FEMALE ATHLETE TRIAD

Andrew J. McBride, MD • Rahul Kapur, MD

 BASICS

Syndrome of three interrelated clinical entities: low energy availability (EA) (with or without disordered eating [DE]), menstrual dysfunction (MD), and low bone mineral density (BMD) (1).

DESCRIPTION

•  Female athlete triad was first described in 1992: Patients may meet criteria for only one or two parts of the triad.

•  Prevention and early intervention are essential to prevent progression to serious clinical end points of eating disorders, amenorrhea, and osteoporosis.

•  2014 Female Athlete Triad Coalition Consensus Statement and the 2007 American College of Sports Medicine (ACSM) Position Stand suggest (1):

–  Each component of the triad represents a spectrum ranging from health to dysfunction.

–  Energy availability is fundamental to the propagation of the triad.

–  Full recovery is not possible without correction of low energy availability.

•  Energy availability (EA)

–  Dietary energy intake minus exercise energy expenditure. The core element of the triad.

–  Represents the amount of dietary energy remaining for bodily functions after correcting for exercise training

–  Low EA results in reduced capacity for cellular maintenance, thermoregulation, and growth.

–  Low EA serves a causal role in the induction of exercise-associated menstrual disturbances.

–  Low EA occurs either intentionally or inadvertently. Examples include increasing training disproportionately to energy intake; DE; and reducing energy intake by restricting, fasting, binging, and purging or use of diet pills, laxatives, diuretics, or enemas. Not all athletes meet diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) for eating disorders.

•  Menstrual dysfunction (MD)

–  Low EA alters the hypothalamic-pituitary axis, resulting in decreased estrogen levels.

–  MD ranges from eumenorrhea to amenorrhea.

–  MD includes athletes who have low estrogen levels but still experience menstruation.

–  Energy deficit results in menstrual dysfunction at ~30 kcal/kg lean body mass per day.

–  MD includes luteal suppression (shortened luteal phase, prolonged follicular phase, and decreased estradiol level), anovulation, oligomenorrhea (menstrual cycle >35 days), and primary and secondary hypothalamic amenorrhea.

–  Primary amenorrhea, although less common, can occur in young athletes. Secondary amenorrhea is defined as the absence of menstrual cycles for >3 months after menarche established.

–  Although hypothalamic suppression is the most common cause of secondary amenorrhea in these athletes, other causes must be ruled out.

•  BMD

–  Ranges from optimal bone health to osteoporosis

–  Bone health encompasses bone strength as well as bone quality. The current practice standard (dual-energy x-ray absorptiometry) measures bone density not bone quality. However, newer research using peripheral quantitative CT scans have shown that amenorrheic female athletes have a lower proportion of cortical bone, which is thought to be related to deficient mineralization and may be responsible for the increased fracture risk (2). This research may help providers better understand why two athletes with the same BMD may have very different bone fracture histories.

  ACSM Position Stand recommends using the International Society of Clinical Densitometry (ISCD) guidelines for BMD Z-scores <−2.0.

  Because most athletes have a higher BMD than nonathletes, ACSM recommends further workup for any athlete with a Z-score <−1, even in the absence of fracture.

–  Endothelial dysfunction

  Emerging evidence suggests that the female athlete triad is associated with endothelial dysfunction. Reduced levels of estrogen alter vasodilation. Athletic amenorrhea is associated with reduced brachial artery flow-mediated dilation, which has a 95% positive predictive value for coronary endothelial dysfunction. Consequences include decreased blood flow to muscles during exercise and accelerated atherosclerosis. In the future, this clinical syndrome may be considered a tetrad (3).

EPIDEMIOLOGY

Prevalence

•  Overall prevalence: 0–16% of female athletes (4). Prevalence of two criteria varies: MD + BMD 0–8% (n = 460), MD + LE 18% (n = 80), and BMD + LE 4% (n = 80) (4)

•  DE higher than general population (4)

•  Menstrual dysfunction: Prevalence of secondary amenorrhea is as high as 60% in female athletes compared to 2–5% in the general population (4).

