Estrogen & ACLs

Is there a link between hormone levels and predisposition to ACL injuries in female athletes? Three new studies are heating up the debate.

By Guillermo Metz

Guillermo Metz is an Associate Editor at Training & Conditioning.

Training & Conditioning, 11.8, November 2001, http://www.momentummedia.com/articles/tc/tc1108/hormones.htm

This year, in the U.S. alone, an estimated 80,000 people will tear their anterior cruciate ligaments. Roughly 70 percent will be noncontact injuries. The vast majority will be among women aged 15 to 25.

The injury is so commonplace, especially among female athletes in sports like basketball and soccer, that athletes, athletic trainers, and orthopedic surgeons expect to see some of their athletes stricken every season. Despite their familiarity with this injury, medical professionals are seeking answers to key questions about ACL tears: why do they occur disproportionately among women, and what can athletes do to protect themselves against these devastating injuries?

The main culprits seem to be anatomical differences between men and women, neuromuscular differences, or the influence of hormones. Now, a couple of recent studies add to the growing body of research supporting a link between hormones and ACL tears.

Researchers have known for years that the ACL contains hormone receptors—including receptors for estrogen. From this, many have theorized that the increased rate of ACL tears among women is somehow related to the fluctuation of hormone levels throughout the menstrual cycle.

Proving that has been difficult, however. Even more difficult is unraveling the role, if any, that estrogen levels play in torn ACLs. Three recent studies, with somewhat contradictory findings, only fuel the debate: one led by Edward Wojtys, MD, Medical Director of the University of Michigan’s MedSports Program; another headed by James Slauterbeck, MD, Vice Chairman of Orthopedics at Texas Tech Medical Center and a team physician for Texas Tech; and a third led by William Romani, PhD, PT, ATC, Assistant Professor in the School of Medicine, Department of Physical Therapy, at the University of Maryland-Baltimore.


The Research
Not enough is known at this point to confirm a causal relationship between hormones and ACL injuries. Research shows that women seem to be more prone to ACL injuries at certain points in their menstrual cycles. Yet, there are conflicting data on just what day or what phase of the cycle women are at greatest risk.

The significance of the Wojtys and Slauterbeck studies primarily lies in the way the timing of the injury was determined in relation to the athletes’ menstrual cycle. In the Wojtys report, researchers at four participating facilities—the University of Michigan, Vermont Orthopaedic Clinic, Vanderbilt Sportsmedicine Center, and Cincinnati Sportsmedicine and Orthopaedic Center—obtained urine samples from athletes within 24 hours of their suffering ACL injuries. Slauterbeck and his coauthors reviewed saliva samples taken within 48 hours of injury. Earlier studies relied on the much less reliable method of self-reporting.

Wojtys and his coauthors found that women are nearly three times more likely to injure their ACL during ovulation (days 10 to 14 after the start of menstruation, which is when estrogen levels peak) than during other times of their cycle. In Slauterbeck’s study, 26 of 37 athletes injured their ACLs during the first half of the menstrual cycle.

However, Slauterbeck’s team also found that while most ACL injures occurred during the follicular phase, more than half occurred during days one through six of the cycle—nearer menses than ovulation. Other studies published in the last few years show a greater risk of ACL injury in the late luteal phase, just before the onset of menses.

Why the discrepancies? Sandra Shultz, PhD, ATC, CSCS, Assistant Professor and Interim Coordinator of Graduate Programs in Athletic Training and Sports Medicine at the University of Virginia, has been looking into the hormone/ACL connection for several years and has found a problem with the methodology used in much of the research. “Estrogen levels change so dramatically throughout the cycle that we really need to look at it on a day-to-day basis rather than clumping things by phase. Women ovulate on different days,” she says. “We did a study where some ovulated as early as day nine and as late as day 14. And with estrogen levels changing 400-fold in a 24-hour period around ovulation, you can see how putting things by phase versus looking at actual day-to-day changes could give you conflicting results.

“Another problem is that we’re still trying to get a large enough population studied,” Shultz adds. “ACL injuries are common, but they’re not everyday. So, it’s not like you’re going to get a study with 150 or 200 athletes. And with so few athletes in these studies, the numbers are easily skewed.”

Shultz is not the only one who questions the methodology of research in this area. Carol Otis, MD, Primary Care Physician in Women’s Sportsmedicine at Kerlan-Jobe Clinic in Los Angeles, a former team physician for UCLA, and current team physician for the Sanex women’s professional tennis tour, cites several reasons for what she calls the “muddiness” of the findings.

