Over the last 2 decades, it has become more apparent that some male athletes may experience a Triad-like syndrome, similar to the Female Athlete Triad. Scientific experiments and clinical research have helped guide clinicians toward better ways of assessing, diagnosing, and treating this Triad-like syndrome in the male athlete, now termed the Male Athlete Triad. The Male Athlete Triad is illustrated by Figure 1, and also described in depth in The Male Athlete Triad: A Consensus Statement from the Female and Male Athlete Triad Coalition Part 1: Definition and Scientific Basis. As in the female athlete, the key etiologic factor in the Male Athlete Triad is energy deficiency/low energy availability (EA), which may result in impaired reproductive and bone health. The Female and Male Athlete Triad Coalition Consensus Statement Part II: Diagnosis, Treatment, and Return-to-Play, demonstrates ways in which the science of the Male Athlete Triad translates into clinical practice. We present the latest clinical research to support current models of assessment, diagnosis, and management for male adolescent and young adult athletes.
As mentioned in the first article, the Female and Male Athlete Triad Coalition convened national and international expert panelists for a Roundtable on the Male Athlete Triad, in conjunction with the 64th Annual Meeting of the American College of Sports Medicine (ACSM) in Denver, Colorado, in May of 2017. Recommendations were set forth based on evidence-based data, as well as expert opinion. Similar to the Male Athlete Triad Part I: Definition and Scientific Basis, an evidence-based taxonomy has been used to grade the summary statements throughout the various sections of this article. Invited Roundtable expert panelists and selected attendees participated in reviewing the evidence statements for the Male Athlete Triad Consensus Statements. The evidence grading taxonomy chosen has been used by the ACSM position stands and by the Agency for Healthcare Research and Quality.1,2 The specific evidence scoring criteria are as follows:
Evidence level A: consistent pattern of findings on the basis of substantial data from randomized controlled trials (RCTs) and/or observational studies.
Evidence level B: strong evidence from RCTs and/or observational studies but with some inconsistent results from the overall conclusion.
Evidence level C: evidence from a smaller number of observational and/or uncontrolled or nonrandomized trials which is generally suggestive of an overall conclusion.
Evidence level D: insufficient evidence for categories A–C; panel consensus judgment.
SCREENING FOR THE MALE ATHLETE TRIAD
Who Should be Screened?
At-risk groups for developing one or more components of the Male Athlete Triad include adolescent and young adult male athletes in sports that emphasize a lean physique (lean-sport athletes), especially endurance and weight-class athletes. Most studies to date that have identified one or more components of the Male Athlete Triad have been in adolescent3,4 and young adult long distance runners,5–7 cyclists,8–11 and jockeys.12–14 However, there is a lack of clinical studies that assess one or more components of the Male Athlete Triad in other lean-sport athletes, as well as in non–lean-sport athletes. Future studies are needed to assess the risk of the Male Athlete Triad among male athletes in other sports, as well as among military recruits.
Evidence level B: male adolescent and young adult lean-sport athletes, especially endurance and weight-class athletes, are at risk for developing one or more components of the Male Athlete Triad.
When Should Screening be Performed?
Early identification and monitoring of athletes at risk for the Male Athlete Triad are key to preventing the more serious outcomes associated with the Triad. Screening should begin in middle school or high school and should continue through college to identify at-risk athletes, so their bone health can be optimized during the critical years of peak bone accrual. Data indicate that men reach their peak bone mass in the third decade of life, with most of their bone mass accrued by the end of the second decade.15–17 At-risk athletes should be screened for the Male Athlete Triad at the time of their preparticipation physical examinations (PPEs), especially because the primary objective of the PPE is to screen for conditions that may be life-threatening, disabling, or predispose to injury or illness.18 The International Olympic Committee (IOC) also recommends a periodic health evaluation (PHE) for elite athletes, stating that the purpose is to provide a comprehensive assessment of the athlete's current health status and risk of future injury or disease.19 Screening for the Male Athlete Triad at the PPE/PHE is particularly important in male adolescent and young adult athletes who participate in sports at higher risk for the Male Athlete Triad, such as endurance or weight-class sports. In addition to screening at the PPE and/or PHE, screening can occur when the male athlete presents with any one of the Male Athlete Triad medical conditions (Figure 4).
How Should Clinicians Screen for the Male Athlete Triad?
The PPE monograph and the PHE both recommend screening questions relevant to the Male Athlete Triad.18,19 However, there is a paucity of screening tools specific to the Male Athlete Triad, and ideally the tool(s) should be practical for use in a clinical setting. The Female Athlete Triad Coalition Consensus Statement recommended specific screening questions for the Female Athlete Triad in 2014.20,21 A similar list of suggested screening questions for use at the time of the PPE in athletes at risk for the Male Athlete Triad can be found in Table 1. Further validation of these questions is needed, and it should not be assumed that questions designed for females can be used for males.
TABLE 1. -
Recommended Screening Questions for the Male Athlete Triad
|Recommended Screening Questions for the Male Athlete Triad
|1. Do you worry about your weight?
2. Are you trying or has anyone recommended that you lose or gain weight?
3. Are you on a special diet, or do you avoid certain types of foods or food groups?
4. Have you ever had an eating disorder?
5. Have you ever had a stress fracture?
6. Have you ever been told that you have low bone density or osteoporosis?
7. Have you ever been diagnosed with low testosterone levels?*
8. Do you have low libido (sex drive)?*
9. Do you have morning erections?*
10. Do you need to shave your facial hair less frequently?*
*Recommend inclusion only on preparticipation physical examinations for postpubertal athletes.
In addition to screening questions for the Female Athlete Triad, the Female Athlete Triad Cumulative Risk Assessment tool has been effectively used to assess Female Athlete Triad–related risk factors.20,21 Kraus et al 22 demonstrated that a modified Female Athlete Triad Cumulative Risk Assessment, which included low EA, low body mass index (BMI), low bone mineral density (BMD), and history of prior stress fracture, was associated with prospective bone stress injury (BSI) in male athletes. A similar Male Athlete Triad Cumulative Risk Assessment tool, presented in Figure 2, provides another method of screening the at-risk male athlete.
Athletes should also be screened for the Male Athlete Triad any time they present to the medical team with conditions associated with the Triad (Figure 4). A new diagnosis of a BSI may be the initial presenting symptom in a patient with the Male Athlete Triad and should prompt thorough screening for other components of the Triad. Additional conditions that warrant screening for the Male Athlete Triad include decreased libido, the absence of morning erections, decreased frequency of shaving facial hair, a decrease in weight, decreased performance, fatigue, unexpected changes in mood, or recurrent injuries and illnesses. Because athletes with unintentional energy deficiency/low EA may not be actively attempting to restrict their intake or lose weight, they may not screen positive on the Male Athlete Triad screening questions suggested in Table 1. It is therefore very important to consider energy deficiency/low EA in the differential diagnosis when athletes present with related medical concerns.
When screening identifies athletes at risk for the Male Athlete Triad during their PPE or another medical visit, a more thorough assessment is warranted and should include a detailed medical history and physical examination.
Evidence level C: it is recommended that clinicians screen the at-risk male athlete with targeted screening questions and risk assessment tools. Further research is needed to validate a best practice screening questionnaire for the Male Athlete Triad.
DIAGNOSIS OF THE MALE ATHLETE TRIAD
How is the Male Athlete Triad Diagnosed?
Each of the 3 inter-related conditions of the Male Athlete Triad can occur on a spectrum, ranging from optimal health to the clinically relevant outcomes of energy deficiency/low EA with or without disordered eating or eating disorder, functional hypogonadotropic hypogonadism, and osteoporosis or low BMD with or without BSI (Figure 1). Furthermore, athletes may not present with all 3 components of the Triad at the same time, but identification of any one of the 3 components should prompt a thorough assessment for the others.
The accurate diagnosis of the Male Athlete Triad is best accomplished by a multidisciplinary medical team composed of a team physician, a sports dietitian, and a mental health professional (if disordered eating or a clinical eating disorder is present). Additional members of the team may include a certified athletic trainer, parents (of athletes <18 years old), medical consultants, and specialists, such as an endocrinologist, depending on the circumstances and the resources available.20,21,23,24 The multidisciplinary team not only assists with diagnosis, but, as will be discussed later, also helps with treatment and clearance decisions for athletes with the Male Athlete Triad. Team members should communicate frequently with one another and provide consistent information to the athlete because inconsistency can result in a lack of trust and confidence from the athlete.25
A thorough history should be performed, including a review of current symptoms and behaviors, medical history, medication history, family history, and psychosocial factors.
- Current symptoms and behaviors: the athlete's dietary behaviors should be explored in detail, including any dietary restrictions, changes in weight or weight cycling, current weight goals, and behaviors intended to control weight, such as purging or compulsive exercise. Athletes should be asked about recent illnesses or injuries and performance. If the athlete has undergone puberty, it is important to screen for symptoms of hypogonadism such as sexual dysfunction, decreased frequency of shaving facial hair, or decreased libido. Although questionnaires are available to identify symptoms of hypogonadism in males, these are generally limited by poor specificity or were developed for use in older men and have not been validated in athletes.26,27 The International Society for Sexual Medicine, the International Society for the Study of the Aging Male, the Endocrine Society, and the American Urological Association do not recommend the use of a specific screening questionnaire to identify hypogonadism or testosterone (T) deficiency in the general population.28–33
- Medical history: this should include a detailed assessment of any prior physician-diagnosed BSI or fractures. In addition, it should include a thorough assessment of the athlete's mental health diagnoses, including any history of depression, anxiety, bipolar disorder, obsessive compulsive disorder, or prior eating disorder. Occurrence of known endocrine disorders, such as hypothyroidism, hyperprolactinemia, and hypogonadism, should be included in this assessment.
- Medication history: the healthcare team should note any medications which might affect long-term bone health, such as glucocorticoids. In addition, athletes should be screened for medications that might affect libido, such as selective serotonin reuptake inhibitors, medications, and substances, that may cause elevations in prolactin and thus impact the hypothalamic–pituitary–gonadal (HPG) axis (antipsychotics, antidepressants, metoclopramide, domperidone, verapamil, cocaine, opiates, and possibly marijuana)34 and medications that may reduce appetite and cause weight loss (such as medications for attention deficit/hyperactivity disorder and topiramate).
- Family history: athletes should be asked about a family history of eating disorders, endocrine disorders, osteoporosis, or fragility fractures.
- Psychosocial factors: it can be helpful to elicit any history of critical comments, regarding body weight or size, or social pressures from coaches, parents, or teammates, because these may be influencing disordered eating behaviors and the maintenance of energy deficiency/low EA. Athletes should be screened for illicit drug use because this might also affect libido.
