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2002 Selected Articles

Bone Health in Young Athletes With Amenorrhea

Dorothy Damore, MD; Lisa Callahan, MD

Over the past few decades, more women have been participating in competitive and recreational sports. Overall, this has had many positive effects on women’s health and well-being, including decreased morbidity and mortality.¹ Indeed, moderate activity decreases overall mortality by 3.5-fold and cardiovascular mortality by eightfold.² Regular exercise also improves control of both hypertension^3,4 and adult-onset (type 2) diabetes,^5,6 lowers rates of some cancers (eg, colon cancer),⁷ and increases bone mineral density (BMD).⁸ Exercise has reduced low back pain and other complications of pregnancy and labor as well.^9,10 In addition, there are numerous psychological benefits associated with exercise, including enhanced self-esteem, self-image, and confidence, plus better mental performance and concentration.^11,12

However, while moderate exercise has a positive impact on health, higher levels of exercise can have negative health consequences, including those seen in the female athlete triad, recognized in the 1990s when an association between disordered eating, amenorrhea, and osteoporosis was reported in female athletes.

THE FEMALE ATHLETE TRIAD

Disordered Eating

Disordered eating (DE) is a term used to describe several unhealthy patterns of eating behaviors, including food restriction, overuse of laxatives and diuretics, and self-induced vomiting. It is imperative that physicians working with female athletes recognize the differences between true eating disorders such as anorexia nervosa and bulimia nervosa and other types of DE. The former are defined by very specific criteria in the American Psychiatric Association’s Diagnostic and Statistical Manual, ed. 4 (DSM-IV) (Table 1), while the latter behaviors are usually more subtle and more difficult to recognize. Originally, DE was reported more commonly in association with sports, emphasizing leanness for appearance or performance (eg, gymnastics, distance running), or those with weight classifications (eg, lightweight rowing, judo). Now, however, these behaviors are emerging in athletes in virtually all sports, including swimming, cycling, and soccer. The American College of Sports Medicine defines DE as a spectrum of unhealthy behaviors with eating disorders on the extreme end of the spectrum.¹³ An athlete can be suffering from severe DE, but she does not meet the criteria for a diagnosis of an eating disorder by DSM IV standards.^14,15

The true incidence of DE among female athletes is unknown. Various reports estimate that 4% to 62% of female college athletes display DE.^16-19 This percentage range represents the prevalence estimates (data obtained from cross-sectional studies) rather than the incidence (data obtained from a longitudinal study). Several explanations exist for this wide variation in reported frequency, including the inherent bias of self-reporting, on which many of these prevalence studies are based. The accuracy of such self-reports is further compromised by many female athletes’ belief that these practices are harmless.

Disordered eating may be especially difficult to recognize in women participating in sports requiring intense training and discipline. Many coaches and athletes believe that the lowest possible percentage of body fat or the lowest weight will improve performance. However, studies show that possessing insufficient body fat, being underweight, or consuming too few calories or too little protein correlates with decreased strength, power, and energy for training and performance, putting the athlete at risk for injury and illness. It is estimated that a level of 10% to 20% body fat must be maintained for optimal performance.^20,21

Amenorrhea

It has long been recognized that the low-estrogen state of menopause results in decreased BMD, leading to osteoporosis. Only in the last decade, though, have clinicians begun to realize that young women with menstrual disorders may also be at risk for osteoporosis. Exercise-associated menstrual disorders include luteal-phase deficiency, anovulation, and both primary and secondary amenorrhea.

Luteal-phase deficiency is associated with lower levels of progesterone, causing a shortening of the luteal phase. As cycle length may be unchanged, this hormonal deficiency often goes unnoticed. Although luteal-phase deficiency is associated with infertility,²² any link to a decline in BMD remains controversial.^23,24 Some experts hypothesize that luteal-phase deficiency represents early-stage menstrual dysfunction in athletes, while others feel that it is simply a physiologic response to athletic training.²⁴ Treatment of luteal-phase deficiency is clearly warranted if the athlete is trying to conceive, and includes decreasing the amount and intensity of exercise. Hormonal manipulation with clomiphene, progesterone suppositories, or gonadotropins may be required.²⁵

Anovulation is also associated with lower levels of progesterone, resulting in unopposed estrogen secretion and raising the possibility of consequent endometrial hyperplasia, irregular bleeding, dysfunctional uterine bleeding, and adenocarcinoma.²⁰ Anovulation can be treated with monthly progestin or low-dose oral contraceptives (OCs).

