The frequency of BMD assessment by DXA will depend on the initial BMD and ongoing clinical status of the athlete. Those with definitive indications for DXA testing may require BMD testing every 1 to 2 years to determine whether there is ongoing bone loss and to evaluate treatment.
Due to the multifactorial etiology of the triad, an optimal treatment approach must address the underlying cause of the triad, that is, low EA (86). Energy status must be normalized primarily through modifications of diet and exercise training with the goal of increasing EA (27,86). Restoration or normalization of body weight is the best strategy for successful resumption of menses and improved bone health (4–8,84,86). It is important to emphasize that the amount of weight gain that typically leads to resumption of menses is variable among individuals (33,59,69). In studies thus far, a range of approximately 5% to 10% of body weight or 1 to 4 kg of weight gain has been associated with resumption of menses (33,59,69). The development of any triad treatment plan should include consideration of goals of the athlete, her unique diet and training practices, coexisting conditions, and a systematic approach for monitoring changes (e.g., regular meetings with treatment team members, use of written contracts).
Specific treatment recommendations depend on identifying how low EA developed in the athlete. There may be four unique pathways to low EA and, as such, four unique treatment recommendations.
Since the treatment goal is to restore or normalize body weight, it is recommended that athletes increase dietary energy intake, decrease exercise energy expenditure, or both. Recommendations should consider individual preferences and may depend on where the athlete is in the competitive season (e.g., reductions in training volume may be not feasible in season, acceptance of increased energy intake better may be received vs reduction in training volume). Prescribed changes in energy intake to achieve increased BMI and/or body weight goal should be gradual, beginning with an approximately 20% to 30% increase in caloric intake over baseline energy needs or the amount of energy required to gain approximately 0.5 kg every 7 to 10 d (33,59,69). For an athlete consuming 2,000 kcal·d−1, this would represent a gradual increase of 200 to 600 kcal·d−1 accomplished over several months. If EA ((intake (kcal) − exercise (kcal)·kg−1 FFM·d−1) can be estimated reliably, the target should be ≥45 kcal·kg−1 FFM·d−1.
A successful treatment plan requires standardized periodic monitoring of body weight. Athletes should be weighed on the same scale while wearing minimal clothing, such as shorts and a T-shirt, to reduce the likelihood of falsifying their weight (51). The frequency of weight monitoring depends on the degree to which weight determines health and eligibility to participate in sport. A reasonable frequency is weekly when initiating a treatment program. The goal of treatment for athletes with ED is to normalize pathological eating behaviors, reduce dieting attempts, and alter negative emotions and beliefs associated with food and body image (122).
The etiology of bone loss among women with amenorrhea includes energy deficiency-related factors and estrogen deficiency (26,49,82). Thus, weight gain and subsequent resumption of menses are keys to prevent further loss of bone mass (79,84). It is estimated that women with amenorrhea will lose approximately 2% to 3% of bone mass per year if the condition remains untreated (8,79,84). In exercising women with low BMD, treatment recommendations include increasing EA and optimizing weight gain in order to promote the resumption of menses (37,79). In addition, calcium and vitamin D status should be optimized.
Weight-bearing exercise is a primary nonpharmacological strategy for increasing and maintaining BMD and geometry across the life-span (9). Bone tissue is highly responsive to dynamic and high-magnitude loading (87), high-impact loading (12,55,111,119), and resistance training (71,113). To date, prospective studies are lacking wherein investigators explore the impact of resistance training and high-magnitude loading on the bone health of athletes with amenorrhea. However lean mass has been reported to be a strong predictor of hip BMD among anorexic adolescents (83) and also adolescent athletes and nonathletes (19). Realizing that high-impact activity in females with low BMD (± fractures), in fact, may result in fracture (68), further studies are necessary to determine the impact of combined weight-bearing programs on BMD and fracture risk in athletes with low BMD.
Treatment of triad conditions by increasing EA will result in recovery of physiological systems at different rates. Notably the time to resumption of menses may vary among exercising women and is dependent on the severity of the energy deficiency and duration of menstrual dysfunction (7,69,84). An increase in EA can alter metabolic hormone profiles positively within days to weeks, with concomitant changes in body weight occurring over weeks and months. Weight gain has been observed as a clinically positive outcome associated with resumption of menses and enhanced bone health in exercising women (37,59,79,84,123). The recovery of menstrual function with strategies to increase EA can occur within several months (69) but may take longer than 1 year (7). Improvements in BMD will occur more slowly, often over several years. Whether or not BMD can be restored to levels appropriate for age and training status remains unclear (31,52,56).