A comprehensive physical examination should be performed by the physician and should specifically seek to identify any signs of gonadal abnormalities or eating disorders. If a genitourinary examination is performed, a chaperone should be present.35 For the purpose of the targeted PPE in the male athlete, the purpose of the genitourinary examination is primarily to ensure that both testicles are in the scrotal sacs, and, for educating and teaching, the testicular examination to screen for testicular cancer. Findings suggestive of hypogonadism can also be assessed at this time if suspected by history and may include a lower than expected testicular volume depending on the time of onset and severity of hypogonadism. Hypogonadism before genital maturity may lead to an underdeveloped phallus and sparse pubic hair.
A low BMI, defined as BMI <18.5 in adults,36 may suggest energy deficiency/low EA with or without disordered eating. A major change in the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) was to remove the weight criterion for anorexia nervosa (AN), which previously required the patient to be <85% of estimated body weight to meet diagnostic criteria. This was replaced with broader statements which identify changes in an individual's growth trajectory.37 In children and adolescents with disordered eating and eating disorders, absolute BMI is not an optimal method to reflect the nutritional status.38 Preferred methods for BMI calculation in adolescence include examination of an adolescent's weight in relation to the 50th BMI percentile (also known as the BMI percentile method or percent median BMI),38 use of the Center for Disease Control (CDC) BMI-for-age growth charts,39 or use of BMI Z-scores.40 Amount and rate of weight loss should also be considered in evaluation of energy deficiency/low EA and disordered eating.40
Physical examination findings suggestive of an eating disorder might include bradycardia, orthostatic hypotension, lanugo, dental erosions, swelling of the parotid glands, or calluses on the proximal interphalangeal joints (Russell's sign).20,21
Based on the history and physical examination, if there is a high degree of suspicion for the Male Athlete Triad, additional laboratory and radiological studies may be indicated. Suggested laboratory studies are listed in Table 2. Indications for proceeding with imaging studies, such as a dual-energy x-ray absorptiometry (DXA) scan or pituitary MRI, are reviewed below.
TABLE 2. -
Suggested Laboratory Studies for the Evaluation of the Male Athlete Triad
|Suggested laboratory studies for the evaluation of the Male Athlete Triad*
| Complete blood count
| Comprehensive metabolic panel
| 25-OH vitamin D
| Total and free testosterone†
| Thyroid stimulating hormone
| Free T4
| Total ± free triiodothyronine (T3)
|Follow-up studies to consider if testosterone levels are low or fall in the gray zone* (8-12 nmol/L)
| Luteinizing hormone
| Follicle-stimulating hormone
| Iron studies, including ferritin
| Erythrocyte sedimentation rate and C-reactive protein
*Additional studies may also be indicated, depending on the patient presentation.
Total testosterone should be routinely ordered. Free testosterone is helpful if total testosterone is low or in the gray zone (8-12 nmol/L). In addition, free testosterone may be considered in conditions expected to alter sex hormone–binding globulin levels, such as thyroid disease, HIV, use of anticonvulsants or glucocorticoids, liver disease, or diabetes.26,30,34
Evidence level C: male athletes are diagnosed with the Male Athlete Triad if they have one or more components along the spectrums of the Male Athlete Triad. The diagnosis includes a thorough history and physical and is best accomplished by a multidisciplinary healthcare team.
How is Energy Deficiency Identified?
Unfortunately, it can be very challenging to determine accurate EA values, particularly because the calculation is dependent on self-reported measures of dietary energy intake (EI), exercise energy expenditure (EEE), and body composition.20,21,41 As stated in the Male Athlete Triad: A Consensus Statement from the Female and Male Athlete Triad Coalition: Part I Definition and Scientific Basis, we recommend that EA is best suited to assessment in laboratory settings where the measurements can be carefully executed. However, although the limitations of these measures are understood, clinicians and sports dietitians may find that explaining the concept of EA and performing example calculations may be useful when the goal is to encourage the athlete to increase energy intake. Such conversations can take the focus off of body weight and provide examples of how the relative contributions of EI and EEE can be manipulated according to the individual's needs and unique circumstances. Consultation with a sports dietitian is highly recommended to quantify energetic status, especially if nutritional deficiencies are suspected.42 Although there are inherent limitations that are well defined in the literature regarding assessment of EI,43,44 EI may be estimated by using dietary logs, 24-hour food recalls, and food-frequency questionnaires.45 EEE may be estimated by using heart rate monitors and accelerometers or by web-based calculators, various phone-based applications, or by using the Physical Activity Compendium.46,47 Fat free mass (FFM)48 may be calculated based on the weight of the athlete in kilograms, as well as the percent body fat, which may be estimated by DXA, air displacement plethysmography, skin-fold measurements, Bod Pod, or bioelectrical impedance.49,50 Discussing patterns of food intake and behaviors with the athlete, and estimating their EA at the time that the athlete is being assessed for any one of the components of the Male Athlete Triad, can serve as an opportunity for the provider to educate and give immediate feedback to the athlete regarding suspected energy deficiency/low EA and under-fueling, as well as the possible relationship to their presenting complaint.
Given the challenges of accurately measuring EA, there are several proxies that may be used which are reliant on physiological adaptations to energy deficiency. Thus, the term ‟energy deficiency” as determined by objective measures of metabolic compensation such as resting metabolic rate (RMR) and metabolic hormone changes, in addition to documenting changes in anthropometrics, is likely valuable conceptually and, in practice, if these measures can be obtained. As mentioned above, in adults, energy deficiency/low EA may be indicated by low body weight, as defined by BMI <18.5.36 In children and adolescents, percent median BMI,38 BMI percentiles using CDC BMI-for-age growth charts,39 or BMI Z-scores40 can be calculated, as well as amount and rate of weight loss and/or change of growth trajectory.39,40 A stable body weight, however, does not ensure normal EA, because an athlete may reach a state of energy balance while at a low EA state because of suppression of normal physiologic and metabolic functions.20,21 Such adaptations to chronic low EA may be suggested by low triiodothyronine (T3) levels (free and total) and a reduced RMR that can be compared with predicted values in calculations of ratios of measured RMR/predicted RMR (mRMR/pRMR).51–57 Ratios of mRMR/pRMR are stable over time and can be used for serial assessments57 to predict low T3 and amenorrhea in exercising women.52 Depending on the data available (ie, weight, FFM, and lean body mass), several prediction equations are available for use to calculate ratios of mRMR/pRMR, and it is important to note that specific cut-off values indicative of metabolic suppression secondary to energy deficiency are unique to each prediction equation in women.52 Specifically, ratios indicative of energy deficiency in exercising women include 0.94 for use with the DXA prediction equation,58 0.92 for the 1991 Cunningham prediction equation,59 and 0.90 for the Harris–Benedict60 and 1980 Cunningham61 prediction equations. In addition, measured RMR was conducted under well-controlled laboratory conditions that included following strict pretest guidelines such as refraining from exercise, caffeine, medications, or alcohol in the prior 24 hours and a 12 hours overnight fast; the efficacy and utility of field-based measures of RMR to calculate ratios of mRMR/pRMR must still be tested. Similarly, the ability of mRMR/pRMR ratios to identify energy deficiency in exercising men has yet to be examined, and much work is needed to identify appropriate cut-off values specific to exercising men.
As previously stated, disordered eating behaviors and eating disorders may contribute to the development of a chronic energy deficiency/low EA. Therefore, identifying behaviors which contribute to undereating may be beneficial in identifying those at risk for energy deficiency. Several screening tools exist62–64 and have been used in the Female Athlete Triad literature to identify disordered eating and as proxy indicators of energy deficiency/low EA51,55,56,65,66; however, few tools exist that have been appropriately validated in men. Because disordered eating behaviors may manifest differently in men and women, tools and criteria specific to male athletes must be developed and tested. The Eating Pathology Symptom Inventory is a validated tool appropriate for use in both men and women and, interestingly, has a muscularity scale.67,68 Notably, this tool also has a scale to assess dietary restriction. An additional option is the EDE-Q, which also includes a dietary restraint subscale, and has male-specific cut-off values.69
Evidence level B: although measurement of energy deficiency or low EA is best quantified in laboratory settings, several proxies can be used clinically when estimating energetic status. These include objective measures of metabolic compensation, hormone changes, anthropometrics, and/or energy prediction equations.
How is Hypogonadotropic Hypogonadism Diagnosed?
tHypogonadism is defined as low testosterone (T) levels and/or defects in spermatogenesis in the presence of symptoms attributed to low T.26,30 Rather than using a questionnaire, most guidelines recommend assessing for symptoms or consequences of hypogonadism, such as low libido, erectile dysfunction, infertility, decreased shaving of facial hair, gynecomastia, low trauma fractures or reduced BMD, reduced muscle mass and strength, decreased energy and motivation, depressed mood, poor concentration, sleep disturbance, or diminished physical performance.26–28,30,34,70,71 If symptoms are identified, or the patient has additional Triad risk factors, a fasting, morning (7 am-11 am) total T level should be assessed.26,34,71 Abnormal T levels should be repeated for confirmation28,30,34,71; please refer to The Male Athlete Triad: A Consensus Statement from the Female and Male Athlete Triad Coalition Part 1: Definition and Scientific Basis for guidance on normal total T values. If hypogonadism is identified, further work-up is indicated to understand the cause. Male athletes with functional hypogonadotropic hypogonadism (secondary hypogonadism not associated with organic or structural pathology) generally have low T levels with low or inappropriately normal luteinizing hormone and follicle stimulating hormone levels.30,34,71,72 It is important to rule out other potential causes of hypogonadism, including genetic causes, drug use (see Medication History), or supplement use (such as anabolic steroids). Depending on the experience of the practitioner, it may be helpful to consult an endocrinologist for further guidance. A pituitary magnetic resonance imaging (MRI) is indicated in specific situations, such as when patients have hyperprolactinemia (that is not medication induced), symptoms of a possible mass effect, multiple pituitary hormone deficiencies, or severely low total T levels (<150 ng/dL or <5.2 nmol/L in a fully pubertal or adult male).30,34,71
Evidence level A: male athletes with symptoms of hypogonadism, or additional Triad-risk factors, should have a morning fasting T level drawn to assess for hypogonadism. If abnormal T levels are identified, these should be repeated for confirmation.
How is Low Bone Mineral Density and Osteoporosis Diagnosed in the Male Athlete?
The International Society for Clinical Densitometry (ISCD) definition for osteoporosis in adolescents and children up to age 19 years requires the presence of both a clinically significant fracture history and low bone mineral content (BMC) or BMD.73,74 In the absence of vertebral compression fractures, a clinically significant fracture history includes one or more of the following: 2 or more long bone fractures by age 10 years or 3 or more long bone fractures at any age up to age 19 years.74 Low BMC or BMD is defined as a BMC or areal BMD Z-score of ≤−2.0, adjusted for age, gender, and body size.73,74 Occurrence of vertebral compression or crush fractures in the absence of local disease or high-energy trauma is consistent with a diagnosis of osteoporosis, regardless of BMD.
