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Evaluating and Treating Exercise-Related Menstrual Irregularities

Kimberly G. Harmon, MD

Practice Essentials Series Editors:
Kimberly G. Harmon, MD; Aaron Rubin, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 30 - NO. 3 - MARCH 2021


In Brief: Menstrual abnormalities, from a few skipped periods to a complete absence of menses, are extremely common in both athletic and nonathletic adolescents and women in their early 20s. Exercise-related menstrual abnormality is linked with hypothalamic pituitary axis dysfunction and is a diagnosis of exclusion. In athletes, treatment of secondary menstrual abnormalities and associated health concerns, such as bone density, may include medication and restriction from activity.

Irregular menses have been reported to range from 1% to 66% among athletes, compared with 2% to 5% of the general population.1 The wide range of reported menstrual abnormalities stems not only from different populations surveyed, but also from different criteria used to define the condition. Primary amenorrhea is defined as the absence of menstruation by age 16 in a girl with secondary sex characteristics; secondary amenorrhea is the absence of three or more consecutive menstrual cycles after menarche; and oligomenorrhea is defined as fewer than eight menses per year. When studies are reviewed and similar definitions of amenorrhea are applied, amenorrhea is 20 times more frequent in athletes than in nonexercising women.2

The normal menstrual cycle represents an exceedingly complex interplay of hormones and is typically divided into three phases: the follicular phase in which a follicle matures, the ovulatory phase in which the egg is released, and the luteal phase in which the endometrium prepares for the implantation of a fertilized ovum. If implantation does not occur, the endometrium is sloughed, and menstruation ensues (figure 1). This cycle is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland, which is itself controlled by the regular pulsed secretion of gonadotropin-releasing hormone (figure 2). Any disruption in this delicate balance can cause hypothalamic pituitary axis (HPA) suppression and result in oligomenorrhea or amenorrhea.


Many theories involving HPA suppression have been postulated for the cause of exercise-induced menstrual irregularities (table 1). Critical analysis of each of these theories reveals numerous methodologic flaws and no definitive answer as to a single cause.2 Interrelationships among nutrition, exercise intensity and volume, body mass index, and psychological stressors contribute to normal menstrual function. Individual tolerances for perturbation of these factors vary considerably. This explains why two athletes of similar body composition may have different menstrual responses to the same training volume and diet, or why athletes of "normal" weight may still experience menstrual dysfunction. Most amenorrheic athletes do not have an eating disorder.

TABLE 1. Possible Causes of and Contributing
Factors for Amenorrhea in Athletes

Critical body weight
Critical body fat
Endogenous opioids
Nutritional deprivation
Rapid body weight changes
Training intensity

Hormonal Workup

HPA suppression is a diagnosis of exclusion. The differential diagnosis for oligomenorrhea or amenorrhea includes pregnancy, thyroid abnormality, prolactinoma, hyperandrogenic anovulatory syndrome (polycystic ovarian syndrome), premature ovarian failure, and HPA suppression. An assessment of the likelihood of different factors in an athlete's history and a thorough physical exam are essential for tailoring the workup of secondary amenorrhea. Thorough evaluation for the female athlete triad (amenorrhea, osteoporosis, and disordered eating) should also be undertaken.

If a woman is not sexually active, concern about undergoing a pelvic examination may prevent her from seeking medical care. If an athlete has never been sexually active and has had previously normal menses, it can be assumed that her menstrual abnormalities do not stem from congenital abnormalities of the genital tract, and a pelvic exam may be postponed until she becomes sexually active. In sexually active women, pregnancy must be ruled out.

Next, thyroid-stimulating hormone and prolactin tests should be done to rule out thyroid abnormalities and prolactinoma. To avoid false-positive prolactin tests, blood should be drawn first thing in the morning, after the patient has fasted for 12 hours and has not exercised. Nipple stimulation should also be avoided for 8 to 12 hours before the test. If these tests are normal and an athlete's history and physical exam are typical of sports-related amenorrhea, many clinicians would consider this an adequate workup.

An athlete who has a less straightforward history requires additional testing. Estrogen status can be assessed either by attempting to induce a withdrawal bleed with progesterone or by checking her estradiol level. In a woman who has an estrogen-primed endometrium, 10 mg of progesterone taken for 5 days typically will produce a withdrawal bleed within 2 to 7 days.3 A woman who has HPA suppression will have no withdrawal bleed or have only minimal spotting, which indicates a lack of estrogen. Alternatively, a patient's estradiol level can be quickly assessed with a blood test. The estradiol level will be low (table 2) if the patient has evidence of estrogen-related menstrual irregularity.

