Somatrem

Summary

Somatrem is a recombinant form of human growth hormone (methionyl‑hGH) that was developed as a biosynthetic alternative to pituitary‑derived GH. It was prescribed for children with growth hormone deficiency, Turner syndrome, and idiopathic short stature, but the product has since been withdrawn from the market. The drug was administered by subcutaneous or intramuscular injection to stimulate linear growth in pediatric patients.

Mechanism of Action

Somatrem binds to the growth‑hormone receptor on target cells, activating the JAK2‑STAT5 signaling cascade. This stimulates hepatic production of insulin‑like growth factor‑1 (IGF‑1) and promotes protein synthesis, cartilage growth, and bone elongation. The downstream effects increase growth velocity and improve body composition, mirroring the actions of endogenous pituitary growth hormone.

What the Research Shows

Clinical experience with somatrem is documented in several late‑1980s studies. A UK multicentre trial in 54 growth‑hormone‑deficient children gave 4 units three times weekly for one year; 42 participants showed >1.5 cm/year growth, while two‑thirds developed low‑titre antibodies that did not affect efficacy, and no adverse events were reported. In a 70‑patient Turner‑syndrome trial, somatrem (0.125 mg/kg three times weekly) increased growth velocity during the first year, with a modest decline in the second year but still above control rates; IGF‑1 levels rose, and adverse events were few. A 2004 review of idiopathic short stature noted modest final‑height gains with recombinant GH (including somatrem) and no clear safety signals at standard doses, though long‑term outcomes remain uncertain.

Reported Benefits

Evidence from controlled trials indicates that somatrem can produce clinically meaningful increases in growth velocity in children with growth‑hormone deficiency and Turner syndrome, with reported height gains exceeding 1.5 cm per year in the majority of responders. The drug also raises circulating IGF‑1, reflecting its anabolic activity, and was generally well tolerated in short‑term studies.

Limitations of the Evidence

The available data are limited to short‑term pediatric trials from the 1980s; long‑term efficacy, optimal dosing, and durability of height gains have not been fully established. Comparative data versus other recombinant GH products are sparse, and the product has been withdrawn, precluding contemporary use. Evidence for idiopathic short stature is indirect, derived from broader reviews rather than dedicated somatrem trials.

Safety Considerations

Short‑term studies reported no serious adverse events, though about two‑thirds of participants developed low‑titer antibodies against GH and the Escherichia coli expression protein; these antibodies did not appear to diminish growth response. Mild side effects such as injection site discomfort were not highlighted. Long‑term safety, including potential effects on glucose metabolism, tumor risk, or antibody‑mediated neutralisation, remains uncharacterised due to limited follow‑up.

How It Is Administered

Somatrem was supplied as a sterile recombinant protein for injection. It could be given subcutaneously or intramuscularly, typically at a dose of 0.125 mg/kg (approximately 4 units) three times per week. The formulation required refrigeration and reconstitution before administration.

Routes of Administration

Goals & Uses

• Growth hormone deficiency (adults)EndocrineHigh
• Increased lean body massBody CompositionModerate
• Reduction of body fatMetabolicModerate
• Chronic renal failure (pediatric)RenalModerate
• Growth hormone deficiency (children)EndocrineHigh
• Turner syndromeIndicationModerate
• Treatment of pediatric growth hormone deficiencyEndocrinology / GrowthHigh

Contraindications

• Active malignancyOncologyHighUse caution or avoid depending on agent and context
• Acute critical illnessCritical CareHigh
• Closed epiphysesSkeletalModerate
• Hypersensitivity to somatrem or excipientsAllergy/ImmunologyHigh
• Diabetic retinopathyOphthalmologyModerate
• Prader-Willi syndrome with severe obesity or respiratory impairmentGenetic SyndromeHigh
• Known hypersensitivity to somatrem or excipientsImmunologyModerate

Adverse Effects

• EdemaFluid BalanceUncommonSwelling from fluid retention
• Injection site reactionsLocalCommon
• Glucose intolerance/diabetes mellitusMetabolicUncommon
• Intracranial hypertensionNeurologicalRare
• Hyperglycemia / insulin resistanceMetabolic / EndocrineUncommon
• Slipped capital femoral epiphysisMusculoskeletalRare
• Antibody formation to somatremImmunologicalCommon

Drug Interactions

• Cytochrome P450-metabolized drugs (e.g., corticosteroids, sex steroids, anticonvulsants)Low
• InsulinModerateMay increase risk of low blood sugar
• GlucocorticoidsModerate
• PegvisomantHigh
• Insulin / antidiabetic agentsModerate
• Oral estrogenLow

Population Constraints

• Pediatric patientsAgeAbsolute
• Pregnant or lactating womenReproductiveAbsolute
• Patients with active proliferative diabetic retinopathyOphthalmologyRelative
• Patients with diabetes mellitusMetabolicRelative
• Pediatric patients with closed epiphysesGrowthRelative
• Patients with hypothyroidismEndocrineRelative

Regulatory Status

• European UnionUnapprovedNever marketed; somatropin used instead.
• United StatesWithdrawnApproved: Growth hormone deficiency (children), Growth hormone deficiency (adults), Turner syndromeApproval withdrawn in 2000s after somatropin became preferred.
• United KingdomUnapprovedNot available; somatropin is the licensed GH product.

FDA approved in 1985 as the first recombinant DNA-derived growth hormone; voluntarily withdrawn from the US market in 2004 by Genentech in favor of somatropin (Nutropin). Higher immunogenicity compared to native-sequence somatropin due to the additional methionine residue.

Evidence & Sources

• Present situation worldwide regarding the use and clinical experience of Somatonorm (somatrem)
  Journal ArticleModerateFlodh H1987-01-01T00:00:00.000000Z
• Growth hormone use in children with idiopathic short stature
  Journal ArticleModerateWeise KL, Nahata MC2004-01-01T00:00:00.000000Z
• Growth hormone for the treatment of growth failure in children
  Journal ArticleModerateHowrie DL1987-01-01T00:00:00.000000Z
• United Kingdom multicentre clinical trial of somatrem
  Journal ArticleModerateMilner RD, et al.1987-01-01T00:00:00.000000Z
• Results from the first 2 years of a clinical trial with recombinant DNA-derived human growth hormone (somatrem) in Turner's syndrome
  Journal ArticleModerateRosenfeld RG, et al.1987-01-01T00:00:00.000000Z

Frequently Asked Questions