Somatropin

Somatropin is the official medical name for laboratory-made human growth hormone: the same 191-amino-acid protein the pituitary gland at the base of the brain releases, grown in bacteria or cell culture instead of being extracted from human tissue. It is an approved prescription medicine in the EU and the US, sold as Genotropin, Norditropin, Humatrope, Omnitrope, NutropinAq, Serostim and Zomacton, and it is at the same time one of the most heavily marketed unapproved products on the internet, promoted for ageing, fat loss and muscle. This record covers the unmodified 191-amino-acid hormone only. The weekly long-acting versions are different molecules with their own official names and are not covered here: somapacitan (Sogroya), lonapegsomatropin (Skytrofa) and somatrogon (Ngenla), which the World Anti-Doping Agency lists separately as growth hormone analogues. Neither is somatrem, the 1985 version that carries one extra amino acid at the front and is named separately in US law. It is made this way because of what came before: until 1985 growth hormone was extracted from the pituitary glands of human cadavers, some of which carried the agent that causes Creutzfeldt-Jakob disease, an untreatable brain infection. 226 people worldwide developed it from contaminated growth hormone, and the cadaver product was withdrawn.

Sold as

Injection under the skin, daily in almost all approved uses.

Legal status in the EU

An approved prescription medicine across the EU. Omnitrope has been authorised EU-wide since 12 April 2006 and NutropinAq since 16 February 2001, alongside long-standing national approvals for other brands. The EU indications are narrow and named: in children, growth failure from growth hormone deficiency, Turner syndrome, chronic kidney disease, being born small for gestational age, and Prader-Willi syndrome; in adults, replacement therapy for pronounced growth hormone deficiency only. US labels add idiopathic short stature, Noonan syndrome, SHOX deficiency and HIV-associated wasting. Nothing to do with ageing, fat loss, sport or muscle is approved anywhere. The United States goes further than most: 21 U.S.C. § 333(e) — which names somatropin in its own definition — makes knowingly distributing human growth hormone for any human use other than an authorised disease or recognised medical condition an offence punishable by up to five years in prison, or ten if a minor is involved.

It docks onto the growth hormone receptor on cells all over the body and, above all, on the liver, which answers by releasing IGF-1 — the second messenger that does much of the actual growing. In children it acts on the growth plates, the strips of cartilage near the ends of the long bones, which is why it stops being able to add height once those fuse at the end of puberty. Throughout life it tells fat cells to release the fat they are storing and the body to hold onto nitrogen, the raw material of muscle protein, and it makes the kidneys retain salt and water. It also works directly against insulin, which is why it pushes blood sugar up.

Part of the bodyWhat happensHow it is knownKind of evidence

Growing bones, in children

This is the one thing it does that nothing else does. Growth hormone acts on the growth plates — the strips of cartilage near the ends of a child's long bones — and on the liver, which responds by releasing a second messenger called IGF-1 that does much of the actual growing. The child gets taller faster than they were getting taller before. It only works while those growth plates are still open, which is why the EU label bars it for growth in children whose plates have closed.

Measured against untreated comparison groups to full adult height. 154 girls with Turner syndrome were randomly assigned to growth hormone or no growth hormone and followed to the end of growing: final height 147.5 cm against 141.0 cm, a gain of 7.2 cm. 68 children with marked short stature and no hormone deficiency were randomly assigned to growth hormone or a placebo injection and followed for a mean 4.4 years: adult height was 3.7 cm greater on treatment.

Measured in people

Source [02]Source [04]Source [12]

Body fat and lean tissue

Growth hormone tells fat cells to release the fat they are storing and tells the body to hold onto nitrogen, which is the raw material of muscle protein. Fat mass goes down and lean mass goes up. The catch, and it is the central catch of this whole compound, is that total weight barely moves, because the two changes roughly cancel — and 'lean mass' as measured by a body scan includes the water the hormone makes people retain, not only muscle.

Pooled from 18 randomised comparisons in 220 healthy older adults who received growth hormone, against people who did not: fat fell 2.1 kg (95 per cent confidence interval 1.35 to 2.8 kg) and lean mass rose 2.1 kg (1.3 to 2.9 kg), while body weight changed by 0.1 kg, which is nothing. Separately pooled across 54 randomised trials of more than 3,400 adults with a confirmed hormone deficiency, against placebo: weight fell 2.31 kg, body fat fell 2.56 kg and lean mass rose 1.38 kg.

Measured in people

Source [05]Source [11]

Muscle strength, and what a person can actually do

Nothing, as far as anyone has been able to measure. This is the finding that separates growth hormone from the story told about it: the extra lean tissue does not turn into extra strength or extra endurance. Trials have measured knee strength, hand grip strength, treadmill endurance, cycling work output and maximum oxygen uptake, in older adults and in fit young ones, and the treated groups did not beat their comparison groups on any of them.

Measured in 52 healthy men over 69 randomly assigned to growth hormone or placebo for 6 months: lean mass rose 4.4 percentage points more than placebo and fat fell 12.8 percentage points more, and there was no statistically or clinically significant difference in knee strength, hand grip strength or endurance. Confirmed in 131 healthy adults aged 65 to 88 in a placebo-controlled trial, where strength did not increase significantly on growth hormone alone in either sex. Pooled across 27 randomised comparisons in 303 fit young people given growth hormone: lean mass rose 2.1 kg against those who did not get it, and strength and exercise capacity did not improve.

