Somatropin (HGH)

Somatropin is human growth hormone made by recombinant DNA technology: the same 191-amino-acid sequence as the pituitary hormone, which is what the "191AA" label refers to. Unlike everything else in this group, it does not persuade the pituitary to release growth hormone — it is the hormone.

Approved uses. Growth hormone deficiency in children and adults, and several other causes of short stature. A Cochrane review of idiopathic short stature found treated children reached an adult height about 3.7 to 7.5 cm above controls in the two trials that measured near-final height, with short-term gains of up to about 0.7 SD in a year — while noting that treated children still end up relatively short [1].

The anti-ageing claim. It starts with a 1990 New England Journal paper: 21 healthy men aged 61-81 with low IGF-1, 12 of whom received 0.03 mg/kg three times weekly for six months. Lean body mass rose 8.8%, adipose mass fell 14.4%, lumbar bone density rose 1.6%, and IGF-1 moved into the youthful range [4]. The paper is the origin of the anti-ageing industry around growth hormone, and it was small, unblinded, and measured no functional outcome at all.

The systematic review that followed is the more useful document. Eighteen study populations, 220 participants on growth hormone, mean age 69, mean dose 14 ug/kg/day, mean 27 weeks: fat mass down 2.1 kg, lean mass up 2.1 kg, weight unchanged, total cholesterol down slightly (not after adjusting for body composition), bone density unchanged, and significantly more soft tissue oedema, joint pain, carpal tunnel syndrome and gynaecomastia, with more impaired fasting glucose and diabetes. Its conclusion: growth hormone cannot be recommended as an anti-ageing therapy [2].

Athletic performance. The parallel review covered 27 study samples in fit people aged 13-45, at a mean dose of 36 ug/kg/day. Lean body mass rose 2.1 kg. Strength and exercise capacity did not improve; exercise lactate was higher in two of three studies measuring it; oedema and fatigue were more common. The conclusion was that claims growth hormone enhances physical performance are not supported [3]. A later meta-analysis of 11 placebo-controlled trials agreed: lean mass up, fat mass down, no change in muscle strength or maximum oxygen uptake, though anaerobic capacity rose in the single study that measured it [5].

Where it does seem to help outside deficiency. In men around 71 given growth hormone together with testosterone for 16 weeks, lean mass, strength and endurance all improved in a dose-related way, with the gains attributed mainly to testosterone and apparently enhanced by growth hormone [6]. An earlier randomised trial of growth hormone, testosterone or both in healthy elderly men reported the same direction of effect [7]. A 2024 systematic review of eight randomised trials in people over 65 with a specific illness — osteoporosis, frailty, heart failure, hip fracture, ALS, haemodialysis — found benefits on body composition, function and quality of life with mild dose-related side effects, while stressing how limited the evidence is [8].

Growth hormone binds its receptor on liver and peripheral tissue, raising IGF-1, which mediates most of the anabolic effects [4]. It is also directly lipolytic, which is why fat falls and free fatty acids and glycerol rise during exercise on treatment [5]. It is counter-regulatory to insulin, which is why glucose intolerance and new diabetes show up in the trials [2].

The gap between body composition and function is the interesting part. Lean mass measured by DXA rises reliably, but a large fraction of that is water: growth hormone causes sodium and fluid retention, which is the same mechanism behind the oedema and carpal tunnel syndrome [2]. That helps explain why 2 kg of extra "lean mass" produces no measurable strength [3].

Injected growth hormone also gives a flat exposure rather than the pulses the pituitary produces, which is the standard argument for using a secretagogue instead [9] — though the secretagogues have not produced better functional outcomes either.

Somatropin is the full 191-amino-acid protein, produced recombinantly — the "191AA" designation distinguishes it from older 192-amino-acid preparations that carried an extra methionine and were more immunogenic. It is given by subcutaneous injection; marketed concentrations from about 1.37 to 4 mg/mL were shown to be bioequivalent [10]. It needs refrigeration. Longer-acting versions, including PEGylated and Fc-fusion forms, are in development [11][12].

Fragments of this molecule are sold separately as their own compounds: HGH Fragment 176-191 and AOD-9604 are its C-terminal tail.

In healthy adults. The adverse events are consistent and dose-related: soft tissue oedema, joint pain, carpal tunnel syndrome and gynaecomastia were all significantly more common than in controls, and impaired fasting glucose and new diabetes were somewhat more common [2]. In young fit people, oedema and fatigue were the common problems [3].

Long-term. The best long-term data come from children treated for growth hormone deficiency. The SAGhE cohort followed 24,232 European patients for more than 400,000 patient-years. In low-risk patients — isolated growth hormone deficiency or idiopathic short stature — all-cause mortality was not significantly raised (SMR 1.1, 95% CI 0.9-1.3). Mortality was substantially raised in those whose underlying disease already carried risk, and was not related to growth hormone dose. Deaths from circulatory and haematological causes were increased across all risk groups [13]. A combined registry analysis reached broadly reassuring conclusions about long-term safety in treated children [14].

That evidence is about replacement doses in people who need them. It says nothing about the supraphysiological doses used for physique purposes, which have no long-term safety data at all [15].

Growth hormone and testosterone together produced larger gains in lean mass, strength and endurance in older men than either alone appeared to, though blood pressure rose in every group [6]. Growth hormone opposes insulin, so it worsens glycaemic control and can unmask diabetes [2]. No other interactions with compounds on this site have been documented.