Female Athlete Triad
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). There is also emerging research to suggest an expanded syndrome referred to as Relative Energy Deficiency in Sport (RED-S), which acknowledges that male athletes maybe at risk (2).
- Female athlete triad was first described in 1992: Patients may meet criteria for only one or two parts of the triad.
- 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.
- EA is fundamental to the propagation of the triad.
- Full recovery is not possible without correction of low EA.
- The International Olympic Committee’s updated position statement from 2014 now considers RED-S to be a more accurate representation of the psychological and physiologic stresses placed on the athlete’s body.
- Metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular and psychological health are all effected (2).
- Prevention and early intervention are essential to prevent progression to serious clinical end points of eating disorders, amenorrhea, and osteoporosis.
- RED-S also takes into account the effects of relative energy deficiency on male athletes, who are often affected in weight-sensitive sports (gymnastics, wrestling, cycling, etc.) (2).
- The changes in physiology should be viewed as a spectrum, with normal EA, BMD, and regular menses at one extreme and clinical eating disorders, osteoporosis, and amenorrhea at the other (2).
- 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
- EA (kcal/kg FFM/day) = [EI (kcal/day) − EEE (kcal/day)] where EEE is effective energy expenditure and FFM is fat free mass
- 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.
- Low EA alters the hypothalamic-pituitary axis, resulting in functional hypothalamic amenorrhea.
- MD ranges from eumenorrhea to amenorrhea.
- MD includes athletes who have low estrogen levels but still experience menstruation.
- Energy deficit results in MD 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 (no menarche by age 15 years), although less common, can occur in young athletes. Secondary amenorrhea is defined as the absence of menstrual cycles for >3 months after menarche has been established.
- Although hypothalamic suppression is the most common cause of secondary amenorrhea in these athletes, other causes must be ruled out.
- Ranges from optimal bone health to osteoporosis
- Peak BMD occurs at 19 years in females and 20.5 years in males.
- Bone health encompasses bone strength as well as bone quality. The current practice standard (dual energy x-ray absorptiometry [DEXA]) measures bone density, not bone quality. This research may help providers better understand why two athletes with the same BMD may have very different bone fracture histories (3).
- ACSM position stand recommends using the International Society for Clinical Densitometry (ISCD) guidelines for BMD Z-scores <−2.0 with a history of clinically significant fracture for diagnosis of osteoporosis.
- 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 (4).
- Overall prevalence: 0–16% of female athletes (5). Prevalence of two criteria varies: MD + BMD 0–8% (n = 460), MD + LE 18% (n = 80), and BMD + LE 4% (n = 80) (3).
- DE higher than general population (3)
- MD: Prevalence of secondary amenorrhea is as high as 60% in female athletes compared to 2–5% in the general population (3).
- 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 (3).
Etiology and Pathophysiology
- In functional hypothalamic amenorrhea, 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 MD.
- 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.
- 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 (2).
- 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)
- 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 are endorsed by AAP, AAFP, ACSM, AOSSM, 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.
- 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]
- EDE-17 is the gold standard for eating disorder diagnosis.
Assess menstrual history (including hormonal 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.
- Height, weight, body mass index (BMI) <17.5% kg/m2, <85% of expected body weight in adolescents, or ≥10% weight loss in 1 month (1)
- 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 in a low estrogen state.
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:
- 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 & InterpretationInitial Tests (lab, imaging)
- Basic metabolic panel, magnesium, phosphorus, albumin, CBC with differential, ESR, thyroid-stimulating hormone (TSH), calcium, 25-OH vitamin D, and urinalysis (1,5)
- Evaluation for secondary amenorrhea includes urine hCG and serum 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 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.
- The goal is to optimize nutritional status and treat maladaptive behavioral disorders (1,3)[A].
- A multidisciplinary team including 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 per 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 per day (1)[A].
- 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. Transdermal estradiol with cyclic oral 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.
- 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.
- cOCPs do have potential to mask signs of RED-S and do not correct underlying energy deficiency. They can also suppress androgen release, potentially causing a decrease in BMD (2).
- Provide calcium (1,500 mg/day) and vitamin D supplementation to maintain serum levels within 32 to 50 mg/mL (1)[A].
- In male athletes, with RED-S, testosterone replacement therapy can be helpful in patients with hypogonadism and osteoporosis (2).
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.
- Patients should have regular follow-up with a multidisciplinary treatment team (6)[A].
- Cognitive-behavioral therapy (CBT) is effective for exercising women with DE 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” helps 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.
- The RED-S Risk Assessment Model can be used to aid decision to clear athletes to return to play (2).
- 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 (1,3)[A].
- RED-S effects on performance: decrease endurance, increased injury risk, decreased training response, impaired judgment, decreased coordination, decreased concentration, irritability, depression, decreased glycogen stores, decreased muscle strength (2)
- 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.
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. [PMID:17909417]
- F50.9 Eating disorder, unspecified
- M81.8 Other osteoporosis without current pathological fracture
- M85.9 Disorder of bone density and structure, unspecified
- N91.2 Amenorrhea, unspecified
- N92.6 Irregular menstruation, unspecified
- R53.83 Other fatigue
- 307.50 Eating disorder, unspecified
- 626.0 Absence of menstruation
- 733.00 Osteoporosis, unspecified
- 780.79 Other malaise and fatigue
- 14302001 Amenorrhea (finding)
- 271795006 Malaise and fatigue
- 64859006 Osteoporosis (disorder)
- 710072005 Female athlete triad (disorder)
- 72366004 Eating disorder (disorder)
- 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. There is emerging research regarding an expanded syndrome called RED-S.
- Screen at-risk women and men 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.
Miranda Gordon-Zigel, MD
Rahul Kapur, MD, CAQSM
- 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. [PMID:24569429]
- Mountjoy M, Sundgot-Borgen J, Burke L, et al. The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S). Br J Sports Med. 2014;48(7):491–497. [PMID:24620037]
- Barrack MT, Ackerman KE, Gibbs JC. Update on the female athlete triad. Curr Rev Musculoskelet Med. 2013;6(2):195–204. [PMID:23613226]
- Lanser EM, Zach KN, Hoch AZ. The female athlete triad and endothelial dysfunction. PM R. 2011;3(5):458–465. [PMID:21570034]
- 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. [PMID:23669090]
- Deimel JF, Dunlap BJ. The female athlete triad. Clin Sports Med. 2012;31(2):247–254. [PMID:22341014]
© Wolters Kluwer Health Lippincott Williams & Wilkins
Female Athlete Triadis the Medicine Central Word of the day!