TABLE 2. Workup for and Test Results of Amenorrhea

DiagnosisTest Results

bHCGTSHProlactinLHFSHEstradiolWithdrawal Bleed

PregnancyPositive

Hypothalmic
pituitary axis
suppression
Negative
to low
NormalNormalLowLowLowWeak or absent

Hyperandrogenic
anovulary
syndrome
(polycystic
ovarian syndrome)
NegativeNormalNormal>2:1
LH/FSH
ratio
Normal
to high
Positive

Premature
ovarian failure
NegativeNormalNormalNormalHighLowAbsent

bHCG = beta human chorionic gonadotropin; TSH = thyroid-stimulating hormone; LH = luteinizing hormone; FSH = follicle-stimulating hormone

FSH and LH testing should be done to rule out hyperandrogenic anovulatory syndrome and premature ovarian failure if the athlete has not had any rapid weight changes and is normal weight or overweight, or has hirsutism, hot flashes, or atrophic vaginitis. In athletic amenorrhea, FSH and LH levels will be normal or low. Any athlete with menstrual dysfunction should also be evaluated for eating disorders.

Assessing Bone Mineral Density

Many athletes find that not having periods is convenient, and they may not be concerned about their menstrual status. In fact, the absence of menses in and of itself is not the problem; rather, it is the lack of estrogen associated with HPA suppression that can lead to osteopenia or osteoporosis.

It is well established that bone mineral density (BMD) directly correlates with duration and severity of menstrual dysfunction.4-9 Resuming menses can increase BMD.10 BMD has been shown to increase in amenorrheic premenopausal athletes when they use oral contraceptives.11,12 However, even after patients resume menses or use oral contraceptives, calcium, and vitamin D, they may never attain the BMD seen in their eumenorrheic peers.13,14 Weight-bearing exercise and calcium supplementation may also partly ameliorate the effect of hypoestrogenemia on BMD, but these athletes still have a significantly lower BMD than exercising or nonexercising women with normal periods.15,16

BMD assessment should be considered for any athlete who has been amenorrheic for more than a year, has had stress fractures, or who is unwilling or unable to take hormone replacement. Many options exist for BMD evaluation, but measuring density at the hip and spine with dual-energy x-ray absorptiometry (DEXA) is the current gold standard. In addition, DEXA is the only assessment technique that has a margin of error low enough to make serial comparisons when measurements are done on the same machine.

A below-normal bone density is a concern in any athlete. Athletes are considered osteopenic when their BMD is between 1.0 and 2.5 standard deviations below the mean of young adults and osteoporotic when their BMD is 2.5 or more standard deviations below the mean. These results should be interpreted carefully, because young athletes have not reached their peak bone density, and BMD standards are not well established for women younger than 30 years old. The results of BMD assessment should be used to help women make wise choices about treatment options.

Exercise-related menstrual irregularity is not a contraindication to activity; however, it should trigger an evaluation of the athlete's training schedule and diet. If the athlete has demonstrated osteopenia or osteoporosis and recurrent stress fractures, the clinician should consider limiting participation until BMD increases. Serial BMD measurements should be made annually.

Treatment Options

Ideal treatment consists of reducing training volume, increasing weight, and maintaining adequate energy intake to reestablish normal menses. These options, however, may be unacceptable to competitive athletes.

Hormone replacement therapy is the next best option for athletes who have exercise-related menstrual irregularity. Either postmenopausal regimens or oral contraceptives can be used by women who have no contraindications. The estrogen potency of low-dose oral contraceptive pills (0.020 mg to 0.035 mg of ethinyl estradiol) is about four to seven times that of most conjugated estrogen replacement products (eg, 0.625 mg of conjugated estrogens).17 Recent research18 shows that 25 to 35 µg (0.025 to 0.035 mg) of ethinyl estradiol or its equivalent is the optimal dosage to preserve bone mass. A dose-response relationship exists between estrogen and increases in BMD.18 A minimum dose of 0.3 mg conjugated estrogen (equivalent to 0.0024 mg ethinyl estradiol) is necessary to preserve BMD in postmenopausal women.19 Even very low-dose oral contraceptives contain 8 times the estrogen (0.020 mg ethinyl estradiol) necessary to preserve bone mass. In addition, oral contraceptives are usually more convenient and acceptable to premenopausal athletes. Because of the higher dose of estrogen, a 0.035-mg oral contraceptive pill should be considered for initial therapy.20 This treatment strategy also offers a contraceptive effect.

Some athletes may be concerned about the effects of oral contraceptives on weight or performance. Athletes should be reassured that studies have shown that most users of oral contraceptives do not gain weight. Also, there is no evidence that oral contraceptives or the menstrual cycle affect performance negatively or positively.1,20 If having a regular menstrual period is a stumbling block to the athlete starting oral contraceptives, continuous therapy with three to four withdrawal bleeds a year should be considered.

Calcium is essential for bone health. All women should get between 1,000 mg and 1,500 mg of calcium and 400 to 800 IU of vitamin D daily. Oligomenorrheic or amenorrheic athletes should be counseled on proper calcium intake and supplementation (see "Banking on Strong Bones for Life").

Bisphosphonates (such as alendronate sodium and risedronate sodium) significantly increase bone density and subsequently decrease fracture rates in postmenopausal women. Bisphosphonates bind irreversibly to bone and have a terminal-life estimated to exceed 10 years.21 However, no studies evaluated premenopausal women who were treated with bisphosphonates and subsequently became pregnant. In studies of rats, pregnancies were adversely affected.21 Because of this, the use of bisphosphonates in premenopausal women cannot be recommended, and a serious assessment of the potential risks and benefits should be made before prescribing them.

