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Testosterone may strengthen the anterior cruciate ligament in men’s knees, helping to explain why women are up to 10 times more likely to suffer ACL damage, a common and serious sports injury.

A new study show that normal male rats with natural supplies of testosterone had stronger ACLs than castrated rats whose bodies no longer produced the male hormone.

“The primary implication of the study is that testosterone may contribute to the ACL’s ability to withstand tensile loads and may be one of multiple factors responsible for the disparate ACL injury rate between men and women,” says William Romani, a physical therapist, sports medicine researcher, and former visiting faculty member in the biomedical engineering department at Johns Hopkins University.

The new finding could eventually lead to using circulating sex hormone levels to identify athletes at higher risk for ACL injury, says biomedical engineer and senior study author Jennifer Elisseeff. Those athletes may benefit from training designed to strengthen the ligament.

The ACL is a flexible, stretchable tissue that tunnels through the knee, connecting the femur, or thigh bone, with the tibia, or shin bone. More than 200,000 people a year in the United States get ACL injuries, ranging from partial to full tears, most often while playing sports. Recovery from an ACL tear can be long and arduous.

Studies have found that girls and women are anywhere from two to 10 times more likely to tear an ACL than men doing similar activities. Explanations for the sex difference include differences in anatomy, strength, reflex times, and hormones. Among the world-class women athletes who have suffered major ACL injuries are US Alpine skier Lindsey Vonn and national soccer stars Megan Rapinoe, Ali Krieger, Alex Morgan, and Christie Rampone.

Earlier research with rats showed that estrogen—a predominantly female hormone—reduces ACL strength, but also that knee ligaments in both sexes contain receptors for testosterone.

“Our thought was that, while estrogen may make the female ACL weaker and more prone to injury, the male hormone testosterone may act to strengthen the ACL and protect it from injury,” Romani says.

In the new research, published in the journal The Knee, researchers removed the ACL—still connected to the tibia and femur—from 16 healthy 12-week-old male rats. Eight of the rats were normal, with testosterone levels averaging 3.54 nanograms per milliliter, and eight had been castrated, giving them nearly undetectable levels of the hormone at 0.14 nanograms per milliliter. The researchers measured each ACL and tested the strength of the ligaments by measuring how much force it took to tear each ACL.

The findings showed it took more force—34.5 newtons, compared to 29.2 newtons—to tear the ACLs from mice with normal levels of testosterone, indicating that the ligaments were stronger. Since researchers have generally accepted that a stronger ACL is less prone to injury, the results support a link between testosterone and ACL injuries.

More work is needed to explain exactly which pathways and molecules testosterone and estrogen use to influence ligament strength, and whether the hormones have the same impact on other ligaments in the body.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the work.

Source: Johns Hopkins University