Pediatric Annals

Special Issue Article 

Amenorrhea in the Female Athlete: What to Do and When to Worry

Kate Berz, DO; Teri McCambridge, MD

Abstract

Functional hypothalamic amenorrhea is a diagnosis of exclusion that is common in female athletes, particularly those participating in aesthetic sports (ballet, other dance genres, figure skating, and gymnastics) and endurance sports (cross-country running). Although common, it should be considered abnormal even in the high-level elite athlete. Amenorrhea in combination with low energy availability and low bone density is labeled “the Female Athlete Triad.” Studies have demonstrated numerous long-term consequences of athletes suffering from all or a portion of this triad, including increased rate of musculoskeletal injuries, stress fractures, abnormal lipid profiles, endothelial dysfunction, potential irreversible bone loss, depression, anxiety, low self- esteem, and increased mortality. This article provides the clinician with the tools to evaluate an athlete with secondary amenorrhea, reviews the recommended treatment options for affected athletes, and discusses when to return to the activity in an effort to facilitate “healthy” participation. [Pediatr Ann. 2016;45(3):e97–e102.]

Abstract

Functional hypothalamic amenorrhea is a diagnosis of exclusion that is common in female athletes, particularly those participating in aesthetic sports (ballet, other dance genres, figure skating, and gymnastics) and endurance sports (cross-country running). Although common, it should be considered abnormal even in the high-level elite athlete. Amenorrhea in combination with low energy availability and low bone density is labeled “the Female Athlete Triad.” Studies have demonstrated numerous long-term consequences of athletes suffering from all or a portion of this triad, including increased rate of musculoskeletal injuries, stress fractures, abnormal lipid profiles, endothelial dysfunction, potential irreversible bone loss, depression, anxiety, low self- esteem, and increased mortality. This article provides the clinician with the tools to evaluate an athlete with secondary amenorrhea, reviews the recommended treatment options for affected athletes, and discusses when to return to the activity in an effort to facilitate “healthy” participation. [Pediatr Ann. 2016;45(3):e97–e102.]

Early identification of female athletes with functional hypothalamic amenorrhea or any elements of the Female Athlete Triad (FAT) is important to the adolescent's current and long-term health. Here we discuss a common presentation of a patient and how to proceed with further evaluation.

Illustrative Case

A mother and her 15-year-old daughter presented to the office for further evaluation of amenorrhea. The daughter achieved menarche at age 13 years, and she had not menstruated for 3 months prior to the office visit; she denies sexual activity. She is an honor student who runs cross-country track and is a self-proclaimed “picky eater.” Mom indicated that her daughter had been focused on her diet and had no desire to gain unnecessary weight that may affect her running performance.

Overview of the Triad

The FAT refers to three interrelated spectrums: low energy availability, menstrual dysfunction, and low bone mineral density (BMD); FAT was first identified in 1992.1 In 2014, relative energy deficiency in sport (RED-S) was introduced to broaden the definition of the triad.2 RED-S refers to inadequate energy availability for optimal health and performance.2 This article focuses on the three original components of the triad.

The prevalence of the triad has been found in 1% to 14% of female athletes/performers, with the highest frequency in professional ballet dancers.3,4 FAT can be present in any female athlete, but those at greatest risk participate in weight class sports or disciplines that favor leanness. Examples include lightweight crew, ballet, distance running, gymnastics, and swimming. Additional “at risk” athletes include those with psychologic stressors such as an injury, family dysfunction, or abuse. Preoccupation with weight and food avoidance can be red flags for coaches and parents for the development of an eating disorder.

Amenorrhea

Functional hypothalamic amenorrhea (FHA) is a disorder of the hypothalamic-pituitary-ovarian axis in an otherwise anatomically and organically normal system and is characterized by a suppression of the gonadotropin-releasing hormone (GnRH) pulsatility. This suppression decreases the frequency of the release of luteinizing hormone from the anterior pituitary resulting in a low estrogen state.5–7 The causes of FHA can be multifactorial and include low body weight, medication, nutrition, excessive training, hormone abnormalities, and psychosocial factors.

