Low Energy Availability in Female Athletes

Since the introduction of title IX in 1972, which barred discrimination based on sex with regard to educational programs and activities receiving federal financial assistance, there have been increased opportunities for females to participate in athletics. The National Coalition for Women and Girls in Education states that the number of female high school and college athletes has increased 10 and 6 fold, respectively, over the past 40 years. ^[1]  The exponential increase of women in sports has resulted in a greater need to understand the unique gender-specific physiology and psychology of the female athlete. 

Low energy availability is a relatively common complaint among female athletes. Energy availability is defined as energy obtained through oral nutrition minus energy expended during exercise. It is reasonable to conclude that low energy may result as a consequence of increased energy expenditure, decreased oral nourishment (either intentional or unintentional), or both. Chronic energy deficit in the female athlete can result in musculoskeletal and reproductive dysfunction. Low energy (with or without an eating disorder) in combination with menstrual disorder and altered mineral bone density is known as the female athlete triad. ^{[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]} Studies have shown that every female athlete in any sport regardless of level of competition has the potential to develop the triad. However those females participating in endurance sports, such as track and field, swimming, and rowing, or in those sports requiring subjective judging, such as gymnastics and figure skating, are most at risk. ^{[4, 18, 19, 20]}

In 2014, a consensus statement was released based on recommendations formulated after the first and second International Symposia on the Female Athlete Triad, providing clinical guidelines with regard to screening for the triad, along with its diagnosis and treatment. Return-to-play recommendations were offered as well. In terms of nonpharmacologic therapy, for example, the statement advises that “successful treatment of athletes and exercising women is contingent on a multidisciplinary approach for recovery from the Triad, including a primary care and/or sports medicine physician, a sports dietitian and mental health practitioner.” The statement also reports that in individual cases, the patient may benefit from consultation with an endocrinologist, an orthopedic surgeon, a psychiatrist, an exercise physiologist, a certified athletic trainer, and/or a team coach, as well as with family members. ^[21]

Energy intake

The limiting factor for performance during training and competition in high-intensity sports of long duration is energy intake. A substantial percentage of energy intake is provided through consumption of carbohydrates and, to a lesser extent, proteins and fats. (A direct correlation exists between carbohydrate availability and reproductive and skeletal health.) In the maintenance of optimal energy availability, increased energy expenditure ideally justifies increased nutritional intake. Many female athletes, however, either deliberately or inadvertently fail to maintain adequate energy intake.  

When this energy deficit is intentional, it is described as disordered eating. Females athletes are 5-10 times more likely to suffer from an eating disorder than men. ^[22]   The prevalence of clinical eating disorders (such as anorexia nervosa and bulimia nervosa) among female elite athletes ranges from 16-47%. ^{[23, 24, 25, 26]}  (It is reasonable to suspect that women with eating disorders may self-select into sports in which low body weight offers a competitive advantage.) A majority of female athletes with a diagnosed eating disorder also have a comorbid mental health disorder, such as depression or anxiety.  Female athletes with eating disorders may also struggle with obsessive-compulsive disorder (41%), substance abuse (30%), or personality disorders (40-60%). Suicide rates among females who suffer from eating disorders are over three-fold that of age-matched, healthy controls. ^[27]

Many female athletes without the diagnosis of an eating disorder exhibit disordered eating habits. Most of the time, this occurs unknowingly, with the athlete failing to obtain appropriate energy intake. There is a large continuum of disordered eating ranging from healthy dieting to fasting, skipping meals, diet pill or laxative use, and binging and purging. ^[28]  Regardless of the cause of decreased energy intake, the athlete will function in a low-energy state.

Energy expenditure

Energy expenditure is defined as energy consumed as a result of exercise and baseline daily metabolic requirements.

The appetite of an athlete is not a reliable indicator of either energy balance or specific macronutrient requirements, because no biologic imperative to match intake to expenditure appears to exist. ^[29] Hunger is actually suppressed for a brief period after a single episode of exercise at greater than 60% maximal oxygen consumption, or VO_2max. ^[30]

Food deprivation increases hunger, but the same low energy availability, when caused by energy expenditure from exercise, does not increase appetite. ^[31] In one study, a 20% increase in energy expenditure during 40 weeks of marathon training did not result in an increase in energy intake. ^{[32, 33]} Even female monkeys with induced amenorrhea secondary to increased energy expenditure must be offered special treats in order to persuade them to consume enough food to restore normal menstrual function. ^[34]

Other factors

Body weight is not a reliable indicator of either energy or macronutrient balance. Because fat stores are associated with less body water than are protein and glycogen stores, the weight gain resulting from an increase in protein or glycogen stores more than counterbalances the weight loss resulting from the equivalent energy reduction in fat stores that occurs in low energy availability. ^{[35, 36]}

If disordered eating patterns are suspected, a therapist or psychiatrist familiar with treating eating disorders should be consulted immediately. For more information on the workup and treatment of eating disorders, please refer to the Medscape Drugs & Diseases article Female Athlete Triad. ^{[4, 5]}

A thorough history should be obtained from all female athletes. In addition to the normal comprehensive history, certain components on which to focus include the athlete's nutritional, musculoskeletal, menstrual, endocrine/metabolic, psychosocial, performance, and medication history.

