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Ruling out secondary causes of amenorrhea is, of course, the first step. Once that’s done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses (strength of recommendation: C, expert consensus).1
I err on the side of hormone supplementatio
Roberta VanZant, MD
UICOMP/MMCI Family Residency, Peoria, Ill
The menstrual cycle is a finely balanced orchestra of events; amenorrhea means that something is out of tune. In athletes, amenorrhea signals that the body is sacrificing the menses to provide energy for more important daily functions.2
Because of the potential negative long-term consequences of hypoestrogenism, I err on the side of hormone supplementation while encouraging the patient to modify her eating pattern and exercise routine to promote the return of menses. For women who desire birth control, I use hormonal contraception.
If pregnancy is not a concern, I prefer to cycle the patient on low-dose estradiol and progesterone that are chemically identical to her own hormones. I believe this gently prods the body’s own hypothalamic-pituitary axis (HPA) to re-engage without overriding the internal HPA-ovarian drive.
Evidence summary
Little evidence and no specific guidelines exist to guide the clinician in evaluating and managing exercise-induced amenorrhea. All athletes with amenorrhea should have a pregnancy test, because pregnancy is the most common cause of secondary amenorrhea.1 After ruling it out, the clinician may choose to exclude other causes of secondary amenorrhea before presuming a diagnosis of hypothalamic amenorrhea.
Useful tests (TABLE) include:
- serum prolactin to rule out prolactinoma
- follicle-stimulating hormone to rule out premature ovarian failure
- thyroid-stimulating hormone to evaluate for thyroid problems.
If all these tests are negative, consider a progesterone challenge test.3 Typically, athletes with hypothalamic amenorrhea don’t experience withdrawal bleeding after progesterone challenge, because of inadequate endogenous estrogen stimulation.
Greater calorie and micronutrient intake—plus rest—is best
A 1999 study in the International Journal of Sport Nutrition found that chronic energy deficit in amenorrheic athletes (N=4) could be reversed in a 20-week program using a sport nutrition supplement, 1 rest day per week, and a dietician to help with food selection.4 A 2002 review similarly recommends 1 rest day per week, increasing caloric intake by 200 to 300 Kcal/d, and increasing intake of calcium, B vitamins, iron, and zinc.5
TABLE
Is it hypothalamic amenorrhea, or something else?
| DIFFERENTIAL DIAGNOSIS | CLINICAL CLUE | POTENTIALLY USEFUL TEST |
|---|---|---|
| Pregnancy | Sexual history | Urine hCG |
| Polycystic ovary syndrome | Obesity, hirsutism | Progesterone challenge |
| Ovarian failure | Family history | Serum FSH |
| Thyroid dysfunction | Physical exam, history | Serum TSH |
| Prolactinoma, psychiatric medications | Galactorrhea | Serum prolactin |
| Asherman’s syndrome | History of pelvic instrumentation | Estrogen/progesterone challenge |
| FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; TSH, thyroid-stimulating hormone. | ||
Oral contraceptives to prevent bone loss? Too little information
Bone loss in amenorrheic athletes may have long-term consequences, even if amenorrhea is only temporary. Some theoretical and disease-based research suggests a possible role for oral contraceptives to prevent bone loss in pre- and postmenopausal women,6 but little research has investigated younger women with hypothalamic amenorrhea. A recent open-label study that did examine bone mineral density (BMD) in women with hypothalamic amenorrhea before and after 13 cycles of oral contraceptives found a significant increase in BMD in the spine, but not at the hip.7
No published study has demonstrated clinically significant advantages for oral contraceptive therapy in women with secondary amenorrhea. These women should take adequate calcium and vitamin D. Bisphosphonates are not appropriate for women of reproductive age, because of their potential teratogenicity.1
Recommendations
The Committee on Sports Medicine and Fitness of the American Academy of Pediatrics (AAP) encourages exercise to help maintain lean body mass and protect against obesity, diabetes, hypertension, and cardiovascular disease. Athletes with amenorrhea, however, may be at risk for sequelae such as osteopenia, fractures, and dyslipidemia. Amenorrhea during adolescence may inhibit the accretion of BMD, and the lost density may not be re-gained. Amenorrheic athletes are also at risk for the “female athlete triad”—disordered eating, amenorrhea, and osteoporosis.8
The potential negative sequelae of amenorrhea are best prevented with measures that restore physiologic menses.3 For exercise-induced hypothalamic bone loss, the AAP recommends decreased exercise, increased caloric intake, or both.
