Amenorrhea Treatment & Management

  • Author: Vaishali Popat, MD, MPH; Chief Editor: Bryan D Cowan, MD,†   more...
 
Updated: Jun 8, 2011
 

Approach Considerations

Treatment is determined by the etiology of the amenorrhea and the desires of the patient. Ideally, treatment should be directed at correcting the underlying pathology. In the case of outflow tract abnormalities (eg, imperforate hymen), surgery may be indicated. In other cases, correcting the underlying pathology should restore normal ovarian endocrine function and prevent the development of osteoporosis.

Dopamine agonists are effective in treating hyperprolactinemia. In most cases, this treatment restores normal ovarian endocrine function and ovulation.

Hormone replacement therapy is required to achieve peak bone density in patients whose underlying pathology cannot be reversed to restore normal endocrine function. In conditions leading to estrogen deficiency, hormone replacement therapy is required to maintain bone density, and it may have other possible health benefits in patients whose underlying pathology cannot be reversed to restore normal endocrine function.

Women with evidence of hyperandrogenism and disordered menses have many other medical issues that must be addressed (eg, polycystic ovarian syndrome).

Gonadotropin therapy or the use of pulsatile gonadotropin-releasing hormone (GnRH) therapy may be required to induce ovulation in patients with infertility whose underlying pathology cannot be reversed.

Other than pregnancy, constitutional delay, anovulation, and chronic illness, most other disorders that cause amenorrhea may require referral to a subspecialist for treatment. Many of the treatment methods require surgery or specific therapies. For the adolescent with constitutional delay and anovulation, the goal should be the restoration of ovulatory cycles. If ovulatory cycles are not spontaneously restored, estrogen-progestin therapy is indicated.

Osteoporosis prevention

Evidence is mounting that loss of menstrual regularity is a risk factor for later development of osteoporosis and hip fractures. Both patients and clinicians need to view the ovary as an important endocrine organ that helps maintain healthy bones. Excessive delay in the evaluation and treatment of disordered menses can contribute to osteoporosis. At some point, failure to promptly evaluate for the presence of ovarian insufficiency could become a medicolegal pitfall.

Many patients are deficient in their body stores of vitamin D, reflected by a serum 25-hydroxy vitamin D level less than 30 nmol/L. If this is the case, patients should be treated for 8-12 weeks with high-dose vitamin D, 50,000 IU/week, for repletion. Once the 25-OH-D level is greater than 30 nmol/L, 1000 IU/d of vitamin D may be instituted.

Emotional health concerns

Primary amenorrhea and the potential for impaired fertility affect the emotional health of the adolescent and her family. Adolescence encompasses a broad spectrum of emotional maturity, which needs to be considered in assessment and treatment. For the adolescent girl, a reproductive disorder impacts her developing sense of self, body-image, and sexuality, which, in turn, can affect her self-esteem and relationships with others.

Because of the sexual nature of a reproductive disorder, feelings of embarrassment, inadequacy, or protectiveness can make it difficult for families. Families should be encouraged to be open and honest regarding the condition and discouraged from keeping the diagnosis a secret.

The family is an emotional unit and a family systems approach to deal with health issues is most appropriate. Parents must first deal with their own feelings about the condition before they can help their child. They must also be provided with tools to build an ongoing conversation with their child. Physicians need to be culturally sensitive because in some cultures a woman's identity in adulthood as a mother could play a crucial role in her life. The objective is to help the adolescent girl formulate positive self-esteem and body image, despite impaired fertility.

Next

Treatment of Common Causes

In the overall management of females with amenorrhea, remembering the most likely causes that may present in an outpatient setting is helpful. The following information is a guide to managing the most common causes.

Although the differential diagnosis for amenorrhea is broad, most patients who present in an outpatient setting with primary or secondary amenorrhea have 1 of 5 common medical problems: PCOS, hypothalamic amenorrhea, hyperprolactinemia, ovarian failure, or thyroid dysfunction.