•  Bone health: Using the World Health Organization (WHO) criteria for low BMD, prevalence of osteopenia (T-score between −1 and −2) ranges from 0% to 40% in female athletes, as compared to ~12% in the general population (4).

ETIOLOGY AND PATHOPHYSIOLOGY

•  Low EA disrupts the hypothalamic-pituitary-ovarian axis, decreasing pulsatile gonadotropin-releasing hormone (GnRH) release (5).

•  Low GnRH levels decrease luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, decreasing estrogen production with resultant menstrual dysfunction.

•  Estrogen deficiency negatively affects bone density. A chronic state of malnutrition reduces the rate of bone formation and increases the rate of bone resorption. Changes in bone metabolism occur within 5 days of reductions in EA.

RISK FACTORS

•  History of menstrual irregularities and amenorrhea; history of stress fractures and recurrent or nonhealing injuries; history of critical comments about eating or weight from parent or coach; history of depression; history of dieting; personality factors including perfectionism and/or obsessiveness, overtraining, and inappropriate coaching behaviors (1)

•  Lean physique, sports with an aesthetic component (ballet, figure skating, gymnastics, distance running, diving, and swimming), or sports with weight classifications (martial arts and wrestling). Frequent weigh-ins, consequences for weight gain, and win-at-all-cost attitude all increase risk (6).

•  A lack of family or social support; intense training hours; social isolation or entering a new environment (boarding school or college); an athlete with comorbid psychological conditions (anxiety, depression, and/or obsessive-compulsive disorder)

GENERAL PREVENTION

•  Education of athletes (middle school through college), coaches, trainers, parents, and physicians. Young athletes are extremely impressionable and may turn negative comments and unhealthy advice into maladaptive eating and exercising habits.

•  General screening during preparticipation exam (PPE) and annual physicals is endorsed by AAP, AAFP, ACSM, AAOSM, and AMSSM (6).

•  Female Athlete Triad Coalition has 11-question screening to use during PPE (1).

•  Screen athletes presenting with “red flag” conditions such as fractures, weight changes, fatigue, amenorrhea, bradycardia, orthostatic hypotension, syncope, arrhythmias, electrolyte abnormalities, or depression.

COMMONLY ASSOCIATED CONDITIONS

•  Anorexia nervosa, bulimia nervosa, avoidant or restrictive food intake disorder, and other psychological disorders, including low self-esteem, depression, and anxiety (5)

•  Low BMD predisposes athletes to stress fractures and may not be fully reversible. This may lead to a higher rate of fractures after menopause.

 DIAGNOSIS

The female athlete triad is a clinical diagnosis based primarily on patient history. Screening for the female athlete triad at annual sports physicals or during routine exams and acute visits if there are concerns (1,5)[A]. There are several screening tools that have been validated for use in female athletes, including Athletic Milieu Direct Questionnaire (AMDQ), Brief Eating Disorders in Athletes Questionnaire (BEDA-Q), and Female Athlete Screening Tool (FAST) (7). However, there is no current consensus on which tool to use in practice (7).

HISTORY

Assess menstrual history (including oral contraceptive use), fracture history, and symptoms of depression. Assess dietary practices, eating behaviors, and history of weight changes. Dietary intake logs and a nutritional assessment by a sports dietitian can help. Assess body image; fear of weight gain; fluctuations in weight; history of DE; and use of laxatives, diet pills, or enemas.

PHYSICAL EXAM

•  Height, weight, body mass index (BMI) <17.5% kg/m² or <85% of expected body weight in adolescents (1)[A]

•  Common findings include bradycardia, orthostatic hypotension, hypothermia, cold or cyanotic extremities, lanugo, parotid gland enlargement or tenderness, epigastric tenderness, eroded tooth enamel, and knuckle or hand calluses (Russell sign).