1. Warren MP, Perlroth NE. The effects of intense exercise on the female reproductive system. J Endocrinol. 2001;170:3-11.
2. Master-Hunter T, Heiman DL. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006;73:1374-1382.
3. American College of Obstetricians and Gynecologists Amenorrhea. (ACOG Technical Bulletin 128). Washington, DC: American College of Obstetricians and Gynecologists; 1989.
4. Kopp-Woodroffe SA, Manore MM, Dueck CA, et al. Energy and nutrient status of amenorrheic athletes participating in a diet and exercise training intervention program. Int J Sport Nutr. 1999;9:70-88.
5. Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32:887-901.
6. DeCherney A. Bone sparing properties of oral contraceptives. Am J Obstet Gynecol. 1996;v:15-20.
7. Warren MP, Miller KK, Olson WH, et al. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study. Contraception. 2005;72:206-211.
8. American Academy of Pediatrics Committee on Sports Medicine and Fitness Medical concerns in the female athlete. Pediatrics. 2000;106:610-613.
Ruling out secondary causes of amenorrhea is, of course, the first step. Once that’s done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses (strength of recommendation: C, expert consensus).1
I err on the side of hormone supplementatio
Roberta VanZant, MD
UICOMP/MMCI Family Residency, Peoria, Ill
The menstrual cycle is a finely balanced orchestra of events; amenorrhea means that something is out of tune. In athletes, amenorrhea signals that the body is sacrificing the menses to provide energy for more important daily functions.2
Because of the potential negative long-term consequences of hypoestrogenism, I err on the side of hormone supplementation while encouraging the patient to modify her eating pattern and exercise routine to promote the return of menses. For women who desire birth control, I use hormonal contraception.
If pregnancy is not a concern, I prefer to cycle the patient on low-dose estradiol and progesterone that are chemically identical to her own hormones. I believe this gently prods the body’s own hypothalamic-pituitary axis (HPA) to re-engage without overriding the internal HPA-ovarian drive.
Evidence summary
Little evidence and no specific guidelines exist to guide the clinician in evaluating and managing exercise-induced amenorrhea. All athletes with amenorrhea should have a pregnancy test, because pregnancy is the most common cause of secondary amenorrhea.1 After ruling it out, the clinician may choose to exclude other causes of secondary amenorrhea before presuming a diagnosis of hypothalamic amenorrhea.
Useful tests (TABLE) include:
- serum prolactin to rule out prolactinoma
- follicle-stimulating hormone to rule out premature ovarian failure
- thyroid-stimulating hormone to evaluate for thyroid problems.
If all these tests are negative, consider a progesterone challenge test.3 Typically, athletes with hypothalamic amenorrhea don’t experience withdrawal bleeding after progesterone challenge, because of inadequate endogenous estrogen stimulation.
Greater calorie and micronutrient intake—plus rest—is best
A 1999 study in the International Journal of Sport Nutrition found that chronic energy deficit in amenorrheic athletes (N=4) could be reversed in a 20-week program using a sport nutrition supplement, 1 rest day per week, and a dietician to help with food selection.4 A 2002 review similarly recommends 1 rest day per week, increasing caloric intake by 200 to 300 Kcal/d, and increasing intake of calcium, B vitamins, iron, and zinc.5
TABLE
Is it hypothalamic amenorrhea, or something else?
