Anabolic Steroid Use and Abuse

Updated: May 27, 2015
  • Author: Stephen Kishner, MD, MHA; Chief Editor: George T Griffing, MD  more...
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Steroids are a general class of agents that all have the steroid ring in common. The steroid ring is comprised of three 6-carbon rings and one 5-carbon ring joined, of which cholesterol is the most basic form and, indeed, the precursor. Although the term steroid includes all agents derived from this ringed structure, this discussion includes only testosterone and the anabolic-androgenic steroids (AASs).

Testosterone is the principle hormone in humans that produces male secondary sex characteristics (androgenic) and is an important hormone in maintaining adequate nitrogen balance, thus aiding in tissue healing and the maintenance of muscle mass (anabolic). Testosterone has a dual action and can be described in terms of its androgenic and anabolic capacities.

AASs are drugs derived from the modification of the testosterone molecule in order to augment or limit certain characteristics of testosterone. In general, testosterone has been altered to produce drugs that are more or less anabolic, are more or less androgenic, have differing affinity for the testosterone receptor, have different metabolic breakdown pathways, or are efficacious for oral use; they can also have any combination of these changes.

Well over a thousand different compounds have been synthesized and studied since the 1950s in the hope of producing compounds that have an anabolic or androgenic effect superior to that of testosterone. Biochemists quickly noted that additions or subtractions to the testosterone molecule at specific locations would have a somewhat predictable effect on the inherent qualities of said compound. Specifically, qualities including (but not limited to) anabolic/androgenic ratio, metabolism, receptor affinity, and oral efficacy were noted.

In general, the goal of altering an AAS is to increase its anabolic characteristics and to decrease its androgenic features, thus multiplying the compound's desirable, anabolic, nitrogen-sparing effects and minimizing its generally undesirable, androgenic, virilizing effects. To date, however, complete dissociation of the anabolic effects of an AAS from its androgenic characteristics has not been possible.

Clinically, AASs have been used to treat a host of conditions, including the following:

Almost since their inception, testosterone and anabolic-androgenic analogues have been used and abused by individuals seeking to augment their anabolic and androgenic potential. By doing so, these persons aim to boost their physical performance in athletic endeavors or improve their physique. Stories of Eastern-bloc athletes receiving testosterone and AASs as part of their training regimens as early as the 1950s abound. The Eastern-bloc weightlifters and track athletes subsequently ruled the athletic stage for decades.

The degree to which AASs affect performance enhancement in healthy athletes is widely debated, as are the precise mechanisms of action. Anecdotal evidence, including increases in strength and lean body mass (LBM), has been reported, but steroid effect is difficult to study in a true placebo-controlled, double-blind fashion. Most athletes would notice testicular atrophy if receiving AASs, which would interfere with a study's double-blind structure. Dosing, nutrition, and training parameters would need to be monitored extensively to completely satisfy the most critical review.

Certainly, the use of AASs has become a worldwide phenomenon, slowly trickling down to collegiate, high school, and even junior high levels. [1] The early assertion from the medical community that "anabolic steroids have not been shown to enhance athletic ability," still in print in the 2002 Physicians Desk Reference, contributed to this phenomenon. Technically, the statement is correct; however, people misusing and abusing these drugs quickly realized that the performance-enhancing effects were real and subsequently dismissed the rest of the medical community's contraindications, dosing recommendations, and warnings. [2, 3]


Biopharmacology of Testosterone

Testosterone, the primary male sex hormone, is manufactured in the testes under the influence of luteinizing hormone (LH) in amounts of 2.5-11 mg/d. [4] Testosterone is produced under a negative feedback loop between the hypothalamus, the anterior pituitary, and the testes. Testosterone, dihydrotestosterone, and estrogen all act at the hypothalamus to exert negative feedback inhibition upon gonadotropin-releasing hormone (GnRH). Since GnRH stimulates follicle-stimulating hormone (FSH) and LH release in the pituitary, this negative feedback can be seen to inhibit subsequent testosterone production and effect spermatogenesis.

