After an injury to the anterior cruciate ligament (ACL), many athletes find that they cannot return to sport at their pre-injury level. A new pilot study, published in The American Journal of Sports Medicine, reports that treatment with human growth hormone (HGH) after ACL reconstruction may help to prevent the loss of quadriceps muscle strength.
“While modern surgical techniques can reconstruct ACLs in a minimally invasive way, the associated muscle atrophy can be a greater challenge to overcome,” said Asheesh Bedi, MD, senior study author, chief of sports medicine and shoulder surgery at Michigan Medicine, and director of the Michigan Center for Human Athletic Medicine and Performance.
“Residual atrophy can slow or limit the safe return to the prior level of competition and contribute to the risk of re-injury and even arthritis.”
In fact, “even after rehabilitation, many patients have muscles that are 30% to 40% weaker when they return to sports compared to their pre-surgery strength,” said Christopher Mendias, PhD, ATC, the lead study author, adjunct associate professor of orthopaedic surgery at Michigan Medicine, and an associate scientist in the Arthritis and Tissue Degeneration Program at the Hospital for Special Surgery.
Dr. Bedi and Dr. Mendias hypothesized that administering HGH supplements to injured athletes may activate HGH within the body to target the ACL tear and prevent the quadriceps muscles from losing strength.
To test their hypothesis, they randomized 19 male athletes to self-inject HGH or a placebo solution into their lower abdominal muscles twice daily over a 6-week period, beginning 1 week prior to surgery. The study participants were ages 18 to 35 and were scheduled for ACL reconstruction surgery at Michigan Medicine.
Prescription HGH is only available for treating growth hormone deficiency syndromes and cannot be used off-label without approval from the US Food and Drug Administration (FDA). An investigational new drug exemption was obtained from the FDA so that study participants could receive the drug.
Collegiate, professional, and elite athletes were excluded from the study because HGH supplements are banned by the World Anti-Doping Agency and in collegiate and professional sports. The researchers also excluded patients with diabetes, as developing type 2 diabetes is a side effect of HGH supplements.
The researchers measured quadriceps strength and volume; evaluated patient-reported outcomes, such as pain and symptoms; and analyzed biomarkers in blood samples from the injured athletes versus individuals without an ACL tear. They found that although HGH did not appear to affect quadriceps muscle volume or patient-reported outcome scores, patients who injected HGH had 29% greater knee extension strength compared with patients who injected the placebo.
Blood analysis revealed other signs of muscle and cartilage change. Patients who injected HGH had a 2.1-fold increase in circulating insulin-like growth factor 1 (IGF1), a protein similar to insulin that plays an important role in muscle growth. In addition, blood samples from patients in the HGH group showed a 36% lower level of matrix metalloproteinase-3 (MMP3), an enzyme that breaks down proteins during growth processes in the body. MMP3 was an indirect biomarker of cartilage wear down in the study.
“We observed a consistent reduction in MMP3 in the HGH group from the first through the 12th postoperative weeks,” Dr. Mendias says. “This finding suggests [that there is] a potential protective effect of HGH after ACL reconstruction and that we should look more closely at its potential for cartilage healing in further studies.”
Dr. Bedi and Dr. Mendias hope the results of this study allow for revisiting the World Anti-Doping Agency and sports agencies’ ban on HGH.
“Perhaps athletes could petition for a Therapeutic Use Exception, which allows a banned substance for a medically appropriate reason, to prevent loss of muscle strength after ACL reconstruction,” Dr. Mendias said.
“Treatment occurs during a time when athletes are not playing due to their injuries. The goal is to prevent muscle weakness, not make athletes stronger than they were before their injuries. Any small performance-enhancing effects of human growth hormone seem to wear off quickly after stopping the medication and do not offer a competitive advantage.”
Mendias CL, Enselman ERS, Olszewski AM, et al. The use of recombinant human growth hormone to protect against muscle weakness in patients undergoing anterior cruciate ligament reconstruction: a pilot, randomized placebo-controlled trial. Am J Sports Med. 2020 May 26. doi: 10.1177/0363546520920591. Online ahead of print.