In men less than 50 years of age, according to the ISCD, a BMD Z-score ≤−2.0 is considered “below the expected range for age” and a Z-score above −2.0 is “within expected range for age.” Osteoporosis cannot be diagnosed in men younger than 50 years of age on the basis of BMD alone. A BMD Z-score ≤−2.0 plus secondary causes of osteoporosis is required for diagnosis.75
Given that repetitive mechanical loading or high impact stress in athletes should provide a beneficial stimulus to bone health, the ACSM has proposed that for the female athlete, a Z-score of <−1.0 (at any weight-bearing site) should be used as a threshold for low BMD in athletes engaged in weight-bearing sports, especially in those with additional risk factors for the Female Athlete Triad.23 Similarly, it is the recommendation of the Female and Male Athlete Triad Coalition Consensus Statement that a Z-score of <−1.0 be used as a threshold for low BMD in the male athlete participating in weight-bearing sports because of concern for an increased susceptibility to a BSI or complete fracture, especially if the athlete has additional risk factors for the Male Athlete Triad. The threshold of concern is therefore lowered for the male athlete in a weight-bearing sport compared with the ISCD criteria for low BMD. However, in the general population and in female and male athletes participating in non–weight-bearing sports, we recommend that the current ISCD recommended value of a Z-score ≤−2.0 should be used for the threshold to categorize low BMD below the expected value for age.
When is a Dual-Energy x-Ray Absorptiometry Indicated in the Male Athlete?
It is the recommendation of the Male Athlete Triad Coalition Consensus Statement that a DXA be considered in male athletes who are at various stages of risk for the Male Athlete Triad (Table 3). Male athletes with one or more “high risk” factors, or 2 or more “moderate risk” factors, or athletes who have been taking a medication which may affect their BMD may warrant screening (Table 3). For athletes undergoing monitoring for low BMD, follow-up testing should be obtained when the expected change in BMD equals or exceeds the least significant change.76 In most cases of the Male Athlete Triad, this would be approximately every 1 to 2 years for those athletes who are at risk and/or for monitoring treatment. If low BMD is identified, it is important to rule out other potential causes of low BMD, such as other causes of hypogonadism, severe vitamin D deficiency, medications (such as glucocorticoids), malabsorption syndromes (such as celiac disease and inflammatory bowel disorders), certain systemic diseases, and genetic conditions.
TABLE 3. -
Who Should Get a Dual-Energy X-Ray Absorptiometry Scan to Assess Bone Mineral Density (BMD)?
|Athletes with one or more high risk factors:
| Body mass index (BMI) ≤17.5 in adults, OR % median BMI ≤85% in adolescents, OR ≥10% weight loss/month
| Two prior bone stress injuries or one prior injury in a high-risk location such as the femoral neck, sacrum, or pelvis
| A clinical eating disorder
| Prior BMD Z-score ≤−2.0
|Athletes with 2 or more moderate risk factors:
| BMI 17.5 < 18.5 in adults, OR % median BMI 86%-89% in adolescents, OR 5 < 10% weight loss/month
| One prior bone stress injury
| Some history of disordered eating behaviors
| Prior BMD Z-score between −1.0 and −2.0 in athletes involved in weight-bearing sports*
|Athletes who have been taking a medication which may affect their BMD may warrant screening
*For athletes in non–weight-bearing sports, a Z-score of −2.0 should be used.
Evidence level C: a DXA scan is recommended in male athletes who are at moderate or high risk for the Male Athlete Triad.
TREATMENT OF THE MALE ATHLETE TRIAD
What are the Nonpharmacologic Treatment Recommendations?
Because a chronic energy deficit is the underlying cause of the Male Athlete Triad, treatment for the Triad should emphasize improving the male athlete's energy status, with the goal of eliminating energy deficiency and ensuring that EI meets all energetic requirements (Figure 4). Although energy deficiency can be reversed by increasing EI or decreasing EEE, or a combination of both, initial efforts to optimize energy status should target an increase in EI relative to EEE. This allows for continued sports participation and promotion of behaviors that support typical training and competition. Because of a lower prevalence of disordered eating and clinical eating disorders in male compared with female athletes,77,78 males may be more amenable than females to recommended changes in dietary patterns and EI. However, in cases where male athletes are not able to sufficiently increase EI, a modification of training may be needed, at least temporarily, to reduce EEE.
In addition to increasing EI to meet expenditure needs, it is important that dietary recommendations support sports-specific recommended intake of macronutrients and micronutrients. An overview of the nutrient recommendations for athletes is described in the 2016 ACSM, Academy of Nutrition and Dietetics, and Dietitians of Canada Joint Position Statement: Nutrition and Athletic Performance.79,80 A subset of male athletes may be at risk for underconsuming carbohydrates78,81–83 and should be monitored accordingly. Athletes should also aim to consume at least the recommended daily allowance (RDA) of micronutrients such as calcium, vitamin D, iron, B vitamins, and magnesium.79,80,84–86 Although supplements may help an athlete reach their recommended daily intake, most of these nutrients should be acquired from an athlete's diet whenever possible.
Although the plan for increasing EI will vary based on the individual, the process should be incremental, as more abrupt increases in EI may not be sustained. Current dietary patterns can be assessed and modified with moderate, high-impact changes. EI should be increased gradually, by adding 300 to 500 kcal/d, which is usually well tolerated and can be accomplished by adding 1 to 2 snacks per day or enhancing the energy content of current snacks and meals. For some athletes, especially those with disordered eating/eating disorders, or others who strongly feel that their performance may be negatively affected by increasing their caloric intake, starting on the lower end of this range may be needed. Athletes with energy deficits beyond 500 kcal/d can increase EI by another 300 to 500 kcal/d after maintaining the initial increase, although caution must be used to prevent failure because the EI prescription is too high to favor success. If not already consumed, the introduction of a postexercise snack containing carbohydrate and protein should be prioritized. Other priorities include optimizing intake before exercise, especially if the athlete is skipping meals or exhibiting long periods of fasting during the day, as within-day energy deficits have been associated with suppressed RMR and markers of catabolism in male athletes.87 Packing snacks and meals that can be taken on-the-go and use of portable and shelf-stable energy dense foods (such as trail mix, whole grain crackers, granola bars, shelf-stable milk, dried fruit, or nuts) may be particularly useful. The clinician and sports dietitian may also find it helpful to discuss increasing EI as “optimizing the athlete's fueling” because athletes often have negative connotations associated with increasing calories.
Evidence level C: optimizing energetic status by increasing EI, reducing EEE, or both, is the first-line treatment for male athletes with one or more components of the Male Athlete Triad.
What are the Recommendations for Calcium and Vitamin D Supplementation?
Given concerns of low BMD in the hypogonadal male athlete, it is important to ensure that athletes are obtaining the RDA of micronutrients such as vitamin D, calcium, and magnesium (Figure 4). When this proves challenging, or if athletes are diagnosed with vitamin D deficiency or insufficiency, supplementation may be necessary. Although data are currently lacking regarding a definitive 25-hydroxy vitamin D (25(OH)D) level below which BMD is compromised, a 25(OH)D level of 20 to 22 ng/mL or higher seems sufficient to avoid deleterious effects on the bone.88,89 Other studies suggest that parathyroid hormone (PTH) levels start to rise and calcium absorption is lower, although still within the normative range, when 25(OH)D levels fall below 30 to 32 ng/ml.90–92 More research is needed on optimal levels of bone building nutrients in athletes, and whether or not an optimal range exists to prevent BSI, decrease injury severity, and/or enhance recovery from BSI. Until more definitive data are available, we suggest maintaining 25(OH)D levels at or above 32 ng/mL, which may require use of supplemental vitamin D. 25(OH)D levels should not exceed the normal range given concerns for hypercalcemia.
Calcium supplementation may also be necessary if athletes are not able to reach the RDA through their diet (1300 mg/d for children and adolescents 9–18 years old, 1000 mg/d for those 19–70 years old, and 1200 mg/d for those >70 years old).86 One study in male adolescent runners demonstrated that receiving <1 serving of calcium-rich food per day was a risk factor for low BMD.3
What is the Role of Pharmacologic Treatment for the Male Athlete Triad?
As in female athletes,20,21 and as discussed above, first-line treatment for the Male Athlete Triad should be nonpharmacological and should focus on optimizing energetic status by increasing EI, reducing EEE, or both (Figure 4). When considering pharmacological therapy in the male athlete, it is important to consider what one is treating and the hormonal status of the athlete. Pharmacological therapy, although rarely needed, may be necessary in some cases to treat low BMD and increased fracture risk, symptoms of hypogonadism, or infertility.
Evidence level D: pharmacologic therapy, although rarely needed, may be necessary to treat low BMD and increased fracture risk, symptoms of hypogonadism, or infertility.
What Therapies May Help Normalize Testosterone Levels in the Hypogonadal Male Athlete?
T Replacement Therapy
Although normalizing T levels would be expected to improve BMD, sexual function, and quality of life in the hypogonadal male athlete, hormone replacement is currently fraught with challenges, both because of the limited evidence available and because of restrictions placed around the use of exogenous T in athletes given that this may provide a competitive advantage.
In adolescent and young adult female hyperexercisers/athletes with oligoamenorrhea, good data now exist for physiologic hormone replacement (such as the 17-β estradiol transdermal patch with cyclic oral progestin) as a strategy to improve BMD,93–95 after lifestyle modification has been optimized to address energy deficiency. This form of hormone replacement therapy has also been demonstrated to improve eating behavior,96 verbal memory and executive function in adolescent and young adult oligoamenorrheic athletes,97 and trait anxiety in low-weight amenorrheic girls with AN.98 Of note, adult hypogonadal women with AN have low T levels, which correlate with lower BMD measures.99 However, a RCT of low dose T replacement in women with AN did not demonstrate a beneficial effect on BMD.100
Although some studies suggest that T levels are associated with bone outcomes in male athletes, others suggest that it is estradiol (from aromatization of testosterone) that drives these outcomes.93,101–103 Studies in adult hypogonadal men indicate a beneficial effect of T replacement on bone outcomes,104–106 mostly related to its aromatization to estradiol.107 In healthy adult men, estradiol levels above 10 pg/mL and testosterone levels above 200 ng/dL were noted to be sufficient to prevent an increase in bone resorption and a decrease in BMD.106
T replacement therapy in hypogonadal men also has the potential to improve other outcomes, such as body composition, muscle strength, impaired sexual function, mood, and quality of life.108–110 However, studies assessing these endpoints are currently lacking in hypogonadal male athletes. This is further complicated by the finding that many athletes with HPG axis dysfunction fall into the “gray zone,” where decreases in T levels often do not meet cut-offs for clinical significance (please refer to The Male Athlete Triad: A Consensus Statement from the Female and Male Athlete Triad Coalition Part 1: Definition and Scientific Basis). Furthermore, such studies are logistically challenging given concerns of being barred from sports activities consequent to receiving T.111 Finally, studies of estradiol replacement are challenging in men given difficulties attaining an estradiol level that is likely to optimize bone health without having deleterious effects on other systems (such as inducing gynecomastia and lipid abnormalities).
Evidence level D: data are lacking in hypogonadal male athletes for a beneficial effect of T replacement on bone outcomes, and this is also complicated because of T being prohibited in sport.