There is no evidence at this time to recommend pharmacological therapy unequivocally for athletes with the triad disorders due to lack of evidenced-based research in this population. Nonpharmacological measures should constitute initial management in female athletes with the triad. For treatment of osteoporosis and/or in those athletes with history of multiple fracture, pharmacological management is to be considered if there is lack of response to nonpharmacological therapy for at least 1 year and if new fractures occur during nonpharmacological management. Pharmacological management also may be necessary in the psychological treatment of ED and DE, especially if there are significant comorbid conditions.
One of the challenges in addressing low EA is that it may be difficult to identify which individuals have an ED that requires more comprehensive treatment. This can be amplified by denial that there is a problem and minimization of the difficulty in changing behaviors, which are common themes for individuals with ED. The team physician should work closely with the multidisciplinary team to determine the best treatment approach for an individual athlete.
Individuals who have unintentional low EA or mild DE may respond well to nutrition education designed to eliminate low EA. Individuals with significant DE may benefit from counseling with a mental health practitioner in addition to nutrition education. In contrast, individuals who have an ED require intensive interdisciplinary attention and treatment. The American Psychiatric Association (APA) Practice Guidelines for the Treatment of Patients with Eating Disorders (5) recommend a multidisciplinary team approach to treatment, including a physician, mental health provider, and sports dietitian. Results of small randomized trials involving treatment approaches that include mindfulness training and dialectical behavior therapy are encouraging (114,120). Antidepressant medications, particularly selective serotonin reuptake inhibitors, can be helpful in the treatment of bulimia nervosa (1). The APA Practice Guidelines (5) describe limited evidence to use medications to restore weight, prevent relapse, or treat chronic anorexia nervosa. Other psychotropic medications can be beneficial in treating comorbid conditions such as anxiety, depression, and obsessive-compulsive behavior.
When considering pharmacological strategies to address amenorrhea and hypoestrogenemia in athletes and exercising women, it is essential to acknowledge that combined oral or nonoral routes of contraceptive therapy do not restore spontaneous menses; indeed contraceptive therapy simply creates an exogenous ovarian steroid environment that often provides a false sense of security when induced withdrawal bleeding occurs (15). Moreover combined oral contraceptive (COC) therapy is not associated consistently with improved BMD in athletes with amenorrhea (20,40,115) and, in fact, may compromise bone health further, given first-pass effects on hepatic production of insulin-like growth factor-1 (IGF-1), an important bone trophic hormone (44,63,117).
The major gonadal steroids include estrogen, progesterone, and testosterone, all of which are low in the athlete with amenorrhea.
Transdermal estradiol administration, when given in replacement doses, does not suppress IGF-1 (18,54,81,117). In a randomized controlled trial in adolescent girls with anorexia nervosa, transdermal estradiol administered at doses of 100 mcg twice weekly, with cyclic progesterone (2.5 mg daily for 10 d of every month to prevent unopposed estrogen stimulation of the uterus) increased BMD in this population without a reduction in IGF-1 levels (81). The use of transdermal estradiol warrants further investigation as a strategy to provide hormone replacement therapy safely to women affected by the Triad.
Vaginal estradiol administration also circumvents hepatic first-pass metabolism, and a vaginal estrogen-progesterone combination contraceptive ring is now available. However data regarding the impact of this form of estrogen administration on BMD are conflicting, with one study suggesting maintenance of BMD and another suggesting that it may bedeleterious to bone compared with no treatment in premenopausal women (73,74). Thus further research on vaginally applied estrogen is necessary.
In summary, in athletes and exercising women with FHA and prolonged amenorrhea of hypothalamic origin who meet criteria for pharmacological therapy, a reasonable option is estrogen administration with cyclic progesterone after ruling out other causes of amenorrhea. It is also essential to consider the contraceptive needs of the athlete. Before starting therapy, a thorough history and examination should be conducted to rule out contraindications for estrogen therapy.
COC therapy containing 20 to 35 mcg of ethinyl estradiol in addition to progesterone may maintain BMD in those with very low BMD measures, although data are not definitive (58,95). Most studies in adolescents and adults with anorexia nervosa and in athletes with amenorrhea suggest that COC therapies are not effective in increasing BMD (20,40,58,105) or in reducing stress fractures (20), although they are effective for contraceptive needs when used in recommended doses.
Transdermal estradiol (100 mcg of 17β estradiol) with cyclic progesterone maintains BMD Z-scores in adolescents with anorexia nervosa (81) and is a consideration for low-weight, amenorrheic athletes who meet criteria for pharmacological intervention, and as hormone replacement for adolescent amenorrheic athletes (who are at an age when they should be accruing bone rapidly towards attainment of peak bone mass). Athletes who are symptomatic with this dose for estrogen-related side effects such as nausea, bloating, and breast tenderness may be started on a lower dose of the transdermal patch (50 mcg) and the dose increased to 100 mcg after one month. Progesterone may be administered as 5–10 mg of medroxyprogesterone acetate or 100–200 mg of micronized progesterone for 12 days of every month.