Nutritional history

It is important to gather information about nutritional intake and eating patterns. The components of each athlete's diet are important in terms of the quantity of protein, carbohydrate, vitamins, and minerals consumed. Also important are the effects of training on an athlete's diet and the modification of the athlete's diet in times of increased training. Assessing whether a female athlete has an inadequate carbohydrate intake and tends to consume meals that are less energy dense may be an important means of avoiding low energy availability conditions and thus preventing the female athlete triad. ^[37]

Musculoskeletal history

A careful review of past and current musculoskeletal injuries in the female athlete should be conducted. There should be a focus on all stress fractures, as well as on other fractures. There is an increase in risk of stress fractures in females with a chronic energy deficit. Any injury that results in loss of training or competition time should be considered major.

Using the Female Athlete Triad Cumulative Risk Assessment tool, a study by Edama et al indicated that there is a greater tendency towards sports injury (specifically, bone stress fractures and bursitis) for female college students in the moderate- and high-risk categories than for those considered to be low risk. ^[20]

Menstrual history

Other than fracture, the most likely manifestation of severe, chronic low energy availability in the female athlete is menstrual disturbance. Because many women do not volunteer information concerning menstrual disturbances, it should be specifically sought during all routine and sick visits by female athletes.

A complete menstrual history should be obtained. This includes the age at menarche, average length of menses, average time between menstrual periods, variations during times of increased training, and number of cycles per year. The possibility of pregnancy should be excluded in the case of amenorrhea. The patient's personal and family history of reproductive disorders, such as premature ovarian failure, should be discussed.

Endocrine/metabolic history

A history of endocrine abnormalities and an accounting of risk factors for them should be obtained. Any personal and family history of thyroid disorders, pituitary disorders, and diabetes should be sought, as should a description of any existing signs and symptoms of polycystic ovarian syndrome (PCOS). Any family history of bone disease should be established.  

Psychosocial history

Eating patterns should be discussed. The Eating Disorder Inventory (EDI) may be used to screen for current and past disordered eating patterns. As with all patients, alcohol, tobacco, and drug use should be documented. The female athlete should also be asked about social support, depression, anxiety, and a history of physical/emotional/sexual abuse.

Performance history

During sustained energy deficiency, an athlete's strength, power, and vertical jump all decline by approximately 20%. ^[38] The athlete should be questioned as to whether she has noticed any change in strength or performance.

Medication history

All medications, dietary supplements, and herbal agents should be reviewed.  The use of oral contraceptives should be elicited separately because patients often do not consider these to be medications.  It is imperative that athletes be asked about the use of anabolic steroids. Patients should also be questioned about the use of emetics, diet pills, stool softeners and laxatives.  Additional attention should be paid to medications, such as corticosteroids and anticonvulsants, that could affect bone health. 

A typical comprehensive physical examination should be performed on all female athletes. There should be a particular focus on weight, percentage body fat, and thyroid function (for evidence of enlargement or irregularity).

For patients with menstrual irregularities, the physical examination should screen for pathologies that could cause metabolic and hormonal abnormalities. Particular attention should be paid to the teeth (given the possibility of tooth decay from repeated vomiting and subsequent hard brushing) and parotid glands (for evidence of hypertrophy, as in bulimia nervosa). Visual-field testing should be performed to assess for pituitary macroadenomas (which, if large enough, may press on the optic chiasm, causing bitemporal nonhomonymous hemianopsia.) 

Skin findings may include evidence of hirsutism, vitiligo, or increased pigmentation of the palmar creases, as in Addison disease; easy bruising or stria, as in endogenous Cushing syndrome; warm, moist skin, as in hyperthyroidism; cool, dry skin, as in hypothyroidism; or any lanugo, as in anorexia nervosa.

A pelvic examination should be performed when appropriate and particularly when a patient presents with delayed menarche.