Although luteal-phase suppression and anovulation are not uncommon in the female athlete, it is amenorrhea that generates the greatest concern due to the relationship between the associated low estrogen state and osteoporosis. Primary amenorrhea is defined as the absence of menarche in an adolescent aged 16 years or more who has developed secondary sexual characteristics, whereas secondary amenorrhea is the absence of three or more menstrual cycles after menstruation has begun. Between 2% and 5% of women in the general population have amenorrhea, while 3% to 66% of athletes are amenorrheic.²⁰ Reasons for this wide range of prevalence data may include a lack of agreement on the definition of amenorrhea, recall bias, small numbers of subjects, and lack of longitudinal studies in this area.

Exercise-induced amenorrhea is believed to be a hypothalamic disorder, in which high-volume and/or high-intensity exercise leads to a decline in gonadotropin-releasing hormone (GnRH) levels, which in turn decreases luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production.²⁶ The suppression of LH and FSH prevents normal ovarian stimulation. There are several hypotheses regarding this phenomenon of hypothalamic suppression. One widely cited theory is that vigorous exercise combined with insufficient caloric intake produces an “energy drain,” decreasing the basal metabolic rate and resulting in hypothalamic dysfunction. Others describe this high-exercise/low-calorie combination as a “stressor” that leads to increased cortisol levels, thus inhibiting the hypothalamic function. Others believe that the production of endogenous opioids associated with intense exercise may suppress the hypothalamic function.^24,27 Effects on fertility from exercise-induced amenorrhea seem to be negligible once menses resume.²⁷

Although amenorrhea in athletes is frequently assumed to be exercise-related, the clinician must recognize that exercise-induced amenorrhea is a diagnosis of exclusion. As with women in the general population, amenorrhea in athletes may be due to a myriad of conditions, including pregnancy, Asherman’s syndrome, hypothalamic tumor, pituitary tumor with hyperprolactinemia, polycystic ovarian disease, Cushing’s syndrome, adrenal tumor, hypothyroidism, chronic medical disease, and OC or anabolic steroid use. In addition, ovarian failure can be secondary to autoimmune diseases, chemotherapy, radiation, galactosemia, or hereditary (eg, Turner’s syndrome).²⁷

Osteoporosis

Amenorrheic athletes have lower BMD than eumenorrheic athletes^28-31 in both the appendicular weight-bearing bones and the axial skeleton.^32-35 Decreased BMD increases the risk of stress fractures, placing the young athlete at risk for osteoporosis.³⁶

Although osteoporosis is traditionally viewed as bone loss in the aging population, it also refers to premature bone loss or inadequate bone formation during the years of peak bone growth. Bone mineral content (BMC) is similar in boys and girls prior to puberty, with BMC increasing at a steady rate in this age group. Mineral content accelerates during puberty, greater in males than females, and reaches a peak about 1 to 2 years after the postpubertal growth spurt. More than 90% of the adult BMC is deposited by the end of adolescence, although some small gains continue until the mid-20s. Physical activity, diet (including calcium intake), and hormonal status are extremely important during this period of bone growth. Whereas healthy adolescent girls gain BMC at a rate of 2% to 4% per year, amenorrheic female athletes are at risk for a 2% annual premature bone loss. Failure to develop adequate BMD places the young athlete at risk for both current and future fractures.³⁷ Additional risk factors for osteoporosis may be either nonmodifiable (eg, female gender, small body frame, positive family history, Caucasian or Asian ethnicity), or potentially modifiable (eg, smoking, corticosteroid use, alcohol abuse, low body weight).³⁸

Bone mineral content can be measured by single and dual photon absorptiometry (SPA, DPA), single and dual energy x-ray absorptiometry (SXA, DEXA), and quantitative computed tomography (QCT). Currently, DEXA is considered to be the “gold standard” for measurement, and is the most widely used. Using DEXA, x-rays are emitted at two different energy levels, allowing for differentiation between bone and surrounding soft tissue. The advantages of DEXA include low radiation dose, precision, and shorter scanning time. As it measures volume of bone rather than area of bone, QCT differs from the other methods, allowing for a three-dimensional image and separation of cortical and trabecular bone.³⁹ However, QCT is more costly and involves more radiation exposure than DEXA. Recently, quantitative ultrasonography has been introduced as another alternative for measuring BMD, although its use is still investigational.³⁷

