What is the Difference Between TRT and HGH?
Testosterone replacement therapy (TRT) and human growth hormone (HGH) are fundamentally different hormones with distinct mechanisms, indications, and effects—TRT replaces deficient testosterone to restore sexual function and metabolic health in hypogonadal men, while HGH stimulates linear growth in children with growth hormone deficiency and has no established role in adult hormone replacement outside of documented GH deficiency.
Core Biological Differences
Hormone Source and Function
TRT replaces testosterone, the primary male sex hormone produced by the testes, which is responsible for sexual development, libido, erectile function, muscle mass, bone density, and metabolic regulation 1, 2.
HGH is growth hormone produced by the pituitary gland, which primarily stimulates linear growth in children through IGF-I production and regulates protein metabolism, body composition, and bone development 3, 4.
Primary Clinical Indications
TRT is indicated for adult men with confirmed hypogonadism—defined as morning total testosterone <300 ng/dL on two separate measurements plus specific symptoms (diminished libido, erectile dysfunction)—to improve sexual function, with a standardized mean difference of 0.35 1, 2.
HGH is FDA-approved primarily for children with growth hormone deficiency to normalize linear growth and adult height, with dosing based on body weight (0.06-0.10 units/kg three times weekly) 3, 4.
Mechanism of Action
TRT Mechanism
Testosterone acts directly on androgen receptors throughout the body to restore physiologic testosterone levels (target 450-600 ng/dL), improving sexual function, increasing bone mineral density, enhancing muscle mass, and modestly improving metabolic parameters including insulin sensitivity 1, 2, 5.
TRT has minimal to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition, even in confirmed hypogonadism, with effect sizes too small to be clinically meaningful for these outcomes 1, 2.
HGH Mechanism
Growth hormone stimulates hepatic and peripheral IGF-I production, which mediates most of GH's growth-promoting effects, increasing protein synthesis (measured by nonoxidative leucine disposal), decreasing protein oxidation, and promoting linear bone growth 6, 4.
HGH increases bone mineral density by 3.2% at the lumbar spine and 1.4% at the femoral neck in growth-deficient children, with greater enhancement of linear growth than epiphyseal development in most treated patients 4.
Synergistic vs. Independent Effects
Combined Effects in Puberty
Testosterone and GH are synergistic on whole-body protein anabolism and body composition in prepubertal boys, with combined therapy producing greater decreases in fat mass and increases in fat-free mass than either hormone alone 6.
Protein oxidation rates decrease 28% with testosterone alone and 36% with combined T/GH treatment, while nonoxidative leucine disposal (whole-body protein synthesis) increases significantly only with the combination 6.
The positive effects of testosterone on protein anabolism and body composition require a basal amount of GH to be fully observed, demonstrating hormone interdependence during pubertal development 6.
Administration and Formulations
TRT Delivery Routes
Transdermal testosterone gel (1.62% at 40.5 mg daily) is first-line due to stable day-to-day testosterone levels and lower erythrocytosis risk (15.4%) compared to injectable preparations (43.8%) 1, 2, 5.
Intramuscular testosterone cypionate/enanthate (100-200 mg every 2 weeks) is a cost-effective alternative ($156 annually vs. $2,135 for transdermal), with peak levels at days 2-5 and return to baseline by days 10-14 5, 7, 8.
Other TRT formulations include buccal, nasal, and subdermal pellets, each with distinct pharmacokinetic profiles and patient preference considerations 7, 8, 9.
HGH Delivery
HGH is administered as daily subcutaneous injections (the only route used in clinical trials), with evening injections recommended to mimic physiological circadian rhythm, and injection sites rotated daily to avoid lipoatrophy 3.
HGH can be administered intramuscularly or subcutaneously with comparable efficacy, and both reference products and biosimilars are approved for use in children with chronic kidney disease 3.
Safety Profiles and Monitoring
TRT Safety Concerns
Erythrocytosis is the most common adverse effect, occurring in 44% of men on injectable testosterone vs. 15% on transdermal preparations, requiring hematocrit monitoring with treatment withheld if >54% 1, 2, 5.
