Somatrem
Protropin and Somatonorm: what the extra methionine changed, what the 1980s trials found, and why the product is no longer sold
Somatrem is human growth hormone made in bacteria with one extra amino acid, a methionine, left on the front end. Sold in the US as Protropin from 1985 and in Europe and Japan as Somatonorm, it replaced growth hormone extracted from human pituitary glands after those extracts were linked to Creutzfeldt-Jakob disease. Trials in children with growth hormone deficiency and in girls with Turner syndrome showed it worked about as well as pituitary hormone, though more children made antibodies to it. Genentech stopped making Protropin at the end of 2002, and somatropin, which has the natural sequence, is what is used today.
Used in human trials: 0.125 mg/kg, Three times a week, Injection (route not stated in the abstract) (Study: Turner syndrome, 70 girls (randomised, US)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Somatrem is the growth hormone that made recombinant hormone treatment possible. Bacteria were given the human gene and made the hormone, but they start every protein with a methionine and did not trim it off, so the product had 192 amino acids instead of the natural 191. Genentech's version, Protropin, gained FDA approval in 1985 and was the company's first medicine; the same molecule was sold as Somatonorm in Europe and Japan, and Japan approved methionyl growth hormone in 1986.
Its timing mattered. Until then children with growth hormone deficiency were treated with hormone extracted from human pituitary glands. In 1984 the US stopped using those extracts after cases of Creutzfeldt-Jakob disease in people who had received them, and a 2022 history of treatment in Japan describes how recombinant hormone then took over. Somatrem was the bridge: an unlimited supply with no risk of carrying that disease.
The extra methionine raised the question of whether the molecule would behave differently. In rats and monkeys it did not: potency and pharmacokinetics matched hormone with the natural sequence, and a crossover study in healthy men found the two products bioequivalent on total exposure. In children an injection under the skin was absorbed slowly, with a peak around four hours later and an apparent half-life near three hours.
What did differ was antibodies. Many children on early batches made antibodies to growth hormone, more often than on pituitary hormone, though usually at low levels that did not slow growth. A few children with high-titre antibodies stopped growing and restarted when switched to another product. The developers later traced the problem to small amounts of altered hormone in the batches, not to the methionine itself, and added purification steps that lowered antibody rates.
Trials from the 1980s showed somatrem roughly doubled growth rates in previously untreated children with growth hormone deficiency, sped growth in girls with Turner syndrome and in children with chronic kidney failure, and raised growth in short children with normal hormone tests. Genentech stopped manufacturing Protropin at the end of 2002, and Drugs@FDA no longer lists it. Somatropin, with the natural sequence, is the growth hormone sold today, and its entry covers current products and doses.
Mechanism of Action
Somatrem acts as natural growth hormone does: it binds the growth hormone receptor, raising IGF-1 (somatomedin C), which drives growth, and it breaks down fat. The extra methionine did not change its potency.
Growth hormone receptor
Binding the receptor raises IGF-1 (somatomedin C), which drives growth at the long-bone growth plates; trials measured IGF-1 and somatomedin rising with treatment.
Fat breakdown
Within hours of an injection or infusion, free fatty acids rise as fat stores are broken down.
Feedback on the pituitary
Raised growth hormone quickly damps the pituitary's own release in response to GHRH.
Antibodies
Early batches provoked antibodies in many children; usually harmless, they slowed growth in a small number, and purer batches made fewer.
Published Research
These studies were read from their PubMed abstracts on October 29, 2026. Most are trials and case reports from the 1980s and early 1990s in children with growth hormone deficiency, girls with Turner syndrome and short children with normal hormone tests, plus pharmacokinetic and bioequivalence studies and the manufacturer's account of the antibody problem. Every card is a study of somatrem itself, under one of its names.
As effective as pituitary hormone in deficient children
Thirty-six children with growth hormone deficiency treated with methionyl growth hormone for up to four years went from growing 3.2 to 10.5 cm a year, matching ten children on pituitary hormone. Antibodies were more common than with pituitary hormone, but poor growth occurred only in the one child with high-titre, high-binding antibodies.