For women with strictly primary amenorrhea, Müllerian abnormalities are second to premature ovarian failure as the most likely diagnosis. The management options of the most common causative processes are below. Unusual and uncommon causative factors of amenorrhea, such as sarcoidosis, require referral and evaluation by a specialist and are not reviewed below.

Polycystic ovarian syndrome

PCOS is characterized by oligomenorrhea or amenorrhea, an excess androgen hormone environment, and polycystic-appearing ovaries on ultrasonography.[43] A high body mass index (BMI) and insulin resistance also play an important role in the pathogenesis of PCO syndrome. Women with PCO syndrome have lifelong increased risks of developing adult-onset diabetes mellitus, hypertension, lipid disorders, hypothyroidism, and endometrial cancer.[44]

If pregnancy is not desired, monthly withdrawal bleeding should be induced. Both cyclic progesterone (10-12 days per month) and oral contraceptives can accomplish monthly withdrawal bleeding; however, oral contraceptives use different mechanisms to control other aspects of PCOS. Oral contraceptives decrease LH secretion, leading to lower androgen production and improvement in acne and hirsutism. Oral contraceptives atrophy the endometrial lining, decreasing the risk of endometrial hyperplasia and endometrial cancer.

Metformin is presently offered to improve ovulation.[45] Further research is needed to determine whether metformin should be used for the prevention of the long-term development of adult-onset diabetes mellitus, cardiovascular disease, and lipid disorders.[46] Patients should be strongly encouraged to maintain a weight-to-height ratio within the reference range and to regularly exercise because both are first-line therapies used to control PCO syndrome.[47]

Hypothalamic amenorrhea

Hypothalamic amenorrhea is most common in patients who exercise to excess and/or have eating disorders, caloric restriction, and psychogenic stress. Hypothalamic amenorrhea is best treated using behavioral modification and a multidisciplinary team approach, depending on the root cause.

An interdisciplinary team approach that involves nutritionists, clinicians, counselors, and family members is most effective.[48] After correcting the behavior that leads to hypothalamic amenorrhea, most women resume normal pulsatile release of GnRH and subsequent normal menstrual cycling.[48]

Women with severe anorexia nervosa may not resume normal menstrual cycling after weight gain.[49, 50] A BMI of less than 15 kg/m2 requires immediate intervention by an eating disorder specialist. Hospitalization may be indicated. This group of women may need hormone replacement and monitoring of bone density.[51] Weight gain may be the most important factor in bone recovery.[52] Gonadotropin therapy may be needed for conception.

Patients with hypothalamic amenorrhea caused by excessive exercise may refuse to correct or change their behavior. This is especially true for professional, competitive college, or elite athletes participating in "leanness" sports. Although controversial, consideration should be given to correcting their low estradiol (E2) level by prescribing oral contraceptives.[53, 54] Many athletes may request to use oral contraceptives continuously to limit or avoid menses.[55]

Functional hypothalamic amenorrhea due to stress is a diagnosis of exclusion. An occult eating disorder and caloric restriction must be ruled out as a compounding factor.[56] Behavioral modification is the first-line treatment. Although controversial, consideration should be given to correcting the low E2 by prescribing oral contraceptives.[53, 54] If oral contraceptive therapy is initiated, it can be intermittently stopped to determine if the GnRH pump has regained pulsatile function. An increase in BMI is associated with the best long-term recovery.[57]

Hyperprolactinemia

Hyperprolactinemia with a normal TSH level requires an MRI to determine the presence of a tumor, microadenomas or macroadenomas, and other organic CNS lesions. Microadenomas and prolactinomas less than 1 cm in diameter are slow growing and are mostly found in the premenopausal population. Treatment should be considered to reverse hypoestrogenemic symptomatology, improve fertility, and/or eliminate bothersome galactorrhea.

Symptomatic hyperprolactinemia from a pituitary disorder should first be treated by dopamine agonists such as bromocriptine (Parlodel) and cabergoline (Dostinex). Pergolide has been associated with heart value abnormalities; it should not be used and was withdrawn from the US market in March, 2007.