Amenorrhea is divided into primary and secondary. Concern for primary amenorrhea arises if an athlete has reached the age 13 years without pubertal development, absence of menarche 5 years after breast development, or if menarche has not occurred by age 15 years.7 Primary amenorrhea is beyond the scope of this article.

Secondary amenorrhea is absent menses for more than three cycles or irregular menses for 6 months after the establishment of normal cycles. Although menstrual irregularity is common during the first few years of menstruation, a cycle greater than 45 days is considered abnormal. The most common cause is pregnancy followed by thyroid dysfunction, FHA, and polycystic ovarian syndrome.5,7 Secondary amenorrhea has been reported in 65% to 69% of dancers and distance runners compared to 2% to 5% of collegiate women.2 The recommended evaluation for secondary amenorrhea is indicated in Table 1.

Diagnostic Tools for Recognizing Secondary Amenorrhea

Table 1.

Diagnostic Tools for Recognizing Secondary Amenorrhea

Bone Mineral Density

BMD is the gold standard for measurement of bone health. A z-score ≤ −2 on a dual energy X-ray absorptiometry (DXA) bone density scan defines low BMD in a premenopausal woman.8 Genetics is the largest predictor of long-term BMD, but estrogen deficiency, glucocorticoid exposure, or hyperparathyroidism have influence. Peak bone mass occurs during adolescence. Reports indicate that decreased energy availability through calorie restriction or excessive exercise can prevent an adolescent from achieving her genetically determined peak BMD.9 Other factors affecting bone health include secondary amenorrhea, tobacco use, alcohol abuse, and the quality of the diet especially calcium and vitamin D intake.

Low Energy Availability

Disordered eating may develop as the athlete attempts to lose weight or improve performance. She may develop unhealthy behaviors or fail to consume enough calories to support metabolic needs. In one study, the prevalence of clinical eating disorders was 46.7% among lean-sport female athletes.10

In general, a body mass index (BMI) <17.5 kg/m2 or <85% of ideal body weight demonstrates low energy availability.8 According to the 2014 Female Athlete Triad Coalition position statement,8 stable body weight should not be used as a predictor of adequate energy availability. It is possible to simultaneously be in a state of energy balance and still have low energy availability.

History Taking

When evaluating a patient with suspected FAT or any of the components, the history should include questions about menarche in the patient, her mother and any sisters, and the date of the patient's last menses. A diet history should include typical meals and eating patterns. Questions about weight changes, life stressors, and exercise habits can identify additional risk factors.

Contraceptives, antidepressants, antihypertensive, or antipsychotic medications can all affect menses as well.7 Continuous combined oral contraceptive pills and depot medroxyprogesterone injections can cause amenorrhea. Alternative diagnoses are considered with questions about chronic medical conditions, thyroid dysfunction, or pituitary/endocrine tumors (headache, galactorrhea, visual field defects).5 A comprehensive list of evaluation questions is included in Table 2.

Evaluation Questions to Ask a Patient with Suspected Secondary Amenorrhea

Table 2.

Evaluation Questions to Ask a Patient with Suspected Secondary Amenorrhea

Physical Examination

When assessing the patient, note the patient's appearance. Wearing large clothing to hide a thin frame signifies an unhealthy body image. Document height and weight in a gown (for consistency), calculate a BMI, and record vital signs. Bradycardia is a late finding in anorexia nervosa. Clinicians should also assess for thyromegaly. Hirsutism, acne, male pattern baldness, and clitoromegaly suggest hyperandrogenemia, which presents in polycystic ovary syndrome, adrenal hyperplasia, or an androgen-secreting tumor.5,7