There are no data available on testosterone administration in athletes with amenorrhea and exercising women. However a recent study in adult women with anorexia nervosa demonstrated no improvement in BMD with low-dose testosterone administration despite increases in lean mass and initial increases in surrogate markers of bone formation (80).
Data regarding the efficacy of other pharmacotherapy in treating low BMD with or without a fracture history in the female athlete are lacking. While pharmacological therapy is recommended for postmenopausal women and men with osteoporosis aged ≥50 years (116), the threshold for pharmacological treatment in the young female athlete with low BMD, stress fractures, and/or impaired bone accrual is less clear.
Caution must be used when considering Food and Drug Administration-approved postmenopausal treatment strategies for use in premenopausal women and children including triad athletes and exercising women. Bisphosphonates have a very long half-life and should be used with extreme caution in women of childbearing age for concerns of teratogenicity (70,91), although data to date are reassuring. The decision to initiate treatment with bisphosphonates in any premenopausal woman should be made on a case-by-case basis. Consideration should include individual fracture risk and potential medication-related adverse effects. Any use of bisphosphonate therapy in young women with the triad should be executed only by or in consultation with a board-certified endocrinologist or specialist in metabolic bone diseases. There are no published studies on bisphosphonate use among exercising and athletic women with triad disorders. Likewise there are no published studies on denosumab or teriparatide use in girls and women with triad disorders. A preliminary report in older women with anorexia nervosa demonstrated that treatment with teriparatide for 6 months increased bone formation (158%) and lumbar spine BMD (anteroposterior spine, 6.0%; lateral spine, 10.5%) compared with placebo (35). There is also a case study that suggests that 4 wk of teriparatide was associated with bone healing, reduced pain, and resumption of normal activities in two premenopausal women with stress fractures (92).
Overall, the decision to treat or not treat with pharmacological therapies does not depend on BMD z-scores alone but also on additional risk factors such as fracture history, genetics (34), cumulative Triad risk factors, which have been associated with an increased risk for low BMD (38) and bone stress injury (11), and rate of bone loss with nonpharmacological management.
Transdermal estradiol replacement with cyclic progesterone may be considered in young athletes ≥16 and <21 years of age with FHA to prevent further bone loss during this critical window of optimal bone accrual if they have the following:
Calcium-rich foods should be recommended with optimal calcium intake between 1,000 and 1,300 mg·d−1 (99). Vitamin D status should be optimized. Daily intake of 600 IU of vitamin D is recommended by the Institute of Medicine for adolescents and adults up to age 70 (99). Higher doses may be needed if deficient or insufficient in vitamin D. Vitamin D levels should be maintained between 32 and 50 ng·mL−1 (48).
In rare instances, pharmacological management other than estrogen replacement/COC therapy can be considered when athletes meet criteria for osteoporosis and have failed nonpharmacological therapy (with recurrent fractures) and meet one of the following criteria:
More recent studies assessing health outcomes of single and combined risk factors for the triad have demonstrated that there is increased cumulative risk for the outcomes of low BMD (38), stress fracture, and bone stress injury (11,108). For example, female collegiate runners with menstrual dysfunction had more severe bone stress injuries on magnetic resonance imaging (MRI) compared with eumenorrheic runners (85). Low BMD and higher-MRI grade bone stress injuries were independent predictors of delay of RTP (85).
According to the 2012 consensus statement on The Team Physician and the Return to Play Decision (46), the physician’s duty is “to return an injured or ill athlete to practice or competition without putting the individual at undue risk for injury or illness”. In addition, the team physician’s role is to establish an RTP process, evaluate the athlete with medical conditions, treat and rehabilitate the athlete, and return the athlete to play after he or she is determined to be safe to do so.
With increasing evidence that the athlete’s risk for unfavorable outcomes of low BMD and/or bone stress injuries is greater with cumulative risk factors for the triad (11,38,108), in addition to evidence that triad risk factors may contribute to more severe bone stress injuries and a delay in RTP (85), and due to the lack of standard of care guidelines for the triad, the panel recommends the following risk stratification protocol be implemented (Figs. 4 and 5). This risk stratification protocol has been translated into a worksheet for the physician (Fig. 4) that incorporates evidence-based risk factors for the triad (11,38,108) and takes into account the magnitude (or severity) of risk, assigning a point value for risk factors in each triad spectrum based on risk severity (low, moderate, and high risk). This cumulative risk stratification protocol then is translated into clearance and RTP guidelines for the triad based on the athlete’s cumulative risk score (Fig. 5). Future research is needed to assess whether implementation of a risk stratification model results in improved outcomes for female athletes with triad disorders.