| DIFFERENTIAL DIAGNOSIS | CLINICAL CLUE | POTENTIALLY USEFUL TEST |
|---|---|---|
| Pregnancy | Sexual history | Urine hCG |
| Polycystic ovary syndrome | Obesity, hirsutism | Progesterone challenge |
| Ovarian failure | Family history | Serum FSH |
| Thyroid dysfunction | Physical exam, history | Serum TSH |
| Prolactinoma, psychiatric medications | Galactorrhea | Serum prolactin |
| Asherman’s syndrome | History of pelvic instrumentation | Estrogen/progesterone challenge |
| FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; TSH, thyroid-stimulating hormone. | ||
Oral contraceptives to prevent bone loss? Too little information
Bone loss in amenorrheic athletes may have long-term consequences, even if amenorrhea is only temporary. Some theoretical and disease-based research suggests a possible role for oral contraceptives to prevent bone loss in pre- and postmenopausal women,6 but little research has investigated younger women with hypothalamic amenorrhea. A recent open-label study that did examine bone mineral density (BMD) in women with hypothalamic amenorrhea before and after 13 cycles of oral contraceptives found a significant increase in BMD in the spine, but not at the hip.7
No published study has demonstrated clinically significant advantages for oral contraceptive therapy in women with secondary amenorrhea. These women should take adequate calcium and vitamin D. Bisphosphonates are not appropriate for women of reproductive age, because of their potential teratogenicity.1
Recommendations
The Committee on Sports Medicine and Fitness of the American Academy of Pediatrics (AAP) encourages exercise to help maintain lean body mass and protect against obesity, diabetes, hypertension, and cardiovascular disease. Athletes with amenorrhea, however, may be at risk for sequelae such as osteopenia, fractures, and dyslipidemia. Amenorrhea during adolescence may inhibit the accretion of BMD, and the lost density may not be re-gained. Amenorrheic athletes are also at risk for the “female athlete triad”—disordered eating, amenorrhea, and osteoporosis.8
The potential negative sequelae of amenorrhea are best prevented with measures that restore physiologic menses.3 For exercise-induced hypothalamic bone loss, the AAP recommends decreased exercise, increased caloric intake, or both.
Ruling out secondary causes of amenorrhea is, of course, the first step. Once that’s done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses (strength of recommendation: C, expert consensus).1
I err on the side of hormone supplementatio
Roberta VanZant, MD
UICOMP/MMCI Family Residency, Peoria, Ill
The menstrual cycle is a finely balanced orchestra of events; amenorrhea means that something is out of tune. In athletes, amenorrhea signals that the body is sacrificing the menses to provide energy for more important daily functions.2
Because of the potential negative long-term consequences of hypoestrogenism, I err on the side of hormone supplementation while encouraging the patient to modify her eating pattern and exercise routine to promote the return of menses. For women who desire birth control, I use hormonal contraception.
If pregnancy is not a concern, I prefer to cycle the patient on low-dose estradiol and progesterone that are chemically identical to her own hormones. I believe this gently prods the body’s own hypothalamic-pituitary axis (HPA) to re-engage without overriding the internal HPA-ovarian drive.
Evidence summary
Little evidence and no specific guidelines exist to guide the clinician in evaluating and managing exercise-induced amenorrhea. All athletes with amenorrhea should have a pregnancy test, because pregnancy is the most common cause of secondary amenorrhea.1 After ruling it out, the clinician may choose to exclude other causes of secondary amenorrhea before presuming a diagnosis of hypothalamic amenorrhea.
Useful tests (TABLE) include:
- serum prolactin to rule out prolactinoma
- follicle-stimulating hormone to rule out premature ovarian failure
- thyroid-stimulating hormone to evaluate for thyroid problems.
If all these tests are negative, consider a progesterone challenge test.3 Typically, athletes with hypothalamic amenorrhea don’t experience withdrawal bleeding after progesterone challenge, because of inadequate endogenous estrogen stimulation.
Greater calorie and micronutrient intake—plus rest—is best
A 1999 study in the International Journal of Sport Nutrition found that chronic energy deficit in amenorrheic athletes (N=4) could be reversed in a 20-week program using a sport nutrition supplement, 1 rest day per week, and a dietician to help with food selection.4 A 2002 review similarly recommends 1 rest day per week, increasing caloric intake by 200 to 300 Kcal/d, and increasing intake of calcium, B vitamins, iron, and zinc.5
TABLE
Is it hypothalamic amenorrhea, or something else?