The World Health Organization (WHO) defines osteoporosis as BMD of less than 2.5 SD below the young adult mean. Density is most often measured in the spine, hip, and wrist, which are the most common sites of osteoporotic fractures, but BMD at one site is a poor predictor of fracture at other sites.³⁷

STRESS FRACTURES

Stress fractures are generally believed to occur more commonly in women than in men, although the reported frequency varies widely.^40-42 The greatest reported incidence is in runners, with stress fractures accounting for up to 15% of all running injuries.⁴¹ Stress fractures may be caused by changes in training patterns (ie, significant increases in training volume or intensity over a short time) and changes in training surface. Decreased muscle mass around the tibia, a narrow tibia, cavus feet, overpronation, varus alignment, and increased external alignment of the hip have also been associated with stress fractures.^43,44

Recently, investigators have come to suspect that decreased BMD in women with the female athlete triad may also promote stress fractures. It is apparent from studies of geriatric patients that for each SD decrease in BMD, the risk of fractures doubles.^37,38 Research is now underway to clarify whether there is a similar association between the exercise-related stress fractures and osteoporosis seen in the female athlete triad.

Management

The presentation of stress fractures can be quite variable. An athlete with a stress fracture may complain of the abrupt onset of pain, or of an ache that persists for weeks to months. Often, the pain initially occurs only with activity and resolves with rest. If the fracture is unrecognized, pain frequently progresses to such a degree that the athlete is forced to discontinue training.

Imaging studies can be used to confirm a suspected stress fracture. Plain radiographs should be obtained first, although they are often negative, especially shortly after the fracture occurs. Overpenetration or coned-down views of the area involved may be helpful in visualizing the fracture. If the initial radiographs are negative, they can be repeated at 2 to 3 weeks, when callus formation may be visible. Alternatively, the diagnosis can be confirmed with radionuclide bone scanning, magnetic resonance imaging (MRI), or computed tomography (CT).³⁸

Once the diagnosis is confirmed, treatment typically includes non-weight—bearing activity (eg, stationary cycling, training in a pool) and a strength training program. Crutches may be needed initially until weight-bearing is not painful. Ice and analgesics may be helpful. Once the offending activity has been curtailed, stress fractures generally heal in 6 to 12 weeks, depending on the fracture site. As a general rule, the athlete can return to training when the fracture site is pain-free for 10 to 14 days. When returning to play, most experts recommend alternating training and resting days.⁴⁵ This conservative treatment suffices for most stress fractures, but some stress fractures (eg, femoral neck, tarsal navicular bones) require longer periods of rest and possibly surgical fixation.³⁸

TREATING THE FEMALE ATHLETE TRIAD

Often, the occurrence of a stress fracture is the catalyst for the athlete to seek medical care. An astute clinician can use this opportunity to evaluate the athlete’s risk for the components of the female athlete triad and make appropriate interventions. If disordered eating is suspected, consultation with a nutritionist and an experienced mental health professional can be extremely helpful.

The history and physical examination can reveal important information about the amenorrheic or oligomenorrheic athlete. A family history of endocrine or reproductive abnormalities may suggest a diagnosis other than exercise-induced amenorrhea. Diet, disordered eating habits, exercise history, and anabolic steroid or supplement use are other important historical factors. The exercise history should include a detailed description of the type, frequency, duration, and intensity.²⁷

Tanner staging of the breasts, axillae, and genitals is important to assess for secondary sexual characteristics. Hirsutism, excessive acne, and striae suggest androgen excess, which can be associated with polycystic ovarian syndrome, adrenal or ovarian tumors, or anabolic steroid use. Serum testosterone and dehydroepiandrosterone levels should be measured in cases of suspected androgen excess. Pigmented striae may indicate steroid use or Cushing’s syndrome. Visual changes or headaches may suggest a hypothalamic or pituitary mass, while galactorrhea suggests hyperprolactinemia. An enlarged thyroid may indicate thyroid dysfunction, while dental erosion and enlarged parotid glands may suggest induced vomiting.²⁷