Measured in people

Source [06]Source [13]Source [16]

Blood sugar

Growth hormone works against insulin. It makes muscle and fat cells less willing to take sugar out of the blood, so blood sugar drifts up and the pancreas has to work harder to hold it down. In people already close to the line, that is enough to tip them into diabetes. The EU label tells doctors to watch anyone with diabetes, with borderline blood sugar, or with other reasons to be at risk, and to adjust their diabetes treatment when growth hormone is started.

Measured in a placebo-controlled trial of 131 healthy older adults: diabetes or glucose intolerance appeared in 18 of the men given growth hormone against 7 of the men who were not (P = 0.006). In the manufacturer's own extension studies of 3,031 adults on treatment, diabetes developed in 12 (0.4 per cent), all of whom already had a reason to be at risk. The EU label lists type 2 diabetes as an effect whose frequency cannot be estimated from the available data.

Measured in people

Source [02]Source [03]Source [13]

Water, and the swelling it causes

The kidneys hold onto sodium and water follows it. Hands and feet puff up, rings stop fitting, joints ache, and the tunnel of bone and ligament in the wrist that the main nerve to the hand passes through gets crowded — which produces the tingling, numbness and night pain of carpal tunnel syndrome. This is the most common thing growth hormone does to an adult, and it is dose-related: the EU label says these effects usually appear in the first months and settle on their own or when the dose is cut.

Measured against a placebo group in the manufacturer's six-month trials of 1,145 adults: swelling in 17.5 per cent on growth hormone against 5.1 per cent on placebo, joint pain 17.3 against 4.2 per cent, pain in the limbs 14.7 against 5.9 per cent, puffy ankles and hands 10.8 against 2.6 per cent, pins and needles 9.6 against 1.9 per cent, stiff limbs 7.9 against 1.6 per cent. In a separate placebo-controlled trial in healthy older adults, carpal tunnel symptoms appeared in 38 per cent of women on growth hormone against 7 per cent on placebo, and 24 per cent of men against none.

Measured in people

Source [02]Source [03]Source [13]Source [14]

The body under severe stress, in intensive care

Here the hormone does harm, and the harm was large enough to end that line of research. The idea was sound on paper — growth hormone slows the wasting of muscle that happens to people who are critically ill for weeks — but when it was tested, more of the people who got it died. It is now an outright contraindication in the EU label: people with complications after heart surgery, abdominal surgery, major accidents or sudden breathing failure must not be given it.

Measured in two parallel randomised, double-blind, placebo-controlled trials running at the same time in 532 adults who had already been in intensive care for 5 to 7 days. Deaths in hospital: 39 per cent on growth hormone against 20 per cent on placebo in the Finnish trial, and 44 per cent against 18 per cent in the multinational one. Among those who survived, growth hormone lengthened the time on a ventilator and the stay in hospital.

Measured in people

Source [02]Source [08]

Muscle and body weight in people wasting from HIV

In people losing weight and muscle because of untreated or poorly controlled HIV, growth hormone puts some of it back. This is a genuine approved use in the United States, granted on trials that measured weight, lean mass and physical work output rather than appearance, and it is the only adult use besides hormone deficiency for which US regulators have authorised distribution.

Measured in a 12-week randomised, double-blind, placebo-controlled trial of 178 people with severe HIV-associated wasting, of whom 140 completed and were analysed. Against placebo, weight rose 1.6 kg more and lean mass 3.1 kg more; median treadmill work output rose 13 per cent on growth hormone with no improvement in the placebo group. A second placebo-controlled trial enrolled 757 people.

Measured in people

Source [17]

Approved on randomised trials with real comparison groups. 154 girls with Turner syndrome were randomly assigned to growth hormone or to none; of the 104 who completed the protocol, final height was 147.5 cm against 141.0 cm, a gain of 7.2 cm (95% CI 6.0–8.4). 68 short children with no hormone deficiency were randomly assigned to growth hormone or to placebo injections, and of those, the 33 who were still in the trial at adult height were 3.7 cm taller on growth hormone (P < 0.02). Across 54 placebo-controlled trials in more than 3,400 adults with confirmed growth hormone deficiency, body fat fell 2.56 kg and lean mass rose 1.38 kg against placebo. Outside those uses the published record is the opposite of promising, and that is the point of this entry. Pooling 18 randomised comparisons in 220 healthy older adults, fat fell 2.1 kg and lean mass rose 2.1 kg against no treatment, while body weight (0.1 kg) and bone density did not change and strength, endurance and everyday function were measured too patchily across the trials to be pooled at all, and swelling, joint pain, carpal tunnel syndrome and breast tissue in men all became significantly more common — the reviewers concluded growth hormone cannot be recommended as an anti-ageing therapy. Pooling 27 randomised comparisons in 303 fit young people, lean mass rose 2.1 kg and strength and exercise capacity did not improve, with exercise lactate higher on growth hormone in 2 of 3 studies. In 532 critically ill adults randomised against placebo, 39 and 44 per cent died on growth hormone against 20 and 18 per cent on placebo, and the EU label now makes that group an outright contraindication. The 1990 New England Journal of Medicine paper the anti-ageing industry rests on gave growth hormone to 12 men and nothing at all to 9 others: it was neither randomised nor blinded, had no dummy injection, and measured no strength, endurance or function of any kind. The sequence above is the mature chain of UniProt P01241, residues 27–217, derived letter by letter; the long-acting analogues are excluded precisely because writing this sequence for them would describe a different molecule.