| DIFFERENTIAL DIAGNOSIS | CLINICAL CLUE | POTENTIALLY USEFUL TEST |
|---|---|---|
| Pregnancy | Sexual history | Urine hCG |
| Polycystic ovary syndrome | Obesity, hirsutism | Progesterone challenge |
| Ovarian failure | Family history | Serum FSH |
| Thyroid dysfunction | Physical exam, history | Serum TSH |
| Prolactinoma, psychiatric medications | Galactorrhea | Serum prolactin |
| Asherman’s syndrome | History of pelvic instrumentation | Estrogen/progesterone challenge |
| FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; TSH, thyroid-stimulating hormone. | ||
Oral contraceptives to prevent bone loss? Too little information
Bone loss in amenorrheic athletes may have long-term consequences, even if amenorrhea is only temporary. Some theoretical and disease-based research suggests a possible role for oral contraceptives to prevent bone loss in pre- and postmenopausal women,6 but little research has investigated younger women with hypothalamic amenorrhea. A recent open-label study that did examine bone mineral density (BMD) in women with hypothalamic amenorrhea before and after 13 cycles of oral contraceptives found a significant increase in BMD in the spine, but not at the hip.7
No published study has demonstrated clinically significant advantages for oral contraceptive therapy in women with secondary amenorrhea. These women should take adequate calcium and vitamin D. Bisphosphonates are not appropriate for women of reproductive age, because of their potential teratogenicity.1
Recommendations
The Committee on Sports Medicine and Fitness of the American Academy of Pediatrics (AAP) encourages exercise to help maintain lean body mass and protect against obesity, diabetes, hypertension, and cardiovascular disease. Athletes with amenorrhea, however, may be at risk for sequelae such as osteopenia, fractures, and dyslipidemia. Amenorrhea during adolescence may inhibit the accretion of BMD, and the lost density may not be re-gained. Amenorrheic athletes are also at risk for the “female athlete triad”—disordered eating, amenorrhea, and osteoporosis.8
The potential negative sequelae of amenorrhea are best prevented with measures that restore physiologic menses.3 For exercise-induced hypothalamic bone loss, the AAP recommends decreased exercise, increased caloric intake, or both.
1. Warren MP, Perlroth NE. The effects of intense exercise on the female reproductive system. J Endocrinol. 2001;170:3-11.
2. Master-Hunter T, Heiman DL. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006;73:1374-1382.
3. American College of Obstetricians and Gynecologists Amenorrhea. (ACOG Technical Bulletin 128). Washington, DC: American College of Obstetricians and Gynecologists; 1989.
4. Kopp-Woodroffe SA, Manore MM, Dueck CA, et al. Energy and nutrient status of amenorrheic athletes participating in a diet and exercise training intervention program. Int J Sport Nutr. 1999;9:70-88.
5. Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32:887-901.
6. DeCherney A. Bone sparing properties of oral contraceptives. Am J Obstet Gynecol. 1996;v:15-20.
7. Warren MP, Miller KK, Olson WH, et al. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study. Contraception. 2005;72:206-211.
8. American Academy of Pediatrics Committee on Sports Medicine and Fitness Medical concerns in the female athlete. Pediatrics. 2000;106:610-613.
1. Warren MP, Perlroth NE. The effects of intense exercise on the female reproductive system. J Endocrinol. 2001;170:3-11.
2. Master-Hunter T, Heiman DL. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006;73:1374-1382.
3. American College of Obstetricians and Gynecologists Amenorrhea. (ACOG Technical Bulletin 128). Washington, DC: American College of Obstetricians and Gynecologists; 1989.
4. Kopp-Woodroffe SA, Manore MM, Dueck CA, et al. Energy and nutrient status of amenorrheic athletes participating in a diet and exercise training intervention program. Int J Sport Nutr. 1999;9:70-88.
5. Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32:887-901.
6. DeCherney A. Bone sparing properties of oral contraceptives. Am J Obstet Gynecol. 1996;v:15-20.
7. Warren MP, Miller KK, Olson WH, et al. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study. Contraception. 2005;72:206-211.
8. American Academy of Pediatrics Committee on Sports Medicine and Fitness Medical concerns in the female athlete. Pediatrics. 2000;106:610-613.
Evidence-based answers from the Family Physicians Inquiries Network