Peyton Manning Doping Allegations: What Is Human Growth Hormone?

Earlier this week Al Jazeera reported that the wife of Denver Broncos star quarterback Peyton Manning received human growth hormone in the mail from Guyer Institute of Molecular Medicine. That story quickly spun into speculation that Manning may have doped through his wife’s prescriptions -- an allegation he has vehemently denied. The NFL explicitly bans players from using the hormone out of concern that it would give them an unfair competitive advantage.

The original source for the Al Jazeera story, a former employee of Guyer, has since retracted his statements. While Manning and his wife were both once patients of Guyer, Manning says he was treated with “holistic” care while recuperating from neck surgeries in 2011. His wife did receive a prescription from Guyer, although the specific medication has not been publicly disclosed.

At the heart of this controversy is a powerful hormone with a checkered history with U.S. regulators. For the past decade, authorities have struggled to temper its growing popularity among athletes and anti-aging proponents while still preserving legitimate medical use for patients who need it. Meanwhile, scientists still have questions about how HGH injections affect some of the body’s basic functions.

What is human growth hormone? Human growth hormone is a protein that promotes growth broadly in children and performs a variety of key functions in adults. Humans naturally produce it in the pea-sized pituitary gland, which rests at the base of the brain. It makes its way through the body in the bloodstream and affects many critical functions, from producing muscle mass to processing fats to creating bones and cartilage.

"[HGH] is important for muscle maintenance and many cells in the body have receptors for the hormone, so it is probably responsible for most aspects of growth," said Dr. Sofiya Milman, an endocrinologist at the Albert Einstein College of Medicine in New York.

Throughout the day, a person’s HGH levels naturally spike after certain activities such as exercise and sleep. Over the course of a person’s lifetime, levels of HGH in the body gradually drop from an all-time high during puberty.

In addition to the HGH that the body naturally produces, companies have figured out how to manufacture synthetic versions of the hormone that can be injected into patients. When this happens, the body wholly replaces its own natural HGH with the synthetic version.

How is human growth hormone used? There are only a handful of FDA-approved uses for HGH, and one analysis estimates the total number of U.S. patients who would qualify for the treatment under those terms is fewer than 45,000.

One approved use is to boost growth in kids who suffer from diseases such as Turner’s syndrome and Prader-Willi syndrome that cause them to be short in stature. Another is to treat kids and adults with growth hormone deficiency, or naturally low levels of the hormone. This is rare but can result from a tumor that grows on the pituitary gland. The FDA has also approved HGH for conditions such as short bowel syndrome, in which a portion of the gut fails to absorb nutrients from food, and muscle loss affiliated with HIV or AIDS.

Some sources have suggested Ashley Manning may have needed the drug for fertility issues becaue she gave birth to twins in 2011. Others have pointed out that Peyton Manning underwent multiple neck surgeries that year and may have used the hormone to aid in recovery. Dr. Alan Rogol, an endocrinologist at the University of Virginia who appeared in the Al Jazeera documentary, said neither of these ailments are currently legitimate uses for HGH.

There are many clinical trials currently underway to test HGH for a variety of purposes, including boosting fertility and rehabilitating an injured tendon in the knee. Mark Cuban, a billionaire tech entrepreneur and owner of the Dallas Mavericks basketball team, is even funding a trial through the University of Michigan to explore whether growth hormone can help athletes recover from a torn ACL.

What are some other reasons that people might take human growth hormone? Doctors may prescribe any medicine for uses other than those for which they are officially approved, in a practice known as off-label prescribing. However, it is illegal to prescribe HGH for anything other than the conditions for which it is FDA-approved under the 1990 Anabolic Steroids Control Act. Violations are considered a felony and punishable by up to five years in a state prison.

Although HGH is not officially approved for these purposes, some people believe it can stave off the physical effects of aging. One study published in 2014 of 184 people in their 90s showed that those with naturally low levels of HGH were actually more likely to live to their 100s than those who had elevated levels of HGH.

Athletes may also request HGH in order to produce muscle mass, although Milman said there is no evidence that the drug actually makes them stronger. “It does improve muscle mass, but there's no evidence to show that it improves muscle strength,” she said.

Rogol said athletes are particularly vulnerable to a placebo effect, which means they believe they are benefiting from HGH more than they actually are. "This does not work if you sit in bed. You've got to work out," he said. "So what they're looking for is just a little bit of an edge. That may very well be what this stuff does, or they may think that's what it does and train a little bit harder."

Where do people get human growth hormone? Accessing HGH does require a prescription that can be written by any doctor. It does not have to be prescribed by an endocrinologist, which is a doctor who specializes in treating hormone imbalances. However, most patients who are seeking HGH for one of its federally designated uses will acquire it from a specialist such as an endocrinologist or a gastroenterologist who specializes in gut disorders. Patients who want HGH can often find physicians willing to prescribe it for illegitimate purposes at "anti-aging" clinics, or they may simply order it from online pharmacies.

A prescription can be picked up from a pharmacy, sent through the mail, or doled out right at the doctor's office. Many "anti-aging" clinics set up their own pharmacies to dispense pills directly to patients, which increases their own profits and subverts the need to work with a pharmacy. Some pharmacies refuse to work with physicians whom they deem untrustworthy.

Selling pills directly to patients is not a standard practice for most doctors, though, and represents a potential loophole for physicians to peddle illicit HGH. "It is really uncommon for doctors to sell drugs legitimately from their offices," Rogol said. "In some places, that's thought to be unethical because [you're supposed to] go through a pharmacist; that's how it's done."

What are the risks? Injecting extra hormones like HGH and estrogen into the body can increase a person’s risk of cardiovascular disease, cancer and joint problems. Up to 30 percent of patients who receive HGH injections suffer side effects.

The main problem with HGH is that it doesn’t simply promote growth in the muscles near where it is injected. The hormone instead broadly promotes muscle growth throughout the body, which means it can lead to an enlarged heart. People who take too much of it for too long can develop a disease called acromegaly, which is associated with diabetes and arthritis. The hormone has also been known to cause people to retain more fluids, which can cause hypertension.

Why is human growth hormone banned by the NFL? HGH is banned by many national and international sports organizations in order to prevent athletes from gaining an unfair advantage and to protect them from side effects. That list includes Major League Baseball and the International Olympic Committee. This year, the NBA began administering three mandatory random blood tests for each player during the season to prevent HGH doping.

The NFL began testing players for HGH in 2014 but recorded no positives in the entire first season. The league has said it is reviewing the claims against Manning, which is standard protocol.

Who manufactures human growth hormone? Synthetic growth hormone is manufactured in two basic forms and sold by at least eight pharmaceutical companies under many brand names, including Genotropin, Humatrope, Norditropin, Nutropin, Saizen and Serostim. Prices can vary from $6,000 to $12,000 a year.

The nation’s largest manufacturer is Genentech, a division of Roche. The company recorded $400 million in HGH sales in 2011 alone. Next in line for top sales were Pfizer and Eli Lilly with $300 million and $220 million, respectively. That same year total HGH sales in the U.S. tallied $1.4 billion, which was more than penicillin, a common antibiotic.

In addition to pharmaceutical sales, there are plenty of other opportunities for people throughout the healthcare system to generate profit from HGH’s expanded use, from the physicians who prescribe it to the pharmacists who dole it out. Sales in the U.S. jumped an astonishing 69 percent between 2005 and 2011, according to a 2012 analysis by the Associated Press and IMS Health. At that time, researchers believed only half of those who were receiving HGH had a legitimate medical need for it.