HGH (human growth hormone): what the trials show, the side effects and the law

Human growth hormone is the pituitary hormone that drives growth in childhood and continues, in adults, to regulate body composition, bone and metabolism, largely through insulin-like growth factor 1 (IGF-1) made in the liver. The licensed drug is somatropin, which the Genotropin label describes as a protein of 191 amino acid residues with a molecular weight of 22,124 daltons, produced by recombinant DNA technology in Escherichia coli, with an amino acid sequence identical to pituitary growth hormone ^[1]. The “191AA” in online listings of the HGH peptide refers to this full-length sequence; somatrem, an older 192-amino-acid version, is no longer marketed.

Before 1985, growth hormone was extracted from the pituitaries of cadavers, and some recipients later developed Creutzfeldt-Jakob disease from contaminated batches. Recombinant somatropin replaced it and has been a standard paediatric endocrine treatment ever since. In adults, replacement of proven deficiency became a licensed indication in the 1990s. Everything else, from anti-ageing clinics to gym use, is off-label or illegal, and the same molecule is bought on grey and black markets as Chinese-made vials, kits and pens of uncertain origin.

HGH sits at the centre of a family of products on this site. Sermorelin, tesamorelin and CJC-1295 are releasing-hormone analogues that make the pituitary secrete its own growth hormone; ipamorelin, GHRP-2 and GHRP-6 are secretagogues that act through the ghrelin receptor; HGH fragment 176-191 is a piece of the molecule sold for fat loss; and IGF-1 LR3 is a modified version of the hormone growth hormone works through. Our guide to what research peptides are explains the research label those products carry.

Growth hormone is secreted in pulses, mostly at night, under the control of growth hormone-releasing hormone and somatostatin from the hypothalamus and ghrelin from the stomach. It acts directly on fat cells to release fatty acids and on muscle and liver to raise IGF-1, which mediates most of its growth-promoting effects. The Genotropin label summarises the pharmacology in adults with deficiency: reduced fat mass, increased lean body mass, beneficial changes in lipid metabolism and normalisation of IGF-1 ^[1]. It also raises blood glucose by opposing insulin, which is the source of one of its main side effects.

After a subcutaneous injection, absorption is slow, which extends the drug’s presence in the body well beyond its intravenous half-life of about 0.4 hours; the Genotropin label gives a subcutaneous half-life of 3 hours in GH-deficient adults ^[1], and the Norditropin label estimates 7 to 10 hours ^[2]. Effects on IGF-1 last longer still, which is why daily dosing works and why weekly long-acting versions such as somapacitan have been developed: in a phase 3 trial in adults with deficiency, once-weekly somapacitan reduced truncal fat by 1.53 percentage points more than placebo at 34 weeks, with effects maintained to 86 weeks and a safety profile similar to daily growth hormone ^[13].

The claimed HGH benefits for healthy adults, less fat, more muscle, more strength, better skin, slower ageing, trace back to a single 1990 study. Daniel Rudman gave growth hormone three times a week for six months to men over 60 with low IGF-1 levels and reported an 8.8% increase in lean body mass, a 14.4% decrease in adipose tissue mass, a 1.6% rise in lumbar spine bone density and a 7.1% increase in skin thickness that did not reach significance ^[4]. The paper was published in the New England Journal of Medicine and has been quoted by anti-ageing marketers ever since, usually without the studies that followed.

A 2007 systematic review pooled 31 articles describing 18 study populations, 220 healthy elderly people in total, with a mean age of 69 and a mean treatment duration of 27 weeks. Growth hormone reduced fat mass by 2.1 kg and increased lean mass by 2.1 kg with no change in weight; bone density and most lipids did not change; and recipients were significantly more likely to develop soft-tissue oedema, joint pain, carpal tunnel syndrome and gynaecomastia, and somewhat more likely to develop diabetes or impaired fasting glucose ^[5]. A separate JAMA trial in healthy older women and men found lean mass gains of 1.0 kg in women and 3.1 kg in men on growth hormone alone, but strength did not increase significantly in either sex, oedema affected 39% of women on growth hormone against none on placebo, carpal tunnel symptoms 32% of men on growth hormone plus testosterone, and diabetes or glucose intolerance occurred in 18 growth-hormone-treated men against 7 untreated ^[8].

The Endocrine Society’s 2011 guideline draws the line where the evidence does: growth hormone therapy offers benefits in body composition, exercise capacity, skeletal integrity and quality of life in adults with confirmed deficiency, and confirmation by stimulation testing is usually required before treatment ^[9]. Nothing in that guideline supports treating normal ageing.