Urinary ketones

Body weight alone is not a good indicator of body composition and energy availability. Unfortunately, a reliable noninvasive biomarker that reflects these variables does not currently exist. Until a better biomarker of body composition and energy availability is established, the measurement of urinary ketones may be the best indicator of sustained carbohydrate deficiency. Ketones are produced from fatty acids in the liver in states of carbohydrate deficiency, as a result of gluconeogenesis, as the body attempts to obtain energy from other stores.  

A baseline urinary acetoacetate measurement should be conducted by a trainer or team physician. Monthly measurements of urinary acetoacetate in times of increased training in normally menstruating athletes could be performed by the athlete herself or by the athletic trainer. The goal should be a complete absence of urinary ketones before and after a meal as well as before and after training.

In amenorrheic athletes or in those who are positive for ketones, daily keto-stick measurements can be made before and after meals, as well as before and after training, and energy intake can be increased until no evidence of acetoacetate is present in the urine and normal reproductive function is observed. ^[39]

Other tests

Other helpful tests in patients with amenorrhea include the following ^[40] :

• Beta human chorionic gonadotropin testing to rule out pregnancy

• A complete metabolic panel to assess electrolyte levels, renal function, and hepatic function and a complete blood cell (CBC) count to evaluate for anemia

• A thyroid panel to determine if the patient has hyperthyroidism or hypothyroidism

Testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin tests are second-line options. These tests should be considered if a patient's reproductive function is not restored with a trial of increased energy intake or if the findings on history and physical exam suggest other causes of amenorrhea. If the patient has signs of hyperandrogenism (hirsutism), free and total testosterone can be tested to assess for androgen excess. ^[41]

In a 2016 study by Łagowska et al, nutritional status and dietary habits were analyzed in relation to testosterone levels in female athletes and ballet dancers with menstrual disorders. The study found an association between testosterone levels in the study subjects and nutritional factors, energy availability, age at the beginning of training, and frequency of training, determining that the subjects with high testosterone had significantly lower daily energy and carbohydrate intakes. ^[42]

An FSH level of approximately 40 mIU/mL indicates ovarian insufficiency; the FSH test should be repeated in 1 month, and if the levels remain elevated in conjunction with at least 4 months of amenorrhea, the diagnosis of premature ovarian failure can be established. If the FSH level is 20-40 mIU/mL in a patient with disordered menses, the diagnosis is overt ovarian insufficiency, also known as prodromal premature ovarian failure.

LH levels are elevated in cases of 17,20-lyase deficiency; 17-hydroxylase deficiency; and premature ovarian failure.

When performing estradiol testing, it is recommended that FSH values be measured at the same blood draw. Serum estradiol levels within the reference range can be found intermittently, despite the presence of well-documented ovarian insufficiency, while finding a concomitantly elevated FSH level is confirmatory. Serum estradiol levels fluctuate during the normal menstrual cycle; during the early follicular phase, levels may be less than 50 pg/mL, while during the preovulatory estradiol surge, levels of approximately 400 pg/mL are not uncommon. The progesterone withdrawal test is not as valuable as the direct measurement of estradiol and FSH in determining ovarian health.

Prolactin levels in excess of 200 ng/mL are pathognomonic for prolactin-secreting pituitary adenoma (prolactinoma). In general, the serum prolactin level is correlated with the size of the tumor. Dopamine antagonistic drugs, such as antipsychotics (both typical and atypical), as well as hypothyroidism, stress, meals, and the postcoital state, can also raise prolactin levels. Repeatedly elevated prolactin levels require further evaluation if the cause is not readily apparent.

If evidence from the patient's history or physical examination suggests the presence of a stress fracture, plain radiography should be the initial test of choice. A three-phase bone scan should be performed if the radiographs are negative. Dual-energy radiographic absorptiometry (DRA) can be used in athletes with multiple stress fractures. DRA scans can also be used to assess for osteopenia or osteoporosis.  

Pelvic ultrasonography can be useful for determining the etiology of primary amenorrhea (eg, presence of ovaries, uterus).

If abnormal pituitary function is suspected, thin-section magnetic resonance imaging (MRI) of the head through the sella turcica should be performed.

Electrocardiography may show bradycardia, which is common in athletes, and a resting heart rate of less than 50 beats per minute should be explored with a baseline electrocardiogram.

A study by Lawson et al found an association between oxytocin secretion in amenorrheic athletes and measures of energy availability and expenditure, indicating that oxytocin may play a regulating role with regard to energy balance in energy-deficient states. ^[43]

Menstrual disorders are more common in athletes than in nonathletes, with menstrual dysfunction in the female athlete having been directly correlated to decreased estrogen levels.

Approximately 31% of athletes who are not using oral contraceptives report symptomatic menstrual irregularities, ^[44] although, if anything, exercise reduces the occurrence of dysmenorrhea. More common irregularities in female athletes include primary or secondary amenorrhea, a shortened luteal phase, and oligomenorrhea.

