Compounds / GH secretagogues

Somatropin

Somatropin (recombinant human growth hormone, rHGH; 191-amino-acid polypeptide)

Recombinant human growth hormone: the actual hormone, not a secretagogue. Direct subcutaneous injection of 191-amino-acid polypeptide identical to pituitary-secreted human GH. FDA-approved since 1985 across multiple brands (Genotropin NDA 020280, Norditropin NDA 021148, Humatrope NDA 019640, Saizen NDA 019764, Omnitrope NDA 021426 (first US biosimilar 2006), Nutropin AQ NDA 020522). Long-acting variants: Sogroya (somapacitan, weekly), Skytrofa (lonapegsomatropin, weekly pediatric).\n\nCRITICAL REGULATORY: Off-label distribution of somatropin (anti-aging, athletic performance, body composition) is restricted under the Anabolic Steroid Control Act (21 USC 333(e)). Distribution outside on-label indications is a federal felony (Schedule III for distribution purposes). Personal use is not criminalized but procurement requires a prescription for an on-label indication. WADA banned for athletes.

At a glance

Half-life

~3 h IV terminal t½ ~20 min. SubQ varies by formulation: Genotropin ~3h, Humatrope ~3.8h, Norditropin ~7-10h, Nutropin AQ ~2.1h. Effect duration much longer than serum t½ because IGF-1 elevation persists 24h+. Long-acting variants (Sogroya, Skytrofa) measured in days.

Routes

SubQ · IM

Vial sizes

2 mg · 4 mg · 5.3 mg · 6 mg · 8.8 mg · 10 mg · 12 mg · 15 mg

Evidence base

3 studies 2 human · 1 review

Mechanism

Somatropin binds the GH receptor on hepatocytes, muscle, bone, adipose, and immune cells, triggering JAK2/STAT5 signaling. Primary downstream effect: hepatic IGF-1 production, which mediates most of the anabolic and growth-promoting effects. Foundational adult GHD trial: 6 months increased lean mass +5.5 kg and decreased fat mass -5.7 kg. Elderly men anti-aging trial: +8.8% lean mass, -14.4% fat mass, +1.6% lumbar BMD over 6 months. Despite body composition changes, GH alone does NOT improve athletic performance (strength, endurance) in healthy young adults. Increases bone mineral density, improves lipid profile, antagonizes insulin (reduced insulin sensitivity), causes sodium/water retention (edema, carpal tunnel symptoms common at start), stimulates T4 → T3 conversion, and modulates cortisol metabolism.

Dosing

Published evidence

1. Meta-analysis 2008

   Systematic review: the effects of growth hormone on athletic performance

   Liu H, Bravata DM, Olkin I, et al. Ann Intern Med

   Meta-analysis of 27 studies: GH alone does NOT improve athletic performance metrics (strength, endurance) in healthy young adults despite body composition changes. Widely cited evidence against GH-as-PED.

   PMID 18347346

2. Human RCT 1990

   Effects of human growth hormone in men over 60 years old

   Rudman D, Feller AG, Nagraj HS, et al. N Engl J Med

   Foundational anti-aging GH trial. 6 months rhGH in elderly men: 8.8% lean mass increase, 14.4% fat mass decrease, 1.6% lumbar bone density increase. Sparked the off-label anti-aging market.

   PMID 2355952

3. Human RCT 1989

   The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency

   Salomon F, Cuneo RC, Hesp R, Sönksen PH N Engl J Med

   Foundational adult GHD trial. 6-month rhGH therapy increased lean body mass 5.5 kg, decreased fat mass 5.7 kg vs placebo.

   PMID 2687691

Reported side effects

Edema / fluid retention

Very common Mild · Most prominent in first 4-8 weeks; usually resolves with dose adjustment. FDA label.

Arthralgia / myalgia

Common Mild · Joint pain, muscle aches; dose-dependent. FDA label.

Carpal tunnel syndrome

Common Moderate · From fluid retention; resolves with dose reduction. FDA label.

Insulin resistance / hyperglycemia

Common Moderate · Can precipitate T2D in susceptible patients. Monitor HbA1c. FDA label.

Headache

Common Mild · FDA label.

Increased nevi / moles

Occasional Mild · Pre-existing nevi may darken; new nevi formation reported. FDA label.

Increased intracranial pressure (pseudotumor cerebri)

Rare Serious · Headache + visual changes; requires immediate evaluation. FDA label.

Pancreatitis

Rare Serious · Reported in pediatric and adult GHD treatment. FDA label.

Hypothyroidism (worsening)

Occasional Moderate · GH may unmask central hypothyroidism; check TSH/T4 baseline + 4-8 weeks. FDA label.

Acromegaly-like features (long-term high dose)

Occasional Serious · Bone overgrowth, organomegaly, cardiomegaly with sustained supraphysiologic dosing (bodybuilder-range).

Theoretical malignancy risk

Theoretical Serious · IGF-1 is mitogenic; long-term effect on cancer risk debated. Considered contraindicated in active malignancy.

Interactions

• CJC-1295 (no DAC) Redundant

  CJC-1295 stimulates endogenous GH; somatropin IS GH. Combined use unnecessary and amplifies side effects.

• CJC-1295 (DAC) Redundant

  CJC-1295 with DAC sustains endogenous GH elevation; somatropin IS GH. Combined use produces supraphysiologic exposure with no incremental benefit.

• Ipamorelin Redundant

  Ipamorelin stimulates endogenous GH release; somatropin IS GH.

• Insulin Caution

  GH antagonizes insulin sensitivity; insulin requirements may increase, then drop unpredictably as GH effects evolve.

• Levothyroxine Caution

  GH increases T4→T3 conversion; can unmask central hypothyroidism.

• Glucocorticoids Caution

  GH may inhibit 11β-HSD1, increasing cortisol clearance; replacement glucocorticoid doses may need adjustment.

Reconstitution and storage

Most brands ship as cartridge for pen device (Genotropin, Norditropin, Humatrope, Saizen, Omnitrope): pre-loaded or with diluent cartridge. No user reconstitution needed for pen formulations. Vial format (Humatrope, Saizen vials, compounded HGH): reconstitute with sterile water for injection (FDA-recommended for some brands) or BAC water (off-label common practice). Typical: 5 mg vial + 1.5-2 mL diluent. Long-acting variants (Sogroya, Skytrofa) have brand-specific reconstitution.

Lyophilized: refrigerated 2-8°C; some brands stable at room temperature for limited periods. Reconstituted: refrigerated; use within 14-28 days depending on brand and diluent. AVOID FREEZING. Denatures protein.

Open the reconstitution calculator for Somatropin