Three clocks, and confusing them is how this compound gets oversold. The molecule itself is fast: injected under the skin it peaks in the blood at about 4 hours and has a half-life there of about 3 hours, against about 0.4 hours when given straight into a vein — the difference is how slowly it leaves the injection site. Second, the side effects: the EU label says swelling, joint pain, stiffness and pins and needles arise within the first months of treatment and then settle by themselves or when the dose is cut. Third, the effects worth having. In body composition, 12 weeks was enough to show the full change in HIV-associated wasting and nothing more accumulated after that; in healthy older adults the pooled trials averaged 27 weeks. In children, the clock is years — the randomised trials that measured adult height treated children for a mean of 4.4 years, and the manufacturer's short-stature trial for a median of 5.7 years, of injections every day. And the window closes: once the growth plates fuse, somatropin cannot add height at any dose or duration, which is why the label bars it for growth after that point.

What was measuredWhat happenedIn whomHow it is known

How tall girls with Turner syndrome ended up

147.5 cm on growth hormone against 141.0 cm in the untreated group (P < 0.001) — a gain of 7.2 cm, with a range from 6.0 to 8.4 cm. Both groups were given the same standard sex-hormone treatment from age 13, so the difference is the growth hormone.

154 girls with Turner syndrome aged 7 to 13, randomly assigned to growth hormone six times a week or to no growth hormone, and followed until they stopped growing; 104 completed the protocol

Measured in people

Source [04]

How tall short children without a hormone deficiency ended up, against a placebo injection

Adult height was 0.51 standard deviations greater on growth hormone than on placebo — 3.7 cm (P < 0.02, range 0.10 to 0.92 standard deviations). Only 33 of the 68 children had adult height measured. In the manufacturer's separate open trial against untreated controls, the average gain was 9.8 cm in girls and 5.0 cm in boys after a median 5.7 years of daily injections, and 10 per cent of untreated children gained a full standard deviation of height anyway.

68 children aged 9 to 16 whose height or predicted height was at least 2.5 standard deviations below average, randomly assigned to growth hormone or placebo injections three times a week for a mean 4.4 years; and a separate open trial of 105 prepubertal children

Measured in people

Source [03]Source [12]

Fat and lean tissue in healthy older adults

Fat fell 2.1 kg (95 per cent confidence interval 1.35 to 2.8 kg) and lean mass rose 2.1 kg (1.3 to 2.9 kg) compared with people not given growth hormone. Body weight did not change: 0.1 kg, with a range from a 0.7 kg loss to a 0.8 kg gain (P = 0.87). Total cholesterol fell 0.29 mmol/l, and that difference disappeared once the change in body composition was accounted for. Bone density did not change.

220 healthy, overweight, community-dwelling older adults (mean age 69) who received growth hormone across 18 randomised comparisons — 107 person-years of treatment in total, mean 27 weeks each

Measured in people

Source [05]

Strength, endurance and everyday function in healthy older adults — the outcomes that decide whether the body-composition numbers mean anything

No difference. In 52 healthy men over 69 randomised to growth hormone or placebo, lean mass rose 4.4 percentage points more and fat fell 12.8 percentage points more on growth hormone, and there was no statistically or clinically significant difference in knee strength, hand grip strength or endurance. Side effects were not evenly matched: 26 men on growth hormone had 48 incidents against 14 incidents in 26 placebo recipients (P = 0.002), and 26 per cent of the growth hormone group needed the dose cut against nobody on placebo. In the 131-person placebo-controlled trial, strength did not rise significantly with growth hormone alone in either sex.

52 healthy men aged 70 to 85, 6 months; and 57 women and 74 men aged 65 to 88, 26 weeks

Measured in people

Source [13]Source [16]

Athletic performance in fit young people

Lean mass rose 2.1 kg (95 per cent confidence interval 1.3 to 2.9 kg) against people not given growth hormone, and strength and exercise capacity did not improve. Blood lactate during exercise — the marker of working anaerobically, which is a sign of doing worse, not better — was significantly higher on growth hormone in 2 of the 3 studies that measured it. Soft-tissue swelling and fatigue were more common on growth hormone. The reviewers' conclusion was that claims growth hormone enhances physical performance are not supported by the scientific literature.

303 lean, physically fit participants (mean age 27, mean maximum oxygen uptake 51 ml/kg/min) who received growth hormone across 27 randomised study samples — 13.3 person-years of treatment, mean 20 days each

Measured in people

Source [06]

How many critically ill adults died

39 per cent on growth hormone against 20 per cent on placebo in one trial, and 44 per cent against 18 per cent in the other, with both results at P < 0.001. The relative risk of death was 1.9 (95 per cent confidence interval 1.3 to 2.9) and 2.4 (1.6 to 3.5). Survivors on growth hormone spent longer on a ventilator and longer in hospital. The EU label now states the pooled figure as 42 per cent against 19 per cent and makes this group a contraindication.

532 adults already in intensive care for 5 to 7 days after heart surgery, abdominal surgery, multiple trauma or sudden breathing failure, treated until discharge from intensive care or for at most 21 days

Measured in people

Source [02]Source [08]

Body composition and quality of life in adults with a confirmed hormone deficiency — the approved adult use

Against placebo: weight fell 2.31 kg (95 per cent confidence interval 1.96 to 2.66 kg), body fat fell 2.56 kg (2.16 to 2.97 kg) and lean mass rose 1.38 kg (1.10 to 1.65 kg). The price was swelling, six times more likely than on placebo (relative risk 6.07, 4.34 to 8.48), and joint stiffness, four times more likely (4.17, 1.4 to 12.38). Body mass index and bone density did not change. Quality-of-life scores improved in 11 of the 16 trials that measured them, but the measures were too different from one another to be pooled into a single number.