“I think there are a lot of limitations to their methodologies,” she says. “In most of these studies, the timing of the injury was determined by questionnaire and it’s sometimes very hard for people to remember what stage of their menstrual cycle they were in when they had an injury. The second problem is that a fair number of these people were on the birth control pill. So, you can’t make assumptions about their menstrual cycles.”

The first limitation that Otis cites may have been dealt with in the Wojtys study, but the latter wasn’t. Although it is possible to separate the women on birth control from those who weren’t, Wojtys and his coauthors went so far as to point out a possible protective effect of being on oral contraceptives. In his most recent study, women who were not on oral contraceptives showed a 2.5-times greater than expected risk of being injured during the ovulatory phase. Women on the pill had a rate much closer to expected, based on the assumption that 50 percent of injuries occur in the first half of the cycle and 50 percent in the second half.

Other researchers, such as Romani and Shultz, have focused on changes in knee laxity relative to hormone fluctuations, rather than injury. By testing athletes on a KT2000 on a daily basis, Romani found that “there was a significant negative correlation between estrogen concentration and the stiffness of the anterior cruciate ligament.”

Shultz’s research produced similar results, but, she says, “There’s still sort of a big ‘So what?’ question. In other words, just because it’s more lax, does that mean someone’s more prone to injury or less prone to injury? We’re still a long way away from knowing how laxity changes may influence injury.”

Others point out that even if a relationship is found between hormone levels and ACL injuries, it may not be as simple as what’s going on in the actual ligament. “Some ACL injuries may be due to coordination issues,” says Otis. “Some of that may be due to brain chemistry changes that take place at different phases of the cycle. A woman may be premenstrual, have water gains, or have pain, and one of those factors may be the mechanism rather than the actual hormone acting on the ACL.”

Given this contradictory evidence, what should athletic trainers do with this information? According to top athletic trainers and the researchers themselves, not much, at least for the time being. “I would think that for an athletic trainer to make a clinical decision based on the information that we have in the literature right now about hormones and ACL injuries would be a gross injustice,” says Romani. “I think that their take-home message, or what they should do, is not intervene in the hormonal milieu until we know more.”


Answering Athletes’ Questions
Even if athletic trainers don’t jump to conclusions about hormonal variations and ACL injuries, that doesn’t mean they’re not confronted with questions about it. “What’s happening is this information is getting out,” Shultz says, “and parents are saying, ‘What does this mean? Does this mean my daughter is going to tear her ACL and should not practice at ovulation or at the beginning of her period? What should we do? Should we put her on birth control pills to keep her estrogen levels constant throughout the month?’ But, we just don’t have the answers yet.”

The question of birth-control pills is especially tricky. Putting aside moral, practical, and logistical matters, the medical issues alone are complicated. First, notes Otis, the pill is a prescription drug, complete with side effects. Not the least of these is that estrogen may give an athlete a tendency for blood clots, usually in the legs. Frequent flying, with its flux in air pressures, can turn this tendency into a risk for pulmonary emboli.

Then there is the effect of pill-form estrogen on bone density gain, a crucial issue for a woman’s long-term skeletal health. Estrogen is needed for bone remodeling, and most research shows that women on the pill gain more bone density while on exercise regimens than do women who similarly exercise but who aren’t on oral contraceptives. But a recent study showed just the opposite—though the women in that study were sedentary, which may have affected the results and would limit their applicability to athletes. Researchers do agree, however, that irregular periods reduce bone density, and the pill is often used to smooth-out irregularities in the cycle.

On top of all this, however, is uncertainty that using birth control pills would actually do any good when it comes to preventing strains and tears. Even if it were clear that estrogen makes ligaments more lax, it’s far from clear that greater laxity equals fewer ACL injuries.

“Based on the knowledge that we have, it would be a mistake to say that female athletes are more or less susceptible to injury at particular points in their cycle, or that just because their ligaments are more lax here they are more at-risk or less at-risk of injury,” says Shultz.

Otis concurs. She says that for most women there’s no physical harm from being on oral contraceptives, and they can help many women athletes by lessening cramps and PMS. But too many questions remain, and she recommends each woman work with an athletic trainer or team physician to individualize a plan for her menstrual cycle. “The plan could be, ‘If you have no problems, you don’t need to do anything.’ Or it could be, ‘If you do have cramps, we need to manage them.’” (See “Managing Menses,” at the end of this article, for more on what athletes can do to ease period discomfort.)

What Now?
At this stage, many people believe that overemphasizing a possible link between hormones and ACL injuries means losing sight of the big picture. When it comes to interpreting the research and making recommendations, the one thing everyone agrees on is that hormones, even if they are a factor in ACL injuries, are just a small part of what’s going on.