Testosterone activity is mediated via an androgen receptor that is present in various tissues throughout the human body. Testosterone binds to an intracellular receptor found in the cytosol of cells, forming a receptor complex that migrates into the nucleus, where it binds to specific deoxyribonucleic acid (DNA) segments. This, in turn, activates specific messenger ribonucleic acid (mRNA) to increase transcription, leading to an increased rate of protein synthesis; in the case of muscle cells, this means increased production of the proteins actin and myosin. After this process is complete, the receptor complex dissociates and is recycled along with the hormone, to repeat this process multiple times prior to metabolism.

These anabolic actions of testosterone are thought to be primarily due to testosterone acting upon the androgen receptor in anabolic-responsive tissues. Androgenic effects are likely mediated via the same androgen receptor in androgen-responsive tissues under the influence of dihydrotestosterone (DHT), which is produced by the interaction of 5-alpha reductase (5AR) with testosterone and the subsequent reduction of the C4-5 double bond. Additionally, DHT cannot undergo further reduction, nor is it a substrate for aromatase; thus, it is not converted to estrogenic metabolites. DHT has been shown to bind avidly to receptors in tissues, such as skin, scalp, and prostate, and to exert 3-4 times the androgenic effect of testosterone. Thus, the primary hormone mediating the androgenic effects of testosterone is actually the 5-alpha reduced DHT.

Other mechanisms of direct and indirect anabolic effects include anti-glucocorticoid activity mediated by displacement of glucocorticoids from their receptor, [5] increases in the creatine phosphokinase activity in skeletal muscle, [6] and increases in circulating insulinlike growth factor (IGF)–1, [7] as well as up-regulation of IGF-1 receptors. [8] These mechanisms may play a much larger role in the anabolic/anticatabolic actions of anabolic-androgenic steroids (AASs) than once thought. At physiologic testosterone levels, nearly all androgen receptors are engaged. Therefore, supraphysiologic doses of testosterone or AASs would have no increased anabolic effect in healthy athletes unless other mechanisms of action existed.


Biochemistry and Pharmacology

Because there are many agents in production and literally hundreds more that have been synthesized, this discussion focuses on the basics involving the steroid ring substitutions and how these substitutions affect the properties of the drug. Detailed analysis is limited to those agents that are available or have been approved for use in the United States.

Anabolic-androgenic steroid (AAS) development was centered on the need for agents that exhibited different characteristics than did testosterone. In general, the goal was to develop agents that were more anabolic and less androgenic than testosterone, that were capable of being administered orally, and that had less effect upon the hypothalamic-pituitary-gonadal axis. Most AASs are derived from 3 compounds: testosterone, dihydrotestosterone, and 19-nortestosterone. The third compound is structurally identical to testosterone except for the deletion of the 19th carbon (hence its name). These parent compounds offer different properties with regard to action and metabolism that are generally constant throughout the entire family of compounds.

One of the first changes made to the testosterone molecule was the addition of a methyl group or an ethyl group to the 17-carbon position. This addition was noted to inhibit the hepatic degradation of the molecule, greatly extending the molecule's half-life and making it active when administered orally. Prior to this, testosterone, dihydrotestosterone, and 19-nortestosterone all required parenteral administration due to hepatic metabolism of 17-ketosteroids; this metabolism occurred on the first pass, when the drugs were administered orally.

However, adding a methyl group or an ethyl group did not produce a drug with the exact properties of the parent compound. The alteration of hepatic metabolism was noted to cause strain on the liver, and indeed all oral compounds with this C-17 addition were found to cause dose-related hepatotoxicity. This small change was also found to lower these agents' interaction with aromatase. [9] Therefore, even small changes to these parent compounds cause multiple alterations in the inherent nature of AASs.


Testosterone Esters and Derivatives

Testosterone esters have increasingly been used in replacement therapy, but abuse of these compounds has risen as well. A feature that all testosterone esters have in common is a testosterone molecule with a carboxylic acid group (ester linkage) attached to the 17-beta hydroxyl group. These esters differ in structural shape and size; they function only to determine the rate at which the testosterone is released from tissue. Generally, the shorter the ester chain, the shorter the drug's half-life and quicker the drug enters the circulation. Longer/larger esters usually have a longer half-life and are released into the circulation more slowly. Once in the circulation, the ester is cleaved, leaving free testosterone.