UK multicentre trial in untreated deficiency
Fifty-four previously untreated children were given somatrem by injection three times a week for a year; 42 grew more than 1.5 cm a year faster than before. About two thirds made antibodies to growth hormone and to E. coli proteins, at low and fluctuating levels that did not affect growth, and no adverse effects were seen.
Spanish multicentre trial
In an open 12-month trial in children with growth hormone deficiency, catch-up growth on intramuscular somatrem was greater in the younger group, bone age kept pace with age, and children already treated with pituitary hormone made antibodies less often than children new to treatment.
Switching from pituitary hormone, and three preparations
Across three small Spanish studies, switching adolescents from pituitary hormone to somatrem for a month changed none of the measures; untreated children caught up in growth; and antibodies to growth hormone and bacterial protein were low, with the later Somatonorm batch less antigenic than the first two preparations.
Double-blind comparison with pituitary hormone
In a randomised double-blind trial in 21 deficient children, growth on Somatonorm matched pituitary hormone over the six months that could be assessed before the pituitary product was withdrawn. In an open study of 14 more children, growth rose from about 3.3 to 7.1 cm a year, and half developed antibodies without clinical problems.
Japanese experience in pituitary dwarfism
Sixty-two Japanese children given methionyl growth hormone by intramuscular injection went from growing 3.5 to 8.2 cm a year on all three preparations used. Antibodies were frequent (76% at 12 months on the most purified batch), fell as purity improved, and slowed growth in only one patient.
National Cooperative Growth Study of Protropin
Nearly 2,000 US patients with growth hormone deficiency were enrolled and followed for up to a year. Most were boys, the average Protropin dose was 0.07 mg/kg three times a week, and growth response rose with dose up to 0.125 mg/kg three times a week.
Turner syndrome: first two years of a randomised trial
Seventy girls with Turner syndrome at 11 centres were randomised to no treatment, oxandrolone, somatrem 0.125 mg/kg three times a week, or both. Every treated group grew faster in year 1 than controls, IGF-1 rose on somatrem, side effects on somatrem alone were few, and oxandrolone caused mild virilisation.
Turner syndrome: three-year results
In the same trial, girls on met-hGH alone grew 6.6, 5.4 and 4.6 cm a year over three years against 3.8 cm for untreated controls in year 1, and those on met-hGH with oxandrolone grew 9.8, 7.4 and 6.1 cm. Predicted adult height rose 4.5 cm with met-hGH alone and 8.2 cm with the combination.
Glucose tolerance in the Turner trial
After a year on somatrem, glucose tolerance and insulin responses in girls with Turner syndrome were unchanged; oxandrolone raised the glucose response, and the combination raised both glucose and insulin responses. All groups showed predicted gains in final height.
Daily injections in Turner syndrome
Sixteen Dutch girls with Turner syndrome given somatrem 4 IU/m² every day grew 7.2 cm in the first year, up from 3.4 cm. The one girl with a weak response had high-binding-capacity antibodies, and the authors suggest daily injection explains why their results beat those of groups injecting less often.
Two-year Dutch results in Turner syndrome
In the same 16 girls, growth was 7.2 cm in year 1 and 5.3 cm in year 2 against 3.4 cm before treatment, bone age advanced 1.8 years in two years, predicted adult height rose, and the only adverse finding was antibodies to growth hormone.
Six months in Japanese girls with Turner syndrome
Twenty girls given met-hGH saw free fatty acids and somatomedin C rise after the first injections; over six months mean growth rose from 3.7 to 5.7 cm a year, more in 16 girls and less in four. Half had antibodies at six months, which did not blunt the growth effect.
Children with chronic kidney failure
Five boys aged about three to seven with chronic renal failure and short stature received somatrem three times weekly for six months; their growth rate roughly doubled from 4.9 to 10.1 cm a year, with no change in glucose tolerance and no other complications.