Regarding low energy availability, examination results may include orthostatic changes in blood pressure such as a ≥10 mm Hg decrease in diastolic pressure, ≥20 mm Hg decrease in systolic pressure, or an increased heart rate of >20 bpm within 3 minutes of standing. Lanugo hair or carotemia may be evident in a child with an eating disorder.11 Erosion of dental enamel, callus formation on the back of the hands, or hoarseness suggests self-induced vomiting.12

Osteoporosis and Which Patients Need DXA

In children and premenopausal women, the International Society for Clinical Densitometry13 recommends using DXA z-scores for BMD. Osteoporosis cannot be diagnosed in children on the basis of DXA alone. The presence of a clinically significant fracture and low BMD are both required. Low BMD is defined as a z-score ≤ −2 and the low normal range is considered to be between −1 and −2. Criteria for clinically significant fracture history includes two or more long bone fractures by age 10 years or 3 or more long bone fractures at any age prior to age 19 years (Table 3).

Who Needs a Dual Energy X-ray Absorptiometry?a

Table 3.

Who Needs a Dual Energy X-ray Absorptiometry?

Treatment

Increase Weight and Decrease Exercise

Studies show that weight gain and reduction in exercise restore normal menses in FHA. A standard amount of increase in body fat, BMI, or weight gain that is needed to achieve menses is unclear. One study showed that a caloric intake of 30 kcal/kg of fat-free body mass per day resulted in a return of the menstrual cycle in four athletes. Adequate fat and protein intake is essential.5 In athletes with a distorted body image or who participate in sports that favor leanness, achieving an appropriate weight can be a challenge.

Caloric intake should be set to a minimum of 2,000 kcal/day. A nutritionist can calculate daily energy intake and expenditure and provide guidance for caloric intake.8 In the athlete with low energy availability who does not respond to nutritional counseling, psychotherapy may be warranted. Cognitive-behavioral therapy has been shown to be effective and is the treatment of choice in bulimia nervosa (BN).14

Vitamins and Minerals

For optimal BMD, the daily recommendation is 1,500 mg/day of calcium and 1,500 to 2,000 IU per day of vitamin D. Additional treatment is recommended for low 25-hydroxyvitamin D defined as <32 ng/mL.2 Calcium intake should occur throughout the day either from dietary intake or supplementation in doses no greater than 500 mg.

Strength Training

High-impact loading and resistance training is recommended 2 to 3 days a week to positively affect bone density in athletes with diminished bone density or for those in low-impact sports such as swimming and cycling.2

Medications

Oral contraceptive pills (OCPs) restore menses by increasing estrogen levels thus reestablishing regular menstruation. However, multiple studies have demonstrated that this approach provides false security that “normal” menstruation has resumed and continues to limit accretion of calcium into the bone.15 An 8-year study comparing athletes with regular menstruation versus athletes with oligomenorrhea/amenorrhea with or without OCPs demonstrated a vertebral BMD in the amenorrheic athlete that was 85% of the level seen in the eumenorrheic athlete.16 The use of progesterone-only pills can contribute to continued bone loss and are not recommended. Because the problem is energy intake/expenditure, metabolic factors that impair new bone formation will not normalize with hormone replacement alone.

Some studies suggest that administration of an OCP may be considered in the athlete older than age 16 years with FHA with continued BMD losses despite normal nutrition and body weight.17 Athletes with osteoporosis and a history of multiple fractures who lack response with 1 year of nonpharmacologic treatment or new fractures may also benefit from treatment.18 Recommended treatment is transdermal estradiol (100 mcg of 17 beta estradiol) with cyclic progesterone of 5 to 10 mg of medroxyprogesterone acetate for 12 days of each month.18,19

Energy-deficient states are associated with decreased leptin, which is produced by adipocytes and has been shown to regulate GnRH. A few studies have shown that normalization of leptin levels with 3 months of exogenous leptin restored menstrual function. Naltrexone, an opiate receptor antagonist, has been shown to restore ovulation in women with FHA.6 However, leptin and naltrexone have not been studied in adolescents.