Common testosterone preparations include the following:

Testosterone esters

See the list below:

  • Testosterone propionate
  • Testosterone cypionate
  • Testosterone enanthate

Testosterone derivatives


Methyltestosterone is a very basic anabolic-androgenic steroid (AAS), with the only addition being a methyl group at C-17. This eliminates first-pass degradation in the liver, making oral dosing possible. It also causes dose-related hepatotoxicity.

Methyltestosterone is metabolized by aromatase to the potent estrogen 17-alpha methyl estradiol and is also reduced by 5AR to 17-alpha methyl dihydrotestosterone.

This compound exhibits very strong androgenic and estrogenic side effects and is generally a poor choice for most, if not all, uses.


Methandrostenolone has an added cis- 1 to cis- 2 double bond that reduces estrogenic and androgenic properties. However, it does undergo aromatization to the rather potent estrogen 17-alpha methyl estradiol, but curiously, it does not show the in-vivo propensity for reduction by 5AR to alpha dihydromethandrostenolone to any large degree. [10]

This steroid was first commercially manufactured in 1960 by Ciba under the brand name Dianabol and quickly became the most used and abused steroid worldwide, remaining so to date. It jokingly came to be known as "the breakfast of champions" in sports circles.

This agent is very anabolic, with a half-life of approximately 4 hours. The methyl group at C-17 makes this AAS an oral preparation and potentially hepatotoxic.

Ciba, as well as generic firms in the United States, discontinued methandrostenolone in the late 1980s, but over 15 countries worldwide still produce it in generic form.


Fluoxymesterone is a potent androgen that is produced under the brand name Halotestin. It is an excellent substrate for 5AR and conversion to dihydrotestosterone (DHT) metabolites. With the addition of a 9-fluoro group, it is a very potent androgen that has little anabolic activity. An added 11-beta hydroxyl group inhibits its aromatization. Again, the C-17 methyl group makes oral administration possible, but with hepatic concerns.

This AAS is not favored in clinical practice due to its poor anabolic effects, yet athletes abuse it for its androgenic nature and lack of peripheral aromatization.

Nandrolone derivatives  [11]

Nandrolone decanoate

Nandrolone decanoate is simply a 19-nortestosterone molecule in which a 10-carbon decanoate ester has been added to the 17-beta hydroxyl group. This addition extends the half-life of the drug considerably. Nandrolone (19-nortestosterone) is a potent anabolic with a relatively favorable safety profile. Nandrolone is reduced by 5AR in target tissues to the less potent androgen dihydronandrolone. Its affinity for aromatization to estrogen is low, being perhaps 3-4 times less than that of testosterone. [12]

Nandrolone and its several esters (decanoate, phenylpropionate) differ only in their half-lives, due to the difference in ester properties.

Nandrolone is a relatively safe drug with minimal androgenic concerns and ample anabolic action at therapeutic doses. Nandrolone decanoate is an intramuscular (IM) preparation and lacks the hepatotoxic C-17 group; however, this agent is one of the most widely abused AASs, due to its efficacy, safety profile, and worldwide manufacture. [13]


Ethylestrenol is an oral 19-nortestosterone derivative and was marketed in the United States under the brand name Maxibolin, but it has since been discontinued.

This agent differs from nandrolone by the addition of a 17-alpha ethyl group to reduce first-pass metabolism, as well as by the deletion of the 3-keto group. This latter omission seems to reduce androgen receptor binding.

Ethylestrenol is a mild AAS, having very little anabolic or androgenic effect at therapeutic doses.


Trenbolone is a derivative of nandrolone with several additions. The addition of a cis- 9 to cis- 10 double bond inhibits aromatization, while a cis- 11 to cis- 12 double bond greatly enhances androgen receptor binding.

This drug is androgenically and anabolically potent. It is comparably more androgenic than nandrolone due to its lack of conversion to a weaker androgen by 5AR, as is seen with nandrolone.

Trenbolone is a European drug with a very high abuse record. In the United States, it is used in veterinary preparations as trenbolone acetate; as such, it has found its way into the hands of persons who wish to exploit its androgenic and anabolic potential.

DHT derivatives


Oxandrolone, a derivative of DHT, is C-17 methylated, making it an oral preparation.

The second carbon substitution with oxygen is thought to increase the stability of the 3-keto group and greatly increase its anabolic component. This AAS is very anabolic, with little androgenic effect at a therapeutic dose. 5AR does not reduce oxandrolone to a more potent androgen, and as a DHT derivative, it cannot be aromatized.