The primary goal of the risk stratification protocol is to optimize health and reduce risk for injury and illness associated with the triad. Best practice for outpatient management of the triad can be accomplished with a multidisciplinary team consisting of the team physician, a sports dietitian, and often a mental health practitioner (53). Other team members may include the athlete’s coach, athletic trainer, family members, and other professionals, depending on the athlete’s unique situation.
The intent of this risk stratification developed for the triad is to determine clearance and RTP recommendations. Athletes at low risk can be cleared fully (assuming otherwise healthy). Athletes at moderate risk for the triad can be cleared provisionally or receive limited clearance. Provisional clearance would include clearance for full training/competition, with the understanding that the athlete will be compliant with the recommendations outlined by the multidisciplinary team. With limited clearance, the athlete is cleared, but there are limitations specified with the athlete’s training and competition based on the athlete’s health status. Athletes determined to be at high risk are restricted from training and competition. In this category, the athlete’s status can be provisional or the athlete may be disqualified. If the health care team determines that the athlete may be able to reach the stated health goals, the status is provisional and a plan is outlined by the multidisciplinary team for a given period and is reevaluated as the athlete’s health status improves. If severity of risk is determined to be too high for the athletic participation at the time of the PPE and prognosis is determined to be poor, the athlete is disqualified and clearance/RTP is reevaluated with clinical progress, if appropriate.
It is hoped that this risk stratification developed for the triad will assist health care providers working with female athletes to minimize risk associated with the triad disorders. With ongoing research, updates to the risk stratification can be implemented in hopes of guiding treatment and decision making for clearance and RTP.
Athletes in the moderate-risk and high-risk categories should receive a written contract that is reviewed and presented to them by the team physician after their initial evaluation. The goal of the written contract is to specify the criteria necessary for ongoing or future clearance and RTP for the female athlete with the multidisciplinary team members and to ensure a shared understanding of how the clinical status of the athlete will be followed with each member of the multidisciplinary team.
The team physician coordinates the treatment goals with each multidisciplinary team member and includes the specific recommendations in the contract in addition to the requested frequency of visits and expectations for each team member. The team physician then reviews the recommendations with the athlete and answers any questions. In the case of the written contract, both athlete and team physician sign the contract after it is discussed. (Please refer to the Appendix on page 232 for an example of a written contract for the triad, which can be modified based on the athlete’s clearance status).
In addition to risk stratification, the team physician must take into account the athlete’s unique situation in making the final decision for clearance and RTP (47). The decision-based RTP model developed by Creighton et al. (21) (Fig. 6) points out the complexities in RTP decision making. It is of paramount importance that the team physician has the ultimate say in the decision making process for clearance and RTP (46,47,75). Although the team physician has this authority to make the final decision, the decision is often the product of consultation with the multidisciplinary team and other concerned parties (which may include parents and coaches). The physician always must have the athlete’s health and safety as the first priority in the decision-making process, which should supersede all other pressures or circumstances that may arise.
Young girls and women with the triad have significant health risks. Historically many of these athletes have been cleared for sport participation without appropriate evaluation, management, and treatment. Similarly after medical illness or injury, athletes with the triad often return to play prematurely and without adequate treatment and follow-up. It is the team physician’s responsibility to ensure that each and every athlete that is cleared for participation in sport or RTP after an injury or illness return only when it is determined safe to do so. This evidenced-based risk stratification point system takes into account magnitude of risk to assist the physician regarding sport participation, clearance, and RTP. Guidelines are offered for clearance categories, management by a multidisciplinary team, and implementation of treatment contracts. Future research is needed to study whether risk stratification, clearance, and RTP guidelines are an effective means to optimize health and reduce risk for injury and illness for the triad.
This consensus article was written and endorsed by the Female Athlete Triad Coalition, an international consortium of leading triad researchers, physicians, and other health care professionals, the American College of Sports Medicine, the American Medical Society for Sports Medicine, and the American Bone Health Alliance, and the National Athletic Trainers Association. The authors and expert panel would like to acknowledge the contributions of Jim Whitehead, executive vice president and chief executive officer, American College of Sports Medicine; Mimi Johnson, MD; and Tyler Wadsworth, MD. Their encouragement, expertise, and support contributed to the successful development of this document.
The authors declare no conflicts of interest and do not have any financial disclosures.
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