The young athlete should not be treated with bisphosphonates. Although approved for treatment of osteoporosis in postmenopausal women, they have no proven efficacy in premenopausal women.

How to Screen?

Screening for elements of FAT should begin during the preparticipation physical examination (PPE). The fourth edition PPE monograph20 incorporates many of the screening questions such as stress fracture history (bone health), weight concerns, dieting, food group avoidance, frank eating disorder (low energy availability), and menarche and cycle frequency (amenorrhea). If these screening questions raise additional concerns, then more sensitive testing can be performed.

If concerns of a possible eating disorder arise, several possible screening tests exist for office use. Options include the Low Energy Availability in Females Questionnaire, the Brief Eating Disorder in Athletes Questionnaire, and the Eating Attitudes Test.21–23 These questionnaires require the completion and review of 9 to 26 questions prior to making a psychology referral decision. A quick and simple screen for use by primary care physicians is the SCOFF screening questionnaire, which requires the patient to answer several questions (Table 4).11,24 A score ≥2 requires a more formal evaluation. This test has been validated in adults, but not yet in the pediatric population. In the primary care setting, comparing the SCOFF test24 to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)25 diagnosis of eating disorder demonstrated 84.6% sensitivity and 89.6% specificity.

SCOFF Screening Questions

Table 4.

SCOFF Screening Questions

Long-Term Complications

Athletes with FAT have increased risk of cardiovascular, psychosocial, musculoskeletal, and endocrine problems compared to their peers. Studies have demonstrated athletes with amenorrhea have a statistically significant decrease in flow-mediated dilation (FMD) of their brachial artery (by noninvasive ultrasound technique) compared to an athlete with oligomenorrhea or regular cycles. A reduced FMD has been associated with an increased risk for atherosclerosis and is considered an early marker of cardiovascular disease.26 In addition, athletes who are amenorrheic have higher levels of cholesterol, apolipoprotein B, and low density lipoprotein, which are risk factors for development of atherosclerosis. It is unclear if these abnormalities are reversible.

Studies have demonstrated an increased mortality risk in athletes suffering from eating disorders, with anorexia nervosa (AN) having the highest mortality rate of all mental disorders. The estimated mortality rate for AN is 0.51% per year, BN is 0.17%, and eating disorder not otherwise specified is 0.33%.27 Other psychologic problems associated with eating disorders include low self-esteem, depression, and anxiety. One study demonstrates a trend toward a 3-fold increase in musculoskeletal injury requiring 7 or more days off from sports in athletes suffering from menstrual irregularity.28 Athletes with menstrual dysfunction had more severe stress bone injuries as assessed on magnetic resonance imaging and an associated increased time to return-to-play.29

Activity Restriction and Return-to-Play

FHA or any components of FAT should be treated like an injury in that restriction and return-to-play decisions are determined on the basis of meeting treatment goals and maintaining athlete safety. Table 5 lists reasons for restriction from sport participation. For FHA, rehabilitation consists of restoration of the energy balance and menses. The athlete should be given clear and concise expectations and attainable goals. Some examples include adding previously avoided food groups, increasing calorie intake by 100 kcal per week, and slow and steady weight gain. Return-to-play should be allowed when the medical team has deemed it safe and without long-term consequences.

Reasons to Restrict from Sports Participation

Table 5.

Reasons to Restrict from Sports Participation

Summary

Secondary amenorrhea resulting from functional hypothalamic amenorrhea can be a common problem identified in athletes. It is a diagnosis of exclusion, and screening should occur at all primary health examinations and at the PPE. The consequences of low energy availability, amenorrhea, and low BMD can result in short- and long-term health complications. Early identification and treatment can help to avoid lifelong problems.