First marketed by Searle, DHT was discontinued in the mid-1990s. BTG remarketed this AAS as Oxandrin, largely for the drug's use in HIV-related disease.

Due to its mild androgenic properties, oxandrolone is one of the few agents to be routinely abused by female athletes. Athletes, from weightlifters to boxers, use oxandrolone, seeking to increase strength without experiencing additional weight gain.


Stanozolol is an active AAS, due to the stability afforded by the 3,2 pyrazole group on the A-ring, which greatly enhances androgen receptor binding. The C-17 methyl group enhances oral availability.

Stanozolol is highly active in androgen- and anabolic-sensitive tissue. It is a weaker androgen than DHT and exerts comparatively less androgenic effect. It will not aromatize to estrogenic metabolites.

This AAS, marketed in the United States and abroad as Winstrol, comes in oral and injectable forms.

Athletes, many in track and field, have abused it. In 1988, Canadian sprinter Ben Johnson was stripped of his Olympic gold medal after testing positive for stanozolol.


This quite potent AAS is a unique agent. Oxymetholone is C-17 methylated and, thus, is an oral agent. The 3-keto stability added by the 2-hydroxymethylene group greatly enhances the drug's anabolic properties. The action of this agent in androgen-sensitive tissues is much like that of DHT and is quite androgenic.

Oxymetholone is the only AAS to date to be considered a carcinogen. [14]

Like this entire class, oxymetholone does not aromatize. It is thought to activate estrogen receptors via the 2-hydroxymethylene group, and it can exert many estrogenic side effects.

Oxymetholone is marketed in the United States as Anadrol-50 and has been abused the world over by weight lifters and strength athletes for its strong anabolic and pronounced androgenic effects.


Adverse Effects

Most of the adverse effects of anabolic-androgenic steroid (AAS) use are dose dependent and are reversible with cessation of the offending agent or agents. This overview of side effects and interactions is just that, an overview, and is not meant to represent the full spectrum of potential side effects that may be seen with this class of agents. Vital signs, including heart rate and blood pressure, and basic chemistries, such as sodium, potassium, hemoglobin, hematocrit, BUN (blood urea nitrogen), creatinine, hepatic, and lipid profiles, must be monitored carefully. Monitoring these parameters will help the clinician to determine drug choice, treatment dose, and duration, and will help to alert the prescriber to potentially serious adverse effects that necessitate the discontinuation of therapy.

Cardiovascular effects

The most common deleterious effects of AAS use on the cardiovascular system include increased heart rate, increased blood pressure, and changes in lipid metabolism, including lowered high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL). The increase in heart rate is thought to be more profound with the androgens, especially those resistant to aromatase, and is believed to be due to the inhibition of monoamine oxidase (MAO). This effect, when combined with the increased renal recovery of ions, such as sodium, causing subsequent fluid retention, can lead to dramatic increases in blood pressure. Combine this with a tendency to lower HDL and raise LDL, and the stage is set for untoward atherogenic and cardiac effects. Anabolic steroid users can have a lower left ventricle ejection fraction. Ananbolic steroid abuse has been associated with ventricular arrhythmias. [11, 15, 16, 17, 18]

Hepatic effects

The changes made to C-17 to inhibit hepatic degradation make nearly all oral preparations hepatotoxic. The alanine aminotransferase/aspartate aminotransferase (ALT/AST) can be seen to rise, usually in a dose-dependent fashion. Levels approaching 2-3 times baseline are often set as upper limits of reference ranges when administering oral AASs, but the risk-to-benefit ratio must be constantly evaluated.

AAS use also results in suppression of clotting factors II, V, VII, and X, as well as an increase in prothrombin time. Another life-threatening, albeit rare, adverse effect that is seen in the liver and sometimes in the spleen is peliosis hepatitis, which is characterized by the appearance of blood-filled, cystic structures. These cysts, which may rupture and bleed profusely, have been found in patients with near-normal liver function test (LFT) values, as well as in individuals who are in liver failure. Fortunately, drug cessation usually results in complete recovery.

Primary liver tumors have been reported, most of which are benign, androgen-dependent growths that regress with the discontinuation of AAS therapy. Several case reports exist of young, healthy athletes who have died from primary malignant liver carcinoma, with the only identifiable risk factor being oral AAS use.

