Somatropin (Growth Hormone) and Cancer Risk: What the Studies Say
Few questions about growth hormone generate as much argument as cancer risk. The biology is plausible enough to take seriously, the registry data are largely reassuring for supervised treatment, and the position for non-medical use in healthy adults is essentially unstudied. Our editorial team sets out what the evidence actually supports.
The biological basis of the concern
Somatropin is recombinant human growth hormone, identical in sequence to the pituitary hormone. Most of its growth-promoting effects are mediated by insulin-like growth factor 1 (IGF-1), produced mainly in the liver in response to growth hormone signalling.
IGF-1 is a potent mitogen. It stimulates cell proliferation, inhibits apoptosis and promotes angiogenesis, which are precisely the processes that favour tumour development and growth. This is not a theoretical nicety: it is the mechanistic core of the concern.
Epidemiological support comes from observational studies in the general population. Pooled analyses, including work from the Endogenous Hormones and Breast Cancer Collaborative Group and large analyses in UK Biobank, have found associations between higher circulating IGF-1 and modestly increased risk of certain cancers, notably breast, prostate and colorectal.
Further indirect evidence comes from rare genetic conditions. People with Laron syndrome, who have growth hormone receptor deficiency and very low IGF-1, appear to have strikingly low rates of cancer and diabetes, as described by Guevara-Aguirre and colleagues. Conversely, acromegaly, a disease of growth hormone excess, has been associated with increased colorectal cancer incidence in several cohorts.
What treatment registries show in children
The largest body of safety data comes from paediatric growth hormone treatment, which has been monitored through industry and academic registries for decades, including KIGS, NCGS and the European SAGhE study.
SAGhE, which followed more than 24,000 patients treated in childhood across several European countries, has published analyses of cancer incidence and mortality. Overall cancer incidence was not clearly increased, although some analyses suggested a relationship between higher doses and specific outcomes, and the French arm reported increased all-cause mortality that other national arms did not replicate. Interpretation has been contested.
A consistent and important finding is that risk is concentrated in patients who already had a cancer predisposition. Children treated after a previous malignancy, and those with conditions such as Fanconi anaemia, Bloom syndrome or neurofibromatosis, show higher rates of second neoplasms. Growth hormone treatment in survivors of childhood cancer has been associated in some analyses with a modest increase in second tumours, particularly meningiomas after cranial irradiation.
Guidance from the Pediatric Endocrine Society and the Growth Hormone Research Society therefore distinguishes sharply between otherwise healthy children with growth hormone deficiency, where the data are reassuring, and children with predisposition syndromes or prior cancer, where caution and specialist oversight apply.
Meta-analyses of adult growth hormone deficiency treatment, including registry analyses from KIMS, have not demonstrated a clear overall increase in cancer incidence compared with the general population.
Where the evidence is weakest
All of the reassuring data come from one setting: treatment of diagnosed deficiency, at replacement doses, with regular monitoring of IGF-1 to keep it within the age-adjusted normal range. Every element of that description is absent in non-medical use.
No cohort study has followed healthy adults using growth hormone for physique or performance purposes over decades. There is therefore no dataset that answers the question people most often ask. Absence of evidence here is not evidence of safety; it reflects the fact that such use is unlicensed, unsupervised and unrecorded.
Non-medical use typically involves amounts intended to push IGF-1 above the normal range, frequently alongside anabolic steroids, insulin or thyroid hormone. Each of those alters the risk picture independently, and combinations have never been studied.