More than 3,400 adults with confirmed growth hormone deficiency across 54 randomised placebo-controlled trials, of fair methodological quality

Measured in people

Source [11]

Weight, muscle and physical work in people wasting from HIV

Against placebo over 12 weeks, weight rose 1.6 kg more (P = 0.011) and lean mass 3.1 kg more (P < 0.001) on growth hormone, and median treadmill work output rose 13 per cent (P = 0.039) while the placebo group did not improve at all. Gains did not increase further beyond 12 weeks. Side effects in a placebo-controlled trial of this use ran at 36 per cent joint pain against 11 per cent on placebo, 30 per cent muscle pain against 12 per cent, and 26 per cent swelling against 3 per cent.

178 people with severe HIV-associated wasting, 140 analysed, 12 weeks; and a 510-person placebo-controlled trial for the side-effect figures

Measured in people

Source [14]Source [17]

Cancer, in people treated with growth hormone as children

No general sign of a cancer-causing effect. Risks were raised across several cancer sites, but that was largely second cancers in people who had been given growth hormone after cancer treatment. In people treated for growth failure without other major disease there was no clear raised risk — only bone and bladder cancer incidence was significantly raised. Cancer risk was unrelated to how long or how much growth hormone people had. The unexplained exception: among those treated after a previous cancer, the risk of dying of cancer rose with the daily dose (P for trend < 0.001).

23,984 people treated with recombinant growth hormone in childhood across eight European countries since 1984, compared against national cancer statistics

Measured in people

Source [20]

How many people were still alive decades after childhood treatment

Deaths ran 33 per cent above what the general French population would predict (standardised mortality ratio 1.33, 95 per cent confidence interval 1.08 to 1.64). The excess concentrated in those given the highest doses — above 50 micrograms per kilogram per day, mortality was nearly three times expected. Deaths from bone tumours and from bleeding in the brain were raised; deaths from cancer overall were not. This is a comparison against the general population, not against an untreated group with the same conditions, so some of the difference may belong to why the children were treated rather than to the treatment.

6,928 French children treated between 1985 and 1996 for isolated growth hormone deficiency, short stature or low birth weight, with vital status known for 94.7 per cent by September 2009

Measured in people

Source [21]

The 1990 study the entire anti-ageing industry is built on — what it actually reported

In the 12 men who received growth hormone for six months, lean mass rose 8.8 per cent, fat fell 14.4 per cent and bone density in the lower spine rose 1.6 per cent (each P < 0.05); skin thickness rose 7.1 per cent, which did not reach significance (P = 0.07). In the 9 men who received nothing, none of these changed. Three things about that comparison matter: the men were not randomly assigned, nobody was blinded, and the comparison group got no injection at all rather than a dummy one. And the trial measured no strength, no endurance and no function of any kind — only body composition, skin and bone density.

21 healthy men aged 61 to 81 with low IGF-1, of whom 12 received growth hormone three times a week for six months and 9 received no treatment

One small study

Source [07]Source [18]Source [19]

The common effects are all the body holding onto water. Measured against a placebo group in six-month trials of 1,145 adults: general swelling 17.5% vs 5.1%, joint pain 17.3% vs 4.2%, pain in the limbs 14.7% vs 5.9%, puffy hands and ankles 10.8% vs 2.6%, pins and needles 9.6% vs 1.9%, stiff limbs 7.9% vs 1.6%. Carpal tunnel syndrome reached 38% of women on growth hormone against 7% on placebo in one trial in healthy older adults, and 24% of men against none. The serious ones: new diabetes or glucose intolerance (18 men on growth hormone against 7 not on it, P = 0.006), raised pressure inside the skull, second tumours in people already treated for cancer, sudden death reported in children with Prader-Willi syndrome who have breathing problems or severe obesity, and death in the critically ill. It must not be given while any tumour is active, to children whose growth plates have closed, or to people with complications after major surgery, major trauma or sudden breathing failure. It is prohibited in sport at all times.

EffectWhat it feels likeHow often

Death, in people who are already critically illSerious

Two randomised placebo-controlled trials in 532 adults who had been in intensive care for at least five days both found the same thing. Nobody has established the mechanism. It is now an outright contraindication in the EU: people with complications after heart surgery, abdominal surgery, multiple injuries or sudden breathing failure must not be given somatropin.

39 per cent against 20 per cent on placebo in one trial and 44 per cent against 18 per cent in the other; the EU label states the pooled figure as 42 per cent against 19 per cent.

Source [02]Source [08]

Sudden death in children with Prader-Willi syndromeSerious

The reported deaths were in children who had one or more of: severe obesity, a history of breathing problems or sleep apnoea, or an unrecognised chest infection. Because of them the label requires that every child with this syndrome be checked for airway obstruction and sleep apnoea before treatment starts, that treatment be interrupted if snoring starts or worsens, and that treatment always be combined with a calorie-controlled diet.

Described in the EU label as rare cases reported after the medicine was on the market; no rate is given, and the label states no causal relationship has been demonstrated.

Source [02]

New diabetes, or blood sugar drifting into the pre-diabetic rangeSerious

Growth hormone directly opposes insulin, so the effect is expected rather than surprising. It matters most for people who are overweight, who have a family history of diabetes, or whose blood sugar was already borderline. The label tells doctors to test fasting blood sugar and insulin before starting in low-birth-weight children and every year afterwards, and to stop the drug if overt diabetes appears.

In a placebo-controlled trial of healthy older adults, 18 of the men given growth hormone developed diabetes or glucose intolerance against 7 of those who did not (P = 0.006). In the manufacturer's extension studies of 3,031 treated adults, 12 (0.4 per cent) developed diabetes, all with an existing reason to be at risk. The EU label lists type 2 diabetes with no estimable frequency.