Anabolic steroid abuse has been considered a risk factor for nonalcoholic fatty liver disease. [19]

Endocrine effects

The endocrine system has a remarkable array of checks and balances that ensure the human body is at or near homeostasis at any point in time. Interruption of one feedback system has been shown to produce changes in other hormone feedback systems via direct receptor changes, as well as through competition for common enzymes and metabolic pathways. Studies have shown that AASs bind to glucocorticoid, progesterone, and estrogen receptors and exert multiple effects. Discussions exist as to how the endogenous testosterone and spermatogenic functions of the testes are inhibited by the use of testosterone and AASs. By suppressing FSH, spermatogenic function should be reduced.

AASs have also been shown to alter fasting blood sugar levels and decrease glucose tolerance, presumably due to either a hepatic effect or changes in the insulin receptor. Thyroxine-binding globulin (TBG) may also be lowered by AASs and result in lowered total T4 levels, with free T4 levels remaining normal. An up-regulation of sex-hormone binding globulin, with a concomitant decrease in TBG, is thought to cause the changes in total T4 levels.

The aromatization of testosterone/AASs to estradiol and related compounds can render many adverse estrogenic effects. The most apparent and common adverse effect is the growth of tender, estrogen-sensitive tissue under the male nipple. This unsightly growth is termed gynecomastia and can be treated medically or surgically. [20]

Urologic effects

The male prostate is very sensitive to androgens, especially those that are reduced in prostatic tissue to dihydrotestosterone (DHT) or DHT analogs. In response to this stimulation, the prostate grows in size, potentially causing or exacerbating benign prostatic hyperplasia (BPH). Worsening BPH may indeed cause severe bladder and secondary renal damage. In addition, the use of AASs in patients with underlying carcinoma of the prostate is absolutely contraindicated due to the potential for hormone-sensitive tumor growth. However, a 3-year study of hypogonadal men on testosterone replacement therapy failed to show significant differences between the group and the controls in urinary symptoms, urine flow rate, or urine postvoid residual. [21]

Hematologic effects

Direct clotting factors may be reduced with an increase in prothrombin time. In patients on concomitant anticoagulant therapy, this increase could cause bleeding. AASs cause increases in hemoglobin and hematocrit and are used in many cases of anemia, although the clinician must be aware of the potential for polycythemia.

Dermatologic effects

Skin, especially the face and scalp, has a high degree of androgen receptors and 5AR. DHT is known to cause increases in sebum production, leading to clinical acne. Also, male pattern baldness is related to scalp DHT production and binding, along with genetic factors influencing hair growth. Male pattern baldness is greatly exacerbated by most AASs in susceptible individuals.


Clinical Uses

Clearly, hormone replacement therapy is the most common use of testosterone. Anabolic-androgenic steroids (AASs) have many other potential clinical uses. [22] Most of these center on the anabolic nature of these drugs and their use in people with cachexia, produced by such disease states as HIV, hepatic and renal failure, chronic obstructive pulmonary disease (COPD), some types of cancer, and burns, as well as during postoperative recovery. In most clinical scenarios, the association of protein-calorie malnutrition increases the morbidity and mortality of the primary disease state. By preventing this loss of LBM, the clinician can hope to prevent many of the adverse effects caused by the disease and, perhaps, by other treatments that have been enacted. In all clinical cases, with the exception of cancer, AASs have shown efficacy in weight gain.

In HIV infection, testosterone replacement and AAS use are generally considered. Commonly used AASs include oxandrolone, nandrolone, and oxymetholone. All 3 agents have been studied for increased LBM and weight gain. [23, 24, 25, 26]

AASs have been studied in COPD-associated cachexia. Stanozolol (12 mg/d), after an initial 250 mg IM testosterone injection, has been shown to produce significant improvement in a patient's weight, body mass index (BMI), and strength compared with controls at 26 weeks. [27] A study of 217 COPD patients randomized to nandrolone plus nutrition and exercise or to nutrition and exercise alone, for a total of 8 weeks showed that the nandrolone group had significant increases in LBM and maximum inspiratory pressure. [28] Studies of oxandrolone (20 mg/d) also showed significant gains in weight and inspiratory parameters in tetraplegic patients. [29]

Hepatic failure is also associated with protein-calorie malnutrition and wasting. In a study of 273 patients with moderate weight loss due to alcoholic hepatitis, oxandrolone (80 mg/d) improved hepatic function and nutrition parameters and increased 6-month survival when compared with controls. [30] Although this was considered a preliminary study, it showed that the use of AASs, including oral agents, can be useful even in some types of liver failure with associated weight loss.

