Little is known about the long-term effects of human growth hormone. Research is scant — and while some doctors feel confident there will be few long-term issues, others fear we could be putting kids at risk for health complications. Is the worry warranted, or are fears more reflective of anti-hormone hype?
Before 2003, parents needed proof of a growth hormone deficiency or related medical condition to get human growth hormone (HGH) treatments for their children, but now, doctors can prescribe them to kids who are simply really, really short, even if it it’s unclear why. Researchers suspect there could be some negative psychological effects as well.
Just over a decade has passed since the U.S. Food and Drug Administration expanded the pool of children eligible to receive human growth hormone treatments by approving the new indication “idiopathic short stature,” which means that a child isn’t growing as expected, but doctors can’t find any clear cause for the stunted growth.
In 2003, studies suggested these kids could add an extra 2 to 3 inches beyond their otherwise projected height with little risk of side effects. Now that one generation of children has had access to the treatment, more data exist to investigate side effects and outcomes. Although researchers have learned a little bit more since 2003, long-term outcomes are still the least understood. One thing hasn’t changed at all: Starting human growth hormone treatments is never a decision doctors or families take lightly.
“You have to be pretty dedicated to maximize the child’s height potential to go through the growth hormone pathway,” says Stephen Lauer, MD, PhD, an associate professor of pediatrics at The University of Kansas Medical Center in Kansas City. “You’re trying to convince an elementary school-aged child that it’s in their best interest to get a shot every day.”
Children undergoing growth hormone treatments receive 6 or 7 shots a week, every week, as long as they remain on the treatment — typically several years. Most children receive treatment for 2 to 3 years, though some may stay on it for 5 to 10 years, according to Bradley Miller, MD, PhD, a pediatric endocrinologist at the University of Minnesota Masonic Children’s Hospital in Minneapolis. How long they undergo treatment generally depends on when they start. “It can start from birth, and you can be treated until you’re done growing,” he says. Many kids are referred to endocrinologists at around 11 years old, and the end of puberty generally marks the end of a person’s growth, about 17 for boys and age 15 for girls. Studies are underway to explore treatment regimens of once-weekly or once-monthly injections, Dr. Miller says, but those preparations are at least 5 years away.
“As drugs go, it’s fairly safe,” says Paul Kaplowitz, MD, an endocrinologist at Children’s National Hospital in Washington, D.C., who literally wrote the book — The Short Child — on short children and growth hormone treatment. “We’re not introducing a foreign substance into the body. The growth hormone that is injected is identical to the growth hormone that is normally made by the pituitary glands.”
Still, he always explains to parents, “There’s no medical treatment that’s completely without risk.” Allergic reactions are extremely rare but not impossible. The most likely side effect is headaches. In about 5 percent of cases, a child can develop such extremely severe headaches that treatment should be halted. Another extremely rare complication is a slipped capital femoral epiphysis, the medical term for a weak hip joint. These occur so rarely, however, that Dr. Kaplowitz has not seen one in more than 30 years of practice.
In children with scoliosis, however, Dr. Miller says, growth hormone can worsen the condition because they’re growing faster. One small study also found that changes in children’s metabolism may lead to exceptional muscular forms.
The bigger question, says Dr. Kaplowitz, is “What happens 20 years down the road?” Despite several European studies seeking to answer this question, long-term effects remain a mystery. Studies have not found evidence that growth hormone increases risk of stroke or death, but concerns over cancer risk are hazier; studies are inconclusive.
“Growth hormone doesn’t make cells become cancerous; it makes cancer cells that already exist grow faster,” explains Dr. Miller, pointing out that the studies do not show children developing new cancers if they’ve taken growth hormone. “There’s no reason that giving someone growth hormone when they’re young should increase their risk of cancer when they’re older.”
But he said it’s a controversial question not yet resolved. Dr. Kaplowitz believes “there’s a possibility that there is an increased risk of cancer,” based on some European studies, but he also says the evidence suggesting a possible risk is weak. In short, not enough data exist to say there is or is not a risk of cancer or any other serious long-term effects.
With that unknown out there, Dr. Kaplowitz reminds parents that treatment decisions are a matter of balancing potential benefit with some unknown risks.
How Short Is Too Short?
