Growth hormone (GH) is a protein secreted by the pituitary gland that regulates growth and metabolism. The hormone is central to development during childhood and continues to play a role in maintaining tissue and organ function in adults. Concerns about the safety of GH arise because its primary function is to stimulate cell growth and division, processes fundamentally linked to the development of cancer. This relationship has led to a question about whether therapeutic use of GH increases cancer risk, or if only pathological overproduction poses a threat.
The Biological Mechanism of Growth Hormone and Cell Proliferation
Growth hormone does not typically act directly on cells to cause proliferation; instead, it initiates a cascade that produces a potent growth factor. After GH is released into the bloodstream, it travels to the liver, where it stimulates the synthesis and release of Insulin-like Growth Factor 1 (IGF-1). This mechanism, known as the GH-IGF-1 axis, is the main pathway through which GH exerts its growth-promoting effects.
IGF-1 is a ubiquitous protein and a powerful mitogen, meaning it promotes cell division. Once released, IGF-1 binds to the Insulin-like Growth Factor 1 Receptor (IGF-1R) found on the surface of nearly all cell types. This binding activates multiple intracellular signaling pathways, including the MAPK and PI3K/Akt pathways, which regulate cell growth and survival.
The activation of these pathways leads to increased cellular proliferation and inhibits apoptosis (programmed cell death). By promoting growth and simultaneously preventing the natural removal of damaged or abnormal cells, the GH-IGF-1 axis creates a highly favorable environment for cell survival and unchecked division. This theoretical framework suggests that chronically elevated levels of IGF-1 could potentially act as a “fertilizer” for pre-existing or developing cancer cells.
Clinical Evidence: Growth Hormone Therapy and Cancer Risk
Extensive long-term studies have focused on the safety of therapeutic GH replacement, particularly in patients with growth hormone deficiency (GHD). The consensus from major international registries and meta-analyses is generally reassuring regarding the risk of developing a new, or de novo, cancer in patients without prior malignancy. For children treated with recombinant human GH due to GHD, there is no clear evidence that the therapy itself causes a rise in the incidence of new cancers compared to the general population.
However, the situation is more complex for individuals who have already survived a childhood cancer, such as those treated for acute lymphoblastic leukemia or brain tumors. Some studies have suggested a small, transient increase in the risk of secondary malignant neoplasms in these vulnerable populations, particularly for those who received cranial radiation. This potential risk is considered minor when compared to the risk factors related to the patient’s original cancer and the radiation treatment itself.
For adults with GHD, often due to pituitary tumors or their treatment, GH replacement therapy has also been studied for its effect on cancer recurrence. Current evidence indicates that GH replacement does not appear to increase the risk of recurrence or regrowth of the original tumor, including non-functioning pituitary adenomas and craniopharyngiomas. A consensus statement from the Growth Hormone Research Society concluded that the evidence does not support an association between GH replacement and the recurrence of primary tumors.
While the overall data is encouraging, caution remains necessary, and GH treatment is typically initiated only after a risk/benefit analysis for adult cancer survivors in remission. Monitoring of IGF-1 levels is a standard part of therapy, with the goal of keeping them within an age-appropriate range. GH replacement therapy is safe when administered under strict medical supervision and monitoring.
The Distinction: Naturally Elevated Growth Hormone and Cancer
The risk profile changes significantly when considering the chronic, pathological overproduction of GH, a condition known as acromegaly. Acromegaly results from a pituitary tumor that secretes uncontrolled, extremely high levels of GH, which in turn leads to persistently elevated IGF-1 concentrations over many years. This sustained, high-level exposure to the entire GH-IGF-1 axis is strongly associated with an increased risk of specific malignancies.
The most consistent and significant link is observed with colorectal cancer (CRC). Patients with acromegaly have been shown to have a two- to four-fold increased risk of developing adenomatous colonic polyps and colorectal cancer compared to the general population. This heightened risk is believed to result from the chronic, mitogenic stimulation of the intestinal epithelial cells by high levels of IGF-1.
Unlike the controlled, dose-limited, and monitored nature of therapeutic GH replacement, acromegaly involves a state of continuous biological overdrive. The uncontrolled nature of this excess growth signaling provides a clear example of how chronic, supraphysiological levels of GH and IGF-1 can promote carcinogenesis and tumor progression. This distinction is important because it separates the risks associated with a disease state from the risks of a carefully managed medical treatment.
The increased cancer risk in acromegaly highlights the underlying mechanism of the GH-IGF-1 axis as a driver of cell proliferation. Therefore, early screening for colorectal neoplasia is recommended for patients diagnosed with acromegaly to mitigate this distinct and elevated risk. Ultimately, the risk of cancer appears to be strongly correlated with the degree and duration of exposure to uncontrolled, high levels of GH and IGF-1.