Short children with normal hormone tests
In a Dutch randomised trial of 30 short, slowly growing children whose growth hormone tests were normal, daily methionyl growth hormone raised growth by about 3 cm a year in the first year while controls did not change; doubling the dose in poor responders added about 1.9 cm a year, but bone age advanced in step, so the effect on final height was uncertain.
Daily beat three-times-weekly injections
Twenty newly diagnosed deficient children got the same weekly amount of methionyl growth hormone split into daily or three-times-weekly injections; the daily group grew faster at one and three months. Procollagen III peptide at one month tracked the six-month growth response.
Pharmacokinetics in deficient children
In the same 20 children, injected methionyl growth hormone was absorbed slowly, peaking about 4.4 hours after the dose, with an elimination half-life of about 3.0 hours after the first dose and 2.8 hours after several weeks. Exposure rose in proportion to dose and did not depend on the injection schedule.
Bioequivalent to natural-sequence somatropin
In a crossover study in 11 healthy men, Somatonorm and Genotropin (somatropin) injected under the skin met the criteria for bioequivalence on total exposure, with peak levels of 62.9 and 53.4 mIU/L reached at about 4.0 and 5.3 hours.
Twelve weeks in adults with deficiency
Six adults with confirmed growth hormone deficiency given somatrem for 12 weeks mostly said they felt better mentally and physically, but objective testing did not confirm it. IGF-1 rose in five and procollagen III peptide in all six, and no side effects were reported.
Short infusion blunts the pituitary's own response
In ten healthy adults, a three-hour met-hGH infusion raised free fatty acids sharply and cut the pituitary's growth hormone response to GHRH by about two thirds compared with saline, without changing insulin-like growth factors, insulin or glucose. Feedback can act within hours at levels like a natural growth hormone burst.
Growth stalled by antibodies, a case
A 10-year-old Japanese boy on Somatonorm grew normally for nine months, then almost stopped as anti-hGH antibodies reached a very high titre; switched to pituitary hormone, he grew 5.6 cm the next year. The authors note it was one of only three such cases then known.
Switching to methionine-free hormone restored growth
A boy whose growth on methionyl hormone failed because of neutralising antibodies was taken off treatment for seven months and then put on methionine-free recombinant hormone; he grew 14.9 cm in 11 months. The authors advise testing for antibodies when growth fails on treatment.
The developer's account of the antibody problem
This history of Protropin's development reports that extra purification steps lowered antibody formation both in a rhesus monkey model and in patients, that no safety problems followed from antibodies, and that growth was slowed by antibodies in under 0.1% of patients. The antibodies were traced to small amounts of subtly altered hormone, not to the methionine or bacterial proteins.
Dosing Data
Protropin is no longer made and no current label exists, so the amounts below are those given in the published trials carded above, as their abstracts state them. Units differ between studies: milligrams per kilogram in the US trials, international units (IU) in the European and Japanese ones.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Somatrem is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: injection (route not stated in the abstract), intramuscular, subcutaneous, subcutaneous or intramuscular). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Somatrem, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Somatrem stays intact once mixed.
How it is taken
As it was given in human studies: Injection (route not stated in the abstract) (Three times a week; Study: Turner syndrome, 70 girls (randomised, US)); Subcutaneous or intramuscular (Three times a week; Study: untreated growth hormone deficiency, 54 children (UK)); Intramuscular (Weekly total, schedule not stated; Study: pituitary dwarfism, 62 children (Japan)); Subcutaneous (Daily; Study: short stature with normal hormone tests, 30 children (Netherlands)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 3 hours (apparent, after a subcutaneous injection in children). After about five half-lives almost none is left.
How long the doses were given: Study: Turner syndrome, 70 girls (randomised, US): Three years reported; Study: untreated growth hormone deficiency, 54 children (UK): One year; Study: Turner syndrome, 16 girls (Netherlands): Two years reported.
When effects appear: unknown; no source on this page gives a time to effect for Somatrem. Results reported in the studies are under Published Research.