Macroadenomas may also be treated with dopamine agonists initially. Occasionally, larger lesions fail to respond to medical therapy or present with acute vision changes. Referral with subsequent surgery or radiation is indicated. The recurrence rate after surgery can be as high as 50%. Patients with hyperprolactinemia associated with medications (eg, antipsychotics, metoclopramide) should consider discontinuation or switching of the causative medication if medically possible.

Some pituitary and hypothalamic tumors may require surgery and, in some cases, radiation therapy.

Hypergonadotropic hypogonadism

In a patient who fails to enter puberty, hypergonadotropic hypogonadism (gonadal failure) is most often associated with Turner syndrome or other gonadal dysgenesis disorders, such as Swyer syndrome. An X chromosome deletion (Turner syndrome), ring formation, partial deletion, or translocation is the most common diagnosis in this setting. A karyotype is required to detect any Y-containing chromatin.

Patients who have a Y chromosome have a 25% chance of developing a gonadal tumor. The gonads should immediately be removed.[58] These gonads are nonfunctioning; therefore adult height and bone mass are not affected by their presence. Hormone replacement therapy (HRT) should be offered to allow completion of puberty in a controlled fashion, similar to her peers, and should facilitate maximum bone density development.[59] Turner syndrome is associated with ear and renal disease; evaluation of these organ systems is indicated.

Premature ovarian failure after puberty occurs in 1% of adult women. Treatment should be decided on an individual basis. Some patients may require estrogen replacement therapy (ERT) for hot flashes and other symptomatic menopausal issues. Long-term E2 use should be individualized.[60] A small number of women with repetitively elevated FSH levels may have a resumption of cycles for a short period before proceeding to complete menopause. No medications or therapies have been found to induce normal cycling; its occurrence is sporadic, spontaneous, and not inducible.

Ovarian failure that occurs in patients younger than 30 years requires a karyotype to detect any Y chromatin and an evaluation of the fragile X area of the X chromosome. A strong family history of premature ovarian failure may require a referral for evaluation of GALT and autoimmune regulatory gene (AIRE) mutations and other autosomal disorders.[61] Documentation of a fragile X area requires other family members to receive genetic counseling. With a normal karyotype, evaluation of other autoimmune disease should be considered, including antithyroid and antiadrenal antibody titers.[62] Bone density should be monitored and treated appropriately using hormonal or nonhormonal therapy.

Thyroid dysfunction

Patients with hypothyroidism and hyperthyroidism should undergo a standard work-up and therapy. Treatment in most cases is straightforward.

Previous
Next

Diet and Activity

Women with findings suggestive of an eating disorder should be evaluated by a multidisciplinary team with special expertise in these disorders. Nutritional counseling alone is inadequate therapy for these women.

In some cases, nutritional deficiencies induced by dieting and exercise can cause amenorrhea even in the absence of a psychiatric disorder. Strict fat restriction often plays a role. Frequently, simply explaining the need to balance energy expenditure with energy intake resolves the problem. In this situation, nutritional counseling may be all that is required.

More than 8 hours of vigorous exercise a week may cause amenorrhea. As noted above, in some cases this resolves with appropriate adjustment of the diet.

Previous
Next

Consultations

The causes of menstrual cycle disturbance leading to the development of amenorrhea are so diverse that in some complex cases, the situation is best addressed by a multidisciplinary team. For example, a patient with complete androgen resistance (testicular feminization) would benefit from the involvement of experts in endocrinology, human genetics, psychiatry, and reproductive surgery.

With hereditary causes of amenorrhea, such as Kallmann syndrome, a geneticist's expertise can be helpful in counseling patients and their families regarding the disorder

In cases of pituitary/hypothalamic tumor, other endocrine disorders (eg, central hypothyroidism, central adrenal insufficiency) may be involved. Generally, the expertise of a medical endocrinologist is required to assist in the treatment of patients who require neurosurgery to treat the underlying condition. In cases of hyperthyroidism or Cushing syndrome, the expertise of a medical endocrinologist is required to treat the underlying pathology.