Clomiphene (Clomifene) Citrate Therapy
Clomiphene Citrate (CC) is a selective estrogen receptor modulator that stimulates gonadotropin-releasing hormone (GnRH) and therefore gonadotropin secretion, which increases Leydig cell secretion of T. It can thus increase T secretion in males with hypogonadotropic hypogonadism. Burge et al 112 have described successfully treating a 29-year-old male runner, who ran 50 to 90 miles/wk, and had symptomatic hypogonadotropic hypogonadism, low BMD, and a pelvic stress fracture, with CC therapy up to 50 mg twice daily over a 5-month period. The patient had normalization of T levels, improved erectile function, and an improved sense of wellbeing.112 One study compared T therapy with CC in men with symptomatic hypogonadism versus eugonadal men not on either medication.113 Both were effective at treating hypogonadism; however, T therapy more effectively increased serum T levels and improved hypogonadal symptoms, whereas CC had a deleterious effect on libido.113 By contrast, development of secondary polycythemia is less likely in those on CC versus T replacement therapy (1.7% vs 11.2%).114 CC is also banned by the World Anti-Doping Agency for use in male athletes.111
Other Therapies to Increase T Levels
There is a report of a male hypogonadal athlete being treated with tamoxifen (an antiestrogenic drug) to increase gonadotropin production and T secretion to the normal physiologic level, with improved sexual drive, well-being, and reduction in muscle injury.115 Aromatase inhibitors reduce aromatization of T to estradiol and raise T levels; however, this strategy is unlikely to be beneficial to bone health, for which optimal estradiol levels are necessary.107,116 Pulsatile GnRH therapy and gonadotropin administration have been demonstrated to normalize T levels and induce spermatogenesis in men with hypogonadotropic hypogonadism (nonathletes).117 No studies have reported on the impact of such therapies to improve bone outcomes in hypogonadal athletes.
What is the Evidence for the Use of Bone Anabolic Agents to Improve Bone Outcomes in Hypogonadal States?
Teriparatide and Abaloparatide
Teriparatide (a PTH analog) and abaloparatide (a parathyroid hormone–related protein [PTHrP] analog) are FDA-approved bone anabolic agents that hold promise for athletes who qualify for pharmacological therapy, based on their effects in other populations that have a high risk for fracture, such as postmenopausal women and older men.118–125 These medications exert their effects through binding to the PTH/PTHrP receptor which is expressed on osteoblasts, osteocytes, renal tubule cells, and other tissues.126 These medications act by improving trabecular bone mass and microarchitecture, increasing bone strength, and reducing fracture risk despite an increase in cortical porosity. Recent data suggest that abaloparatide may be even more effective than teriparatide in this regard.127,128 At this time, studies have not examined the impact of teriparatide or abaloparatide on bone outcomes in male athletes. Reports of teriparatide use in athletes are limited to case reports and small trials129,130 for healing of BSI, for which its efficacy remains questionable. Of note, a 6-month study of teriparatide (20 mg daily subcutaneous) versus placebo in older women with AN did show a 6% to 10% improvement in PA and lateral lumbar spine BMD in those who received teriparatide.131 However, teriparatide has been associated with an increased risk of osteosarcoma in animal studies and carries a black box warning for those at increased baseline risk for osteosarcoma (children with open epiphyses, individuals with Paget's disease, or a history of external beam radiation therapy or implant radiotherapy to the skeleton).
Evidence Level D: although teriparatide and abaloparatide improve trabecular bone mass and microarchitecture, increase bone strength, and reduce fracture risk, studies of these agents on bone outcomes have not yet been performed in the male athlete with hypogonadism.
This is a monoclonal antibody that increases bone density and reduces fracture incidence in postmenopausal women and older men by inhibiting sclerostin and received FDA approval in 2019.132–135 Sclerostin is a protein secreted by osteocytes that both inhibits osteoblast proliferation, differentiation, and survival by inhibiting the canonical Wnt signaling pathway and stimulates receptor activator of nuclear factor-κB ligand (RANKL), thus increasing osteoclastic activity and bone resorption.136 Romosozumab causes an initial increase in bone formation followed by a more prolonged decrease in bone resorption.126 Data are lacking for use of romosozumab in other populations, including the male athlete.
Insulin-like Growth Factor-1 and Leptin
Insulin-like Growth Factor-1 (IGF-1) is a bone anabolic hormone that is low in conditions of low EA compared with controls.137,138 Administration of recombinant human IGF-1 (rhIGF-1) increases bone formation markers in adolescents and adults with AN,138,139 and when given with a combined oral contraceptive pill, increases BMD at the spine and hip in adults with AN.140 However, data are lacking for effects of rhIGF-1 administration on bone in athletes with low BMD or increased risk of BSI.
Leptin is a bone anabolic hormone with stimulatory effects on GnRH secretion. In adult women with hypothalamic amenorrhea, metreleptin was effective in improving reproductive function141,142 and increasing levels of bone formation markers. One small study reported an increase in lumbar BMC (but not BMD) in women who received metreleptin versus placebo.142 There are no studies to date that have examined the effects of metreleptin administration on bone outcomes in male athletes, and its anorexigenic effect makes metreleptin a worrisome choice in athletes at risk of energy deficiency/low EA.
What is the Evidence for the Use of Antiresorptive Medications to Improve Bone Outcomes in Hypogonadal States?
Bisphosphonates may be effective in increasing BMD in those with evidence of increased bone resorption. However, data are limited for bisphosphonate use in male athletes to optimize bone outcomes, with mostly case series and retrospective studies reported to date.143,144 One retrospective study of intravenous bisphosphonates (ibandronate) and vitamin D to treat bone marrow edema in 22 male professional athletes reported pain reduction and improved mobility within the first 2 weeks in the trunk and lower extremity bones after the first ibandronate infusion.144 Time to return to competition was about 3.5 months on average. However, the lack of a control group limited assessment of clinical efficacy for this intervention.
Bisphosphonates have proven efficacy in improving bone density in postmenopausal women and older men.145–147 Furthermore, one RCT of risedronate versus placebo in adult women with AN demonstrated a 2% to 3% increase in spine and hip BMD in those who received risedronate versus placebo.100 However, another RCT of alendronate versus placebo in adolescent females with AN demonstrated no improvement in spine BMD and only a small improvement in femoral neck BMD in the alendronate arm for this younger group.148 Such therapy should be continued for a defined period before considering alternative measures to improve bone health.
Evidence Level C: there are limited data (case series and retrospective reports) for using bisphosphonates to improve bone outcomes in the male athlete with hypogonadism.
Denosumab (an inhibitor of RANK ligand) is a very effective medication for treatment of postmenopausal osteoporosis,149 and studies are currently ongoing of denosumab versus placebo in adult women with AN. However, data are not available for effects of denosumab on bone outcomes in male hypogonadal athletes. Of note, denosumab is the most rapidly acting antiresorptive agent currently in use, but its effects are rapidly reversible.126
What is the Role of Combination Therapy?
Combination therapy using a bone anabolic agent followed by antiresorptive medications may be more effective in improving BMD and reducing fracture risk than either therapy alone or use of antiresorptive therapies followed by bone anabolic therapy (summarized in121). Studies are necessary to examine the effect of drug monotherapy, as well as combination therapy, in male athletes at risk for fracture.
Which Athletes May be Considered for Pharmacological Therapy?
Although evidence is currently lacking to definitively recommend when and which specific pharmacological approach to consider in the Male Athlete Triad, the Female and Male Athlete Triad Coalition developed the following suggestions to guide clinical management until such evidence becomes available.
An athlete may be considered for pharmacological treatment of low BMD after institution of at least a year of nonpharmacological therapy, if the athlete has a diagnosis of low BMD and/or a clinically significant fracture history AND demonstrates lack of response to nonpharmacological therapy over this period (Figure 4). Lack of response refers to a clinically significant reduction in BMC or BMD Z-scores after at least a year of nonpharmacological therapy OR development of new fractures during such therapy. Such individuals should be referred to a specialist in bone metabolic disorders or an endocrinologist for administration of pharmacological treatment to improve bone health. Treatment may include a bone anabolic agent such as teriparatide (not in children with open epiphyses) or, rarely, an antiresorptive agent such as a bisphosphonate. At this time, there are no data to support the use of T replacement therapy; therapies that increase T levels through other mechanisms; administration of recombinant human IGF-1, metreleptin, or novel bone agents such as RANK-ligand inhibitors; or combinations of such agents to improve bone health in male athletes with low BMD or at high risk for stress fracture.
Evidence level C: an athlete may be considered for pharmacological treatment of low BMD after institution of at least a year of nonpharmacological therapy if the athlete has a diagnosis of low BMD and/or a clinically significant fracture history and demonstrates lack of response to nonpharmacological therapy over this period.
PREVENTION OF THE MALE ATHLETE TRIAD
Are There Strategies to Prevent the Male Athlete Triad?
Although investigations on methods to prevent the Male Athlete Triad are limited, studies have explored ways to optimize individual components of the Triad. Because energy deficiency/low EA is the underlying cause of the Triad, male athletes should be encouraged to consume sufficient calories throughout the day to provide adequate energy for supporting musculoskeletal health, acquiring lean tissue, and accumulating sufficient bone mass. Detailed nutritional recommendations to improve energetic status have already been discussed above—when possible, it would be advantageous to educate athletes regarding these recommendations proactively, even in the absence of clinical pathology.
It is also important to optimize athlete intake of micronutrients such as calcium and vitamin D. A systematic review and meta-analysis examined the association between serum 25(OH)D levels and stress fractures, specifically in the military.150 The analysis included 8 studies published between 2000 and 2013, consisting of 2634 military personnel, with 761 stress fracture cases and 1873 controls. The authors found that the overall mean serum 25(OH)D level was significantly lower for stress fracture cases than controls.150 Other studies investigating the military population have demonstrated similar findings to the meta-analysis. A prospective study following 1082 Royal Marine recruits concluded that baseline serum 25(OH)D concentration below 50 nmol L−1 was associated with an increased risk of stress fractures.151 Another study involving 37 British Army recruits demonstrated a shorter recovery time from lower-limb stress fractures with sufficient 25(OH)D at the time of injury, with a statistically significant mean difference of 17.8% in recovery time between recruits with sufficient 25(OH)D (>50 nmol L−1) and insufficiency (<50 nmol L−1).152 The mean recovery time in weeks was 10.1 (±2.5) in the 25(OH)D sufficient group, 11.9 (±2.4) in the insufficient group (25-50 nmol L−1), and 13 (±1.6) in the deficient group (<25 nmol L−1).152 In a cumulative case–control study, researchers evaluated serum 25(OH)D concentration in 37 Japanese male university soccer athletes, 18 of whom had a fifth metatarsal stress fracture and 19 controls.153 Results showed that a 25(OH)D level less than 30 ng mL−1 was associated with statistically significantly increased odds of stress fracture.153 In a 2-year prospective cohort study, researchers evaluated young female athletes aged 18 to 26 years, for an average of 1.85 years, and measured longitudinal changes in bone density and incident stress fractures.154 The authors found that vitamin D intake predicted gains in spine and hip BMD. In addition, the study demonstrated the protective effects of vitamin D on stress fracture risk in female athletes, with an adjusted hazard ratio of 0.67 (0.34-1.31). The authors also found that a higher intake of calcium, skimmed milk, and dairy products was associated with lower rates of stress fracture. Each additional cup of skimmed milk consumed per day was associated with a 62% reduction in stress fracture incidence (P < 0.05). A dietary pattern of high dairy and low-fat intake was associated with a 68% reduction (P < 0.05). Higher intakes of skimmed milk, dairy foods, calcium, animal protein, and potassium were associated with significant (P < 0.05) gains in whole-body BMD and BMC. These findings are further supported by research in military recruits during basic training that demonstrated supplemental calcium (2000 mg/d) and vitamin D (800-1000 IU/d) can reduce BSI incidence by 20% in female Navy recruits155 and lead to greater increases in volumetric BMD in male and female Army recruits.156 Although a systematic review and meta-analysis assessing the prevalence of vitamin D insufficiency (defined as serum 25(OH)D < 32 ng/mL) in athletes was reported to be high (56%) and varied by geographic location, the relationship to both bone stress injuries and soft-tissue injuries was found to be inconclusive.157 Further research is needed in the athlete population to assess the relationships between 25(OH)D serum concentrations (with and without calcium supplementation), BSI incidence, and return-to-play time after sustaining a BSI.
