Female Athlete Triad

With the increase in female participation in sports (much of it attributable to Title IX legislation in the United States), ^{[1, 2]} the incidence of a triad of disorders particular, but not exclusive, to women—the so-called female athlete triad—has also increased.

The female athlete triad, though more common in the athletic population, can also occur in the nonathletic population. However, even though this triad was first described at the 1993 meeting of the American College of Sports Medicine (ACSM), ^{[3, 4]} associations between bone mineral density (BMD), stress fractures, eating disorders, and female athletics had been observed for decades before the syndrome was formally named.

The components of the female athlete triad, as put forth by the 1997 ACSM positional stand, consisted of disordered eating, amenorrhea, and osteoporosis. ^[5] Not all patients have all 3 components of the triad, and newer data suggest that even having only 1 or 2 elements of the triad greatly increases these females’ long-term morbidity.

In addition, a study by Burrows et al has suggested that the current triad components do not identify all at-risk women; rather, the authors suggest that criteria such as exercise-related menstrual alterations, disordered eating, and osteopenia may be more appropriate. ^[6]

Subsequent research on the female athlete triad culminated in an updated definition published by ACSM in 2007. The 2007 ACSM positional stand looks at each disorder as a point on a continuous spectrum rather than as a severe pathologic endpoint, as follows ^[7] :

• “Disordered eating” has been replaced by a spectrum ranging from “optimal energy availability” to “low energy availability with or without an eating disorder”

• “Amenorrhea” has been replaced by a spectrum ranging from “eumenorrhea” to “functional hypothalamic amenorrhea”

• “Osteoporosis” has been replaced by a spectrum ranging from “optimal bone health” to “osteoporosis”

The 2007 ACSM positional stand also emphasizes that energy availability is the cornerstone on which the other 2 components of the triad rest. ^[7] Without correction of this key component, full recovery from the female athlete triad is not possible.

Often difficult to recognize, the female athlete triad can have a significant impact on morbidity and even mortality in a relatively young segment of the population. Indeed, the full impact of this syndrome may not be realized until these women reach menopause, when bone loss is accelerated.

Significant research of the triad has been ongoing. Recently, there have been a series of meetings that have resulted in consensus statements released in 2014 by the International Consensus Conference on the Female Athlete Triad, in 2014 by the International Olympic Committee (IOC) and in 2017 by a Committee Opinion from the American College of Obstetricians and Gynecologists (ACOG) on Adolescent Health Care. The Consensuses and ACOG Committee opinion reiterated the 2007 ACSM positional stand on the etiology and the need to view the components of the triad as a spectrum. ^{[8, 9, 10]} The main purpose of the consensus statements were to provide specific guidelines in treatment and return to play to providers of athletes at risk and/or diagnosed with the female athlete triad. ^{[8, 9]} The main purpose of the ACOG Committee Opinion was to discuss the role of obstetricians and gynecologists in participating in the healthcare team for athletes with the female athlete triad. ^[10]

Furthermore, the IOC has proposed changing the name of the female athlete triad to the "relative energy deficiency in sport" or "RED-S". ^[9] They believe the name change would more accurately describe the myriad of health issues affected by decreased energy availability, including "metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular and psychological health" and include men, who can also be affected negatively by an imbalance in energy availability. ^[9]

Reduced energy availability

The first component of the female athlete triad, energy availability, ^{[7, 11]} is defined as “dietary energy intake minus exercise energy expenditure” and is intended to capture those athletes who, due to lack of education, may be inadvertently undereating or may have eating and weight concerns but do not have “significant psychopathology” and therefore do not meet the criteria for disordered eating.

The term disordered eating itself was coined to include pathologic eating behaviors that do not meet the strict Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) requirements for anorexia or bulimia; thus, it includes, but is not limited to, anorexia nervosa and bulimia nervosa.