Cases of major depression, anorexia nervosa, bulimia nervosa, or other major psychiatric disorders warrant consultation with a psychiatrist.

In some unusual cases, such as with vaginal agenesis, consult with a reproductive surgeon with extensive experience in the specific disorder.

In many cases, exercise-induced amenorrhea is due to an imbalance in energy intake and expenditure. Nutritional counseling to increase energy intake without reducing exercise is a means of reversing the underlying pathology. Women who are underweight or who appear to have nutritional deficiencies should receive nutritional counseling and can be referred to a multidisciplinary team specializing in eating disorders.

In certain cases in which an underlying chronic disease process is present, the insights of an internist may be needed.

Previous
Next

Long-Term Monitoring

The need for ongoing care is defined by the mechanism disrupting the menstrual cycle and the patient's desires.

See patients with primary ovarian insufficiency annually to monitor their ovarian hormone replacement and to detect the development of associated conditions that may be related to the original pathogenic mechanism that led to the disruption of the menstrual cycle.

See patient every 3-6 months for the first 2 years to monitor ovarian hormone replacement and to detect the development of associated conditions that may be related to the original pathogenic mechanism that led to the disruption of the menstrual cycle.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Vaishali Popat, MD, MPH  Clinical Investigator, Intramural Research Program on Reproductive and Adult Endocrinology, National Institutes of Child Health and Human Development, National Institutes of Health

Vaishali Popat, MD, MPH is a member of the following medical societies: American College of Physicians and Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Shannon D Sullivan, MD, PhD  Staff Physician, Department of Endocrinology, Washington Hospital Center

Shannon D Sullivan, MD, PhD is a member of the following medical societies: American Medical Association, American Thyroid Association, Endocrine Society, and Society for the Study of Reproduction

Disclosure: Nothing to disclose.

Suzanne R Trupin, MD, FACOG  Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center

Suzanne R Trupin, MD, FACOG is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, Association of Reproductive Health Professionals, International Society for Clinical Densitometry, and North American Menopause Society

Disclosure: Nothing to disclose.

Lawrence M Nelson, MD, MBA  Head of Integrative Reproductive Medicine Group, Intramural Research Program on Reproductive and Adult Endocrinology, National Institutes of Child Health and Human Development, National Institutes of Health

Lawrence M Nelson, MD, MBA is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Endocrine Society, and Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Elizabeth Alderman, MD  Director of Fellowship Training Program, Director, Adolescent Ambulatory Service, Professor, Clinical Pediatrics, Department of Pediatrics, Division of Adolescent Medicine, Albert Einstein College of Medicine and Children's Hospital at Montefiore

Elizabeth Alderman, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, North American Society for Pediatric and Adolescent Gynecology, and Society for Adolescent Medicine

Disclosure: Merck Honoraria Speaking and teaching

Wayne Wolfram, MD, MPH  Associate Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center

Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Kenneth M Bielak, MD  Clinic Director of Family Practice Center, Associate Professor, Department of Family Medicine, University of Tennessee Health Science Center College of Medicine

Kenneth M Bielak, MD is a member of the following medical societies: American Academy of Family Physicians, American College of Sports Medicine, American Medical Association, and American Medical Society for Sports Medicine

Disclosure: Nothing to disclose.

Tamara Prodanov, MD  Research Assistant, National Institutes of Child Health and Human Development, National Institutes of Health

Disclosure: Nothing to disclose.

Sharon N Covington, LCSW-C, BCD  Clinical Assistant Professor, Department of Obstetrics and Gynecology, Georgetown University School of Medicine; Associate Investigator, Integrative Reproductive Medicine Unit, Reproductive Biology and Medicine Branch, National Institutes of Child Health and Human Development, National Institutes of Health; Private Practice, Covington and Hafkin and Associates; Director of Psychological Support Services, Shady Grove Fertility Reproductive Science Center

Sharon N Covington, LCSW-C, BCD is a member of the following medical societies: Academy of Certified Social Workers, American Orthopsychiatric Association, American Society for Reproductive Medicine, National Association of Social Workers, and Society for Assisted Reproductive Technologies

Disclosure: Nothing to disclose.