As explored earlier in this article, BMD is often compromised in athletes with the Male Athlete Triad. The literature has suggested that participation in weight-bearing sports emphasizing high and multidirectional impacts result in improved bone geometry and greater BMD, whereas nonimpact and repetitive impact activities did not lead to a significant improvement.158 These findings support consensus statement recommendations for young athletes to avoid early single-sport specialization, particularly in endurance sports, to reduce the risk of overuse injury159 while also allowing for benefits to overall skeletal health from other forms of high and multidirectional loading, such as basketball and soccer. Resistance training is often prescribed to patients with low BMD because of its osteogenic effects.160 As noted previously, studies have demonstrated improvements in BMD or attenuation of BMD loss in cyclists and distance runners who engaged in resistance training compared with their athlete peers or to sedentary controls.10,161,162 These studies suggest that the high magnitude bone strain provided by resistance exercise (per recommendations outlined in the latest position statement on youth resistance training) is an effective stimulus for generating higher BMD160 and may play a preventative role for future BSI.
Evidence level B: young male endurance athletes who engage in early sports specialization may incur a greater risk of the Male Athlete Triad. Participation in a variety of sports, especially those with higher impact and multidirectional loading, along with resistance training, is advisable for optimization of BMD.
CLEARANCE AND RETURN-TO-PLAY
There are no current universally accepted guidelines for clearance and return-to-play in the male adolescent and young adult athlete at risk for the Male Athlete Triad. However, with knowledge that young male athletes, especially those in endurance sports and leanness sports, represent a group that is at highest risk for low BMD and BSI, clearance and return-to-play guidelines are recommended to optimize prevention and treatment. Because of the importance of bone mass acquisition in adolescence, and health concerns in this age group, screening should ideally start during this time period.20,21,163 Repeated screening assessment is also recommended after BSI or fracture, recurrent injury or unexplained illness, and if other components of the Male Athlete Triad are identified.163
Has Risk Stratification Been Assessed to Evaluate Health and Participation Risk in the Male Athlete?
Cumulative risk factors for low BMD have been reported in adolescent male athletes, with the risk of low BMD increasing with additional risk factors.3 This highlights the importance of implementing screening in young male athletes. Kraus et al 22 found that a modified version of the Female Athlete Triad cumulative risk score20,21—including the cumulative risk factors of low EA (defined by the presence of current or past disordered eating or DSM-V eating disorder), low BMI, prior BSI, and low BMD values—was associated with prospective BSI in male collegiate runners.22 Because runners are considered an at-risk group of male athletes,3,164 these findings provide an evidence-based method to quantitatively assess male athletes at elevated risk for BSI. An updated version of this screening tool is presented in Figures 2 and 3 and can be used along with a preparticipation clearance examination or during assessment for return-to-play in the male athlete at risk for the Male Athlete Triad.
The finding that risk factors for low BMD and BSI in the male athlete are cumulative is consistent with the literature on female athletes.165,166 Prospective return-to-play studies in male and female collegiate track and field athletes have demonstrated that in those athletes who sustain a BSI, low BMD and higher MRI grade are independent predictors of delayed return-to-play in both sexes.6 There are various proposed return-to-play protocols for BSI in runners that are primarily based on the average number of weeks for return-to-play, the risk level of the fracture site (low risk or high risk), and/or severity based on imaging.167–172 In addition, male and female athletes with a BSI at skeletal sites of predominantly trabecular bone structure (femoral neck, sacrum, and pelvis) had a delay in return-to-play compared with athletes with a BSI of predominantly the cortical bone.6 Further research is needed to provide evidence-based protocols that take into account all of the above factors in return-to-play protocols for BSI in the male athlete.
Evidence level B: similar to the female athlete, risk for low BMD and BSI is cumulative in male athletes with the presence of one or more components of the Male Athlete Triad.
What are the Recommendations for Clearance and Return-To-Play Based on Risk Stratification?
It is the team physician's responsibility to clear the athlete for return-to-play when it is safe to do so.173 Given our knowledge that cumulative risk factors can prospectively predict low BMD and BSI in the male athlete at risk,22 the authors recommend using the Male Athlete Triad Cumulative Risk Assessment tool at the PPE and/or PHE as an evidence-based translation to help the team physician with return-to-play decisions in athletes at risk for the Male Athlete Triad (Figures 2 and 3). This is similar to the Female Athlete Triad Cumulative Risk Assessment tool which is used for clearance and return-to-play in the female athlete.20,21 At the time of the PPE and for return-to-play decisions, the team physician may still need to gather additional information, such as laboratory tests and/or a DXA, before making a final clearance decision. In such instances, the athlete will schedule a follow-up appointment with the team physician and may also need to see other members of the multidisciplinary team.20,21,24
The athlete's risk factors, prior injury history, test results, and feedback from the multidisciplinary team are all considered in the final clearance and return-to-play decision.
According to the Male Athlete Triad Cumulative Risk Assessment tool (Figures 2 and 3),22 male athletes with a low risk score can be fully cleared, assuming they are otherwise healthy, with follow-up as needed or as determined by the team physician. Athletes at moderate risk for the Male Athlete Triad can be either provisionally cleared or receive limited clearance. Provisional clearance would include full training/competition, with the understanding that the athlete follows the recommendations made by members of the multidisciplinary team. With limited clearance, the athlete is cleared, but there are limitations specified for training and competition, based on the athlete's health status. It is recommended that the athlete at moderate or high risk be referred to one or more members of the multidisciplinary team, that requested testing be obtained, and that they follow-up as scheduled with the team physician to review results and assess progress. The athlete at high risk may not be cleared for training or competition, or for return to his sport, unless approved by the team physician after further treatment or follow-up. In this situation, other members of the athlete's health care team may be used to assess the athlete's readiness for return-to-sport. If the athlete is sustaining recurrent BSIs, is unable to maintain a positive energy balance, and has decreasing bone density despite a comprehensive treatment approach, it is reasonable to consider recommending medical retirement from sport.
The IOC has proposed a return-to-play model for relative energy deficiency in sport174 to aid in return-to-play decisions for both male and female athletes,175 but to date, it has not been validated, and many of the factors included are vaguely defined.176 Future research is needed to refine screening tools for the male athlete, determine at-risk groups in which screening is recommended, and develop return-to-play algorithms.
Although risk assessment tools can be extremely helpful in guiding physicians, clinical judgment should be used in clearance and return-to-play decision-making so that the treatment plan is individualized based on the athlete's unique situation, and not based on risk scores alone.20,21,24,177
Evidence level B: risk assessment tools can be helpful in guiding clearance and return-to-play decisions in the male athlete with one or more components of the Male Athlete Triad.
Are Treatment Contracts Recommended for the Athlete With the Male Athlete Triad?
With female athletes at risk for the Female Athlete Triad, a written contract has been recommended (refer to online appendices).20,21,174 There is a lack of literature on the utility of written contracts in the male athlete. Benefits include ensuring follow-up with the team physician and multidisciplinary team members and maintaining consistency. Future research is needed on the utility of verbal versus written contracts in the male athlete at risk for the Male Athlete Triad. If verbal recommendations are not followed, and the athlete does not partake in recommended treatment strategies, a written contract may be needed.
FINAL RECOMMENDATIONS AND SUMMARY
In summary, a subgroup of adolescent and young male athletes, especially in lean-sport and weight-class sports, is at risk for the Male Athlete Triad. Evidence-based risk assessment protocols for the male athlete at risk for the Male Athlete Triad have been shown to be predictive for bone stress injuries and impaired bone health, and their use should be encouraged for male athletes in endurance and weight-class sports and for other male athletes in which the Male Athlete Triad is suspected. Risk assessment protocols may be implemented at the PPE and/or PHE or during other clinical encounters to determine best practice clearance and return-to-play strategies for adolescent and young adult athletes with the Male Athlete Triad.
Diagnostic work-up for male athletes who are suspected to have the Male Athlete Triad includes assessing for symptoms of hypogonadism. If symptoms are identified, or if the athlete has additional Triad risk factors, a morning fasting T level should be assessed and repeated for confirmation. If hypogonadism is identified, further work-up is indicated to determine the cause and to rule out other important causes of hypogonadism.
For young athletes in weight-bearing sports, a Z-score of <−1.0 is considered to be low bone mass, but in non–weight-bearing sports, the ISCD definition for low bone mass is used with a Z-score of <−2.0.
Because energy deficiency/low EA is the key causal factor leading to impaired reproductive and skeletal health, improving energetic status through optimal fueling is the mainstay of treatment for athletes with the Male Athlete Triad. Pharmacologic management is presented for nonpharmacologic treatment failures but is rarely indicated in athletes with the Male Athlete Triad. In these cases, the team physician should consult an endocrinologist or other bone health specialist (Figure 4).
CALLS FOR RESEARCH AND GAPS IN KNOWLEDGE
- Research on the utility of screening questions for adolescent and young adult athletes to identify athletes at risk for the Male Athlete Triad.
- Research on screening for the prevalence of one or more components of the Male Athlete Triad in adolescent and young adult male athletes in various sports.
- Research on specific energetic and metabolic factors that are associated with one or more of the Male Athlete Triad outcomes.
- Research on the presentation of disordered eating and eating disorders in male athletes and their relationship to Male Athlete Triad outcomes.
- Research on cut-off values for measures of energy deficiency specific to exercising men.
- Research on the efficacy and effectiveness of clearance and return-to-play guidelines in the male athlete.
- Research on screening for the prevalence of one or more components of the Male Athlete Triad in military recruits, as well as clearance and return-to-play guidelines in this population.
