Human growth hormone

Mechanism of action

hGH binds to the GH receptor (GHR) on the cell membrane, inducing receptor dimerization and activation of the JAK2/STAT pathway (as well as MAPK and PI3K/AKT in specific contexts). Its effects include: (1) stimulation of IGF-1 synthesis (mainly in the liver, but also locally in tissues), which mediates many anabolic and growth-related actions; (2) increased lipolysis and reduced glucose oxidation in some tissues; (3) effects on protein metabolism with increased protein synthesis under selected conditions; (4) modulation of fluid and electrolyte balance with possible sodium and water retention. The GH–IGF-1 axis is regulated by negative feedback (IGF-1 and GH) and by nutritional factors (energy, protein, insulin).

Supported benefits

• Treatment of GH deficiency (children and adults): improved linear growth in children and improved body composition/selected metabolic parameters in adults with documented deficiency (strong)
• Increase in lean mass and reduction in fat mass in adults (including those without deficiency) in controlled studies; the increase in lean mass may partly reflect water retention in addition to tissue changes (moderate)
• Improved bone mineral density in GH deficiency treated long term (gradual effect, also mediated by IGF-1) (moderate)
• Improved athletic performance (strength/power/endurance) in healthy subjects: overall inconsistent results; some studies show limited improvements in anaerobic capacity, not in maximal strength (limited)
• Anti-aging/general well-being in eugonadal/eutrophic subjects without deficiency: evidence is not robust and the risk/benefit balance is unfavorable (limited)

Safety & side effects

• Fluid retention, peripheral edema, weight gain related to fluids
• Arthralgia, myalgia, stiffness, paresthesias
• Carpal tunnel syndrome
• Hypertension (also due to sodium/water retention) in some individuals
• Worsening glucose tolerance, hyperglycemia, increased risk of diabetes in predisposed individuals
• Headache; rarely benign intracranial hypertension (more often described in pediatric age)
• Gynecomastia (rare) and indirect endocrine alterations
• Injection-site reactions
• Possible increase in IGF-1 beyond the physiological range with potential proliferative implications (theoretical/context-dependent risk, especially relevant in the presence of neoplasms or predispositions)

FAQ

Are hGH and IGF-1 the same thing?

No. hGH is the pituitary hormone that, among its various actions, stimulates the production of IGF-1 (especially in the liver). IGF-1 mediates many growth and anabolic actions, but it has its own regulation and risk profile.

Does hGH really increase muscle strength in healthy adults?

The evidence shows increases in lean mass and reductions in fat mass, but improvements in maximal strength and performance are often absent or modest. Part of the increase in lean mass may depend on fluid retention.

Why doesn’t hGH work orally?

As a protein, it is degraded by gastric acid and proteolytic enzymes; it does not reach the circulation in active form. Effective formulations are parenteral in medical settings.

What are the main metabolic risks?

Reduced insulin sensitivity and increased blood glucose, with a possible increase in diabetes risk in predisposed individuals or those with risk factors.

Is hGH “anti-aging”?

There is no robust evidence that use in subjects without deficiency produces overall longevity or health benefits sufficient to justify the risks. Adverse effects (edema, pain, glycemic alterations) are relatively common in trials.

Exercise and sleep increase endogenous hGH: is that equivalent to administration?

No. Sleep and exercise modulate physiological pulsatile secretion within ranges regulated by the body. Exogenous administration alters the endocrine state and can push IGF-1 outside the normal range, with different risks.