The use of supraphysiologic doses of anabolic androgenic steroids (AAS) has extended beyond competitive bodybuilding into the general gym-going population, often without an adequate understanding of the associated harms. Reported complications include structural heart disease with ventricular hypertrophy and heart failure, markedly increased risk for atherothrombotic events, psychiatric disorders, sexual dysfunction, and severe infertility with uncertain recovery of spermatogenesis. For clinicians, the message is straightforward: High-dose AAS misuse carries multisystem risks that may be severe, sometimes irreversible, and frequently overlooked in routine clinical practice.

“Fulminant myocardial infarctions have been documented in bodybuilders younger than 30 years, with extensive coronary lesions identified at autopsy,” Charlotte Methorst, MD, urologic surgeon specializing in andrology at the Center Hospitalier des Quatre Villes in Saint-Cloud, France, spoke at the 119th French Congress of Urology 2025.

Therapeutic Use

AAS are synthetic derivatives of testosterone developed to promote muscle anabolism while reducing androgenic effects through receptor binding in the muscle, bone, cardiac, and testicular tissues. At therapeutic doses, these agents have established indications for primary or secondary hypogonadism in males.

They may also be used less commonly to stimulate erythropoiesis in certain anemias that do not respond to erythropoietin therapy. Direct action on the bone marrow produces moderate but clinically meaningful increases in hemoglobin and hematocrit levels. These molecules also exert anabolic effects on skeletal muscle protein synthesis and are used in select cases of severe cachexia characterized by pronounced muscle loss, which may increase lean body mass and contribute to the improvement of sarcopenia.

“At physiologic doses, testosterone replacement therapy is generally safe,” said Methorst. “Monitoring focuses on hematocrit and prostate-specific antigen levels. Lipid profiles often improve with favorable effects on cardiovascular risk factors, bone density, muscle mass, mood, and sexual function. Contraindications are limited and include untreated active prostate or breast cancer, untreated obstructive sleep apnea, polycythemia, and men planning to have children. However, the use of androgens at supraphysiologic doses is linked to significantly more serious complications.”

Nonmedical Use

The prevalence of supraphysiologic AAS use is increasing, with doses reaching 10-50 times the physiologic levels. Among men, the estimated lifetime prevalence is approximately 10%. Among women, a 2024 systematic review reported a pooled prevalence of 4% (95% CI, 2%-9%), with rates as high as 16.8% among female bodybuilders and 4.4% among recreational gym users. In North America alone, more than 3 million individuals are estimated to be AAS users, and these substances account for approximately half of all positive anti-doping tests.

In a society where social media intensifies pressure around body image — particularly the ideal of a sculpted six-pack — the use of these substances has spread beyond competitive sports.

Users typically follow regimens known as “cycles”: 6- to 12-week periods of use separated by drug-free intervals. Another common practice is “stacking,” using several AAS concurrently, which increases the risk for drug interactions and adverse effects. Pyramid regimens involve gradual dose escalation to a peak, often reaching 1000 mg of testosterone equivalent per week, followed by tapering. This far exceeds therapeutic replacement doses, which generally range from 50 to 100 mg/wk depending on the formulation.

These practices usually occur without medical supervision, and substances are obtained on the black market, where quality, purity, and sterility are not assured. Contamination, dosing errors, and product substitution are common, exposing users to significant toxicologic risk. Injectable testosterone esters are the most used, often combined with other derivatives such as nandrolone, trenbolone, drostanolone, and boldenone to enhance anabolic effects.

Users typically alternate between the “bulking” and “cutting” phases. Bulking combines a caloric surplus with high-load resistance training to increase muscle mass. Cutting aims to reduce body fat through a calorie-restricted diet, resistance training, and cardiovascular exercise. During the cutting phase, agents such as trenbolone, stanozolol, and drostanolone are used more frequently.

Cardiovascular Toxicity

The cardiovascular risks associated with AAS are serious and primarily involve the myocardium.

“Prolonged exposure leads to concentric left ventricular hypertrophy, with pathological thickening of the myocardial wall that may reach 15-20 mm compared with less than 11 mm under normal conditions,” said Methorst. “This can occur in addition to the physiological cardiac enlargement seen in trained athletes. However, AAS-related remodeling is often accompanied by interstitial fibrosis, which reduces ventricular compliance and impairs diastolic dysfunction.”

These structural changes may only be partially reversible and can progress to heart failure, even in young individuals without prior cardiovascular diseases.

High-dose prolonged AAS exposure is associated with arrhythmia and conduction abnormalities. Myocardial hypertrophy combined with interstitial fibrosis creates an arrhythmogenic substrate that predisposes patients to serious ventricular arrhythmias. This electrical instability increases the risk for sudden cardiac death due to ventricular fibrillation. Severe hypertension affected more than 60% of the users.

Metabolically, AAS induces marked atherogenic dyslipidemia. Low-density lipoprotein cholesterol may exceed 200 mg/dL, whereas high-density lipoprotein cholesterol may fall below 20 mg/dL (normal > 40 mg/dL). This lipid profile accelerates atherosclerosis and increases the risk for major cardiovascular events four- to sixfold.

Although thrombotic risk and infarction remain low at physiologic doses, the risk increases substantially at high doses, Methorst noted. Acute coronary thrombosis has been reported in very young users and appears to result from hypercoagulability, dyslipidemia, and endothelial dysfunction.