Until the FDA’s 2003 approval, only children with growth hormone deficiency or very specific rare conditions qualified for treatment. Those conditions included chronic renal insufficiency, Prader-Willi syndrome, Turner syndrome, growth hormone or pituitary hormone deficiency or being small-for-gestational-age (underweight for the pregnancy week of birth). But the expansion to idiopathic short stature opened up the treatment to children who were “short-normal,” Dr. Miller says. “They’re otherwise healthy but not growing like they should.”
To qualify, children’s height must be in the first percentile for their age with no expectation of catching up to any of the 99 percent of peers taller than them.
“There are lots of kids who are below the first percentile who are growing quite normally, and if you leave them alone, they’ll catch up just fine,” says Dr. Kaplowitz. In adults, the first percentile means 4 feet 11 inches for women or 5 feet 3 inches for men.
Even these kids, however, may have some condition doctors simply cannot detect, so the FDA’s 2003 approval provided them with the human growth hormone option.
“Our tools to diagnose growth hormone deficiency aren’t perfect,” Dr. Miller says. “So there are some kids in the idiopathic group who probably don’t make enough human growth hormone.”
That’s likely what happened with Daniel Scarborough, a 13-year-old from Manteca, California, who began growth hormone treatments two years ago. As a micro preemie born at 24 weeks gestation — four months early — Daniel had always been tiny and required special feeding during his first 4 years. He never caught up.
His lab work was always borderline, never definitively showing him to be deficient in growth hormone. X-rays showed his hand bones to be 2 years younger than his chronological age, and a brain MRI showed a grossly underdeveloped pituitary gland — but these symptoms fell short of any diagnosis besides idiopathic short stature.
“It took a little more than 2 years of tests, frequent endocrinology visits, daily ice cream milk shakes and a lot of discussions before we all could figure out a way to get coverage for HGH therapy,” Laura says. Her only regret was not starting sooner, but his earlier doctors disagreed on his need for it.
Keeping It Real
Nearly every doctor has encountered the parents who want their child eye-to-eye with Michael Jordan despite an unlikely family history, says Dr. Lauer. “The most basic thing to consider before treatments is parents’ expectations for their child’s height,” he says. “If the parents are 5 feet 6 inches and 5 feet 2 inches, and they have in the back of their mind that their kid will be 6 feet tall, that’s not going to happen. Part of it is just getting the parents to look at each other.”
In some very rare situations, though, a child might qualify if they’re above the first percentile but dramatically shorter than their genetics suggest they should be.
“If you have a super tall family and you should grow to 6 feet 2 inches, but you’re targeting 5 feet 6 inches because you’re not growing like you should for your family, you would meet the criteria for treatment because you’re so far below your own genetic curve,” Dr. Miller says.
Daniel’s growth has taken off since starting his treatment. Before treatment, his height was projected to be 4 feet 11 inches, but he has grown 8 inches in the last 2 years — “[which is] practically miraculous,” Laura says, since his previous 2-year growth might have yielded a half-inch. He’s now projected to reach 5 feet 6 inches to 5 feet 8 inches tall.
Measuring the Benefits
But that kind of growth is unusual for most who receive treatment. Early studies found a gain of 2 to 3 inches with treatment, and more recent studies have suggested up to 4 or 5 inches, particularly for younger children, who tend to grow better, Dr. Miller says. In one recent study, researchers assessed the growth of 733 children with no diagnosis other than short statute. After 5 years of treatment, the children made up 60 percent of the difference between their original height and that of their average-height peers.
“It’s hard to predict in an individual case,” Dr. Kaplowitz says. “We’ve all seen patients we thought would improve with growth hormone and saw little improvement and other cases where improvement is significantly better than we expected.”
More typical is the experience of Alayna Dibo, a 26-year-old gymnast and social work graduate student from Chicago who took growth hormone from age 7 to age 16. With a 5-foot tall mom and a 5-feet-8-inch tall dad, her predicted height was 4 feet 7 inches before beginning treatment. Today, she’s exactly 5 feet and happy she spent those years getting 6 injections a week.
“I think about being 4 feet 7 inches tall in a professional environment and what that means,” she says. “I think I’m happier because it’s 1 less thing to worry about each day. Even at 5 feet, my height affects me. People think I’m younger than I am, and I’m not taken as seriously in the workplace.”