Indeed, disordered eating includes a spectrum of behaviors ranging from simple failure to take in enough food to offset energy expenditure to preoccupation with eating and a profound fear of becoming fat (typically expressed by instituting measures such as food restrictions or the use of diet pills, laxatives, or diuretics).

Menstrual dysfunction

The second component of the triad, menstrual dysfunction, ^[7] describes the spectrum of menstrual function from eumenorrhea to amenorrhea and enables clinicians to capture a large portion of athletes who may have low estrogen levels but who still experience menstruation.

Menstrual dysfunction includes luteal suppression, anovulation, oligomenorrhea, and primary and secondary amenorrhea. Luteal suppression is marked by a shortened luteal phase and a prolonged follicular phase in which estradiol levels decrease. The cycle length usually does not change; the athlete will continue to ovulate—although it may be later in the cycle—and usually has regular menstruation.

Anovulation is marked by low levels of estradiol and progesterone, which deter follicular development, as well as by an absence of ovulation. Although the circulating hormone levels are decreased, female athletes will often menstruate, some experiencing shortened or prolonged cycles because of the stimulation of their uterine lining by the low levels of estradiol. Oligomenorrhea is defined as “greater than 35 days between cycles.”

Amenorrhea usually refers to secondary amenorrhea, though delayed menarche (primary amenorrhea) can occur in young athletes. By consensus, secondary amenorrhea is defined as the “absence of menstrual cycles lasting more than 3 months after menarche has occurred.” Physicians are cautioned that a full workup should be completed to rule out any other causes of menstrual dysfunction such as hormonal pathology, structural anomaly, medications, pregnancy, etc before such dysfunction is attributed to low estradiol levels stemming from low energy availability. ^{[12, 10]}

Impaired bone health

The final component of the female athlete triad, bone health, ^{[7, 13]} describes a continuum extending from optimal bone health to osteoporosis and focuses on bone strength, which consists of BMD (or bone mineral content) and bone quality.

Bone quality refers to factors related to bone turnover rates (eg, resorption versus formation, microarchitecture or trabeculae, time for maturation of the new bone matrix, and bone geometry and size). Our current inability to measure bone quality leaves one half of the equation for bone health empty and offers an explanation for why some athletes with the same poor BMDs as their colleagues may suffer more fractures. Therefore, dual-energy x-ray absorptiometry is used as a quantitative measure of bone health.

When reporting BMD, T-scores are used for the diagnosis of osteopenia and osteoporosis. However, the T-score measures the standard deviations (SDs) below the mean to predict fracture risks for postmenopausal woman. Concern over mislabeling of our premenopausal athletes, adolescents and children, led the International Society for Clinical Densitometry (ISCD) to issue a positional stand in 2004. ^[13]

The ISCD’s recommendation is to determine BMD by comparing chronologic age and sex using a Z-score distribution. The Society further recommends that the term osteopenia not be used in describing bone density and that the term osteoporosis be reserved for “low BMDs” with secondary clinical risk factors such as “chronic malnutrition, eating disorders, hypogonadism, glucocorticoid exposure, and previous fractures.” ^[13]

Athletes with a Z-score 2 SDs below the mean are to be termed “low bone density below the expected range for age” if they are premenopausal women and “low bone density for chronologic age” if they are children. The 2007 ACSM positional stand further defined “low BMD” as “a history of nutritional deficiencies, hypoestrogenism, stress fractures, and/or other secondary clinical risk factors for fracture together with a BMD Z-score between –1.0 and –2.0” and osteoporosis as “secondary clinical risk factors for fracture with a Z-score ≤ –2.0.” ^[7]

Because most athletes already have a higher BMD than nonathletes, the ACSM also recommends that physicians consider performing further workup for any athlete with a BMD Z-score below -1.0, even in the absence of fracture. ^[7]

The bones of the lower extremities, pelvis, and vertebrae are the ones most commonly affected by poor bone health in women with the female athlete triad; stress and frank fractures of these areas are the typical manifestations. Peak bone mass is obtained between the ages of 20 and 30 years, with peak bone mineral content reached between the ages of 9 and 20 years.