The pelvic examination ensures normal anatomy of the vagina, cervix, uterus, and ovaries, while also diagnosing imperforate hymen, vaginal septum, or absent cervix. If the cervix and uterus are absent, a karyotype should be performed to check for an XY karyotype with testicular feminization.²⁷

Initial laboratory studies in the assessment of amenorrhea should include a pregnancy test, levels of thyroid-stimulating hormone, prolactin, LH, and FSH, and a complete blood chemistry panel. If the pregnancy test is negative and the thyroid-stimulating hormone values are normal, then a progestin challenge test can be performed using 5 to 10 mg of progestin orally for 5 to 10 days or 100 to 200 mg of progesterone-in-oil intramuscularly. A lack of bleeding over the ensuing 10 days in response to progestin indicates estrogen deficiency or outflow obstruction. If estrogen deficiency is suspected, CT or MRI of the sella tursica should be considered to rule out a pituitary tumor. Bleeding in response to progestin indicates a state of unopposed estrogen secretion, and may be due to polycystic ovary disease or a tumor.^25,27 Bleeding in response to estrogen and progestin challenge indicate estrogen deficiency while no bleeding indicates an outflow tract obstruction.

It is imperative that the clinician recognize the importance of determining the cause of amenorrhea and instituting treatment as early as possible, as optimal treatment may protect bone health.^46,47 However, several studies suggest that treatment may not be able to fully compensate for BMD losses associated with amenorrhea.^48-50

Depending on the athlete and her individual circumstances, treatment of exercise-induced amenorrhea may include estrogen replacement, calcium supplementation, decreased exercise, and increased caloric intake. Cyclic estrogen-progestin treatment or OCs is often recommended for adolescents aged 16 years and older with amenorrhea, although there is a dearth of outcomes data regarding this common practice. Many experts believe that younger adolescents with a stress fracture and primary amenorrhea or secondary amenorrhea lasting for 2 years should also be considered for some type of estrogen therapy.⁵¹ Absolute contraindications to estrogen treatment include vaginal bleeding, breast or uterine cancer, history of stroke, thrombophlebitis, severe hypertension, or liver disease. Possible contraindications to estrogen therapy include hypertension, migraines, and smoking.

As the athlete may have adjusted to the hypoestrogenic state, estrogen treatment may cause breast tenderness and bloating, and the patient should be assured that these symptoms are only temporary. Additionally, patients should be advised that cyclic estrogen-progestin therapy may not provide effective contraception.²⁷

It is important to note that progesterone-only or medroxyprogesterone therapy may not increase BMD, and may actually cause it to decrease. Therefore, it is not recommended for the treatment of the amenorrheic female athlete.^52,53

Even if the athlete has significant bone loss, pharmacotherapeutics such as bisphosphonates (eg, alendronate, risedronate), and selective estrogen receptor modulators (SERMs) (eg, raloxifene) should be avoided, as these medications are only approved for use in postmenopausal women. These agents are antiresorptive, uncoupling bone resorption and formation. The bisphosphonates are poorly absorbed by the gastrointestinal tract, but once they are absorbed, they are readily taken up in the bone and removed from the bone only when it is resorbed 1 to 10 years later⁵⁴—which cautions against their use by premenopausal women.

Dietary modifications are appropriate and important for the young athlete. Calcium intake from food sources or supplementation should total 1,200 to 1,500 mg/d, and vitamin D intake should be evaluated as well (Table 2). If caloric intake is inadequate, total calories should be increased by 250 to 350 kcal/d. Finally, training should be decreased by at least 1 day per week.⁵⁵

CONCLUSION

Physicians must be aware of the presentation, diagnosis, and ramifications of the female athlete triad. All young female athletes must be questioned regarding activity level, eating habits, and menstrual cycles at every visit. Coaches and athletic trainers need to know the signs of DE so they can provide sound advice to athletes, emphasizing the importance of a healthy, balanced diet to ensure adequate calories and nutrition to meet the demands of training. If amenorrhea develops, early treatment is imperative to optimize BMD. There is a lack of research on the female athlete triad as a whole as well as on the three individual components.

Dorothy Damore, MD, is director of education and outreach services in pediatric emergency medicine at New York– Presbyterian Hospital, and Lisa Callahan, MD, is medical director of the Women’s Sports Medicine Center at the Hospital for Special Surgery, both in New York City.

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