Wound and burn healing have been treated with AASs, including testosterone esters, stanozolol, oxandrolone, and nandrolone. These agents increase collagen synthesis and the activity of dermal fibroblasts [31] and have a positive effect on healing rates in previously nonhealing wounds. [32]

Cancer-associated cachexia and anemia are very common. AASs have been proposed for use in cancer-associated weight loss and in the treatment of the hypogonadal state that often accompanies severe cachexia. AASs have also been used for their erythropoietic effects, usually in leukemia treatment.

AAS use in renal failure, especially in patients on hemodialysis, has been investigated. A double-blind, placebo-controlled study of 29 dialysis patients receiving either nandrolone (100 mg/wk) or placebo for 6 months showed significant gains in LBM and in functional parameters. [33] Studies also indicate that the erythropoietic effect of AASs (nandrolone decanoate) is useful in chronic renal disease and that when an AAS is used in combination with recombinant human erythropoietin, the gains in hematocrit are greater than when either agent is used alone. [34]

These are just a sample of the many disease states that AASs are used to treat. In most cases in which the anabolic properties of AASs are desired, an increased ingestion of protein and calories must accompany their use. Topics not explored in this article include hormone replacement therapy and the general use of androgenic agents as such. Indeed, in cases such as endometriosis and fibrocystic breast disease, androgens are used clinically to negatively affect the hypothalamic-pituitary-gonadal axis and to limit disease symptoms or progression.


Anabolic-Androgenic Steroid Abuse

AASs were first classified as schedule III controlled substances in 1990. Newer legislation was passed in 2004 that included substances that could be converted into testosterone in this controlled group.

The topic of drug abuse of any kind is very complex and often difficult to assess accurately and objectively. The abuse of anabolic-androgenic steroids (AASs) is no different. The complex myriad of neurologic effects of AASs is still being studied. Relating this biopharmacology to the individual abusing AASs is a particularly difficult task because of several factors. For one, many individuals abusing AASs have done so in relative secrecy, and many have been reluctant to engage in valid medical research. The lack of a standard when performing research—because of the vast numbers of agents that are sold worldwide on the black market and their relative potency, or complete lack thereof—is another problem. Many counterfeit products are sold and used, which complicates the study of abuse.

In more than a few cases, contradictory data exist, especially concerning psychological effects. One must remember that the interaction of forces, which ultimately influences the abuser, is vast and multidimensional, a complex web of presumed gain and reward that exists due to conditioning and related psychosocial issues. The use of performance-enhancing substances is not a novel idea and can be dated back to the Greeks. The use of AASs for performance enhancement began in the 1950s with elite athletes, and the use has slowly trickled down to include the high school and junior high school levels. With a "win at all costs" mentality and the high regard our society has for successful athletes, it is easy to see how this has occurred. AAS use in teenage years can prematurely fuse epiphyseal plates and stunt growth, as well as cause psychological problems.

When testosterone and/or AASs are used in the nonclinical setting, many problems arise. Athletes' self-prescribing habits are usually excessive and are often based more on fiction than on fact. It is very common for the AAS abuser to "stack" drugs, or to use multiple drugs at the same time. Surveys of weightlifters have documented the concurrent use of multiple drugs, employed in a cyclic fashion for a period of 12-16 weeks; the dose used is typically 2-8 times higher than the therapeutic dose range. The use of multiple drugs greatly increases side effects and risks to the user. These factors, coupled with decreased medical surveillance, place the AAS abuser at high risk for serious complications.

AASs have been shown to alter moods by a number of mechanisms. [35, 36, 37] Studies show that testosterone and AASs may act as a central MAO inhibitor. Indeed, AASs are mood elevators and have been studied in depressed individuals. Vogel and colleagues compared the antidepressant effects of amitriptyline (75 mg/d, up to a maximum of 300 mg/d) with those of mesterolone (100 mg/d, up to a maximum of 550 mg/d) in a double-blind design with 34 depressed male outpatients. [38] The investigators found that the 2 drugs were equally effective in reducing depressive symptoms and that mesterolone produced significantly fewer adverse effects than did amitriptyline.