Menstruating athletes gain approximately 2-4% of bone mass per year, whereas amenorrheic athletes tend to lose 2% of BMD per year. Thus, it is easy to see why athletes who are involved in high-impact sports can still be more susceptible to fractures than their nonathletic and menstruating athletic counterparts. Often these fractures are due to the increased stress sustained by these bones in the course of physical activity. In this respect, athletes with the female athlete triad are not unlike their healthy counterparts. However, those who have the triad or portions of it are more susceptible to multiple fractures, and they are also more likely to sustain fractures in larger, less commonly affected bones (eg, femoral neck, pelvis, and vertebrae).

A study by Edama et al showed that athletes with one component of the triad have a 3-5 times higher risk of developing bone stress fractures than athletes who have no components of the triad. ^[14]  Similarly, Nose-Ogura et al found that secondary amenorrhea, low BMD, and a low ratio of actual body weight to ideal body weight raised the risk of stress fractures in adolescent female athletes by 12.9, 4.5, and 1.1 times, respectively. ^[15]

Other physiologic dysfunction

Ongoing research is looking at athletes diagnosed with the female athlete triad and the link to many other psychological and physiological dysfunctions affecting the cardiovascular, renal, hepatic, gastrointestinal, endocrine, reproductive, skeletal, and central nervous systems. ^[9] Issues including “anemia, chronic fatigue, increased risk of infection and illness, esophagitis, electrolyte imbalance, slowing of the metabolic rate, decreased production of growth hormone, unfavorable lipid panels, endothelial dysfunction, reduced muscle protein synthesis, unexpected pregnancy, possible long term reproductive repercussions, and depression” can all concurrently occur with the female athlete triad. ^{[16, 17, 9]}

The theory behind the female athlete triad is that this syndrome is caused by an energy drain or caloric deficit (ie, the athlete’s energy expenditure exceeds her dietary energy intake). ^{[7, 11]} This low energy availability, whether subconscious or conscious, disrupts the hypothalamic-pituitary-ovarian axis, resulting in decreased gonadotropin-releasing hormone (GnRH) pulsatility and low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. ^[18]

These changes eventually lead to decreased estrogen production, causing menstrual dysfunction. The decreased estrogen levels, in turn, affect calcium resorption and bone accretion, causing decreased bone health.

Studies have indicated that 30 kcal/kg of lean body mass is a crucial threshold for maintaining menstrual function ^[7] ; they have also demonstrated that increasing exercise drastically while covering the energy expenditure with increased caloric intake did not result in disruption of LH pulsatility. Conversely, decreasing an athlete’s caloric intake to less than 30 kcal/kg within 5 days resulted in decreased LH pulsatility. All of these findings support the energy drain theory.

The hormone leptin, which is secreted by adipocytes, has also garnered increased interest. Leptin appears to influence the metabolic rate, and levels are proportional to body mass index (BMI). It may be a significant mediator of reproductive function, and many studies have demonstrated that low levels of leptin correlate positively with amenorrhea and infertility. Furthermore, leptin receptors have been found on hypothalamic neurons involved in the control of GnRH pulsatility and in bone, which may also affect osteoblastic function.

Athletes in some sports that are linked to an aesthetic component or a weight class are more likely to develop the female athlete triad. These athletes often attempt to reach unrealistic weight and body fat goals dictated by their sport, to the detriment of their health. ^{[19, 20, 21, 22]}

Emotional stressors can also often be identified as inciting factors in athletes with the triad. The death of a coach or a family member, growth spurts, an illness that prevents training, and other events that an athlete cannot control often lead to disordered eating and excessive training—areas of life that the athlete can control.

For many, moving to a university setting initiates the triad cascade. Some young women move far away from family and friends, and they may carry the added responsibilities of a sports scholarship and a demanding academic workload. Collegiate athletes have the additional pressure of performing to higher competitive standards with a new coach and trainer and alongside athletes who may have had 2-3 years more experience. Not surprisingly, the prevalence of the female athlete triad suddenly increases in college freshmen.