- Research on risk assessment tools for BSI and poor bone health, incorporating additional risk factors specific to the male athlete.
- Research on interventions directed at prevention and treatment of the Male Athlete Triad.
In summary, in the Male Athlete Triad Part II: Diagnosis, Treatment, and Return-to-Play, prospective controlled studies and observational studies are presented, and evidence-based statements (Table 4) are provided regarding recommendations for risk assessment, diagnosis, management, and return-to-play in the athlete with the Male Athlete Triad. Future studies are needed in the areas of risk assessment, diagnosis, treatment, and return-to-play for male athletes at risk for the Male Athlete Triad.
TABLE 4. -
Summary of Evidence Statements
|Male adolescent and young adult lean-sport athletes, especially endurance and weight-class athletes, are at risk for developing one or more components of the Male Athlete Triad.
|It is recommended that clinicians screen the at-risk male athlete with targeted screening questions and risk assessment tools. Further research is needed to validate a best practice screening questionnaire for the Male Athlete Triad.
|Male athletes are diagnosed with the Male Athlete Triad if they have one or more components along the spectrum of the Male Athlete Triad. The diagnosis includes a thorough history and physical and is best accomplished by a multidisciplinary healthcare team.
|Although measurement of energy deficiency or low energy availability (EA) is best quantified in laboratory settings, several proxies can be used clinically when estimating low EA. These include objective measures of metabolic compensation, hormone changes, anthropometrics, and/or energy prediction equations.
|Male athletes with symptoms of hypogonadism, or additional Triad-risk factors, should have a morning fasting T level drawn to assess for hypogonadism. If abnormal T levels are identified, these should be repeated for confirmation.
|A dual-energy x-ray absorptiometry is recommended in male athletes who are at moderate or high risk for the Male Athlete Triad.
|Optimizing EA by increasing energy intake, reducing exercise energy expenditure, or both, is the first-line treatment for male athletes with one or more components of the Male Athlete Triad.
|Pharmacologic therapy, although rarely needed, may be necessary to treat low bone mineral density (BMD) and increased fracture risk, symptoms of hypogonadism, or infertility.
|Data are lacking in hypogonadal male athletes for a beneficial effect of T replacement on bone outcomes, and this is also complicated because of T being prohibited in sport.
|Although teriparatide and abaloparatide improve trabecular bone mass and microarchitecture, increase bone strength, and reduce fracture risk, studies of these agents on bone outcomes have not as yet been performed in the male athlete with hypogonadism.
|There are limited data (case series and retrospective reports) for using bisphosphonates to improve bone outcomes in the male athlete with hypogonadism.
|An athlete may be considered for pharmacological treatment of low BMD after institution of at least a year of nonpharmacological therapy, if the athlete has a diagnosis of low BMD and/or a clinically significant fracture history AND demonstrates lack of response to nonpharmacological therapy over this period.
|Young male endurance athletes who engage in early sport specialization may incur a greater risk of the Male Athlete Triad. Participation in a variety of sports, especially those with higher impact or multidirectional loading, along with resistance training, is advisable for optimization of BMD.
|Similar to the female athlete, risk for low BMD and bone stress injury is cumulative in male athletes with one or more components of the Male Athlete Triad.
|Risk assessment tools can be helpful in guiding clearance and return-to-play decisions in the male athlete with one or more components of the Male Athlete Triad.
The authors thank the American College of Sports Medicine for their support in holding the Male Athlete Triad Roundtable in conjunction with the 64th Annual ACSM Meeting in Denver, Colorado, in 2017, and to the invited expert panelists for their participation in the meeting and review of the final evidence statements. All of the authors and the additional invited members of the Male Athlete Triad Expert Panel participated in the Roundtable held in Denver, Colorado, in May of 2017. Male Athlete Triad Roundtable in conjunction with the 64th Annual ACSM Meeting May 2017: Co-Chairs: M. Fredericson, A. Nattiv; Invited Expert Panelists that Reviewed Evidence-Statements: M. T. Barrack, G. Close, Mary J. De Souza, E. Joy, K. Koehler, M. Misra, A. Shu, A. Tenforde, N. Williams.
1. West S, King V, Carey TS, et al. Systems to Rate the Strength of Scientific Evidence. Rockville (MD): Agency for Healthcare Research and Quality (US); 1998–2005.
2. American College of Sports Medicine; Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, et al. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc. 2009;41:1510–1530.
3. Barrack MT, Fredericson M, Tenforde AS, et al. Evidence of a cumulative effect for risk factors predicting low bone mass among male adolescent athletes.
Br J Sports Med. 2017;51:200–205.
4. Tenforde AS, Fredericson M, Sayres LC, et al. Identifying sex-specific risk factors for low bone mineral density in adolescent runners.
Am J Sports Med. 2015;43:1494–1504.
5. Fredericson M, Chew K, Ngo J, et al. Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls.
Br J Sports Med. 2007;41:664–668.
6. Nattiv A, Kennedy G, Barrack MT, et al. Correlation of MRI grading of bone stress injuries with clinical risk factors and return to play: a 5-year prospective study in collegiate track and field athletes.
Am J Sports Med. 2013;41:1930–1941.
7. Tam N, Santos-Concejero J, Tucker R, et al. Bone health in elite Kenyan runners.
J Sports Sci. 2018;36:456–461.
8. Barry DW, Kohrt WM. BMD decreases over the course of a year in competitive male cyclists.
J Bone Miner Res. 2008;23:484–491.
9. Nichols JF, Palmer JE, Levy SS. Low bone mineral density in highly trained male master cyclists.
Osteoporos Int. 2003;14:644–649.
10. Nichols JF, Rauh MJ. Longitudinal changes in bone mineral density in male master cyclists and nonathletes.
J Strength Cond Res. 2011;25:727–734.
11. Penteado VS, Castro CH, Pinheiro MM, et al. Diet, body composition, and bone mass in well-trained cyclists.
J Clin Densitom. 2010;13:43–50.
12. Wilson G, Hill J, Sale C, et al. Elite male flat jockeys display lower bone density and lower resting metabolic rate than their female counterparts: implications for athlete welfare.
Appl Physiol Nutr Metab. 2015;40:1318–1320.
13. Dolan E, Crabtree N, McGoldrick A, et al. Weight regulation and bone mass: a comparison between professional jockeys, elite amateur boxers, and age, gender and BMI matched controls.
J Bone Miner Metab. 2012;30:164–170.
14. Jackson KA, Sanchez-Santos MT, MacKinnon AL, et al. Bone density and body composition in newly licenced professional jockeys.
Osteoporos Int. 2017;28:2675–2682.
15. Lu J, Shin Y, Yen MS, et al. Peak bone mass and patterns of change in total bone mineral density and bone mineral contents from childhood into young adulthood.
J Clin Densitom. 2016;19:180–191.
16. Boot AM, de Ridder MA, van der Sluis IM, et al. Peak bone mineral density, lean body mass and fractures.
17. Walsh JS, Henry YM, Fatayerji D, et al. Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study.
Osteoporos Int. 2009;20:355–362.
18. Bernhardt DT, Roberts WO; American Academy of Pediatrics. PPE—Preparticipation Physical Evaluation. Vol 8. 5th ed. Itasca, IL: American Academy of Pediatrics; 2019:240.
19. Ljungqvist A, Jenoure PJ, Engebretsen L, et al. The International Olympic Committee (IOC) consensus statement on periodic health evaluation of elite athletes, March 2009.
Clin J Sport Med. 2009;19:347–365.
20. 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, California, May 2012 and 2nd International Conference held in Indianapolis, Indiana, May 2013.
Br J Sports Med. 2014;48:289.
21. 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, 2013.
Clin J Sport Med. 2014;24:96–119.
22. Kraus E, Tenforde AS, Nattiv A, et al. Bone stress injuries in male distance runners
: higher modified female athlete triad cumulative risk assessment scores predict increased rates of injury.
Br J Sports Med. 2019;53:237–242.
23. Nattiv A, Loucks AB, Manore MM, et al. American College of Sports Medicine position stand. The female athlete triad.
Med Sci Sports Exerc. 2007;39:1867–1882.
24. Joy EA, Nattiv A. Clearance and return to play for the female athlete triad: clinical guidelines, clinical judgment, and evolving evidence.
Curr Sports Med Rep. 2017;16:382–385.
25. Thein-Nissenbaum J, Hammer E. Treatment strategies for the female athlete triad in the adolescent athlete: current perspectives.
Open Access J Sports Med. 2017;8:85–95.
26. Arver S, Lehtihet M. Current guidelines for the diagnosis of testosterone deficiency.
Front Horm Res. 2009;37:5–20.
27. Buvat J, Maggi M, Guay A, et al. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment.
J Sex Med. 2013;10:245–284.
28. Dean JD, McMahon CG, Guay AT, et al. The international society for sexual medicine's process of care for the assessment and management of testosterone deficiency in adult men.
J Sex Med. 2015;12:1660–1686.
29. Lunenfeld B, Mskhalaya G, Zitzmann M, et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men.
Aging Male. 2015;18:5–15.
30. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline.
J Clin Endocrinol Metab. 2018;103:1715–1744.
31. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline.
J Urol. 2018;200:423–432.
32. Park HJ, Ahn ST, Moon DG. Evolution of guidelines for testosterone replacement therapy.
J Clin Med. 2019;8:410.
33. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations.
Eur J Endocrinol. 2008;159:507–514.
34. Basaria S. Male hypogonadism.
35. Miller SM, Peterson AR. The sports preparticipation evaluation.
Pediatr Rev. 2019;40:108–128.
36. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee.
World Health Organ Tech Rep Ser. 1995;854:1–452.
37. American Psychiatric Association, American Psychiatric Association, DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Vol xliv. 5th ed. Washington, DC: American Psychiatric Association; 2013:947.
38. Le Grange D, Doyle PM, Swanson SA, et al. Calculation of expected body weight in adolescents with eating disorders.
39. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States.
Adv Data. 2000;10:1–27.
40. Golden NH, Golden NH, Katzman DK, et al. Position Paper of the Society for Adolescent Health and Medicine: medical management of restrictive eating disorders in adolescents and young adults.
J Adolesc Health. 2015;56:121–125.
41. Burke LM, Lundy B, Fahrenholtz IL, et al. Pitfalls of conducting and interpreting estimates of energy availability in free-living athletes.
Int J Sport Nutr Exerc Metab. 2018;28:350–363.
42. Rodriguez NR, DiMarco NM, Langley S. Position of the American dietetic association, dietitians of Canada, and the American College of Sports Medicine: nutrition and athletic performance.
J Am Diet Assoc. 2009;109:509–527.
43. Maughan RJ, Burke LM, Dvorak J, et al. IOC consensus statement: dietary supplements and the high-performance athlete.
Int J Sport Nutr Exerc Metab. 2018;28:104–125.
44. Dhurandhar NV, Schoeller DA, Brown AW, et al. Response to ‟energy balance measurement: when something is not better than nothing”.