TRT absolutely contraindicated in men seeking fertility preservation because exogenous testosterone suppresses spermatogenesis and causes prolonged, potentially irreversible azoospermia 1, 2, 5.
Cardiovascular safety is established: the 2023 TRAVERSE trial (5,246 men, mean follow-up 21.7 months) showed no significant increase in major adverse cardiac events or stroke with transdermal testosterone gel vs. placebo 5.
PSA monitoring required in men >40 years, with urologic referral if PSA rises >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 1, 2, 5.
HGH Safety Profile
HGH adverse effects are similar across dosages and to untreated control populations in randomized controlled trials, with no significant association between GH therapy and malignancy, slipped capital femoral epiphysis, glucose intolerance, or rapid CKD progression 3.
Intracranial hypertension reported in 3 of 1,376 CKD patients (all after GH discontinuation), requiring baseline fundoscopy before initiation and immediate work-up if persistent headache or vomiting develops 3.
Insulin secretion increases during the first year of GH treatment, with hyperinsulinemia persisting during long-term therapy, though evidence suggests ≤5 years of treatment does not typically impair glucose tolerance 3.
Secondary hyperparathyroidism may be aggravated by GH therapy, requiring adequate treatment of CKD-MBD before initiation and withholding GH in patients with persistent severe secondary hyperparathyroidism 3.
Expected Clinical Outcomes
TRT Outcomes
Small but significant improvements in sexual function and libido (standardized mean difference 0.35), with modest quality-of-life improvements primarily in sexual function domains 1, 2, 5.
Metabolic benefits include improvements in fasting glucose, insulin resistance, triglycerides, and HDL cholesterol, particularly in men with metabolic syndrome 2, 5.
Bone mineral density increases modestly (3.2% lumbar spine, 1.4% femoral neck), reducing osteoporosis risk in hypogonadal men 2, 5.
HGH Outcomes
The ultimate goal of GH treatment in children with CKD is to normalize adult height, with monitoring necessary to evaluate response and detect potential adverse effects 3.
GH treatment for ≤5 years does not typically have adverse effects on glucose tolerance, though close monitoring is advised in obese CKD patients due to increased risk of impaired glucose tolerance 3.
Critical Distinctions for Clinical Practice
Diagnostic Requirements
TRT requires two separate morning testosterone measurements <300 ng/dL (8-10 AM) plus specific symptoms (diminished libido, erectile dysfunction) before initiation 1, 2, 5.
HGH requires documented growth hormone deficiency with growth failure in children, typically diagnosed through stimulation testing and IGF-I levels 3, 4.
Contraindications
TRT is contraindicated in men with active prostate or breast cancer, hematocrit >54%, untreated severe sleep apnea, and those seeking fertility 1, 2, 5.
HGH should be withheld in patients with persistent severe secondary hyperparathyroidism and requires adequate treatment of underlying metabolic bone disease before initiation 3.
Monitoring Protocols
TRT monitoring includes testosterone levels at 2-3 months then every 6-12 months, hematocrit at each visit, PSA annually in men >40, and digital rectal examination 1, 2, 5.
HGH monitoring includes ongoing assessment of growth response, glucose metabolism (especially in obese patients), secondary hyperparathyroidism, and fundoscopy if symptoms of intracranial hypertension develop 3.
Common Pitfalls to Avoid
Never prescribe TRT for weight loss, energy improvement, or athletic performance—these are not evidence-based indications, and testosterone produces little to no benefit for physical functioning, energy, or cognition 1, 2, 5.
Never initiate TRT without confirming the patient does not desire fertility, as exogenous testosterone causes prolonged azoospermia, whereas men with secondary hypogonadism can use gonadotropin therapy (hCG plus FSH) to restore both testosterone and fertility 1, 2, 5.
Never diagnose hypogonadism on symptoms alone or a single testosterone measurement—always require two morning values <300 ng/dL plus specific sexual symptoms 1, 2, 5.
Never assume HGH has a role in adult "anti-aging" or performance enhancement—its primary indication is pediatric growth hormone deficiency, and use outside documented GH deficiency lacks evidence 3, 4.