As noted (see above), though all female athletes are at risk for the female athlete triad or any of its components, sports that have an aesthetic component (eg, ballet, figure skating, or gymnastics) or are tied to a weight class (eg, tae kwon do, judo, or wrestling) have a higher prevalence of affected female athletes. ^{[7, 19, 20, 23, 24]}

Obtaining exact epidemiologic data is difficult because of the lack of reporting or gathering of data from athletes. Like individuals with anorexia or bulimia, many athletes with the triad try to hide their symptoms or behavior from friends, family, trainers, or coaches. This is the main reason why diagnosis is so difficult. In fact, the vast majority of cases are diagnosed only after advanced symptoms become apparent. Milder cases may be extremely difficult to diagnose if the physician does not already have a high degree of suspicion. ^{[7, 25, 26, 27, 28]}

Many validated sources for evaluating for disordered eating in athletes exist: the Athletic Milieu Direct Questionnaire (AMDQ) ^[29] , the Female Athlete Screening Tool (FAST) ^[30] , and the American Physiological Screening Test for eating disorders among Female College Athletes (PST) ^[31] to name a few. The prevalence of low energy availability in female athletes is difficult to assess and until recently a validated source for evaluation did not exist. Multiple factors (eg, the difficulty of gathering accurate caloric intake data from athletes, inability to measure energy expenditure, uncertainty regarding which sports to include or which eating attitude survey to use, and varying definitions of eating disorders) compound the issue. In 2014, the Low Energy Availability in Females Questionnaire (LEAF-Q) was released to capture athletes who may be suffering from low energy availability and therefore are at risk for the female athlete triad. ^[32]

It is known, however, that an athlete is at increased risk for the spectrum of reduced-to-low energy availability, with or without an eating disorder, if she has a comorbid psychological disorder, such as anxiety, depression, or obsessive compulsive disorder (OCD). In some studies, the incidence of disordered eating in the female athletic population has been estimated to be as high as 62%, with the incidence of anorexia nervosa and bulimia (as defined in DSM-IV) estimated at 4-39%.

The prevalence of menstrual dysfunction is also difficult to assess. Over a number of studies, it has ranged from as low as 6% to as high as 79%, depending on the sport studied, the patient’s age, the definition and assessment of menstrual dysfunction, the use of oral contraceptives, the training volume, and the presence of subclinical menstrual disorders, such as luteal suppression and anovulation. Studies continue to be performed, and it is hoped that more and better data will become available.

The prevalence of impaired bone health, as indicated by reduced BMD, is likewise difficult to assess because of the prohibitively high cost of DXA scans. Osteopenia has been reported to occur in 22-50% of athletes, compared with 12% of nonathletes. Osteoporosis has also been reported in 0-13% of athletes, compared with 2.3% of nonathletes. Now that the ISCD has recommended using Z-scores instead of T-scores, more research will have to be done to obtain accurate data for athletes.

Although good epidemiologic data regarding the female athlete triad continues to mount, the 2014 Female Athlete Triad Coalition Consensus still maintains that preparticipation physical evaluations remain the first line for early detection. ^[8] Questionnaires should include inquiry about whether the athlete is satisfied with her current weight and about how much weight she would like to gain or lose, as well as a full menstruation history, dietary concerns/restrictions, and a bone health history. ^[8] Simple inquiries such as these may reveal the first warning signs of an athlete at risk or suffering from the female athlete triad.

A study that categorized athletes into low-, moderate-, and high-risk groups for bone stress injuries using the Female Athlete Triad Cumulative Risk Assessment score found that moderate-risk athletes were twice as likely to sustain a bone stress injury when compared to the low-risk group and high-risk were 4 times as likely. The study also found that bone stress injuries were most common in cross-country runners. ^[33]

 

For many athletes, the long-term prognosis is good. Few athletes with the female athlete triad are admitted to the hospital for inpatient treatment, and few die from their disease. However, significant long-term morbidity may affect these women later in life.