Source [02]Source [03]Source [13]

Raised pressure inside the skullSerious

It shows as severe or repeated headache, vision problems, nausea and vomiting. The label tells doctors to look at the back of the eye for a swollen optic nerve, and to stop the growth hormone if they find one. What to do afterwards is not settled: the label says there is not enough evidence to advise on restarting, only that anyone restarted must be watched closely.

Listed as uncommon in children in the EU label — between 1 in 1,000 and 1 in 100 — and with no estimable frequency in adults.

Source [02]

A second tumour, in people who have already had cancerSerious

The most common second tumours in the label's description are tumours of the membranes covering the brain, in people who had radiation to the head for their first cancer. Somatropin is contraindicated outright while any tumour is active, and treatment must be stopped if a tumour is found to be growing.

Not given as a rate in the label. In the 23,984-person European cohort, raised cancer risks were largely second cancers in people given growth hormone after cancer treatment, and there was no clear raised risk in those treated for growth failure without other major disease.

Source [02]Source [20]

Leukaemia in childrenSerious

Cases have been reported since the 1980s in children with growth hormone deficiency treated with somatropin, with the older methionylated version, and with the pituitary-derived hormone that preceded both. Both the EU and US labels say the same thing: nobody has been able to conclude that the treatment caused them, and there is no evidence of raised risk in children without a predisposing factor such as radiation to the head.

Listed as uncommon in children in the EU label — between 1 in 1,000 and 1 in 100 — with the label's own footnote stating the rate appears similar to that in children without growth hormone deficiency.

Source [02]Source [03]

The growth plate at the top of the thigh bone slipping out of placeSerious

A child growing quickly can have the head of the thigh bone slip at its growth plate, which causes a limp and pain in the hip or knee and can need surgery. The label notes this already happens more often in children with hormone disorders than in other children, and says plainly that whether somatropin makes it more likely is unknown. Any child who limps during treatment is to be examined.

Reported in the EU label with no frequency given.

Source [02]

A severe allergic reactionSerious

Some somatropin products also contain benzyl alcohol as a preservative, which can itself cause allergic reactions; the EU label flags 9 mg of it per millilitre as an ingredient with a known effect. A known allergy to the hormone or to anything else in the injection is the label's first contraindication.

Not given as a rate. The US label reports serious whole-body allergic reactions, including anaphylaxis and swelling under the skin, from use after approval rather than from trials.

Source [02]Source [03]

Inflammation of the pancreasSerious

The label's instruction is to consider it in anyone on somatropin who develops abdominal pain, and it names children specifically. It is the kind of pain that does not settle and belongs in an emergency department rather than in a waiting list.

The EU label calls it rare and gives no number; the US label lists it among the reactions described elsewhere in the labelling.

Source [02]Source [03]

Swelling — puffy hands, feet and ankles

This is the single most characteristic thing somatropin does to an adult body. The hormone makes the kidneys hold onto salt and water follows. The EU label says these effects are usually mild to moderate, appear in the first months and settle on their own or when the dose is reduced — and that they get more likely with a higher dose and with older age.

Very common in adults in the EU label, meaning more than 1 in 10. Measured against placebo in 1,145 adults over six months: general swelling 17.5 per cent on somatropin against 5.1 per cent on placebo, and puffy ankles and hands 10.8 per cent against 2.6 per cent.

Source [02]Source [03]

Aching joints

Related to the same fluid retention. It shows up in the first months and generally settles or responds to a smaller dose. In the trials of growth hormone for HIV-associated wasting, joint pain was among the most common reasons people cut the dose or stopped: 36 per cent against 11 per cent on placebo.

Very common in adults in the EU label, meaning more than 1 in 10; common in children. Against placebo in 1,145 adults: 17.3 per cent against 4.2 per cent. In healthy older adults given growth hormone in a placebo-controlled trial: 46 per cent of women against 7 per cent on placebo, and 41 per cent of men against none.

Source [03]Source [13]Source [14]

Carpal tunnel syndrome — tingling, numbness and night pain in the hand

Retained fluid crowds the narrow tunnel in the wrist that the main nerve to the hand runs through. Of the 61 cases in the extension studies, 52 improved when the dose was cut or treatment paused and 9 needed surgery. Pins and needles more generally ran at 9.6 per cent against 1.9 per cent on placebo.

Common in adults in the EU label, meaning between 1 in 100 and 1 in 10. In a placebo-controlled trial of healthy older adults it was far more common than that: 38 per cent of women on growth hormone against 7 per cent on placebo, and 24 per cent of men against none. In the manufacturer's 3,031-patient extension studies, 61 people (2 per cent) developed it.

Source [02]Source [03]Source [13]Source [14]

Breast tissue developing in men and boys

It was one of the effects that showed up significantly more often on growth hormone than on no growth hormone in the pooled trials in healthy older adults, alongside soft-tissue swelling, joint pain and carpal tunnel syndrome.

Listed as uncommon in the EU label for both adults and children — between 1 in 1,000 and 1 in 100.

Source [02]Source [05]

The thyroid and the adrenal glands being quietly pushed off balance

Growth hormone converts more of one thyroid hormone into another, which can uncover an underactive thyroid in someone who was borderline; the label requires thyroid testing in everyone on treatment. It can also lower cortisol, the body's stress hormone, which can uncover an adrenal problem nobody knew about — and people already on steroid replacement may need their dose raised when somatropin is started.

Both listed in the EU label with no estimable frequency. Reduced blood cortisol is listed with its clinical significance stated as unknown.

Source [02]

Antibodies against the injected hormone

The label says the antibodies bind weakly and have not affected how fast children grow. It also says that anyone who stops responding for no other apparent reason should be tested for them. Preparations made in bacteria also carry traces of bacterial protein, and antibodies to those are found in a small number of people with no apparent consequence.

