NOT FOR HUMAN CONSUMPTION

191-aa Somatropin (recombinant human GH)  is the 191–amino-acid, 22-kDa recombinant human growth hormone (rhGH), identical to pituitary GH. After SC injection, it binds the GH receptor (GHR), activating JAK2–STAT5 and downstream IGF-1 production (hepatic and local). Results include anabolism (protein synthesis), lipolysis, bone remodeling, and fluid/electrolyte shifts. Daily somatropin remains the standard; long-acting GHs (e.g., somapacitan, lonapegsomatropin) are alternatives but are distinct products.

Additional Benefits of Somatropin Now Under Investigation

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

Somatropin → GHR dimerization → JAK2–STAT5/STAT3, MAPK/ERK, PI3K–Akt. Hepatic and local IGF-1mediates many anabolic effects; GH also exerts direct lipolysis (hormone-sensitive lipase), sodium/water retention(renal/RAAS), and anti-insulin actions acutely.

2.2 Down-stream Biology

3. Pharmacokinetics

• Route: SC (abdomen, thigh; rotate sites).

• Absorption/peak: C_max ~3–6 h post-SC; bioavailability ~70%.

• Half-life: Serum ~2–3 h (pharmacodynamic effects persist via IGF-1 ~18–24 h).

• Unit context: For somatropin, 1 mg ≈ 3 IU (brand labels may vary).

• Note on “15 IU”: 15 IU ≈ 5 mg total content. Daily use at this amount is supraphysiologic for most adults and increases adverse-event risk; clinical dosing is condition-, weight-, and IGF-1-target–dependent under specialist supervision.

4. Pre-clinical and Translational Evidence

4.1 Adult & Pediatric GHD

Placebo-controlled trials show body-composition, lipid, BMD, and QoL gains when titrated to age-adjusted IGF-1 Z-scores.

4.2 Metabolic & Hepatic

Improved hepatic steatosis and transaminases reported in selected NAFLD phenotypes; glycemic impacts require vigilance.

4.3 Musculoskeletal/Recovery

Enhanced collagen synthesis and tendon matrix organization noted; functional recovery depends on rehab plus nutrition.

Evidence quality note: Robust for GHD and approved indications; mixed for off-label athletic/body-composition goals due to metabolic side-effects and risk–benefit concerns at high doses.

5. Emerging Clinical Interests

6. Safety and Tolerability

• Common (dose-related): Peripheral edema, arthralgia/myalgia, paresthesias/carpal-tunnel-like symptoms, morning stiffness, headache, injection-site reactions.

• Metabolic: Insulin resistance, ↑ fasting glucose/HbA1c—risk rises with higher doses, age, adiposity.

• Cardiovascular/renal: Fluid retention may raise BP or worsen heart failure.

• Endocrine: Gynecomastia (rare), altered thyroid/adrenal labs (binding-protein shifts).

• Neurologic/ocular: Rare benign intracranial hypertension (papilledema), especially early or with dose jumps.

• Oncology: Contraindicated in active malignancy. In cancer survivors, use only with oncology/endocrine oversight; current data do not show increased de-novo cancer with physiologic replacement, but supraphysiologic exposure is avoided.

• Pediatrics-specific: Slipped capital femoral epiphysis, scoliosis progression—monitor growth and hip pain.

Contraindications/Cautions
Active malignancy, critical illness (post-major surgery/trauma/respiratory failure), proliferative/severe non-proliferative diabetic retinopathy, uncontrolled diabetes, severe OSA (caution), pregnancy/lactation (unless specifically indicated).

Comparative safety matrix

7. Regulatory Landscape

• Approved uses (vary by region): Pediatric/adult GHD, Turner syndrome, Prader–Willi (careful selection), chronic renal insufficiency, SGA failure to catch up, SHOX deficiency, AIDS wasting, short bowel (select contexts), idiopathic short stature (regional).

• Sport: WADA-prohibited (S2, peptide hormones); detection via isoform tests and biomarkers (IGF-1, P-III-NP).

• Formulations: Multiple brands/pens; IU↔mg labeling differs—verify brand-specific conversion (commonly 1 mg = 3 IU).

8. Future Directions

• Precision dosing: IGF-1 Z-score–based titration with CGM/lipid monitoring to minimize metabolic cost.

• Head-to-head with long-acting GH for glycemic neutrality, QoL, adherence, and BMD outcomes.

• Phenotype targeting: Low-IGF-1 NAFLD, sarcopenic obesity, and post-operative cohorts with standardized rehab.

• Biomarkers & imaging: DXA/MRI for body comp, MRI-PDFF for liver fat, tendon US/elastography for connective-tissue endpoints.

• Safety registries: Long-term CV, glycemic, oncologic surveillance, especially with real-world dose ranges.

Selected References

• Journal of Clinical Endocrinology & Metabolism; Endocrine Reviews — Adult/pediatric GHD diagnosis, dosing principles, outcomes.

• Osteoporosis International; Bone — BMD and bone-turnover responses to GH.

• Circulation; Atherosclerosis — Cardiometabolic risk markers under GH replacement.

• Hepatology; Liver International — GH/IGF-1 axis and NAFLD improvement signals.

• Medicine & Science in Sports & Exercise; Clinical Endocrinology — Exercise capacity, QoL changes in GHD on therapy.

• American Journal of Sports Medicine; Journal of Orthopaedic Research — Collagen synthesis/tendon biology with GH/IGF-1.

• NEJM; AIDS — HIV-related wasting and visceral adiposity indications.

• WADA/Drug Testing & Analysis — GH isoform/biomarker detection methods in sport.

Practical note (safety-first): Somatropin should be prescribed and titrated by an endocrinology specialist, targeting age-adjusted IGF-1 within the normal range while monitoring glucose, lipids, BP, edema, CTS symptoms, and fundoscopy when indicated. “15 IU” per day (~5 mg) is typically supraphysiologic for adults and raises complication risk—avoid fixed high-dose use outside a medical indication and supervision.