What is the difference between Testosterone Replacement Therapy (TRT) and anabolic steroids in a patient with diagnosed hypogonadism?

TRT vs. Anabolic Steroids: Key Differences

Testosterone Replacement Therapy (TRT) is a medical treatment for diagnosed hypogonadism using physiologic doses to restore normal testosterone levels, while anabolic steroids involve supraphysiologic doses of testosterone or synthetic androgens used for performance enhancement or muscle building—the fundamental difference lies in medical indication, dosing, and monitoring.

Medical Indication and Diagnosis

TRT requires confirmed biochemical hypogonadism:

• Two separate morning total testosterone measurements below 300 ng/dL are required to establish hypogonadism 1
• Must have documented symptoms including diminished libido, erectile dysfunction, or diminished sense of vitality 2, 1
• Requires measurement of LH and FSH to distinguish primary from secondary hypogonadism 1
• FDA-approved indication is "replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone" 3

Anabolic steroids are used without medical indication:

• Used by eugonadal individuals for muscle building, athletic performance, or body composition 1
• The European Association of Urology explicitly recommends against testosterone therapy in eugonadal men, even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength 1
• Approximately 20-30% of men receiving testosterone in the United States do not have documented low testosterone levels before treatment initiation 1

Dosing and Testosterone Levels

TRT uses physiologic replacement doses:

• FDA-approved dosing for testosterone cypionate is 50-400 mg every 2-4 weeks 1
• Target mid-normal testosterone levels of 500-600 ng/dL 1
• Transdermal testosterone gel at 40.5 mg daily provides stable physiologic levels 1
• Peak serum levels occur 2-5 days after injection, with return to baseline by days 10-14 2, 1

Anabolic steroids use supraphysiologic doses:

• Doses often exceed physiologic replacement by 5-10 fold or more 4
• Weekly dosing exceeding standard practice increases risk of supraphysiologic levels and erythrocytosis 1
• Results in testosterone levels well above the normal range 4

Medical Supervision and Monitoring

TRT requires comprehensive monitoring:

• Testosterone levels checked at 2-3 months after initiation, then every 6-12 months 1
• Hematocrit monitored periodically—treatment withheld if >54% 2, 1
• PSA monitoring in men over 40 years 1
• Digital rectal examination to assess for prostate abnormalities 1
• Risk of erythrocytosis ranges from 3-18% with transdermal administration to up to 44% with injections 2

Anabolic steroid use lacks medical oversight:

• No systematic monitoring of adverse effects 4
• Users often unaware of cardiovascular, hepatic, and reproductive risks 4
• No assessment of baseline contraindications 4

Impact on Fertility and HPG Axis

Both TRT and anabolic steroids suppress the HPG axis:

• Exogenous testosterone suppresses hypothalamic-pituitary-gonadal axis resulting in diminution of spermatogenesis 4
• Testosterone therapy is absolutely contraindicated in men seeking fertility preservation 1
• Causes azoospermia through negative feedback on LH and FSH secretion 1, 4
• Recovery of spermatogenesis may occur with cessation, but some patients may not recover normal spermatogenesis 4

Critical difference in fertility counseling:

• TRT patients receive mandatory fertility counseling before initiation 1
• Men with secondary hypogonadism desiring fertility should receive gonadotropin therapy (hCG plus FSH) instead of testosterone 1
• Anabolic steroid users typically receive no fertility counseling and may be unaware of reproductive consequences 4

Expected Clinical Outcomes

TRT produces modest, specific benefits in hypogonadal men:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 1
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 2, 1
• Modest improvements in bone mineral density at lumbar spine 2
• Improvements in fasting glucose, insulin resistance, and lipid parameters 1

Anabolic steroids in eugonadal men:

• No evidence of benefit for muscle building in eugonadal men when used for athletic performance 1
• Primary indication for testosterone is sexual dysfunction in biochemically confirmed hypogonadism—not athletic performance or body composition 1

Cardiovascular and Safety Considerations

TRT cardiovascular risk remains controversial:

• The TOM trial showed increased CV events in the TRT arm (23 vs 5 events), though this has not been consistently replicated 2
• FDA issued Safety Announcement in 2015 regarding possible increased risk of heart attack and stroke 2
• Most level 1 trials found no difference in CV adverse events compared with placebo 2
• Injectable testosterone may carry higher cardiovascular risk than transdermal preparations due to fluctuating levels 1

Additional safety concerns with both:

• Fluid retention, benign prostatic hyperplasia, potential prostate cancer stimulation 2
• Sleep apnea, gynecomastia, acne, testicular atrophy 2
• Hepatotoxicity limited to oral agents 2

Legal and Regulatory Status

TRT is FDA-approved and regulated:

• Requires prescription from licensed physician 3
• Indicated for primary hypogonadism and hypogonadotropic hypogonadism 3
• Subject to DEA scheduling as controlled substances 3

Anabolic steroids without prescription are illegal:

• Use without medical indication violates federal law 4
• Often obtained through non-medical channels 4

Treatment Formulations

TRT offers multiple FDA-approved formulations:

• Intramuscular injections (cypionate, enanthate) every 2-3 weeks at lower cost ($156.24 annually) 1
• Transdermal gel providing stable levels at higher cost ($2,135.32 annually) 1
• Buccal, nasal, and subdermal preparations available 5
• Choice depends on patient preference, cost, and desired stability of levels 1

Anabolic steroid formulations vary widely:

• Often include synthetic androgens not approved for medical use 4
• May involve "stacking" multiple compounds 4
• Dosing protocols lack medical evidence base 4

Key Clinical Algorithm for Differentiation

When evaluating a patient on testosterone:

1. Verify original indication: Was hypogonadism confirmed with two morning testosterone levels <300 ng/dL? 1

2. Assess dosing: Are doses within FDA-approved physiologic range (50-400 mg every 2-4 weeks IM or 40.5 mg daily transdermal)? 1, 3

3. Check monitoring: Are testosterone levels, hematocrit, and PSA being monitored appropriately? 1

4. Evaluate fertility counseling: Was the patient counseled about fertility suppression before initiation? 1

5. Review prescriber: Is testosterone prescribed by a licensed physician for documented hypogonadism? 3

If any of these elements are absent, the use pattern resembles anabolic steroid abuse rather than legitimate TRT.