Source: half-life: PMID 2022713; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Antibodies to growth hormone in many children on early batches, usually low-level and without effect on growth (PMIDs 3310915, 3830068, 2870221); Growth slowed or stopped in a few children with high-titre antibodies, recovering on another product (PMIDs 3678156, 12014526); Antibodies to E. coli proteins from the manufacturing process (PMIDs 3310915, 3296638); Bone age advanced along with growth, so gains in final height were uncertain in short children with normal hormone tests (PMID 2809902); No specific side effects in the double-blind comparison with pituitary hormone (PMID 3296637), and none reported in the UK multicentre trial (PMID 3310915). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Somatrem. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Reported in the trials and case reports carded above”).
Interactions
Unknown: a PubMed search for human interaction studies of Somatrem (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Somatrem products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (FDA-approved in 1985 as Protropin, Genentech's first medicine). Sport: Prohibited at all times (S2.2.3).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Reported in the trials and case reports carded above.
Contraindications & Cautions
Somatrem is no longer made; these points are for readers comparing it with current growth hormone.
Legal Status
Somatrem was once approved in the US, Europe and Japan; it is no longer marketed in the US.
Frequently Asked Questions
?What is somatrem?
Recombinant human growth hormone with one extra methionine at its start, 192 amino acids instead of 191. It was sold as Protropin in the US and as Somatonorm elsewhere.
?Is somatrem the same as somatropin?
Nearly. Somatropin has exactly the natural 191-amino-acid sequence; somatrem has the extra methionine. Animal studies and a bioequivalence study in healthy men found no difference in potency or exposure.
?Is somatrem still available?
No. Genentech stopped making Protropin at the end of 2002, and Drugs@FDA no longer lists it. Growth hormone prescribed today is somatropin.
?Why did children make antibodies to it?
Many children on early batches made antibodies, more often than on pituitary hormone. The developers traced this to small amounts of altered hormone rather than to the methionine, and purer batches caused fewer. In under 0.1% of patients the antibodies slowed growth.
?What was it used for?
Mainly growth hormone deficiency in children. Trials also tested it in Turner syndrome, chronic kidney failure, short children with normal hormone tests, and adults with deficiency.
?How long does it last in the body?
In children an injection under the skin peaked after about four hours and had an apparent half-life of about three hours, reflecting slow absorption.
References
- [other] Genentech, approvals timeline (company page), read October 29, 2026: Protropin, Genentech's first medicine, FDA-approved in 1985; Protropin manufacturing discontinued at the end of 2002. https://www.gene.com/media/company-information/approvals-timeline
- [fda] US FDA, Drugs@FDA (openFDA): no record for somatrem or Protropin. Read October 29, 2026.
- [clinical-trial] Kaplan SL, et al. "Clinical studies with recombinant-DNA-derived methionyl human growth hormone in growth hormone deficient children." Lancet, 1986;1(8483):697-700. PMID: 2870221.
- [clinical-trial] Milner RD, et al. "United Kingdom multicentre clinical trial of somatrem." Arch Dis Child, 1987;62(8):776-9. PMID: 3310915.
- [clinical-trial] Vicens-Calvet E, et al. "Spanish multicentre trial on somatrem (1985-1986)." Acta Paediatr Scand Suppl, 1987;337:126-9. PMID: 3324633.
- [clinical-trial] Vicens-Calvet E, et al. "Clinical experience with somatrem in growth hormone deficiency." Acta Paediatr Scand Suppl, 1986;325:33-40. PMID: 3296638.
- [clinical-trial] Girard F, et al. "Clinical experience with Somatonorm." Acta Paediatr Scand Suppl, 1986;325:29-32. PMID: 3296637.
- [clinical-trial] Takano K, et al. "Treatment of pituitary dwarfism with methionyl human growth hormone in Japan." Endocrinol Jpn, 1986;33(5):589-96. PMID: 3830068.
- [clinical-trial] Sherman BM. "A National Cooperative Growth Study of Protropin." Acta Paediatr Scand Suppl, 1987;337:106-8. PMID: 3481174.