Another study combined methyltestosterone (15 mg/d) with imipramine (25-50 mg/d) and found a prompt paranoid response in 4 of 5 men treated. [39] This was likely due to the central MAO inhibition by methyltestosterone, combined with the known effects of imipramine. The response quickly abated when the methyltestosterone was discontinued.

Other studies have indicated that testosterone, particularly in the prenatal period but also during puberty and adulthood, is important in establishing a biological readiness for normal aggressive behavior and in facilitating the expression of aggression in appropriate social settings. The reports have also indicated that social factors and learning significantly influence the actual expression of aggression in adulthood. [40] In a 1983 study of 32 weightlifters using AASs, 56% reported a temporary increase in self-defined irritability and aggressive behavior. When these psychoactive effects combine with strong positive reinforcement from weight and strength gains, as well as from improved self-image, AASs can prove addictive. [1, 13]

A retrospective study released in the British Journal of Sports Medicine in 2013, studied Swedish strength athletes (weightlifters, powerlifters, throwers, wrestlers) who competed at the elite level between 1960 and 1979. Of the 700 athletes that were included, 20% admitted to using AASs during their athletic careers. The AAS users were more likely to have been treated for depression, concentration issues, and aggressive behavior. Additionally, it was found that AAS users were more likely to have abused other illicit drugs. However, the study was not able to determine the cause and effect relationship between the mental health problems and steroid use. [41]

AAS addiction is generally held as a psychic addiction, but the withdrawal effects that occur when AAS use stops clearly indicate an element of physical addiction as well. Multiple studies have shown that the withdrawal symptoms include depression, fatigue, paranoia, and suicidal thoughts and feelings. [35] Furthermore, a strong desire to continue abusing AASs exists even in the face of negative consequences; thus, the drugs are continued in order to provide a continuation of their perceived positive effects and to inhibit withdrawal effects.

A 1989 review suggested that the psychoactive effects, withdrawal symptoms, and underlying biological mechanisms of AASs appear to be similar to the mechanisms and complications that accompany cocaine, alcohol, or opioid abuse. The review also proposed that a portion of AAS abusers may develop a sex-steroid hormone dependence disorder. Some patients may require treatment to restore physiologic hormonal regulation after abuse of AASs, whereas supportive counseling and antidepressant medications can help with the psychological aspects.

Abuse of AASs has also increased in female athletes of all levels. Additional concerns specific to female abusers include growth of facial hair, male-pattern baldness or regression of frontal hairline, breast atrophy, coarsening of the skin, alteration of the menstrual cycle or amenorrhea, enlargement of the clitoris, and deepened voice. The alterations to the female reproductive system are caused by the artificial increase in testosterone levels, which are normally present in females in small amounts. Due to the negative feedback system, the release of LH and FSH decline, leading to a decrease in estrogens and progesterone.

AAS use by a pregnant woman can cause pseudohermaphroditism or virilization in the female fetus or even fetal death. In a committee opinion released by the American College of Obstetricians and Gynecologists in 2011, healthcare professionals were encouraged to address the use and consequence of the substances, encourage cessation, and refer patients to substance abuse treatment centers.

The abuse of AASs, especially since the late 20th century, has had a deleterious effect on the clinical use of these compounds. These drugs are now considered controlled substances in the United States (schedule 2 and 3), and this, along with excessive negative media attention, has resulted in a steep decline in their appropriate clinical use.

Indeed, many AASs have been withdrawn from the US market; however, clinical interest in the beneficial effects of these drugs has once again been coming to the forefront. With recent increases in use (estimated at 400%), AASs are once again being prescribed for known applications, and ongoing research will continue to uncover novel uses for these agents and will further define their mechanisms of action. Physicians should be aware of the clinical and underground worlds of AASs and, as with opioids and other potential drugs of abuse, should not allow the abuse of these drugs to limit their appropriate therapeutic use. A particular agent is not inherently good or evil; instead, it is the end use of that compound that can be viewed positively or negatively. Thus, the physician must help to ensure that AASs are used appropriately and are not abused.