On average, menarche appears to occur at a later age in athletes. Generally, females in the United States tend to get their first menstrual period between ages 12 and 13 years. For female athletes, studies have found an average age of menarche of 13.6 years in track and field athletes, ^[45] 14.2 years in Olympic volleyball candidates, ^[46] 14 years in elite figure skaters, 12.9 years in elite Alpine racers, 13.4 years in competitive swimmers, ^[47] and 15.6 years in elite gymnasts. ^[48]  Such retrospective surveys, however, are inherently biased. ^[49]  It has been showed that longer bones are conducive to athletic success. ^[50]  Long bones will continue to grow until increased estrogen levels close off the growth plates shortly after menarche. It is postulated that later-maturing girls who are more athletically successful may choose to continue to participate in athletics, whereas earlier-maturing girls may be less athletic and tend to shy away from sports. ^[50] Although athletic training may delay menarche and even though animal research suggests this as a possibility, no studies have validated this theory.

The incidence of luteal suppression and anovulation is high in regularly menstruating recreational and competitive athletes. Approximately 78% of regularly menstruating female runners have luteal suppression or anovulation at least 1 month out of 3. ^[51]

The term amenorrhea refers to the absence of menstrual cycles. Primary amenorrhea is defined as the absence of menstruation by age 14 years with no development of secondary sexual characteristics, or by age 16 years, even if the female has undergone other normal changes of puberty. The rate of primary amenorrhea in the United States is less than 0.1%.

The persistent absence of menstrual cycles beginning sometime after menarche is called secondary amenorrhea. Because ovarian follicular development, ovulation, and luteal function are deficient in amenorrheic women, they are infertile. While recovering, however, they ovulate prior to menstruating (ie, before they know that their fertility is restored). Therefore, amenorrhea should not be relied on for birth control purposes. ^{[52, 53, 54, 55]}

The prevalence of amenorrhea strongly depends on how the term is defined. When the definition requires more months without menstrual periods, lower prevalence rates are reported. Studies of the general population have specified 3 months, because menstrual cycles longer than 90 days are extremely rare, even in the first and last decades of reproductive life. In large epidemiologic studies of college-age women in which amenorrhea was defined as the absence of menstrual cycles for 3 consecutive months, prevalence rates of 2-5% have been reported. ^{[56, 57, 58]}

Large-scale studies have yet to be performed using the same 3-month definition of amenorrhea to directly compare data from female college athletes with that from the general population of college-age women. However, smaller studies of athletes using the same 3-month definition of amenorrhea have shown a prevalence as high as 44% in dancers and 65% in long-distance runners. ^[59]

Different menstrual disorders can be symptoms of the same medical condition, and the same menstrual disorder can be a symptom of various conditions. Since the discovery in the late 20th century of progressive skeletal demineralization in amenorrheic athletes, most research has focused on amenorrhea in athletes. For inferential reasons, amenorrheic athletes have been compared with athletes who have highly regular menstrual cycles and with equally regular sedentary women. These studies have identified undernutrition as the primary cause—and indeed the only demonstrated cause—of amenorrhea and luteal suppression in athletes.

Consequently, if no evidence suggests the presence of musculoskeletal injury (eg, stress fracture) in an amenorrheic or oligomenorrheic patient, discontinuing or decreasing physical activity is not necessary for menstruation to return. Animal studies have shown that an increase in energy intake is sufficient to restore menstrual function, ^[39] although future studies on refeeding in amenorrheic females are needed to confirm that this is the safest and most effective treatment.

The term oligomenorrhea (from the Greek oligos, meaning few) refers to menstrual cycles longer than 36 days. By far, most cases of oligomenorrhea occur in the first decade after menarche and in the last decade before menopause. Because the length of their cycles is so irregular, oligomenorrheic women may have difficulty conceiving. Oddly enough, however, they may also be at increased risk of an unintended pregnancy secondary to the difficulty of predicting the precise date of ovulation.

As with amenorrhea, if no evidence suggests musculoskeletal injury in an oligomenorrheic patient, discontinuing or decreasing physical activity is not necessary for menstruation to return, since animal studies have shown that an increase in energy intake is sufficient to restore menstrual function. ^[39] Again, future studies on refeeding in amenorrheic women are needed to confirm that this is the safest and most effective treatment.