- [clinical-trial] Rosenfeld RG, et al. "Results from the first 2 years of a clinical trial with recombinant DNA-derived human growth hormone (somatrem) in Turner's syndrome." Acta Paediatr Scand Suppl, 1987;331:59-69. PMID: 3300157.
- [clinical-trial] Rosenfeld RG, et al. "Three-year results of a randomized prospective trial of methionyl human growth hormone and oxandrolone in Turner syndrome." J Pediatr, 1988;113(2):393-400. PMID: 3397807.
- [clinical-trial] Lippe B, et al. "Treatment of Turner's syndrome with recombinant human growth hormone (somatrem)." Acta Paediatr Scand Suppl, 1988;343:47-52. PMID: 3057808.
- [clinical-trial] Rongen-Westerlaken C, et al. "Methionyl human growth hormone in Turner's syndrome." Arch Dis Child, 1988;63(10):1211-7. PMID: 3196048.
- [clinical-trial] Rongen-Westerlaken C, et al. "Two-year results of treatment with methionyl human growth hormone in children with Turner syndrome. Dutch Growth Hormone Working Group." Acta Paediatr Scand, 1990;79(6-7):658-63. PMID: 2386058.
- [clinical-trial] Takano K, et al. "Treatment of Turner's syndrome with methionyl human growth hormone for six months." Acta Endocrinol (Copenh), 1986;112(1):130-7. PMID: 3521183.
- [clinical-trial] Lippe B, et al. "Accelerated growth following treatment of children with chronic renal failure with recombinant human growth hormone (somatrem): a preliminary report." Acta Paediatr Scand Suppl, 1988;343:127-31. PMID: 3057804.
- [clinical-trial] Wit JM, et al. "Effects of two years of methionyl growth hormone therapy in two dosage regimens in prepubertal children with short stature, subnormal growth rate, and normal growth hormone response to secretagogues. (Dutch Growth Hormone Working Group)." J Pediatr, 1989;115(5 Pt 1):720-5. PMID: 2809902.
- [clinical-trial] Kemp SF, et al. "Clinical and biochemical correlates of growth associated with short-term administration of methionyl growth hormone." Dev Pharmacol Ther, 1993;20(3-4):199-204. PMID: 7828454.
- [clinical-trial] Kearns GL, et al. "Single and multiple dose pharmacokinetics of methionyl growth hormone in children with idiopathic growth hormone deficiency." J Clin Endocrinol Metab, 1991;72(5):1148-56. PMID: 2022713.
- [clinical-trial] Wilton P, et al. "Bioequivalence of Genotropin and Somatonorm." Acta Paediatr Scand Suppl, 1987;337:118-21. PMID: 3481177.
- [clinical-trial] Degerblad M, et al. "Substitution therapy with recombinant growth hormone (somatrem) in adults with growth hormone deficiency." Acta Paediatr Scand Suppl, 1987;337:170-1. PMID: 3481181.
- [clinical-trial] Rosenbaum M, et al. "Short-term met-hGH infusion inhibits somatotroph response to growth hormone releasing hormone (1-44)." Metabolism, 1988;37(2):131-5. PMID: 3123873.
- [clinical-trial] Okada Y, et al. "A case report of growth attenuation during methionyl human growth hormone treatment." Endocrinol Jpn, 1987;34(4):621-6. PMID: 3678156.
- [clinical-trial] Pitukcheewanont P, et al. "Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone." J Pediatr Endocrinol Metab, 2002;15(5):653-7. PMID: 12014526.
- [review] Jones AJ. "The use of an animal immunogenicity model in the development of Protropin somatrem (methionyl human growth hormone)." Dev Biol (Basel), 2002;109:107-18. PMID: 12434920.
- [pubmed] Moore JA, et al. "Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine." Endocrinology, 1988;122(6):2920-6. PMID: 3371267.
- [pubmed] Tanaka T. "History of GH treatment in Japan." Clin Pediatr Endocrinol, 2022;31(1):1-9. PMID: 35002062.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Approval and discontinuation dates come from Genentech's approvals timeline and from Drugs@FDA (openFDA), read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.