Product quality adds another layer. Analyses of illicit growth hormone products have found counterfeits, incorrect potency and non-sterile preparations, and some products sold as somatropin have contained nothing active.
| Setting | IGF-1 target | Monitoring | Cancer evidence |
|---|---|---|---|
| Childhood GH deficiency | Age-adjusted normal range | Specialist, long-term registries | No clear overall increase; caution in predisposition syndromes |
| Adult GH deficiency | Normal range | Endocrinologist, periodic IGF-1 | No clear increase in registry analyses |
| Cancer survivors | Normal range, individualised | Oncology and endocrinology jointly | Modest increase in second neoplasms reported |
| Acromegaly (disease) | Pathologically high | Specialist treatment to normalise | Increased colorectal cancer incidence reported |
| Non-medical use in healthy adults | Deliberately supraphysiological | None | No long-term data at all |
Other documented harms of non-medical use
Cancer risk is the headline question, but it is not the most immediate concern for someone using growth hormone outside medicine. The adverse effects reported in clinical trials and case series are considerable:
- Insulin resistance and diabetes: growth hormone is diabetogenic; impaired glucose tolerance and new-onset diabetes are documented.
- Fluid retention and carpal tunnel syndrome: common dose-related effects, sometimes requiring treatment.
- Arthralgia and myalgia: joint and muscle pain are frequently reported.
- Acromegalic changes: growth of the jaw, brow, hands and feet, and organ enlargement with prolonged excess.
- Cardiac effects: concentric cardiac hypertrophy is described in acromegaly and is a plausible consequence of sustained excess.
The Endocrine Society's statement on performance-enhancing drugs notes that growth hormone's effects on actual athletic performance are modest at best. Liu and colleagues' systematic review found increases in lean body mass, largely attributable to fluid, without convincing improvements in strength or aerobic capacity, alongside more adverse effects.
Somatropin is a prescription-only medicine in the UK, and it is prohibited at all times in sport. Supplying it without a prescription is unlawful.
Anyone using it who develops persistent headaches, visual changes, numbness in the hands, swelling, unexplained weight change or new lumps should seek medical assessment and disclose the use.
How clinicians manage the risk when treatment is indicated
In legitimate practice, the approach to cancer risk is systematic. Before treatment, a history of malignancy and any predisposition syndrome are established, and active malignancy is a contraindication.
During treatment, IGF-1 is measured periodically and the dose adjusted to keep it within the age-adjusted reference range rather than at the top of it. This is the single most important safety measure and the one entirely absent from non-medical use.
Patients are kept in routine population cancer screening programmes, and in the UK that means bowel, breast and cervical screening as appropriate for age and sex. Growth hormone treatment is not a reason to screen more intensively in the absence of specific risk factors, according to current guidance.
Survivors of childhood cancer receiving growth hormone are managed jointly between endocrinology and oncology, with surveillance tailored to their original diagnosis and treatment, particularly where cranial radiotherapy was involved.
Conclusions of the editorial team
The mechanistic concern about growth hormone and cancer is legitimate: IGF-1 promotes proliferation and inhibits cell death, and higher IGF-1 levels are associated with modestly increased risk of several cancers in population studies.
For supervised replacement therapy at physiological doses, decades of registry data do not show a clear overall increase in cancer incidence, with the important exception of patients who have a cancer predisposition or a previous malignancy.
For non-medical use in healthy adults at supraphysiological doses, often combined with other substances, there are no long-term data. Given the biology, that gap should be read as uncertainty rather than reassurance, and the documented short-term harms are substantial on their own.
Related reading from our team includes our articles on IGF-1 as a laboratory marker, on insulin misuse and its life-threatening risks, and on what the evidence shows about growth hormone and athletic performance.
References
- Carel JC, Ecosse E, Landier F, et al. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab. 2012;97(2):416–425.
- Swerdlow AJ, Cooke R, Beckers D, et al. Cancer risks in patients treated with growth hormone in childhood: the SAGhE European cohort study. J Clin Endocrinol Metab. 2017;102(5):1661–1672.
- Allen DB, Backeljauw P, Bidlingmaier M, et al. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol. 2016;174(2):P1–P9.
- Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3(70):70ra13.
- Liu H, Bravata DM, Olkin I, et al. Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med. 2008;148(10):747–758.
- Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
- Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346–1353.