“I think it’s a valid area of study,” says Jenny Moshak, MS, ATC, CSCS, Assistant Athletic Director for Sports Medicine at the University of Tennessee. “I think we all want to know and try to figure out what is happening with ACLs and the high incidence of injuries we’re seeing. But I don’t think you can ever isolate it to one factor; we’re too much of an interconnected, multifactorial being.”

“Whether it is hormones or anatomy or an athlete’s ability to neuromuscularly complete an activity, each of those things are only one component of the big picture,” agrees Romani. “In taking a look at the hormones, we’re actually looking at the one component where there is the least amount known.”

Indeed, athletic trainers, re-searchers, and team physicians agree that the main things to focus on at this point are those that we do know something about and that have been shown to benefit athletes. “I think what you have to focus on are factors or possible factors that we can make a change in,” says Shultz. “Part of that is through preventative training. Studies show that doing some kind of preventative training program that works on landing, on cutting with good technique, and on hamstring strength does appear to lead to a reduction in injury rate.”

“Athletes also need to be very careful about their footwear,” adds Otis. “They need to make sure they have the proper footwear for the surfaces they’re going to be playing on.”

In the summer of 2000, the Journal of the American Academy of Orthopedic Surgeons published the findings of a study group convened to look at noncontact ACL injuries. They cited four categories of risk factors for these injuries: environmental, anatomic, hormonal, and biomechanical. Of these, only neuromuscular training programs were noted as showing potential to decrease ACL injuries.

According to Romani, little has changed since then. “The findings that came out of that retreat are pretty well founded,” he explains. “And the advice that I would give is that we know we can make changes with how we train athletes. So we should make changes in teaching them how to jump and land and cut and complete their functional activities in better position so that the knee is not placed in a position of risk to be injured.”

“This type of training program can be extremely beneficial not just to ACL prevention but increased performance as a whole,” adds Moshak.

Focusing on the training will also help take care of another potential problem. Parents and athletes hearing about these studies may not be able to properly analyze them and put them in context. And there is not only the concern that they may blindly turn to oral contraceptives as a panacea but also that athletes may take the fear of injury out on the court, track, or field with them.

“There’s the old axiom that if you’re worried about getting hurt, you will get hurt,” acknowledges Romani. “I think as an athlete you have to train hard under the guidance of athletic trainers or certified strength and conditioning coaches who know what they’re doing. And you play hard, because there’s nothing conclusive yet to suggest that you are at a higher risk at any point in the cycle or that you are at a higher risk because of the way your hormones are fluctuating.”

For more information on a jump-training program that was the first to show a benefit among athletes, log onto and enter “Restoring the Balance” in the search window.

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Managing Menses
It’s no secret that many women are hit pretty hard every month by their periods. For athletes, that can mean days of not being able to practice or play at their peak, or at all.

“These symptoms should be managed, not ignored,” says Carol Otis, MD, a Primary Care Physician in Women’s Sportsmedicine at Kerlan-Jobe Clinic in Los Angeles, a former team physician for UCLA, and lead author of the American College of Sports Medicine’s “Strategic Health Initiative for Women.” Here are some of her suggestions for managing menses:

Calcium Intake: “We know that if a woman experiences PMS, either the physical symptoms (which can include bloating, weight gain, and breast tenderness) or the mood changes (which can include irritability, depression, and anxiety), those symptoms can be moderated and managed by exercise and by 1200 milligrams of calcium a day, every day. That would be the first line of treatment for PMS. Athletes have no problem with the exercise part. But most women don’t get enough calcium, and I would certainly advocate that all women make an effort to get adequate calcium.”

Managing Cramps: “Cramps should be managed with over-the-counter medications, taken in conjunction with the advice of an athletic trainer. For cramps, we know that the earlier you start managing them the better. Because they’re caused by prostaglandins, athletes can take anti-prostaglandin drugs, like ibuprofen or naproxen.”

Physician’s Advice: “If an athlete does need to consider a prescription medicine, she should consult with a physician who is familiar with active women and can discuss the benefits and risks of being on the birth control pill. You need to look at the background of the team physician. I say that because many team physicians are orthopedic surgeons and may not be comfortable or as well versed in managing a woman’s menstrual cycle. Many of them are, but not all. So, you may want to find a team physician who is a primary care/sports medicine doctor. Or, you may want to refer her to a gynecologist who understands and works with active women, because she may need a gynecologic exam as well.”

For more information on this topic, go to Dr. Otis’ Web site, www.sportsdoctor.com.