“We believe the tens of thousands of people worldwide who are treated with growth hormones should be informed about this risk,” said corresponding study author Joël Coste, MD, PhD, of Paris Descartes University and AP-HP in Paris, France. “More research is needed to show whether the growth hormone treatment is the cause of this increased risk, but in the meantime parents and doctors should consider this association as they weigh their options for treatment.”
The study looked at children who took growth hormone treatment for short stature or growth hormone deficiency with no known cause. The study involved 6,874 people in France who were treated with recombinant growth hormone (not pituitary-derived growth hormone) and were born before 1990 and started treatment between 1985 and 1996. Researchers then followed up from 2008 to 2010 with health questionnaires and a review of medical records and checked death certificates for the cause of death for any participants who had died.
The average time between the start of treatment and the last follow-up was 17 years. Participants were an average age of 11 when they started the growth hormone treatment and took it for an average of 3.9 years. During the follow-up period, 11 of the participants had a stroke. Of those, eight people had hemorrhagic strokes, which involve bleeding in or around the brain. The strokes occurred at an average age of 24. Four of the people died as a result of the stroke. The rate of stroke in this group was then compared to the rate of stroke in two registries that collect information on strokes occurring in Dijon, France, and Oxford, United Kingdom. Those registries showed that the expected number of strokes in the group would have been between three and seven cases, rather than the 11 that occurred, making the people treated with growth hormone between 50 percent more likely and 3.6 times more likely to have a stroke than people of similar ages in the general population. A registry of children with small stature who were not treated with recombinant growth hormone would have been a better comparison group, but such a registry is not available. The results were stronger when looking at just hemorrhagic stroke, where about two cases would have been expected to occur, rather than the eight that did occur, making people treated with growth hormone three to more than four times more likely to have a stroke than those in the general population. Because the researchers were not able to collect all possible information on every participant, they used a statistical analysis to account for any stroke cases that were missed.
That analysis estimated that an additional five strokes may have been missed in the growth hormone group, and that people taking growth hormone were up to nine times more likely to have a hemorrhagic stroke than those in the general population. “There has been a long-running debate about the usefulness, ethics and cost of growth hormone treatment, especially for otherwise healthy children,” said Rebecca N. Ichord, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and a member of the American Academy of Neurology, who wrote an editorial accompanying the study. “These new results will likely intensify the debate. Doctors who prescribe growth hormone treatment will need to discuss this association, consider its strengths and weaknesses and weigh it in their recommendations. And people who have taken the therapy or start it should be informed about the signs of stroke, the importance of seeking treatment quickly and prevention strategies.” Coste noted that people who misuse growth hormone treatment to improve athletic performance or body building results should also learn about these findings. The study received specific funding from the French Ministry of Health, following funding from the French drug safety agency, the French National Institute of Cancer and Commission of European Communities. To learn more about stroke, please visit www.aan.com/patients.
The American Academy of Neurology, an association of more than 27,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.