Findings from two studies suggest that in many athletes, the mechanism for oligomenorrhea may differ from that for amenorrhea. A study measuring the diurnal pattern of testosterone and pituitary hormone in female endurance athletes with menstrual disorders showed that in amenorrhea, hypothalamic inhibition due to energy deficiency appeared to play a major role. However, hyperandrogenism (increased testosterone secretion) seemed to be the major cause of oligomenorrhea. ^[60]

The 24-hour hormone profiles in amenorrheic athletes showed decreased LH pulsatility and a peak amplitude of prolactin, as well as increased baseline levels of growth hormone and cortisol. In oligomenorrheic athletes, higher diurnal testosterone secretion was observed and levels of LH, prolactin, growth hormone, and cortisol were similar to those of regularly menstruating subjects.

High testosterone levels and oligomenorrhea (and occasionally amenorrhea) are symptoms of polycystic ovary syndrome, which is thought to be the most common cause of infertility in the United States. Just as it is plausible that women with eating disorders may choose sports in which low body weight offers a competitive advantage and that later-maturing females may self-select into athletics because of the rewards they receive for developing longer bones, women with polycystic ovary syndrome may gravitate towards sports in which high testosterone levels offer an advantage. This possibility warrants focused research, because the treatment for polycystic ovary syndrome completely differs from that for undernourishment.

The term luteal suppression refers to an entirely asymptomatic, subclinical menstrual disorder that is evident only by measuring ovarian steroid hormone concentrations in the blood or urine over a number of weeks. In luteal suppression, follicular development progresses more slowly than usual; therefore, ovulation occurs later in the cycle. The luteal phase that follows may be short, and/or progesterone concentrations may be low. Often, the overall length of the menstrual cycle is indistinguishable from that in eumenorrhea. The incidence of a short luteal phase is 30-45% during the first decade after menarche, after which it declines to approximately 5%. ^{[61, 62]}

The term anovulation refers to an asymptomatic subclinical menstrual disorder in which follicular development is so impaired that ovulation does not occur. Estrogen and progesterone levels are low, but enough estrogen is produced to stimulate some proliferation of the uterine lining, and bleeding occurs when the lining is sloughed. The incidence of anovulation declines from approximately 55% to less than 5% during the first decade after menarche and increases to approximately 20% in the last decade before menopause. ^[61]

The issue of whether a female athlete should take oral contraceptives is a personal one. The importance of a drug's contraceptive and regulatory effects should be balanced against possible performance effects. Athletes should discuss this issue with their healthcare provider, as there are numerous contraceptives on the market that vary in route of administration, estrogen and progesterone content, and efficacy. Studies have not shown oral contraceptives to have a major impact on performance, but several effects are discussed below.

Studies on monophasic and triphasic low-dose oral contraceptives have found a decrease in maximal oxygen consumption (VO_2max) in females from all athletic backgrounds after more than 1 month's use of these drugs. Athletes should be educated regarding this effect. ^{[63, 64]} Because these same studies have shown a reversal of this effect within 1 month of the cessation of oral contraceptives, women who choose to take an oral contraceptive should be counseled that the decrease in VO_2max is likely reversible.

Another area of interest is the effect of contraception on body composition. Rosenberg et al found that moderately active students reported feeling bloated as a commonly reported adverse effect. ^[65] Furthermore, Notelovitz et al showed an average body mass increase of 2 kg in active women compared with controls. ^[66] This can be detrimental in many sports, such as running and esthetic sports (eg, gymnastics), in which body image is pivotal. The effect varied across monophasic and triphasic use, with some studies finding a body mass and fat mass increase by 3% and 9%, respectively. ^[67] Further studies need to be conducted to discern differences between doses and compilations of hormones across various oral contraceptive pills as stated earlier. As with VO_2max, cessation of the oral contraceptive pills resulted in the body mass returning to baseline.

Few reports have studied the effects of oral contraceptive pills on cardiovascular performance, but current data showed no significant effects of monophasic or triphasic oral contraceptive pill formulation on cardiovascular responses at rest or during exercise. ^[67]

However, a study by Cauci et al found an association between oral contraceptive use in athletes and a significant elevation in chronic, low-grade inflammation, a phenomenon that could increase the chances of a higher inflammatory response to physical stress and lead to increased cardiovascular risk. ^[68]

With regard to oral contraceptive pills' effect on strength, current literature states that the formulations do not provide adequate androgens to cause a difference. ^[69]

Oral contraceptives are prescribed to female athletes for several purposes, including contraception, cycle regulation, and control of dysmenorrhea (menstrual cramps). The oral contraceptive comes in many different brands with different synthetic hormones, doses, and dosing regimens. Those currently prescribed are usually given at doses lower than those of first-generation pills; therefore, they may have fewer adverse effects.

Just as in the general population, oral contraceptives induce a hypercoagulable state and can predispose female athletes to deep venous thrombosis (DVT) and pulmonary embolism.

