addition, thyroid binding globulin (TBG). These changes reversed within weeks after discontinuation of AS use.
A serious consequence of AS use may be the multiple drug abuse. On the one hand athletes use different kinds of drugs in an attempt to counterbalance the side effects: hCG, thyroid hormones, anti-estrogens, anti-depressants. On the other hand people try to support the anabolic effects of AS by using additional anabolic hormones as for instance: different types of AS at the same time, growth hormone, insulin, erythropoietine, and clenbuterol. Because most of this takes place outside the official medical circuit, it is likely that these practices may lead to serious conditions.
(not referred to in the above review)
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