•  Patients with amenorrhea should undergo a pelvic exam to verify the presence of a uterus and evaluate for outflow tract abnormalities. Vaginal atrophy may be present if the patient is hypoestrogenic.

DIFFERENTIAL DIAGNOSIS

Screen for anorexia nervosa, bulimia nervosa, avoidant/restrictive food intake disorder, and rumination disorder using the DSM-5 criteria. Rule out the following in amenorrheic patients:

•  Pregnancy

•  Endocrine abnormalities: thyroid dysfunction, Cushing syndrome

•  Hypothalamic dysfunction: psychological stress-induced amenorrhea, medication-induced amenorrhea, Kallmann syndrome

•  Pituitary dysfunction: prolactinoma, Sheehan syndrome, sarcoidosis, empty sella syndrome

•  Ovarian dysfunction: polycystic ovarian syndrome, premature ovarian failure, menopause, gonadal dysgenesis, Turner syndrome, ovarian neoplasm, autoimmune disease

•  Uterine dysfunction: Asherman syndrome, absence of uterus

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

•  Basic metabolic panel, magnesium, phosphorus, albumin, CBC with differential, ESR, thyroid-stimulating hormone (TSH), calcium, 25-OH vitamin D, and urinalysis (1,6)

•  Evaluation for secondary amenorrhea includes urine hCG, FSH, LH, prolactin, and TSH.

•  Pelvic ultrasound in patients with hyperandrogenism to exclude polycystic ovaries or virilizing ovarian tumors

•  ECG to rule out prolonged QT interval

Follow-Up Tests & Special Considerations

•  BMD testing by dual-energy x-ray absorptiometry (DEXA) is based on a risk stratification model (1). Risk factors include DE, eating disorders >6 months, hypoestrogenism, amenorrhea, oligomenorrhea, and/or in patients with a history of stress fractures or fractures from minimal impact.

•  If components of the triad persist, ISCD 2013 guidelines suggest reevaluation by the same DEXA machine every 1 to 2 years.

 TREATMENT

•  The goal is to optimize nutritional status and treat maladaptive behavioral disorders (1,4)[A].

•  A multidisciplinary team includes a physician, registered dietitian, and behavioral health provider. Build open lines of communication with coaches, trainers, and family.

•  A positive EA of >30 kcal/kg of fat-free muscle mass/day is sufficient to restore menses (5)[A].

•  Physically active females should strive for an EA of >45 kcal/kg of fat-free muscle mass/day (1)[A].

MEDICATION

First Line

•  Increasing EA through appropriate nutrition is the best strategy for normalizing gonadotropin pulsatility and release. The use of combination oral contraceptive pills (cOCPs), hormone replacement therapy (HRT), and/or bisphosphonates has not been clearly shown to increase BMD or aid in the restoration of normal menstrual cycling. cOCPs or transdermal estradiol with cyclic progesterone can be considered in patients with particularly low BMD Z-scores and fracture histories who do not respond to 1 year of nonpharmacologic management.

•  cOCP or transdermal estradiol can also be given to minimize further bone loss in patients >16 years and <21 years who, despite adequate nutrition and body weight gain, continue to have decreasing BMD and functional hypothalamic amenorrhea.

•  Provide calcium and vitamin D supplementation to maintain serum levels within 32 to 50 mg/mL (1)[A].

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Evaluate patients with eating disorders for potentially life-threatening conditions requiring hospital admission, including bradycardia, severe orthostatic hypotension, significant electrolyte imbalances, hypothermia, arrhythmias, or prolonged QT interval.

 ONGOING CARE

•  Patients should have regular follow-up with a multidisciplinary treatment team (6)[A].

•  Cognitive-behavioral therapy (CBT) is effective for exercising women with ED and may be more beneficial than nutritional counseling alone in women with DE behavior.