Oral contraceptives usually contain an estrogen and a progestin. The estrogen is commonly ethinyl estradiol, at doses of 20-50 mcg per pill. The progestin is often norethindrone, norgestrel, or levonorgestrel, with typical doses of 0.05-2.5 mg per pill.

The regimens are typically monophasic or triphasic. Triphasic dosing regimens more closely simulate the natural menstrual cycle and contain lower per-cycle progestin levels than do those of their monophasic counterparts. ^{[44, 63]} The estradiol levels in most oral contraceptives contain approximately 3-5 times the estrogen and 1-2 times the progestin levels present in the normal menstrual cycle. ^[70]

Because oral contraceptives might mask symptoms of amenorrhea induced by low energy availability, ketone measurements are even more essential in athletes taking oral contraceptives than they are in others.

Female athletes can be chronically energy deficient. ^[39] With the exception of cross-country skiers, female endurance athletes consume approximately 70% as much energy and carbohydrates (controlled for body weight) as male athletes. ^[71] Biochemical markers in female athletes indicate a mobilization of fat stores, slowing of the metabolic rate, and a decline in glucose utilization, with more extreme abnormalities in amenorrheic athletes and less extreme abnormalities in regularly menstruating athletes. ^[39]

Studies in humans and monkeys have shown that this chronic energy deficiency causes reproductive disturbances in many female athletes. In 1998, Loucks and colleagues demonstrated that the stress of exercise did not suppress LH pulse frequency, because the disruption of LH pulsatility in exercising women could be prevented with dietary supplementation. On the other hand, low energy availability, caused either by an increase in exercise energy expenditure or by dietary energy restriction alone, did disrupt LH pulsatility. ^[72] This low-energy state also suppressed levels of triiodothyronine (T3), insulin, insulinlike growth factor–1, and leptin and raised levels of growth hormone and cortisol in a pattern similar to those seen in amenorrhea and luteal suppression with eumenorrhea. ^[72]

Menstrual function can also be restored by increasing energy availability. In female monkeys, amenorrhea induced by increasing exercise energy expenditure, with no reduction in dietary intake, was restored simply by means of dietary supplementation, without any moderation of the animals' exercise regimen. ^[34]

Similar effects of low energy availability on the reproductive system have been noted in men. ^[73] One week of dietary supplementation reversed disruptions of metabolic and reproductive hormones in US Army Ranger trainees despite continued exposure to strenuous exercise, sleep deprivation, cold, heat, injuries, infections, and other stresses. Therefore, exercise and other stresses appear to have no disruptive effect on the reproductive system apart from the impact of energy cost on energy availability.

Curiously, LH pulsatility is less disrupted in women who exercise than in women whose energy availability is reduced by exactly the same amount because of dietary restriction. This is surprising, because no one had previously suggested that exercise might be protective against menstrual disorders. On closer examination, working muscle in energy-deprived women who exercised reduced its glucose utilization, so that substantially more carbohydrate was available to the brain. This finding strengthens the hypothesis that reproductive function in women specifically depends on brain glucose availability. ^[39]

The dose-response relationship between energy availability and LH pulsatility has also been investigated. LH pulsatility was found to have been disrupted below a threshold of energy availability of approximately 30 kcal/kg of lean body mass (LBM) per day. The dose-dependent effects on LH pulsatility most closely resembled the metabolic substrates glucose and beta-hydroxybutyrate and the metabolic hormones cortisol and growth hormone. These findings support the reported hypothesis that "reproductive function reflects the availability of metabolic fuels, especially glucose, which may be signaled in part by activation of the adrenal axis." ^[39]

Bone is a dynamic tissue that is constantly being remodeled. This remodeling is performed by osteoclasts (which resorb old bone) and osteoblasts (which form new bone) under the control of polypeptides, steroid hormones, thyroid hormones, cytokines, and growth factors. ^[74]  Secondary to hypothalamic dysfunction, female athletes with chronic low energy function at a low estrogen state. The principal role of estrogen in bone is to directly act on osteoblasts, although it also has an indirect effect on osteoclasts. ^[75]  Altered bone mineral density will increase bone fragility and risk for fractures. Therefore, even though athletes should normally have a 5-15% higher bone mineral density than age-matched controls, the incidence of stress fractures is greater in amenorrheic athletes, with bone density having been shown to be negatively correlated with the number of missed menstrual cycles since menarche.

In the past, it has been theorized that the decreased bone densities observed in females with anorexia nervosa and in amenorrheic athletes were due solely to chronic hypoestrogenemia. However, estrogen replacement in these individuals does not fully reverse the decrease in bone density. ^{[76, 77, 78, 79, 80, 81]} This finding prompted researchers to investigate chronic undernutrition as an estrogen-independent mechanism for decreased bone mineral density in these patients.