Int J Obes (Lond). 2015;39:1175–1176.
45. Heaney S, O'Connor H, Gifford J, et al. Comparison of strategies for assessing nutritional adequacy in elite female athletes' dietary intake.
Int J Sport Nutr Exerc Metab. 2010;20:245–256.
46. Ainsworth BE, Haskell WL, Herrmann SD, et al. 2011 Compendium of Physical Activities: a second update of codes and MET values.
Med Sci Sports Exerc. 2011;43:1575–1581.
47. Loucks AB. Low energy availability in the marathon and other endurance sports.
Sports Med. 2007;37:348–352.
48. Hoch AZ, Pajewski NM, Moraski L, et al. Prevalence of the female athlete triad in high school athletes and sedentary students.
Clin J Sport Med. 2009;19:421–428.
49. Meyer NL, Sundgot-Borgen J, Lohman TG, et al. Body composition for health and performance: a survey of body composition assessment practice carried out by the ad hoc research working group on body composition, health and performance under the auspices of the IOC medical commission.
Br J Sports Med. 2013;47:1044–1053.
50. Toombs RJ, Ducher G, Shepherd JA, et al. The impact of recent technological advances on the trueness and precision of DXA to assess body composition.
Obesity (Silver Spring). 2012;20:30–39.
51. De Souza MJ, Lee DK, VanHeest JL, et al. Severity of energy-related menstrual disturbances increases in proportion to indices of energy conservation in exercising women.
Fertil Steril. 2007;88:971–975.
52. Strock NC, Koltun KJ, Southmayd EA, et al. Indices of resting metabolic rate accurately reflect energy deficiency in exercising women.
Int J Sport Nutr Exerc Metab. 2020;30:1–11.
53. De Souza MJ, West SL, Jamal SA, et al. The presence of both an energy deficiency and estrogen deficiency exacerbate alterations of bone metabolism in exercising women.
54. O'Donnell E, Harvey PJ, De Souza MJ. Relationships between vascular resistance and energy deficiency, nutritional status and oxidative stress in oestrogen deficient physically active women.
Clin Endocrinol (Oxf). 2009;70:294–302.
55. Gibbs JC, Williams NI, Scheid JL, et al. The association of a high drive for thinness with energy deficiency and severe menstrual disturbances: confirmation in a large population of exercising women.
Int J Sport Nutr Exerc Metab. 2011;21:280–290.
56. Scheid JL, Williams NI, West SL, et al. Elevated PYY is associated with energy deficiency and indices of subclinical disordered eating in exercising women with hypothalamic amenorrhea.
57. Strock NC, Koltun KJ, Mallinson RJ, et al. Characterizing the resting metabolic rate ratio in ovulatory exercising women over 12 months.
Scand J Med Sci Sports. 2020;30:1337–1347.
58. Hayes M, Chustek M, Wang Z, et al. DXA: potential for creating a metabolic map of organ-tissue resting energy expenditure components.
Obes Res. 2002;10:969–977.
59. Cunningham JJ. Body composition as a determinant of energy expenditure: a synthetic review and a proposed general prediction equation.
Am J Clin Nutr. 1991;54:963–969.
60. Harris JA, Benedict FG. A biometric study of human basal metabolism.
Proc Natl Acad Sci U S A. 1918;4:370–373.
61. Cunningham JJ. A reanalysis of the factors influencing basal metabolic rate in normal adults.
Am J Clin Nutr. 1980;33:2372–2374.
62. Stunkard AJ, Messick S. The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger.
J Psychosom Res. 1985;29:71–83.
63. Melin A, Tornberg AB, Skouby S, et al. The LEAF questionnaire: a screening tool for the identification of female athletes at risk for the female athlete triad.
Br J Sports Med. 2014;48:540–545.
64. Garner DM, Olmstead M, Polivy J. Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia.
Intl J Eat Disord. 1983;2:15–34.
65. Vescovi JD, Scheid JL, Hontscharuk R, et al. Cognitive dietary restraint: impact on bone, menstrual and metabolic status in young women.
Physiol Behav. 2008;95:48–55.
66. Heikura IA, Uusitalo AL, Stellingwerff T, et al. Low energy availability is difficult to assess but outcomes have large impact on bone injury rates in elite distance athletes.
Int J Sport Nutr Exerc Metab. 2018;28:403–411.
67. Forbush KT, Wildes JE, Hunt TK. Gender norms, psychometric properties, and validity for the eating pathology symptoms inventory.
Int J Eat Disord. 2014;47:85–91.
68. Forbush KT, Wildes JE, Pollack LO, et al. Development and validation of the eating pathology symptoms inventory (EPSI).
Psychol Assess. 2013;25:859–878.
69. Schaefer LM, Smith KE, Leonard R, et al. Identifying a male clinical cutoff on the eating disorder examination-questionnaire (EDE-Q).
Int J Eat Disord. 2018;51:1357–1360.
70. Davidiuk AJ, Broderick GA. Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy.
Transl Androl Urol. 2016;5:824–833.
71. Hackett G, Kirby M, Edwards D, et al. British society for sexual medicine guidelines on adult testosterone deficiency, with statements for UK practice.
J Sex Med. 2017;14:1504–1523.
72. Dwyer AA, Chavan NR, Lewkowitz-Shpuntoff H, et al. Functional hypogonadotropic hypogonadism in men: underlying neuroendocrine mechanisms and natural history.
J Clin Endocrinol Metab. 2019;104:3403–3414.
73. Crabtree NJ, Arabi A, Bachrach LK, et al. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions.
J Clin Densitom. 2014;17:225–242.
74. ISCD. 2019 ISCD Official Positions—Pediatric. Available at: https://www.iscd.org/official-positions/2019-iscd-official-positions-pediatric/
. Accessed May 29, 2020.
75. ISCD. 2019 ISCD Official Positions—Adult. Available at: https://www.iscd.org/official-positions/2019-iscd-official-positions-adult/
. Accessed May 29, 2020.
76. Schousboe JT, Shepherd JA, Bilezikian JP, et al. Executive summary of the 2013 international society for clinical densitometry position development conference on bone densitometry.
J Clin Densitom. 2013;16:455–466.
77. Sundgot-Borgen J, Torstveit MK. Prevalence of eating disorders in elite athletes is higher than in the general population.
Clin J Sport Med. 2004;14:25–32.
78. Hinton PS, Sanford TC, Davidson MM, et al. Nutrient intakes and dietary behaviors of male and female collegiate athletes.
Int J Sport Nutr Exerc Metab. 2004;14:389–405.
79. Thomas DT, Erdman KA, Burke LM. Position of the Academy of nutrition and Dietetics, dietitians of Canada, and the American College of Sports Medicine: nutrition and athletic performance.
J Acad Nutr Diet. 2016;116:501–528.
80. Thomas DT, Erdman KA, Burke LM. American college of sports medicine joint position statement. Nutrition and athletic performance.
Med Sci Sports Exerc. 2016;48:543–568.
81. Jenner SL, Trakman G, Coutts A, et al. Dietary intake of professional Australian football athletes surrounding body composition assessment.
J Int Soc Sports Nutr. 2018;15:43.
82. Burke LM, Loucks AB, Broad N. Energy and carbohydrate for training and recovery.
J Sports Sci. 2006;24:675–685.
83. Burke LM, Slater G, Broad EM, et al. Eating patterns and meal frequency of elite Australian athletes.
Int J Sport Nutr Exerc Metab. 2003;13:521–538.
84. Volpe SL. Magnesium and the athlete.
Curr Sports Med Rep. 2015;14:279–283.
85. Nielsen FH, Lukaski HC. Update on the relationship between magnesium and exercise.
Magnes Res. 2006;19:180–189.
86. Ross AC; Institute of Medicine (U.S.). Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes: Calcium Vitamin D. Vol xv. Washington, DC: National Academies Press; 2011:1115.
87. Torstveit MK, Fahrenholtz I, Stenqvist TB, et al. Within-day energy deficiency and metabolic perturbation in male endurance athletes.
Int J Sport Nutr Exerc Metab. 2018;28:419–427.
88. Outila TA, Kärkkäinen MU, Lamberg-Allardt CJ. Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density.
Am J Clin Nutr. 2001;74:206–210.
89. Jones G, Dwyer T, Hynes KL, et al. Vitamin D insufficiency in adolescent males in Southern Tasmania: prevalence, determinants, and relationship to bone turnover markers.
Osteoporos Int. 2005;16:636–641.
90. Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D.
J Am Coll Nutr. 2003;22:142–146.
91. Bischoff-Ferrari HA, Dietrich T, Orav JE, et al. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults.
Am J Med. 2004;116:634–639.
92. Vieth R, Ladak Y, Walfish PG. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D.
J Clin Endocrinol Metab. 2003;88:185–191.
93. Misra M, Katzman D, Miller KK, et al. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa.
J Bone Miner Res. 2011;26:2430–2438.
94. Ackerman KE, Singhal V, Baskaran C, et al. Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial.
Br J Sports Med. 2019;53:229–236.
95. Ackerman KE, Singhal V, Slattery M, et al. Effects of estrogen replacement on bone geometry and microarchitecture in adolescent and young adult oligoamenorrheic athletes: a randomized trial.
J Bone Miner Res. 2019;35:248–260.
96. Plessow F, Singhal V, Toth AT, et al. Estrogen administration improves the trajectory of eating disorder pathology in oligo-amenorrheic athletes: a randomized controlled trial.
97. Baskaran C, Cunningham B, Plessow F, et al. Estrogen replacement improves verbal memory and executive control in oligomenorrheic/amenorrheic athletes in a randomized controlled trial.
J Clin Psychiatry. 2017;78:e490–e497.
98. Misra M, Katzman DK, Estella NM, et al. Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial.
J Clin Psychiatry. 2013;74:e765–e771.
99. Miller KK, Biller BM, Beauregard C, et al. Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study.
J Clin Endocrinol Metab. 2006;91:1683–1690.
100. Miller KK, Meenaghan E, Lawson EA, et al. Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study.
J Clin Endocrinol Metab. 2011;96:2081–2088.
101. Ackerman KE, Skrinar GS, Medvedova E, et al. Estradiol levels predict bone mineral density in male collegiate athletes: a pilot study.
Clin Endocrinol (Oxf). 2012;76:339–345.
102. Travison TG, Araujo AB, Beck TJ, et al. Relation between serum testosterone, serum estradiol, sex hormone-binding globulin, and geometrical measures of adult male proximal femur strength.
J Clin Endocrinol Metab. 2009;94:853–860.
103. Araujo AB, Travison TG, Leder BZ, et al. Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men.
J Clin Endocrinol Metab. 2008;93:2135–2141.
104. Behre HM, Kliesch S, Leifke E, et al. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men.
J Clin Endocrinol Metab. 1997;82:2386–2390.
105. Leifke E, Körner HC, Link TM, et al. Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men.
Eur J Endocrinol. 1998;138:51–58.
106. Katznelson L, Finkelstein JS, Schoenfeld DA, et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism.
J Clin Endocrinol Metab. 1996;81:4358–4365.