About 1 per cent of patients, stated directly in the EU label for this product.

Source [02]Source [03]

Reactions where the needle goes in, including dents in the fat

The US label lists pain or burning, scarring, lumps, rash, inflammation, changed skin colour, bleeding, and loss of the fat under the skin leaving a dent. This is a daily injection for years in children, so where it is given and how often the site is moved is not a small detail.

Injection-site reactions are common in children in the EU label — between 1 in 100 and 1 in 10 — and have no estimable frequency in adults.

Source [02]Source [03]

These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.

The approved paediatric doses in the EU product information, which differ by condition rather than by how much growth is wanted

Growth hormone deficiency 0.025–0.035 mg per kg of body weight per day; Prader-Willi syndrome 0.035 mg/kg/day, never above 2.7 mg a day; Turner syndrome and chronic kidney disease 0.045–0.050 mg/kg/day; short children born small for gestational age 0.035 mg/kg/day. Injected under the skin, daily.

Until the growth plates close; in the manufacturer's short-stature trial the median was 5.7 years of daily injections

Source [02]Source [03]

The approved adult dose for growth hormone deficiency. It is not a fixed amount: the label starts low and adjusts against a blood measure of IGF-1, the second messenger the liver releases in response

Adult-onset deficiency: start at 0.15–0.3 mg a day and increase gradually. Continuing from childhood: restart at 0.2–0.5 mg a day. Injected under the skin.

Open-ended; the placebo-controlled portions of the trials behind the approval ran 6 months, with open follow-on to 24 months

Source [02]Source [03]

Rudman 1990, the study the anti-ageing industry cites — 12 healthy men over 60 given growth hormone against 9 given nothing

About 0.03 mg per kg of body weight, injected under the skin three times a week

6 months, after a 6-month observation period

Source [07]

The randomised, double-blind, placebo-controlled follow-up work in healthy older adults, which measured strength and endurance as well as body composition

0.03 mg per kg three times a week against placebo in 52 men; and 30 micrograms per kg three times a week, reduced to 20, against placebo in 57 women and 74 men

6 months and 26 weeks respectively

Source [13]Source [16]

The pooled randomised trials in fit young people, which is the closest published literature to how growth hormone is used in gyms

Mean 36 micrograms per kg per day, with wide variation between studies (standard deviation 21)

Mean 20 days across the studies that gave it for more than a single day — 13.3 person-years of treatment in 303 people in total

Source [06]

The intensive-care trials, in which growth hormone was given at roughly twice the highest approved paediatric dose and more people died

Mean 0.10 mg per kg of body weight per day against placebo

Until discharge from intensive care or at most 21 days, in 532 adults

Source [08]

The US-approved use in HIV-associated wasting, which uses a much larger daily amount than the hormone-deficiency dose

0.1 mg per kg of body weight once daily at bedtime, up to 6 mg, injected under the skin

12 weeks in the placebo-controlled trials; the label notes gains did not increase further beyond that

Source [17]

What people report

• Whether growth hormone does anything for a healthy person that a healthy person would notice — every randomised trial that measured strength, endurance or everyday function found no difference against the comparison group
• How much of the 'lean mass' gained on growth hormone is muscle and how much is retained water — the body scans used in these trials cannot separate the two, and swelling is the drug's most common effect
• Whether taking it for ageing does anything over years — no study has ever assessed the long-term efficacy or safety of growth hormone as an anti-ageing treatment in humans, and of 815 registered somatropin trials, none mentions anti-ageing at all
• Whether treating short children who are not hormone-deficient makes any difference to their lives — the randomised trial measured centimetres, and the psychological measures it ran alongside found no difference in self-concept and only a trend in parent-reported behaviour
• Whether growth hormone helps a child with a genuine deficiency reach a normal adult height compared with no treatment — no placebo-controlled trial to adult height exists in that group, and none will ever be run
• Why more critically ill adults died on it — the effect was large and reproduced in two parallel trials, and the mechanism has never been established
• Whether the raised death rate decades after childhood treatment is caused by the treatment, by the dose, or by whatever the children were treated for — the French cohort was compared against the general population, not against untreated children with the same conditions
• Whether it raises the risk of cancer in people who never had one — the 23,984-person European cohort found no clear raised risk overall, an unexplained rise in bone and bladder cancer, and an unexplained dose-related rise in cancer deaths only among those treated after a previous cancer
• How often the serious effects actually happen — the EU label gives no frequency at all for raised pressure inside the skull in adults, for the hip growth plate slipping, for pancreatitis, or for type 2 diabetes
• Whether the quality-of-life improvement reported in adults with a hormone deficiency is real or a measurement artefact — it improved in 11 of 16 placebo-controlled trials, and the instruments were too different from one another to be pooled into a single number
• What the doses used outside medicine do, in either direction — the published trials in fit young people averaged 20 days of treatment, which tells you nothing about years of it
• What is actually in growth hormone bought outside a pharmacy — counterfeit product has been chemically analysed and prosecuted, but nobody has surveyed the grey market to say how much of it is real, weak, or something else entirely
• How it interacts with the anabolic steroids and insulin it is almost always taken with in gyms — in the one survey that asked, 95 per cent of hormone-using bodybuilders were also on steroids and 38 per cent on insulin, and no trial has ever tested that combination
• Whether the visible abdominal swelling attributed to growth hormone in bodybuilding has anything to do with growth hormone — it is widely asserted and has never been measured in a study of any kind
• What happens to people who take it continuously for decades — the longest randomised evidence is measured in years, and adults on replacement therapy stay on it indefinitely with no trial covering that span
• Whether pills, sprays and 'releasers' sold as HGH do anything at all — regulators state there is no reliable evidence that they do, which is not the same as evidence that they do not, and nobody has run the trial

Does somatropin actually work?

