Somatropin (recombinant human growth hormone) binds to dimeric GH receptors located within the cell membranes of target tissue cells. This interaction results in intracellular signal transduction and subsequent induction of transcription and translation of GH-dependent proteins including IGF-1 (Insulin-like Growth Factor-1), IGF BP-3 and the acid-labile subunit. Somatropin has direct tissue and metabolic effects that are either direct or mediated indirectly by IGF-1, including stimulation of chondrocyte differentiation and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis. [Citation: Humatrope Prescribing Information, Eli Lilly]

A comprehensive review from the Department of Kinesiology at McMaster University examined whether endogenous anabolic hormones (including GH and IGF-1) play a causal role in resistance exercise-induced muscle hypertrophy. The authors concluded: "The acute postexercise rise in systemic 'anabolic hormones' does not play a major role in stimulating muscle protein synthesis, leading to hypertrophy." Furthermore, "acute increases in anabolic hormones neither enhance muscle protein synthesis nor contribute to muscle hypertrophy with resistance exercise training." [Citation: Van Every DW, D'Souza AC, Phillips SM. Exercise and Sport Sciences Reviews. 2024;52(4):117-125]

A systematic review by Liu et al. examined the effects of growth hormone on athletic performance in healthy young adults. Key findings:
➜ Lean body mass increased - but this was largely due to fluid retention, not contractile muscle tissue
➜ No significant increase in muscle strength or power
➜ No improvement in aerobic exercise capacity (VO₂max)
➜ Basal metabolic rate increased - explaining some fat loss effects
A separate randomized controlled trial by Meinhardt et al. found a small increase in sprint capacity (anaerobic performance) but noted this effect was not maintained after six weeks of discontinuation. No improvements were seen in endurance, strength, or power. [Citations: Liu et al. 2008; Meinhardt et al. 2010; Physiopedia summary]

In a randomized, double-blind, placebo-controlled study of resistance-trained young men, participants received either rhGH (0.1 IU/kg/day) or placebo for two weeks. While IGF-I and P-III-NP (collagen markers) were markedly elevated in the GH group, the study found no effect of exercise on either marker. Notably, the GH-2000 discriminant function identified 4 of 8 subjects taking rhGH with no false positives - demonstrating that GH detection is possible but performance benefits remain questionable. [Citation: Velloso CP, et al. 2011; QxMD]

This comprehensive chapter in Contemporary Endocrinology concluded: "GH decreases fat mass and significantly increases lean body mass in young, healthy physically fit adults. However, fluid retention accounts for most of the increase in LBM induced by GH, rather than an increase in muscle mass." The authors note that improved body composition does not necessarily translate into improved strength or power, though anaerobic sprint capacity may show modest improvement. [Citation: Nelson AE, Ho K, Birzniece V. Growth Hormone Related Diseases and Therapy. Humana Press; 2011]

According to FDA prescribing information for somatropin, subcutaneous administration of 0.033 mg/kg in healthy volunteers resulted in increased median IGF-1 levels from 202 ng/mL (men) and 107 ng/mL (women) predose to maximal levels of 362 ng/mL (men) and 234 ng/mL (women) after a median of 21 hours (men) and 14 hours (women). This IGF-I elevation mediates many of GH's metabolic effects, including lipolysis and protein synthesis. [Citation: Humatrope Prescribing Information, Pharmacodynamics section]

While no published research has formally evaluated the athletic effects of combining GH with anabolic steroids, theoretical mechanisms include:
➜ Testosterone promotes greater muscle protein synthesis (myofibrillar contractile proteins)
➜ GH may exert anti-catabolic effects (reducing muscle breakdown)
➜ GH spares muscle glycogen while promoting fat oxidation, complementing androgen-driven muscle growth
➜ Insulin (often added to the "anabolic cocktail" in advanced protocols) may correct GH-induced hyperglycemia and enhance nutrient partitioning
However, side effects are likely worsened by co-administration, including myocardial hypertrophy, insulin resistance, and acromegaly-like changes. [Sources: Nelson et al. 2011; Iron Man Pharmacology]

Insulin resistance: GH excess impairs insulin signaling, leading to hyperglycemia and increased diabetes risk. This is particularly concerning when HGH is combined with high-carbohydrate diets or insulin use.
Cardiac changes: Acromegaly is associated with concentric cardiac hypertrophy, diastolic dysfunction, and increased risk of arrhythmias. Myocardial hypertrophy is likely worsened by co-administration of anabolic androgenic steroids [citation: Nelson et al. 2011].
Fluid retention: GH's antinatriuretic effects can cause significant edema, carpal tunnel syndrome, and joint pain - side effects frequently reported by bodybuilders using HGH.

What HGH DOES do (supported by evidence):
➜ Reduces fat mass - via increased lipolysis and metabolic rate [Meinhardt, Nelson, multiple RCTs]
➜ Increases lean body mass - but largely from fluid retention, not contractile protein [Liu meta-analysis]
➜ Elevates IGF-1 levels - mediating many metabolic effects [FDA prescribing info]
➜ May improve anaerobic sprint capacity - small effect, not sustained after discontinuation [Meinhardt 2010]

What HGH does NOT do (based on current evidence):
➜ Does not significantly increase muscle strength or power in healthy trained adults [Liu, Nelson, McMaster reviews]
➜ Does not enhance aerobic exercise capacity (VO₂max) [Nelson, Springer 2011]
➜ Does not directly stimulate muscle protein synthesis to a meaningful degree [Van Every, Phillips, 2024]

Significant risks documented in clinical literature:
➜ Insulin resistance and diabetes risk [Nature Reviews Endocrinology]
➜ Fluid retention, carpal tunnel syndrome, arthralgias [FDA labels, Nature]
➜ Acromegaly with long-term high-dose use (facial changes, organ enlargement, cardiomyopathy) [Nature]
➜ Potential increased malignancy risk (long-term, theoretical based on acromegaly data) [Nature]

Practical takeaway for bodybuilders: HGH is most valuable for fat loss, recovery, and connective tissue health - NOT as a primary muscle-building agent. For significant muscle growth, anabolic androgenic steroids are far more effective based on the strength of evidence. HGH should be viewed as an adjunct for cutting phases and recovery enhancement, not a substitute for androgens. The "anabolic cocktail" (GH + testosterone + insulin) carries significant risks that are likely synergistic (additive or multiplicative) and should only be considered by advanced users who understand and accept these risks.