Nasal calcitonin-salmon has also been used to treat osteoporosis in postmenopausal women. This hormone can increase bone density but not as much as estrogen replacement therapy or bisphosphonates. However, an increase in bone density does not always correlate with a decreased fracture risk. Elemental fluoride, for example, will increase BMD, but it also increases bone fragility and fracture rates. Nasal calcitonin-salmon has recently been shown to reduce vertebral fracture in postmenopausal women with osteoporosis.22 It has a short half-life and does not cross the placental barrier. This is a reasonable option to consider for women who cannot or will not take estrogen and whose bone density is low, although its limitations—including the fact that treatment of premenopausal low BMD is an off-label indication—should be clearly explained to the patient.

Taking the Problem Seriously

Exercise-related menstrual dysfunction is common in athletes, especially those competing in endurance or appearance-related sports. The condition is not normal and should trigger a search for the cause. If HPA suppression is diagnosed, nutrition, training, and stress management should be optimized. The athlete should be counseled about hormone replacement therapy and considered for BMD assessment.

References

  1. Burrows M, Bird S: The physiology of the highly trained female endurance runner. Sports Med 2021:30(4):281-300
  2. De Cree C: Sex steroid metabolism and menstrual irregularities in the exercising female: a review. Sports Med 192021;25(6):369-406
  3. Speroff L, Glass RH, Kase NG (eds): Clinical Gynecologic Endocrinology and Infertility, ed 5. Baltimore, Williams & Wilkins, 1994, pp 401-456
  4. Biller BM, Coughlin JF, Saxe V, et al: Osteopenia in women with hypothalamic amenorrhea: a prospective study. Obstet Gynecol 1991;78(6):996-1001
  5. Cann CE, Martin MC, Genant HK, et al: Decreased spinal mineral content in amenorrheic women. JAMA 120214;251(5):626-629
  6. Drinkwater BL, Nilson K, Chesnut CH III, et al: Bone mineral content of amenorrheic and eumenorrheic athletes. N Engl J Med 120214;311(5):277-281
  7. Drinkwater BL, Bruemner B, Chesnut CH III: Menstrual history as a determinant of current bone density in young athletes. JAMA 1990;263(4):545-548
  8. Otis CL, Drinkwater B, Johnson M, et al: American College of Sports Medicine position stand: the female athlete triad. Med Sci Sports Exerc 1997;29(5):i-ix
  9. Rencken ML, Chesnut CH, Drinkwater BL: Bone density at multiple skeletal sites in amenorrheic athletes. JAMA 1996;276(3):238-240
  10. Drinkwater BL, Nilson K, Ott S, et al: Bone mineral density after resumption of menses in amenorrheic athletes. JAMA 120216;256(3):380-382
  11. Cumming DC: Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy. Arch Intern Med 1996;156(19):2193-2195
  12. Haenggi W, Casez JP, Birkhaeuser MH, et al: Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel. Osteoporos Int 1994;4(2):99-103
  13. Keen AD, Drinkwater BL: Irreversible bone loss in former amenorrheic athletes. Osteoporos Int 1997;7(4):311-315
  14. Jonnavithula S, Warren MP, Fox RP, et al: Bone density is compromised in amenorrheic women despite return of menses: a 2-year study. Obstet Gynecol 1993;81(5 pt 1):669-674
  15. Marcus R, Cann C, Madvig P, et al: Menstrual function and bone mass in elite women distance runners: endocrine and metabolic features. Ann Intern Med 120215;102(2):158-163
  16. Okano H, Mizunuma H, Soda M, et al: Effect of exercise and amenorrhea on bone mineral density in teenage runners. Endocr J 1995;42(2):271-276
  17. Van Winter JT, Bernard ME: Oral contraceptive use during the perimenopausal years. Am Fam Physician 192021;58(6):1373-1377, 1381-1382
  18. DeCherney A: Bone-sparing properties of oral contraceptives. Am J Obstet Gynecol 1996;174(1 pt 1):15-20
  19. Kenny AM, Prestwood KM: Osteoporosis: pathogenesis, diagnosis, and treatment in older adults. Rheum Dis Clin North Am 2021;26(3):569-591
  20. Frankovich RJ, Lebrun CM: Menstrual cycle, contraception, and performance. Clin Sports Med 2021;19(2):251-271
  21. Physicians' Desk Reference 2021, ed 54. Montvale, NJ, Medical Economics, pp 172021-1802
  22. Chesnut CH, Silverman S, Andriano K, et al: A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2021;109(4):267-276


Dr Harmon is a clinical assistant professor in the Department of Family Medicine and the Department of Orthopedics and Sports Medicine at the University of Washington in Seattle. She is an editorial board member of The Physician and Sportsmedicine. Address correspondence to Kimberly G. Harmon, MD, 4110 NE 142nd St, Seattle, WA 2021125: e-mail to [email protected].

Disclosure information: Dr Harmon has no significant relationship to disclose with any manufacturer of any commercial product mentioned in this article. The following drugs are mentioned in this article for unlabeled use: conjugated estrogens and progesterone.


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