The diagnosis of the female athlete triad was established in the early 1990s, although this set of symptoms had been noted for years before it was named. ^{[3, 21, 34, 35]} However, no long-term data on future problems are available. The first generation of athletes in whom this condition was diagnosed is still years away from menopause. Thus, it is unclear whether osteopenia/osteoporosis occurring at a younger age affects mortality or leads to more advanced osteoporosis later in life or to an increased risk of significant fractures (eg, hip fractures). ^[36]

For mild to moderate cases of the female athlete triad, some improvement in bone health is thought to occur. The lost BMD is unlikely to be replaced in its entirety, and the bone mass that should have been accumulated during this important time in bone development may or may not be fully regained. ^[36] Unfortunately, no long-term, double-blind, controlled studies are available (or even performable).

As more information about the female athlete triad and its complications is gathered, everyone involved may better understand the significant morbidity that can occur years or decades after the disease is diagnosed and treated.

Complications

Continued bone loss leading to irreversible osteoporosis is the most worrisome complication of the triad. Some evidence exists to suggest that bone mineral density (BMD) can be regained to a small degree, but it is doubtful that a significant loss can be completely corrected, even with years of therapy.

A cross-sectional study that evaluated the associations between BMD and exercise performed in women with a history of anorexia nervosa found that currently ill participants had a lower BMD than recovered patients. ^[37]  The authors concluded that excessive moderate loading exercise may put these patients at higher risk of low BMD. Recovering patients may benefit from high bone-loading exercise by provoking bone accrual.

Multiple stress fractures or complete fractures can lead to an increased incidence of osteoarthritis, depending on the site of the fractures. Other fractures may heal without any long-term sequelae. These fractures should be carefully monitored; they may take longer to heal than one would expect. The negative nutritional balance often leads to slowed or delayed healing of fractures.

End-stage eating disorders can result in more serious complications, such as prolonged hospitalization, cardiac arrhythmias, or even death. Anorexia nervosa has an estimated mortality of 15% once the diagnosis is made. Compared with other individuals, athletes are less likely to meet the criteria for anorexia or bulimia, but significant morbidity and mortality can occur.

As research continues and long-term data are followed, possible other complications may include many other psychological and physiological dysfunctions affecting the cardiovascular, renal, hepatic, gastrointestinal, endocrine, reproductive, skeletal, and central nervous systems. ^[9]  Issues such as anemia, chronic fatigue, increased risk of infection and illness, esophagitis, electrolyte imbalance, slowing of the metabolic rate, decreased production of growth hormone, unfavorable lipid panels, endothelial dysfunction (which is a strong predictor of coronary artery health and a possible increase in atherosclerotic disease and cardiovascular event rates), reduced muscle protein synthesis, unexpected pregnancy, possible long term reproductive repercussions, and depression can all concurrently occur with the female athlete triad. ^{[16, 17, 9]}

Educating athletes may lead to earlier detection of the female athlete triad. If women know that amenorrhea is not a positive sign of hard work but a harbinger of disease, they may seek treatment sooner. Of course, the triad may have a secretive nature, and by the time an athlete shows signs of disordered eating, education may not be enough to help these women seek help. If the general athletic population and the providers taking care of athletes are aware of the signs and symptoms of this disease, the female athlete triad has a better chance of being be caught in its early stages.

A survey of female figure skaters, dancers, and runners aged 25 years or younger found that runners had greater knowledge of the triad than skaters and dancers. Overall, 12% of survey participants were aware of the triad. ^[38]

Physicians need to do better in educating trainers, coaches, and parents (as well as the athletes themselves). These are the people who will have daily contact with the athlete, and they may be the persons who first raise concerns about a particular individual. Taking the time to talk to the athletic staff about the warning signs may help in preventing the disease or catching it in its early stages.