For what it is approved for, yes, and the evidence is unusually solid: girls with Turner syndrome randomly assigned to it ended up 7.2 cm taller than those who were not, and adults whose pituitary has stopped making the hormone lose about 2.6 kg of body fat and gain about 1.4 kg of lean tissue against placebo across 54 trials. For everything else it is sold for, the honest answer is that it was tested and it did not deliver. In healthy older adults it changed body composition and left strength, endurance, bone density and function exactly where they were.

Source [04]Source [05]Source [11]Source [16]

Is somatropin the same thing as HGH?

Yes. Somatropin is the official medical name for laboratory-made human growth hormone, and it is the same 191 amino acids in the same order as the hormone a human pituitary gland makes. HGH, hGH, human growth hormone, rhGH and growth hormone are all the same thing under different names. What is not the same thing: pills and sprays sold as 'HGH', which contain no growth hormone, and the newer weekly injections somapacitan, lonapegsomatropin and somatrogon, which are deliberately altered molecules with their own names.

Source [01]Source [10]Source [22]

What are the side effects of somatropin?

The common ones are all versions of the same thing: the body holds onto water. Against a placebo group in the manufacturer's own six-month trials of 1,145 adults, general swelling ran at 17.5 per cent against 5.1 per cent, joint pain at 17.3 against 4.2 per cent, pins and needles at 9.6 against 1.9 per cent, and stiff limbs at 7.9 against 1.6 per cent. Carpal tunnel syndrome — tingling and pain in the hand — reached 38 per cent of women on growth hormone against 7 per cent on placebo in one trial of healthy older adults. The serious ones are new diabetes, raised pressure inside the skull, and death in people who are already critically ill.

Source [02]Source [03]Source [13]Source [14]

Is somatropin legal?

As a prescription medicine for its approved conditions, yes, everywhere it is licensed. Outside those conditions the United States is unusual and strict: 21 U.S.C. § 333(e) makes it an offence to knowingly distribute human growth hormone — the statute names somatropin — for any human use other than a disease or recognised medical condition the Secretary of Health and Human Services has authorised, punishable by up to five years in prison, or ten if a minor is involved. That means distributing it for ageing, fat loss or sport is a crime rather than off-label prescribing. It is also prohibited in sport at all times, in and out of competition.

Source [09]Source [10]Source [14]

Can you buy somatropin?

Not legally without a prescription for an approved condition, and this register does not link to sellers. What is bought online falls into two categories, both bad. Pills, sprays and drops sold as 'HGH' contain no growth hormone and cannot — it is a protein and swallowing it digests it; the US Federal Trade Commission won up to $20 million in consumer redress against two sellers of exactly these and warned more than 90 other marketers. Injectable vials bought outside a pharmacy are unregulated: counterfeit growth hormone has been analysed in the laboratory and prosecuted, and nothing about an unlabelled vial tells you what is in it.

Source [14]Source [22]Source [23]

Can HGH make you taller as an adult?

No. Growth in height happens at the growth plates, strips of cartilage near the ends of the long bones, and once those fuse — which happens at the end of puberty — there is nothing left for growth hormone to act on. The EU product information puts this in the contraindications: somatropin must not be used for growth promotion in children whose growth plates have closed. In adults it will change body composition and make tissue swell, and none of that is height.

Source [02]Source [03]

Does HGH build muscle?

It builds lean mass on a body scan, and that is not the same as building muscle you can use. Pooling 27 randomised comparisons in 303 fit young people, growth hormone added 2.1 kg of lean mass against people who did not receive it — and strength and exercise capacity did not improve. Blood lactate during exercise, a sign of working harder for the same output, was significantly higher on growth hormone in two of the three studies that measured it, and swelling and fatigue were more common. The reviewers concluded that claims growth hormone enhances physical performance are not supported by the literature.

Source [06]Source [16]

Does HGH work for anti-ageing?

The whole idea rests on one 1990 study of 12 men who got growth hormone for six months and 9 who got nothing — not randomised, not blinded, no dummy injection, and measuring no strength, endurance or function at all. When the question was tested properly, the answer came back flat: across 18 randomised comparisons in 220 healthy older adults, fat fell about 2.1 kg and lean mass rose about 2.1 kg, weight did not change, bone density did not change, and swelling, joint pain, carpal tunnel syndrome and breast tissue in men all became significantly more common, with new diabetes and raised fasting blood sugar somewhat more common. The reviewers' verdict was that growth hormone cannot be recommended as an anti-ageing therapy. The journal that published the 1990 paper later criticised the industry built on it in print. Thirty-six years on, of the 815 clinical trials registered on ClinicalTrials.gov that use somatropin, not one mentions anti-ageing.

Source [05]Source [07]Source [19]Source [24]

Does somatropin help you lose weight?

It moves fat off the body without moving the number on the scales. In the pooled randomised trials in healthy older adults, fat fell 2.1 kg against people not given it while total body weight changed by 0.1 kg — because the lean tissue and retained water went up by about as much as the fat went down. In adults with a genuine hormone deficiency, weight did fall, by 2.31 kg against placebo. It is not approved for weight loss anywhere, and distributing it for that purpose in the United States is a federal offence.

Source [05]Source [09]Source [11]

Somatropin vs sermorelin, ipamorelin and MK-677 — what is the difference?