Psychological Impact Is Unclear
Although Dibo is grateful for her treatment, study data don’t show a clear increase in overall quality of life for children who receive treatment. In fact, a great deal of research in adults has linked short stature with a range of negative outcomes.
“The taller you are, the more likely you are to make more money, the more likely you’ll marry a taller person and be married at all and the lower your risk of suicide,” Dr. Miller says. But does receiving HGH treatment make a difference?
“We have no idea,” he says. “There are societal differences we’re aware of, but we don’t know if treatment actually helps that.”
Current studies are exploring how much being short affects children psychologically and whether treatment helps, but it’s a challenging question to answer.
“Does adding that inch or 2 improve their quality of life, their social functioning?” Dr. Kaplowitz says. “That’s a hugely controversial question because it’s harder to measure.”
One analysis considered about 80 studies on this question, but the studies were not very scientifically sound, he says. Many children he has treated have been teased about their height, but most have developed strategies for dealing with it, and even with a couple extra inches, the child will be much shorter than his or her peers. “You can add an inch or 2 or, if you’re lucky, 3,” Dr. Kaplowitz says. “It doesn’t necessarily mean they’re going to be a happier child or happier adult.”
Further, sending kids the message that being short is a medical problem may have its own harms, Dr. Miller says.
“For some people, it’s normal to be short,” he says. “[But] I do think that telling people that there’s something wrong with them because they’re short is a negative thing.”
The more severely short a child is, the more aggressively he believes they should be helping the child grow, “but if it doesn’t bother them and it’s not interfering with their lives, then there’s really no reason for us to intervene,” he adds.
When parents push for growth hormone but a child is less enthusiastic, the child’s self-esteem can take a hit, Dr. Kaplowitz says. “Unless the child is really short, I would try to convince the parents that their child is well-adjusted, they don’t want the treatment and the benefit is uncertain,” he says.
He also makes clear that most of the benefit for idiopathic short stature kids occurs in the first year: “After that, you don’t see continued extremely good growth in most cases.”
Practical concerns are the tipping point where doctors might advocate more for treatment, such as whether someone could fully participate in daily activities without significant effort.
“If I had a boy who would barely make it to 5 feet or a girl who might not make it to 4 feet 6 inches tall, I might try to convince the kid,” Dr. Kaplowitz says. “There’s a certain height where it’s inconvenient reaching things and driving cars.”
But buy-in from the child is key because the daily injections can take an emotional toll, particularly early on in treatment. Alayna Dibo’s mother, Carol, remembers having to chase Alayna around the house and then hold her down, screaming, to give her the injections.
“It was hard on me and hard on the other children, and I would cry at night,” Carol says. They returned to the endocrinologist to explain to Alayna through pictures what her height would be compared to her mom and her aunt, who stands 4 feet 11 inches, without the shots, and they got an Inject-Ease applicator that made the shots less painful. After that, the injections were just a normal part of her life. She even took them at camp with several other girls receiving daily growth hormone or insulin shots.
“A child who is very short and not growing very well and really wants growth hormone is less likely to complain about daily injections and daily visits than a child who is dragged into it unwillingly by their parents,” Dr. Kaplowitz points out.
Seeing fast results helped Daniel deal with the shots, too.
“It was a big adjustment for him as a child to deal with a daily injection,” says Laura. “He did understand, though, that his body needed the medicine to grow. We saw results fairly soon, and that encouraged him. Now it’s just a part of his nightly routine, no big deal.”
What Other Side Effects Exist?
“There are plenty of well-adjusted short people out there, both kids and adults, who accept that they’re short and function at a very high level,” Dr. Kaplowitz says. “Having said that, there are individual patients who are extremely grateful and have benefited tremendously.”
- Concerns about Growth Hormone Experiments in Short Children (Physicians Committee for Responsible Research)
- Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop (pdf)(Growth Hormone Research Society)
- Childhood Growth and Height Issues, (Children’s Hospital of Philadelphia)
- Medscape: Idiopathic Short Stature (MedScape)
- Little People of America (lpaonline.org)
- The Magic Foundation (MagicFoundation.org)
- Short Persons Support (ShortSupport.org)