107. Burnett-Bowie SA, McKay EA, Lee H, et al. Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels.
J Clin Endocrinol Metab. 2009;94:4785–4792.
108. Finkelstein JS, Yu EW, Burnett-Bowie SA. Gonadal steroids and body composition, strength, and sexual function in men.
N Engl J Med. 2013;369:2457.
109. Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men.
J Clin Endocrinol Metab. 2000;85:2839–2853.
110. Bhasin S, Storer TW, Berman N, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men.
J Clin Endocrinol Metab. 1997;82:407–413.
111. Hooper DR, Tenforde AS, Hackney AC. Treating exercise-associated low testosterone and its related symptoms.
Phys Sportsmed. 2018;46:427–434.
112. Burge MR, Lanzi RA, Skarda ST, et al. Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate.
Fertil Steril. 1997;67:783–785.
113. Dadhich P, Ramasamy R, Scovell J, et al. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men.
Indian J Urol. 2017;33:236–240.
114. Wheeler KM, Smith RP, Kumar RA, et al. A comparison of secondary polycythemia in hypogonadal men treated with clomiphene citrate versus testosterone replacement: a multi-institutional study.
J Urol. 2017;197:1127–1131.
115. Naessens G, De Slypere JP, Dijs H, et al. Hypogonadism as a cause of recurrent muscle injury in a high level soccer player. A case report.
Int J Sports Med. 1995;16:413–417.
116. Leder BZ, Rohrer JL, Rubin SD, et al. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels.
J Clin Endocrinol Metab. 2004;89:1174–1180.
117. Kliesch S, Behre HM, Nieschlag E. High efficacy of gonadotropin or pulsatile gonadotropin-releasing hormone treatment in hypogonadotropic hypogonadal men.
Eur J Endocrinol. 1994;131:347–354.
118. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial.
119. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
N Engl J Med. 2001;344:1434–1441.
120. Finkelstein JS, Wyland JJ, Lee H, et al. Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis.
J Clin Endocrinol Metab. 2010;95:1838–1845.
121. Leder BZ, Tsai JN, Neer RM, et al. Response to therapy with teriparatide, denosumab, or both in postmenopausal women in the DATA (denosumab and teriparatide administration) study randomized controlled trial.
J Clin Densitom. 2016;19:346–351.
122. Hansen S, Hauge EM, Beck Jensen JE, et al. Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT.
J Bone Miner Res. 2013;28:736–745.
123. Macdonald HM, Nishiyama KK, Hanley DA, et al. Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis.
Osteoporos Int. 2011;22:357–362.
124. Keaveny TM, Donley DW, Hoffmann PF, et al. Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis.
J Bone Miner Res. 2007;22:149–157.
125. Tsai JN, Uihlein AV, Burnett-Bowie SM, et al. Effects of two years of teriparatide, denosumab, or both on bone microarchitecture and strength (DATA-HRpQCT study).
J Clin Endocrinol Metab. 2016;101:2023–2030.
126. Leder BZ, Optimizing sequential and combined anabolic and antiresorptive osteoporosis therapy.
JBMR Plus. 2018;2:62–68.
127. Miller PD, Hattersley G, Lau E, et al. Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: results from the ACTIVE phase 3 trial.
128. Watts NB, Hattersley G, Fitzpatrick LA, et al. Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.
Osteoporos Int. 2019;30:1187–1194.
129. Almirol EA, Chi LY, Khurana B, et al. Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: a pilot study.
J Clin Transl Endocrinol. 2016;5:7–14.
130. Gende A, Thomsen TW, Marcussen B, et al. Delayed-union of acetabular stress fracture in female gymnast: use of teriparatide to augment healing.
Clin J Sport Med. 2019;30:e163–e165.
131. Fazeli PK, Wang IS, Miller KK, et al. Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa.
J Clin Endocrinol Metab. 2014;99:1322–1329.
132. Lewiecki EM, Blicharski T, Goemaere S, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis.
J Clin Endocrinol Metab. 2018;103:3183–3193.
133. Liu Y, Cao Y, Zhang S, et al. Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials.
134. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis.
N Engl J Med. 2016;375:1532–1543.
136. Sølling AS, Harsløf T, Langdahl B. The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis.
Ther Adv Musculoskelet Dis. 2018;10:105–115.
137. Misra M, Miller KK, Bjornson J, et al. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism.
J Clin Endocrinol Metab. 2003;88:5615–5623.
138. Grinspoon S, Baum H, Lee K, et al. Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa.
J Clin Endocrinol Metab. 1996;81:3864–3870.
139. Misra M, McGrane J, Miller KK, et al. Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa.
140. Grinspoon S, Thomas L, Miller K, et al. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa.
J Clin Endocrinol Metab. 2002;87:2883–2891.
141. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea.
N Engl J Med. 2004;351:987–997.
142. Chou SH, Chamberland JP, Liu X, et al. Leptin is an effective treatment for hypothalamic amenorrhea.
Proc Natl Acad Sci U S A. 2011;108:6585–6590.
143. Chambers SA, Clarke A, Wolman R. Treatment of lumbar pars interarticularis stress injuries in athletes with intravenous bisphosphonates: five case studies.
Clin J Sport Med. 2011;21:141–143.
144. Simon MJ, Barvencik F, Luttke M, et al. Intravenous bisphosphonates and vitamin D in the treatment of bone marrow oedema in professional athletes.
145. Chen L, Wang G, Zheng F, et al. Efficacy of bisphosphonates against osteoporosis in adult men: a meta-analysis of randomized controlled trials.
Osteoporos Int. 2015;26:2355–2363.
146. Nayak S, Greenspan SL. Osteoporosis treatment efficacy for men: a systematic review and meta-analysis.
J Am Geriatr Soc. 2017;65:490–495.
147. Wilkes MM, Navickis RJ, Chan WW, et al. Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials.
Osteoporos Int. 2010;21:679–688.
148. Golden NH, Iglesias EA, Jacobson MS, et al. Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial.
J Clin Endocrinol Metab. 2005;90:3179–3185.
149. Beaudoin C, Jean S, Bessette L, et al. Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis.
Osteoporos Int. 2016;27:2835–2844.
150. Dao D, Sodhi S, Tabasinejad R, et al. Serum 25-hydroxyvitamin D levels and stress fractures in military personnel: a systematic review and meta-analysis.
Am J Sports Med. 2015;43:2064–2072.
151. Davey T, Lanham-New SA, Shaw AM, et al. Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training.
Osteoporos Int. 2016;27:171–179.
152. Richards T, Wright C. British Army recruits with low serum vitamin D take longer to recover from stress fractures.
BMJ Mil Health. 2018;166:240–242.
153. Shimasaki Y, Nagao M, Miyamori T, et al. Evaluating the risk of a fifth metatarsal stress fracture by measuring the serum 25-hydroxyvitamin D levels.
Foot Ankle Int. 2016;37:307–311.
154. Nieves JW, Melsop K, Curtis M, et al. Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners.
PM R. 2010;2:740–794.
155. Lappe J, Cullen D, Haynatzki G, et al. Calcium and vitamin D supplementation decreases incidence of stress fractures in female navy recruits.
J Bone Miner Res. 2008;23:741–749.
156. Gaffney-Stomberg E, Lutz LJ, Rood JC, et al. Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial.
157. Farrokhyar F, Tabasinejad R, Dao D, et al. Prevalence of vitamin D inadequacy in athletes: a systematic-review and meta-analysis.
Sports Med. 2015;45:365–378.
158. Tenforde AS, Fredericson M. Influence of sports participation on bone health in the young athlete: a review of the literature.
PM R. 2011;3:861–867.
159. DiFiori JP, Benjamin HJ, Brenner J, et al. Overuse injuries and burnout in youth sports: a position statement from the American Medical Society for Sports Medicine.
Clin J Sport Med. 2014;24:3–20.
160. Layne JE, Nelson ME. The effects of progressive resistance training on bone density: a review.
Med Sci Sports Exerc. 1999;31:25–30.
161. Duplanty AA, Levitt DE, Hill DW, et al. Resistance training is associated with higher bone mineral density among young adult male distance runners
independent of physiological factors.
J Strength Cond Res. 2018;32:1594–1600.
162. Mathis SL, Caputo JL. Resistance training is associated with higher lumbar spine and hip bone mineral density in competitive male cyclists.
J Strength Cond Res. 2018;32:274–279.
163. Tenforde AS, Nattiv A, Ackerman K, et al. Optimising bone health in the young male athlete.
Br J Sports Med. 2017;51:148–149.
164. Tenforde AS, Sayres LC, McCurdy ML, et al. Identifying sex-specific risk factors for stress fractures in adolescent runners.
Med Sci Sports Exerc. 2013;45:1843–1851.
165. Barrack MT, Gibbs JC, De Souza MJ, et al. Higher incidence of bone stress injuries with increasing female athlete triad-related risk factors: a prospective multisite study of exercising girls and women.
Am J Sports Med. 2014;42:949–958.
166. Gibbs JC, Nattiv A, Barrack MT, et al. Low bone density risk is higher in exercising women with multiple triad risk factors.
Med Sci Sports Exerc. 2014;46:167–176.
167. Boden BP, Osbahr DC. High-risk stress fractures: evaluation and treatment.
J Am Acad Orthop Surg. 2000;8:344–353.
168. Boden BP, Osbahr DC, Jimenez C. Low-risk stress fractures.
Am J Sports Med. 2001;29:100–111.
169. Kahanov L, Eberman LE, Games KE, et al. Diagnosis, treatment, and rehabilitation of stress fractures in the lower extremity in runners.
Open Access J Sports Med. 2015;6:87–95.
170. Chen YT, Tenforde AS, Fredericson M. Update on stress fractures in female athletes: epidemiology, treatment, and prevention.
Curr Rev Musculoskelet Med. 2013;6:173–181.
171. Dobrindt O, Hoffmeyer B, Ruf J, et al. Estimation of return-to-sports-time for athletes with stress fracture - an approach combining risk level of fracture site with severity based on imaging.
BMC Musculoskelet Disord. 2012;13:139.
172. Miller TL, Jamieson M, Everson S, et al. Expected time to return to athletic participation after stress fracture in division I collegiate athletes.
Sports Health. 2018;10:340–344.
173. Herring SA, Kibler WB, Putukian M. Team physician consensus statement: 2013 update.
Med Sci Sports Exerc. 2013;45:1618–1622.
174. 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;48:491–497.
175. Mountjoy M, Sundgot-Borgen J, Burke L, et al. The IOC relative energy deficiency in sport clinical assessment tool (RED-S CAT).
Br J Sports Med. 2015;49:1354.
176. Koltun KJ, Strock NC, Southmayd EA, et al. Comparison of female athlete triad coalition and RED-S risk assessment tools.
J Sports Sci. 2019;37:2433–2442.
177. Creighton DW, Shrier I, Shultz R, et al. Return-to-play in sport: a decision-based model. Clin J Sport Med. 2010;20:379–385.