A 2008 systematic review, by the same group as the elderly review, pooled 44 articles describing 27 study samples, 303 young, lean and fit participants (mean age 27) given growth hormone at a mean dose of 36 micrograms per kilogram a day for a mean of 20 days. Lean body mass rose by 2.1 kg, but strength and exercise capacity did not seem to improve, lactate levels during exercise were higher, and recipients more often had soft-tissue oedema and fatigue. The authors concluded that claims that growth hormone enhances physical performance are not supported by the scientific literature, while noting that the doses studied may not reflect those used covertly by athletes ^[6].

The one controlled trial designed to find a performance effect was funded by WADA. Recreational athletes received growth hormone, placebo, and (in men) testosterone for eight weeks. Growth hormone reduced fat mass and increased lean mass, but the lean mass gain came from extracellular water rather than body cell mass unless testosterone was added. Sprint capacity on a bicycle rose by 3.9% overall and 8.3% in men given both drugs; endurance, strength, power and other measures did not change; and the sprint gain was gone six weeks after stopping ^[7]. That is the most positive performance finding in the controlled literature, and the authors called its athletic significance unclear.

The gap between this evidence and gym folklore is partly explained by dose and duration, which are far higher in illicit use than in any trial, and partly by combination with anabolic steroids and insulin. What the controlled data show is that HGH for bodybuilding at studied doses changes body composition modestly, mainly through water and fat, and does not make people stronger.

The US Genotropin label licenses somatropin for children with growth failure due to growth hormone deficiency, Prader-Willi syndrome, being born small for gestational age, Turner syndrome and idiopathic short stature, and for adults with adult-onset or childhood-onset growth hormone deficiency confirmed by testing ^[1]. The UK SmPC covers children with growth hormone deficiency, Turner syndrome, chronic renal insufficiency, small-for-gestational-age growth failure and Prader-Willi syndrome, and adults with pronounced deficiency of hypothalamic or pituitary origin, who should undergo a dynamic test to confirm the diagnosis ^[3]. Other brands carry additional indications, such as HIV-associated wasting and short bowel syndrome in the US.

The long-term safety of childhood treatment has been studied in the SAGhE cohort of 24,232 patients treated across eight European countries, with more than 400,000 patient-years of follow-up. In low-risk children with isolated deficiency or idiopathic short stature, all-cause mortality was not significantly increased (standardised mortality ratio 1.1), mortality was not related to dose, and the increased mortality seen in higher-risk groups tracked the underlying diagnosis rather than the drug, although deaths from circulatory and haematological diseases were raised in all groups ^[10]. The cancer analysis did not generally support a carcinogenic effect, but flagged possible signals for bone and bladder cancer and Hodgkin lymphoma, and a dose-related rise in cancer mortality in patients treated after a previous cancer, for further study ^[11].

None of this is evidence about adults with normal pituitary function using black-market vials at several times the replacement dose. The trials of that population are the ones described above, and they are short.

In the controlled studies, body-composition changes were measured after weeks to months: 20 days on average in the athlete review ^[6], eight weeks in the WADA-funded trial ^[7], 27 weeks on average in the elderly review ^[5], and six months in Rudman’s study ^[4]. Fluid retention and joint symptoms tend to appear early; the Genotropin label describes the fluid-retention events in adults as reported early in therapy and usually transient or responsive to dose reduction ^[1]. In children, growth velocity is assessed over 6 to 12 months. There is no evidence for effects within days, and the sprint-capacity gain in the WADA trial had disappeared six weeks after the drug was stopped ^[7].

Reported for information; none of these figures is a recommendation, and none can be applied to a vial of unknown content. The US Genotropin label gives two approaches for adults with deficiency: a non-weight-based start of about 0.2 mg a day (range 0.15 to 0.30 mg), increased every one to two months in steps of 0.1 to 0.2 mg a day; or a weight-based start of not more than 0.04 mg/kg a week, increased to not more than 0.08 mg/kg a week at four- to eight-week intervals, with the dose adjusted to IGF-1 levels and side effects ^[1]. Paediatric doses are higher per kilogram: 0.16 to 0.24 mg/kg a week for growth hormone deficiency, up to 0.48 mg/kg a week for children born small for gestational age ^[1].

The research doses in healthy adults were of the same order or larger: a mean of 14 micrograms per kilogram a day in the elderly studies ^[5] and 36 micrograms per kilogram a day in the athlete studies ^[6], which for an 80 kg man is roughly 1.1 mg and 2.9 mg a day respectively. Online HGH dosage protocols are usually written in international units; the conversion is 3 IU per milligram, so 2 IU is about 0.67 mg and 4 IU about 1.3 mg. The peptide calculator converts an HGH vial labelled in IU or milligrams into syringe units, but only a laboratory assay can say whether a black-market vial contains the stated amount, or growth hormone at all.