Stress fractures are common among female athletes. In one survey of competitive collegiate cross-country runners, 44% had experienced at least one stress fracture and 21% had suffered multiple stress fractures (Stanford B-Fit Web site). The incidence of stress fractures is greater in amenorrheic athletes, and bone density has been shown to be negatively correlated with the number of missed menstrual cycles since menarche. ^[82]

Another study examined the resulting bone quality and muscle strength in female athletes who sustained stress fractures. Bone strength, density, and muscle torque were analyzed using computer tomography, x-ray absorptiometry, and areal bone mineral density. The stress fracture group had lower trabecular bone mineral density (-19.8%, P = .02), less cortical area (-5.2%, P = .02), and reduced knee extension strength (-18.3%, P = .03) compared with the non–stress fracture group. ^[83]

The effects of low energy availability on bone health are evident even in normally menstruating sedentary women. In a landmark study, Ihle and Loucks demonstrated for the first time that bone formation is impaired within 5 days of the onset of low energy availability. At levels of energy deficit milder than that in bone resorption and at extreme energy restriction (10 kcal/kg LBM/day), increased bone resorption becomes uncoupled from decreased bone formation. ^[84]

The findings of the study are applicable to female athletes, because normally menstruating athletes have reported energy availabilities of approximately 30 kcal/kg LBM/day, and amenorrheic athletes have reported energy availabilities of approximately 16 kcal/kg LBM/day. ^[85]

A diversity of metabolic hormones—including carboxyterminal propeptide of type I procollagen and osteocalcin—are disrupted by all levels of energy restriction. ^[86] The dose-response relationships of insulin, T3, and insulinlike growth factor–1 closely resemble those of propeptide of type I procollagen and osteocalcin and could be involved in mediating the effect of low energy availability on bone. In addition, as with N -telopeptide, estradiol is unaffected until energy restriction becomes severe. Because the primary role of estrogen in the skeletal system is to suppress osteoclast activity, this relationship is an expected finding. ^[84]

Peak bone mass is a significant predictor of risk for the development of osteoporosis. ^[75] The decrease in bone formation and increase in resorption (uncoupling) that occurs in a severe, chronic energy-deficient state is dangerous at any age. ^[87] Because approximately 50% of peak bone mass is achieved in adolescence and is completed in most women by the end of the second decade, ^{[15, 88]} the consequence of suppressing bone formation in adolescence can be disastrous.

Appetite is not a reliable means of determining the energy needs of the female athlete; exercise appears to suppress appetite. Therefore, nutritional counseling is important for normally menstruating athletes and for athletes with menstrual disturbances.

Athletes need to eat by discipline, not by appetite. Studies have shown that a threshold of 20-30 kcal/kg LBM/day is needed for reproductive function and bone health, and a diet comfortably greater than 30 kcal/kg LBM/day is recommended.

Counseling should focus on how a patient's diet can provide close to 45 kcal/kg LBM/day in order for the patient to maintain reproductive and skeletal health. A balanced, nutrient-rich sample diet of 45 kcal/kg LBM/day tailored to individual weight or a general sample diet for weights of 55, 60, 65, and 70 kg on either a poster in the training room or a handout would be helpful. In addition, an estimation of the energy expenditure during a typical daily training regimen and the replacement of this expenditure are important.

According to the 2015 Recommendations for Healthy Nutrition in Female Endurance Runners, the minimal energy requirement for a female endurance runner is "45 kcal/kg fat free mass/day plus the amount of energy needed for physical activity." The recommendations favor increasing protein intake in these runners from 1.2-1.4 g/kg/day to 1.6 g/kg/day. ^[89]

Tables of energy expenditure in various athletic activities can be used for this calculation. For instance, a track coach could estimate the approximate energy expenditure during one practice (miles run). From this, he or she could determine how many power bars or containers of yogurt are needed to replace the expended energy and encourage athletes to eat these snacks after practice. A poster of snacks that replace, for instance, the energy lost during 1 hour of intermittent running (eg, during soccer practice) or after a run of a certain number of miles (eg, during track practice) could be displayed in the training room.

Athletes should be counseled that if they underconsume, they are actually slowing their metabolic rate and that an increase in energy intake helps to restore their metabolic rate, prevent deleterious effects on reproductive and skeletal health, and even improve performance. Therefore, if the athlete's weight increases while her metabolic rate is adjusting, at least part of it is likely due to an increase in LBM, which even further improves performance.

