S tier · elite
Approved by the FDA since 1987 across six distinct indications with a randomized-trial evidence base and a fully characterised label-level safety profile, it is the only compound in this set with regulatory-grade human data.
hgh 191aa
Somatropin is recombinant human growth hormone, structurally identical to the 191-residue mature pituitary hormone, and is approved in the United States for growth hormone deficiency and several defined growth disorders on the basis of randomized controlled trials. The evidence supporting those approved indications is strong, but the evidence for use in healthy adults seeking body-composition or anti-ageing effects is weak and is offset by consistently reported adverse effects.
the explanation
This is lab-made human growth hormone, the same protein the pituitary gland normally produces, manufactured in bacteria. Doctors prescribe it for specific conditions where the body does not make enough, and it is the only compound in this index with decades of proper clinical trial evidence behind it.
regulatory status
FDA-approved prescription biologic (US); non-medical distribution federally criminalised; prohibited in sport
Approved in the US since 1987, with labelled indications covering paediatric growth failure due to GH deficiency, Prader-Willi syndrome, small for gestational age, Turner syndrome, idiopathic short stature, and adult-onset or childhood-onset adult GH deficiency. Human growth hormone is not itself a Schedule III controlled substance under the Controlled Substances Act; instead 21 U.S.C. 333(e) makes it a federal offence to knowingly distribute or possess with intent to distribute hGH for any use in humans other than a disease or recognised medical condition authorised by the Secretary of Health and Human Services, punishable by up to 5 years imprisonment (10 years where a person under 18 is involved), with convictions treated as felony Controlled Substances Act violations for forfeiture purposes only. It is also prohibited in sport, and WADA maintains a dedicated hGH isoform immunoassay for detection.
how it works · proposed mechanism
Somatropin acts through a single cell-surface receptor to produce both indirect effects mediated by IGF-1 and direct metabolic effects on fat, liver and muscle.
Growth hormone receptor dimer
Somatropin binds a preformed growth hormone receptor homodimer at the cell surface and reorients it, apposing the two associated JAK2 kinases. This single event initiates essentially all downstream growth hormone signalling.
JAK2-STAT5b drives IGF-1
Activated JAK2 phosphorylates STAT5b, which enters the nucleus and transcribes IGF1 and IGFBP3, predominantly in the liver. Circulating IGF-1 mediates most of the growth-promoting and anabolic effects and serves as the clinical monitoring biomarker.
Direct metabolic counter-regulation
Independently of IGF-1, growth hormone stimulates adipocyte lipolysis and hepatic glucose output while antagonising insulin action in skeletal muscle. These direct actions explain the fluid retention and impaired glucose tolerance that appear as labelled warnings.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The strong evidence base belongs specifically to diagnosed growth hormone deficiency and a handful of paediatric growth disorders, and does not transfer to healthy adults pursuing body-composition or anti-ageing goals. In healthy older adults the pooled randomized evidence shows only about 2 kg of lean and fat mass shift alongside significantly increased soft-tissue oedema, arthralgia, carpal tunnel syndrome and gynecomastia, which is why the authors of that meta-analysis concluded growth hormone cannot be recommended as an anti-ageing therapy.
key published findings
- Human trial (non-placebo-controlled, n=21): Rudman et al. (NEJM 1990;323:1-6) reported an 8.8% increase in lean body mass, a 14.4% decrease in adipose tissue mass and a 1.6% increase in lumbar vertebral bone density over 6 months in 12 treated men aged 61-81 versus 9 untreated controls, with skin thickness up 7.1% (p=0.07) and IGF-I rising into the 500-1500 U/L range.
- Human trials (meta-analysis, 18 RCTs, n=508, mean age 68): Liu et al. (Ann Intern Med 2007;146:104-115) found lean body mass +2.13 kg (95% CI 1.32 to 2.94) and fat mass -2.08 kg (95% CI -2.80 to -1.35) with no significant weight change, alongside significantly increased soft-tissue oedema, arthralgia, carpal tunnel syndrome and gynecomastia; the authors concluded GH cannot be recommended as an anti-ageing therapy.
- Human trials (regulatory dataset): the Genotropin US label reports peripheral swelling in 17.5% and arthralgia in 17.3% of adults with GH deficiency during the first 6 months of treatment, with peripheral oedema, myalgia, paraesthesia and hypoaesthesia each occurring in 5% or more.
- Regulatory pharmacokinetics: the label gives a terminal half-life of 3.0 h after subcutaneous administration in GH-deficient adults versus 0.4 h intravenously, with approximately 80% of subcutaneously administered somatropin systemically available.
- Structural (human protein data): the mature GH1 chain is 191 residues (UniProt P01241, residues 27-217 of the 217-residue precursor), and residues 176-191 of that chain are exactly FLRIVQCRSVEGSCGF, the sequence marketed separately as 'HGH fragment 176-191'.
limitations of the evidence
- Nearly all high-quality randomized data derive from populations with diagnosed GH deficiency or defined paediatric growth disorders, so extrapolation to healthy adults is not supported by the trial base.
- The Rudman 1990 study most often cited to justify anti-ageing use was small (n=21), ran only 6 months, and used an untreated rather than placebo control group.
- Long-term neoplasia and cardiovascular outcomes in adults treated outside approved indications have not been characterised in controlled trials of adequate duration.
documented safety signals
- Fluid retention and peripheral oedema, reported in 17.5% of adults in label trials and significantly increased versus control in pooled elderly RCTs
- Arthralgia (17.3% in label trials), myalgia and stiffness of the extremities
- Carpal tunnel syndrome, significantly increased versus control in the pooled healthy-elderly RCT meta-analysis
- Impaired glucose tolerance, insulin resistance and new-onset diabetes mellitus (labelled warning)
- Gynecomastia, significantly increased versus control in the pooled elderly RCT meta-analysis
- Neoplasms, requiring monitoring per labelled warning
- Intracranial hypertension, pancreatitis, hypothyroidism, hypoadrenalism and lipoatrophy (labelled warnings)
- Contraindicated in acute critical illness per labelled warning
- Slipped capital femoral epiphysis and progression of pre-existing scoliosis in paediatric patients
identity
| full name | Somatropin (recombinant human growth hormone, 191 amino acids) |
| category | Growth Hormone |
| modality | protein hormone |
| molar mass | 22124 g/mol |
| cas | 12629-01-5 |
| half-life | Terminal half-life ~3.0 h after subcutaneous administration in GH-deficient adults and ~0.4 h after intravenous administration; subcutaneous bioavailability ~80% (Genotropin US prescribing information). |
| sequence | FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
laboratory handling
| storage | Supplied as a lyophilised powder; licensed somatropin presentations are stored refrigerated at 2-8 °C and protected from light, with in-use stability defined by each product's label. |
| solubility | Water-soluble as formulated with buffers and stabilisers; supplied lyophilised for reconstitution in the manufacturer-supplied diluent. |
| co-studied with | No controlled human trial evaluates somatropin in combination with any other compound in this index; combination claims have no published evidence base. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedDailyMed / US Food and Drug Administration · 2025 · official
United States Code (Cornell Legal Information Institute) · 2024 · official
UniProt Knowledgebase · 2025 · official
New England Journal of Medicine 323(1):1-6 · 1990 · peer-reviewed
Annals of Internal Medicine 146(2):104-115 · 2007 · review
Frontiers in Endocrinology · 2026 · review
others in Growth Hormone