References

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Diagnostic Tools for Recognizing Secondary Amenorrhea

Physical examination and ultrasound to evaluate for abnormalities of the uterus, cervix, and vagina to rule out foreign body or tumor

Beta subunit of human chorionic gonadotropin to rule out pregnancy

Complete blood count and chemistry panel to rule out chronic disease

Thyrotropin and free thyroxine (primary and central hypothyroidism); can resemble central hypothyroidism in a patient with an eating disorder

Serum prolactin to rule out prolactinoma

Follicle-stimulating hormone to evaluate for ovarian insufficiency and luteinizing hormone to rule out premature ovarian failure; these can also be low in a patient with an eating disorder

“Free” testosterone and dehydroepiandrosterone sulfate (only if signs of masculinization)

A progesterone challenge may be useful to evaluate for estrogen sufficiency. Medroxyprogesterone acetate of 10 mg is administered for 10 days. Menstrual bleeding within 7 days after stopping the medicine signifies estrogen sufficiency

In athletes demonstrating malabsorption symptoms, screening for celiac disease with a tissue transgulatminease antibody test is recommended

Magnetic resonance imaging of the brain should be obtained if there are signs of a pituitary tumor

Karyotype in a patient with amenorrhea and short stature to rule out Turner's syndrome

Evaluation Questions to Ask a Patient with Suspected Secondary Amenorrhea

At what age did you achieve menarche?

When was your last period?

Do you take medicine, like oral contraceptive pills, to regulate your periods?

At what age did mom and sisters achieve menarche?

How many days per week and for how many hours do you play, practice, or exercise?

Are there food groups that you avoid?

What do you typically eat for breakfast, lunch, dinner, and snacks?

Have you recently experienced any changes in your weight?

Are there stressors at home or at school?

Are you sexually active?

Who Needs a Dual Energy X-ray Absorptiometry?a

Either one or more of the following   History of eating disorder   BMI ≤17.5 kg/m2, <85% estimated weight, or recent weight loss of ≥10% in 1 month   Menarche ≥ age 16 years   <6 menstrual cycles over a 12-month period   Two prior stress injuries, one high-risk stress injury, or a low-energy nontraumatic fracture   Z-score of < −2 at least 1 year from baseline DXA Or two or more of the following   History of ≥6 months of disordered eating   BMI 17.5 to 18.5 kg/m2, <90% estimated weight, or recent weight loss of 5% to 10% in 1 month   Menarche age between 15 and 16 years   6 to 8 menstrual cycles over a 12-month period   One prior stress injury   Z-score between −1 and −2 at least 1 year from baseline DXA Additional considerations   History of ≥1 central or ≥2 peripheral long-bone traumatic fractures in the presence of 1 or more of the above risk factors   ≥6 months of medication use that may impact bone health   Repeat testing every 1 to 2 years to evaluate treatment and look for ongoing bone loss

SCOFF Screening Questions

Do you make yourself Sick (vomit) because you feel uncomfortably full?
Do you worry you have lost Control over how much you eat?
Have you recently lost more than One stone (15 lbs) in a 3-month period?
Do you believe yourself to be Fat when others say you are thin?
Would you say that Food dominates your life?

Reasons to Restrict from Sports Participation

Body mass index <17 kg/m2 or weight that crosses two lines on the growth chart

Failure to meet targeted weight gains

Acutely ill requiring hospitalization for disordered eating

Bradycardia or electrocardiogram abnormality

Acute injury/stress fracture

Electrolyte abnormalities

Failure to schedule appointments with medical team

Authors

Kate Berz, DO, is an Assistant Professor of Pediatrics, Divisions of Sports Medicine and Emergency Medicine, Cincinnati Children's Hospital Medical Center. Teri McCambridge, MD, is an Assistant Professor of Pediatrics and Orthopedics, University of Maryland School of Medicine.

Address correspondence to Kate Berz, DO, Assistant Professor of Pediatrics, Divisions of Sports Medicine and Emergency Medicine, Cincinnati Children's Hospital Medical Center, MLC 10001, 3333 Burnet Avenue, Cincinnati, OH 45229-3026; email: Kate.Berz@cchmc.org.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00904481-20160210-03

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