For athletes with menstrual disturbances, energy intake should be even more closely monitored to ensure that it approximates 45 kcal/kg LBM/day along with the replacement of energy used during exercise. While intake is increased over a period of 1-2 weeks, electrolytes and hematocrit values should be monitored at least once a week during the transition.

Iron deficiency in female athletes

Iron is a crucial factor in the formation of hemoglobin and intracellular metabolism. Iron deficiency (ID) and iron deficiency anemia (IDA) can have profound effects on the body. A deficit of body iron resulting from inadequate dietary intake and/or excessive losses can negatively affect immune function, temperature regulation, cognitive abilities, efficiency of energy metabolism, and sports performance. ^{[90, 91]} ID is screened through blood work and treated with increased oral intake or supplementation.

ID and IDA affect more women than men. Studies comparing ID in female athletes have shown mixed results. One study of elite female soccer players showed 55% of players were iron depleted, which was higher than expected compared with known prevalence figures in nonathletes. ^[92] A study comparing ID and IDA among high school athletes showed no difference between female athletes and nonathletes. ^[90] Percentages were 48% and 52%, respectively (P >.3). There was also no significant difference in hemoglobin (P >.30). In total, 8.6% of athletes had IDA compared with 3.3%, the difference being not statistically significant (P = .24).

A paper by Clénin et al made recommendations regarding ID and iron replacement in athletes, stating that sports-related ID occurs primarily through increased iron demand, elevated iron loss, and impairment of iron absorption as a result of hepcidin bursts. ^[93]  According to the report, in healthy male and female athletes over age 15 years, ferritin values below 15 mcg/L are equivalent to empty iron stores, while values from 15 to 30 mcg/L signify low iron stores. For children aged 6-12 years and younger adolescents aged 12-15 years, the recommended ferritin cutoff values signifying iron deficiency were given as 15 and 20 mcg/L, respectively. In adult elite athletes, however, it was recommended that a ferritin value of 50 mcg/L be reached prior to altitude training, due to greater iron demands on these individuals. ^[93]

Some research draws a distinction between low serum ferritin with normal hemoglobin levels from true ED, but there is a paucity of data on this subject. One paper sites that true ID among female athletes is around 1%. ^[94] “Sports anemia,” a phenomenon that occurs when an athlete’s plasma volume dilutes at the start of endurance training does not affect sports performance. ^[95]

However, nonanemic energy deficiency is a common finding among female athletes, particularly adolescent distance runners. In any group of training endurance athletes, 1 of every 3-4 females can be expected to satisfy criteria for nonanemic ID. ^[96] Blood tests in female athletes, therefore, should include iron, vitamin B12, and folate studies.

Calcium intake is a key determinant of peak bone mass in adolescent women. ^[75] Supplementation of calcium from adolescence through young adult life, with a recommended daily allowance of 1200 mg/day, is advised. In women aged 25-50 years, 1000 mg/day is recommended. ^[75]

Vitamin K is a cofactor necessary for the gamma-carboxylation of several bone matrix proteins, one of which is osteocalcin. In one study of elite amenorrheic athletes, vitamin K supplementation induced an increase in bone formation markers and an even greater decrease in bone resorption markers. ^[97] Therefore, supplementation with a multivitamin containing vitamin K might optimize bone health in female athletes. A multivitamin also contains other vitamins and minerals that serve as cofactors in the modification of the bone matrix, such as vitamin C, manganese, copper, and zinc.

Athletes who perform weight-bearing exercises have higher bone mineral densities than those who do not, although the advantage in bone mineral density tends to be site specific, depending on where the load has been applied. Studies have shown conflicting results in terms of the magnitude of force required to function as an osteogenic stimulus. It is unclear whether the increased bone mineral density from weight-bearing exercise persists into adulthood after the cessation of exercise.

The first published follow-up study of a 7-month, high-impact exercise program in prepubertal children after 7 months of detraining showed a persistent skeletal effect at the femoral neck. ^[98] Follow-up studies of childhood exercise intervention after detraining will clarify this issue.

The addition of 50 vertical jumps per day has been shown to increase femoral and trochanteric bone mineral density by 2-3% in premenopausal women after 5 months ^[99] and might prove valuable in creating an osteogenic stimulus in athletes, such as swimmers, who do not regularly load their skeleton during training. ^[100]

Consultations include the following:

• A nutritionist can make recommendations for a balanced, nutrient-rich diet

• An obstetrician/gynecologist may be helpful for patients whose amenorrhea is resistant to refeeding

• A psychiatrist or counselor may be consulted in cases involving disordered eating (intentional energy [caloric] restriction)

• Regular follow-up with an athletic trainer, physiatrist, obstetrician/gynecologist, or team nutritionist or school dietary expert is necessary