Licensed somatropin is a subcutaneous injection, supplied as freeze-dried powder in two-chamber cartridges (Genotropin) or as ready-to-use solution in pens (Norditropin), in strengths from 0.2 mg to 12 mg or more ^{[1] [2]}. Long-acting weekly forms, somapacitan, somatrogon and lonapegsomatropin, are now licensed for some indications. Growth hormone is a 22 kDa protein: it is not absorbed by mouth, and oral “HGH releasers”, sprays and homeopathic products sold as growth hormone contain either none or an irrelevant quantity. Grey-market growth hormone injections come as 10 IU vials in kits of ten, sometimes in pens, with brand names and colour-coded caps that are not evidence of anything.

In 1,145 adults with deficiency in Genotropin trials, most adverse events were mild to moderate fluid retention: peripheral swelling, joint pain, pain and stiffness in the limbs, oedema, muscle pain, tingling and numbness, reported early and tending to be transient or responsive to dose reduction ^[1]. The label’s warnings cover the same ground and more: impaired glucose tolerance and diabetes, which may be unmasked and need monitoring; intracranial hypertension; fluid retention including carpal tunnel syndrome, especially in adults; serious hypersensitivity; low cortisol in people with pituitary disease; hypothyroidism that may first become evident on treatment; and, in childhood cancer survivors treated with cranial radiation, an increased risk of a second tumour, particularly meningioma ^[1].

Somatropin is contraindicated in acute critical illness, in active malignancy, in active diabetic retinopathy and in children with Prader-Willi syndrome who are severely obese or have severe breathing problems, because of reports of sudden death ^[1]. The systematic reviews in healthy people confirm the pattern the label predicts: oedema, arthralgia, carpal tunnel syndrome, gynaecomastia and new diabetes or impaired fasting glucose in older adults ^{[5] [8]}, and oedema and fatigue in young athletes ^[6]. Long-term high-dose use in bodybuilders adds the risk of acromegalic changes, which the labels describe as the known effects of excess growth hormone, and is not studied in any trial.

Black-market vials carry risks of their own. The product may be under-dosed, mislabelled or a different substance altogether, and a 2005 JAMA analysis of anti-ageing growth hormone provision noted that the drug was being sold and prescribed for indications for which its distribution is illegal in the US, without evidence of benefit and with known harms ^[14]. A sterile 22 kDa protein is also difficult to make and store, so contamination and denatured product are realistic possibilities for anything without a pharmaceutical supply chain.

Somatropin is a prescription-only medicine in every market PepFinder covers. In the US it has a criminal provision of its own: under 21 USC 333(e), it is a crime to distribute human growth hormone, or to possess it with intent to distribute, for any use in humans other than the treatment of a disease or condition authorised by the FDA and prescribed by a physician, with penalties of up to five years in prison ^[15]. This is the rule Perls and colleagues described in JAMA as making anti-ageing provision of growth hormone illegal ^[14]. It applies to somatropin itself, not to the releasing peptides; the US legal status page draws that distinction.

In the UK, somatropin, somatrem and somatotropin are Class C controlled drugs under Part III of Schedule 2 to the Misuse of Drugs Act 1971, alongside anabolic steroids and HCG ^[16]. Supply and import for supply are offences; the UK legal status page explains how possession is treated. Rules for Canada, Australia and Europe differ again. Growth hormone is prohibited at all times under section S2.2.3 of the WADA Prohibited List, which also names its analogues (lonapegsomatropin, somapacitan, somatrogon) and fragments (AOD-9604 and hGH 176-191) ^[17]. Anti-doping laboratories detect it by the isoform test, which distinguishes recombinant 22 kDa growth hormone from the mixture of isoforms the pituitary makes, and by biomarkers such as IGF-1 and collagen peptides ^[12].

A vial sold as “HGH 191AA” for research is not a licensed medicine anywhere, is not made under a marketing authorisation, and is not covered by the safety data on this page.

Genotropin powder is stored refrigerated at 2 °C to 8 °C until its expiry date, protected from light and never frozen; after reconstitution the cartridge is kept refrigerated between uses for up to 28 days and then discarded, and it must not be shaken ^[1]. Norditropin pens are likewise refrigerated before first use, with product-specific in-use periods after that ^[2]. A protein this size unfolds with heat and agitation and loses activity, so a vial that has travelled unrefrigerated from an overseas seller has an unknown history. Our guides to storing peptides and bacteriostatic water cover reconstitution and storage for research-grade powder.

PepFinder does not sell growth hormone, and in the UK and US the sale of somatropin outside a prescription is unlawful. Our HGH price comparison, with UK and US listings, exists to show what research-labelled vendors charge and which of them publish testing. For HGH, the tests that matter are identity and quantity by a validated protein assay and a check of dimer and aggregate content, since degraded growth hormone is both less active and more likely to provoke antibodies; a mass-spectrometry identity check alone does not measure potency. Our guides to reading a peptide COA and third-party peptide testing explain what to look for, the third-party tested list shows who publishes results, and how to spot a fake peptide supplier covers the warning signs, of which HGH for sale without a prescription is one.