•  “Clearance and Return to Play (RTP) Guidelines by Medical Risk Stratification” help determine when to allow an athlete to return to competition. More research is needed to validate this model (1)[A].

•  To continue training and competing, athletes with eating disorders must agree to the following stipulations as part of a behavioral contract: to comply with all treatment strategies; to be closely monitored by health care providers; to place treatment goals over training goals; and to modify the type, duration, and intensity of training or competition as necessary.

PATIENT EDUCATION

All young female patients should be counseled on the importance of proper nutrition, calcium, and vitamin D intake and the benefits of regular weight-bearing exercise. Patients presenting with ≥1 components of the triad should be educated about the short- and long-term effects of low BMD (1,4)[A].

PROGNOSIS

•  The short- and long-term prognosis for patients with female athlete triad depends on time to diagnosis and response to treatment.

•  It is estimated that amenorrheic women will lose 2–3% of bone mass per year without intervention.

•  With early diagnosis and treatment using a multidisciplinary team, the prognosis for patients with the female athlete triad is good. Patients regain normal menstrual cycling and increase BMD.

•  Because the triad often occurs within the age window of optimal bone strengthening, patients with a prolonged disease course may suffer from complications of decreased BMD throughout their adolescent and adult life.

•  Patients with DE behaviors often require long-term therapy to manage their disease.

REFERENCES

1.  De Souza MJ, Nattiv A, Joy E, et al. 2014 Female Athlete Triad Coalition consensus statement on treatment and return to play of the female athlete triad: 1st International Conference held in San Francisco, CA, May 2012, and 2nd International Conference held in Indianapolis, IN, May 2013. Clin J Sport Med. 2014;24(2):96–119.

2.  Mallinson RJ, De Souza MJ. Current perspectives on the etiology and manifestation of the “silent” component of the female athlete triad. Int J Womens Health. 2014;6:451–467.

3.  Lanser EM, Zach KN, Hoch AZ. The female athlete triad and endothelial dysfunction. PM R. 2011;3(5):458–465.

4.  Barrack MT, Ackerman KE, Gibbs JC. Update on the female athlete triad. Curr Rev Musculoskeletal Med. 2013;6(2):195–204.

5.  Temme KE, Hoch AZ. Recognition and rehabilitation of the female athlete triad/tetrad: a multidisciplinary approach. Curr Sports Med Rep. 2013;12(3):190–199.

6.  Deimel JF, Dunlap BJ. The female athlete triad. Clin Sports Med. 2012;31(2):247–254.

7.  Knapp J, Aerni G, Anderson J. Eating disorders in female athletes: use of screening tools. Curr Sports Med Rep. 2014;13(4):214–218.

ADDITIONAL READING

Nattiv A, Loucks AB, Manore MM, et al. American College of Sports Medicine position stand. The female athlete triad. Med Sci Sports Exerc. 2007;39(10):1867–1882.

 SEE ALSO

Algorithms: Amenorrhea, Primary (Absence of Menarche by Age 16); Amenorrhea, Secondary; Weight Loss, Unintentional

 CODES

ICD10

•  F50.9 Eating disorder, unspecified

•  N91.2 Amenorrhea, unspecified

•  R53.83 Other fatigue

CLINICAL PEARLS

•  The female athlete triad consists of: low EA (with or without DE), MD, and low BMD. Athletes may exhibit varying degrees of dysfunction in any of these three areas.

•  Screen at-risk women to allow for early diagnosis and intervention.

•  Early intervention by a multidisciplinary team, including physicians, registered dietitians, mental health professionals, coaches, trainers, and parents, is the most successful strategy to minimize further bone loss, recover BMD, and regain normal menstrual function.

•  Current guidelines recommend screening for abnormal BMD using DEXA studies for patients with DE, eating disorders >6 months, hypoestrogenism, amenorrhea, oligomenorrhea, and/or in patients with a history of stress fractures or fractures from minimal impact.