Somatropin is the hormone itself, injected. Sermorelin, ipamorelin and MK-677 are all attempts to make your own pituitary release more of it, which is a different and weaker proposition — and the register grades them far lower, because their studies mostly measured hormone levels rather than whether anything happened to a person. The regulator does not distinguish: the World Anti-Doping Agency's 2026 list bans growth hormone, its analogues and fragments in one clause and growth-hormone-releasing factors and secretagogues in the next. And note what the properly controlled evidence shows for the real hormone: extra lean mass, no extra strength. Anything that only raises your own growth hormone has that ceiling to work under, not a higher one.

Source [06]Source [10]

Is somatropin banned in sport?

Yes, at all times — in competition and out of it. The World Anti-Doping Agency's 2026 Prohibited List covers it at S2.2.3, "Growth hormone (GH), its analogues and fragments", which also names the weekly versions lonapegsomatropin, somapacitan and somatrogon, and the fragments AOD-9604 and hGH 176-191. The next clause, S2.2.4, separately bans everything that makes your body release its own.

Source [10]

Each letter represents one amino acid.

1. [01]UniProt P01241 (SOMA_HUMAN) — Somatotropin, Homo sapiens; signal peptide 1–26, mature chain 27–217, i.e. the 191 amino acids above
2. [02]European Medicines Agency — Omnitrope (somatropin), product information: section 4.1 indications, 4.3 contraindications, 4.4 warnings, 4.8 undesirable effects with frequency bands, 5.2 half-life; EU authorisation 12 April 2006 (2006)
3. [03]DailyMed — GENOTROPIN (somatropin), US prescribing information: Table 1 gives the adult adverse-event rates beside the placebo column (swelling 17.5% vs 5.1%, arthralgia 17.3% vs 4.2%), plus section 14.5 idiopathic short stature
4. [04]Impact of growth hormone supplementation on adult height in Turner syndrome: results of the Canadian randomized controlled trial (154 girls, 147.5 cm vs 141.0 cm untreated, gain +7.2 cm), J Clin Endocrinol Metab (2005)
5. [05]Liu H et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly (18 RCTs, 220 treated participants; fat −2.1 kg, lean +2.1 kg, weight and function unchanged), Annals of Internal Medicine (2007)
6. [06]Liu H et al. Systematic review: the effects of growth hormone on athletic performance (27 study samples, 303 treated participants; lean mass +2.1 kg, strength and exercise capacity not improved), Annals of Internal Medicine (2008)
7. [07]Rudman D et al. Effects of human growth hormone in men over 60 years old (12 treated, 9 untreated, not randomised, not blinded, no functional measures), New England Journal of Medicine (1990)
8. [08]Takala J et al. Increased mortality associated with growth hormone treatment in critically ill adults (532 patients; 39% vs 20% and 44% vs 18% in-hospital mortality), New England Journal of Medicine (1999)
9. [09]21 U.S. Code § 333(e) — prohibited distribution of human growth hormone; up to 5 years' imprisonment, 10 if a minor is involved; paragraph (4) defines the term as "somatrem, somatropin, or an analogue of either of them"
10. [10]WADA World Anti-Doping Code International Standard — Prohibited List 2026, S2.2.3 "Growth hormone (GH), its analogues and fragments", in the section prohibited at all times (in and out of competition) (2026)
11. [11]Hazem A et al. Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis (54 placebo-controlled trials, >3,400 adults with growth hormone deficiency; fat mass −2.56 kg and lean mass +1.38 kg against placebo), Eur J Endocrinol 2012;166(1):13-20 (2012)
12. [12]Leschek EW et al. Effect of growth hormone treatment on adult height in peak pubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial (68 randomised, adult height available for 33; +3.7 cm against placebo, P < 0.02), J Clin Endocrinol Metab 2004;89(7):3140-8 (2004)
13. [13]Blackman MR et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial (the source of the carpal tunnel and glucose-intolerance figures against the untreated arms), JAMA 2002;288(18):2282-92 (2002)
14. [14]Perls TT, Reisman NR, Olshansky SJ. Provision or distribution of growth hormone for antiaging: clinical and legal issues (2004 US prescription counts, and the carpal tunnel and diabetes rates as reported from Blackman 2002), JAMA 2005;294(16):2086-90 (2005)
15. [15]Brown P et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment (226 cases worldwide from cadaver-derived growth hormone), Emerging Infectious Diseases 2012;18(6):901-7 (2012)
16. [16]Growth hormone replacement in healthy older men improves body composition but not functional ability, Annals of Internal Medicine (1996)
17. [17]DailyMed — SEROSTIM (somatropin), US prescribing information, section 14 clinical studies, HIV-associated wasting or cachexia
18. [18]Can growth hormone prevent aging?, New England Journal of Medicine (editorial revisiting the 1990 paper) (2003)
19. [19]Inappropriate advertising of dietary supplements, New England Journal of Medicine (the journal's own response to how the 1990 paper was being used to sell products) (2003)
20. [20]Cancer risks in patients treated with growth hormone in childhood: the SAGhE European cohort study, Journal of Clinical Endocrinology and Metabolism (2017)
21. [21]Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study, Journal of Clinical Endocrinology and Metabolism (2012)
22. [22]FTC: bogus anti-aging claims for pills and sprays promising human growth hormone benefits (2005)
23. [23]Mass spectrometric analysis of innovator, counterfeit, and follow-on recombinant human growth hormone, Biotechnology Progress (2009)
24. [24]ClinicalTrials.gov API: 815 registered studies with somatropin as an intervention; the same query with the phrase "anti-aging" returns 0 (also 0 for "antiaging" and "anti-ageing"), checked 3 August 2026