Renal and hepatic toxicities are also a concern. Chronic kidney disease may develop due to direct glomerular and tubular toxicity, severe hypertension leading to nephrosclerosis, and chronic dehydration, which is common among bodybuilders. Focal segmental glomerulosclerosis has been reported in long-term users, along with episodes of rhabdomyolysis associated with intense resistance training during AAS use. Hepatotoxicity can be severe, with reported manifestations including intrahepatic cholestasis and peliosis hepatis, the latter of which may lead to subcapsular hematoma or spontaneous hepatic rupture in rare cases.

Black market products further increase the risk for hepatitis B, hepatitis C, and HIV infection through contamination, heavy metal exposure, substitution with veterinary formulations, inaccurate dosing, and non-sterile injection practices.

Fertility at Stake

Misuse of AAS results in severe infertility, with azoospermia observed in many users. “Recovery of spermatogenesis may take 18-36 months, a period during which testosterone levels are often very low,” Methorst noted. “In approximately 10%-20% of cases, recovery is incomplete, and treatment to stimulate sperm production is required.”

Prolonged use of AAS can result in persistent hypogonadotropic hypogonadism even after discontinuation. Sustained suppression of the hypothalamic-pituitary-gonadal axis may prevent spontaneous recovery. In extreme cases of prolonged high-dose AAS exposure, the testes may undergo severe atrophy, with a reduction in testicular weight to approximately 6 grams. Histological examination may show 30% parenchymal sclerosis, absence of spermatogenesis, and a substantial reduction in functional Leydig cells.

Published studies indicated that men who use high-dose AAS for several years have fewer children than nonusers.

Treatment relies on gonadotropin therapy. Follicle-stimulating hormone is administered at 150-225 International Units (IU) subcutaneously three times weekly, and human chorionic gonadotropin at 1500-2500 IU intramuscularly or subcutaneously 2-3 times weekly. These regimens can restore spermatogenesis and induce puberty in adolescent patients. Adverse effects are generally limited to gynecomastia and acne only. Exogenous testosterone is contraindicated because it suppresses the production of endogenous gonadotropins.

Mental Health and Addiction

AAS exposure is associated with significant psychiatric risks, including violence, addiction, and psychological distress. Massive hormonal fluctuations can trigger serious mood disorders characterized by intense emotional instability, extreme irritability, disproportionate aggression, and uncontrollable outbursts of anger, particularly during periods of high hormone doses. Severe depressive episodes frequently occur during withdrawal and are associated with anhedonia, overwhelming fatigue, and suicidal ideation.

The use of AAS can significantly impair the quality of life, affecting family, professional, and social relationships. Social withdrawal may develop progressively, and preoccupation with physical appearance can become obsessive, creating a cycle of psychological distress. The risk for suicide increases during post-cycle depressive episodes or when quitting permanently, highlighting the need for close psychiatric monitoring.

Methorst stated that “AAS addiction is characterized by loss of control and progressive dose escalation despite awareness of the risks.” “Stopping leads to withdrawal symptoms, and muscle dysmorphia — a distorted perception of being insufficiently muscular — reinforces continued use. ‘Steroid rage’ describes episodes of impulsive, disproportionate aggression that have been documented in numerous forensic cases. These behaviors are linked to neurologic changes, including alterations in serotonergic and dopaminergic pathways that impair emotional regulation and impulse control.”

She emphasized that treatment should not be discontinued without medical supervision.

Erectile Dysfunction and Hormonal Effects

Sexual health is also affected. “Some men develop significant erectile dysfunction, often resistant to phosphodiesterase type 5 inhibitors,” Methorst noted. “The mechanisms are multifactorial. Vascular changes, such as hypertension and dyslipidemia, also contribute. Chronic exposure may alter androgen receptor sensitivity at the cortical level, where receptors remain persistently saturated, thereby disrupting sexual desire. Body image also plays an important role in this regard. Despite increased muscle mass, some individuals view their bodies negatively, feeling insufficiently muscular or overweight, which contributes to psychological distress and reduced libido.”

Clinical Management

AAS use is not limited to bodybuilders and may only become apparent during infertility evaluations.

“Typically, we see elevated testosterone levels combined with markedly suppressed follicle-stimulating hormone, the most reliable indicator of anabolic steroid use,” Methorst said. “After stopping androgens, some patients feel unwell. Treatment should not be discontinued without medical supervision. If stopped abruptly, testosterone levels can fall to extremely low levels before the testes resume normal function.”

The approach involves discontinuing the substance and initiating appropriate medical management. Depending on the objective — restoration of spermatogenesis or maintenance of normal hormone levels — therapy is adjusted to either stimulate endogenous production or provide carefully monitored exogenous testosterone levels. Hormonal support must be individualized because some patients metabolize these agents more rapidly.

Patients should not be made to feel guilty, she added. “Many delay seeking care because they fear judgment or medical advice. Therefore, the care provided should be comprehensive. Psychiatric or addiction support is recommended when stopping AAS because its use can lead to addiction. Cardiac care is also essential, as some damage may not be fully reversible and may require targeted treatment. Recovery of spermatogenesis is possible but not guaranteed and depends on the duration of high-dose AAS use and whether other substances were used. These men should be referred to experienced specialists; this condition is well recognized and manageable.”

Testosterone alone does not lead to muscle gain but enhances the effects of resistance training. A dose-response relationship exists between the amount of testosterone administered and the resulting serum testosterone levels, as well as gains in muscle mass, size, strength, and power, and reductions in body fat.

Methorst reported having relationships with Besins, Organon, Theramex, IBSA, Ipsen, Servier, Astellas, Effik, and Kranus Health.

This story was translated from Medscape’s French edition.