Karim Anton Calis, PharmD, MPH, FASHP, FCCP  Adjunct Clinical Investigator, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Clinical Professor, Medical College of Virginia, Virginia Commonwealth University School of Pharmacy; Clinical Professor, University of Maryland School of Pharmacy

Karim Anton Calis, PharmD, MPH, FASHP, FCCP is a member of the following medical societies: American College of Clinical Pharmacy, American Society of Health-System Pharmacists, and Endocrine Society

Disclosure: Nothing to disclose.

Gayla S Harris, MD  Associate Professor, Department of Obstetrics and Gynecology, University of Tennessee Medical Center

Gayla S Harris, MD is a member of the following medical societies: American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Thomas Michael Price, MD  Associate Professor of Reproductive Endocrinology, Director of Reproductive Fellowship Training Program, Duke University Medical Center

Thomas Michael Price, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Phi Beta Kappa, and Society for Gynecologic Investigation

Disclosure: Clinical Advisors Group Consulting fee Consulting; MEDA Corp Consulting Consulting fee Consulting; Gerson Lehrman Group Advisor Consulting fee Consulting; Roche/GSK Spokesperson Consulting fee Consulting; Adiana Grant/research funds PI

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

A David Barnes, MD, PhD, MPH, FACOG  Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association

Disclosure: Nothing to disclose.

Andrea L Zuckerman, MD  Assistant Professor of Obstetrics/Gynecology and Pediatrics, Tufts University School of Medicine; Division Director, Pediatric and Adolescent Gynecology, Tufts Medical Center

Andrea L Zuckerman, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, North American Society for Pediatric and Adolescent Gynecology, and Society for Adolescent Medicine

Disclosure: Nothing to disclose.

Chief Editor

Bryan D Cowan, MD,†  Former Professor and Chairman, Department of Obstetrics and Gynecology, University of Mississippi College of Medicine; Former Consulting Staff, Department of Obstetrics and Gynecology, Veterans Affairs Medical Center; Former Medical Director, Wiser Hospital for Women, University of Mississippi Medical Center

Bryan D Cowan, MD,† is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Gynecological and Obstetrical Society, American Medical Association, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Endocrine Society, Sigma Xi, Society for Assisted Reproductive Technologies, Society for Gynecologic Investigation, Society for the Study of Reproduction, and Society of Laparoendoscopic Surgeons

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Somya Verma, MD, to the development and writing of a source article.

References

  1. Current evaluation of amenorrhea. Fertil Steril. Sep 2004;82 Suppl 1:S33-9. [Medline].

  2. Pletcher JR, Slap GB. Menstrual disorders. Amenorrhea. Pediatr Clin North Am. Jun 1999;46(3):505-18. [Medline].

  3. Greenspan FSFS1GDG. Basic & clinical endocrinology. 7th ed. McGraw-Hill; 2001.

  4. Santoro N, Filicori M, Crowley WF Jr. Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone. Endocr Rev. Feb 1986;7(1):11-23. [Medline].

  5. Current evaluation of amenorrhea. Fertil Steril. Sep 2004;82 Suppl 1:S33-9. [Medline].

  6. De Souza MJ, Toombs RJ, Scheid JL, O'Donnell E, West SL, Williams NI. High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Hum Reprod. Nov 26 2009;[Medline].

  7. Miller KK, Grinspoon SK, Ciampa J, et al. Medical findings in outpatients with anorexia nervosa. Arch Intern Med. Mar 14 2005;165(5):561-6. [Medline].

  8. Kawano Y, Kamihigashi S, Nakamura S, et al. Delayed puberty associated with hyperprolactinemia caused by pituitary microadenoma. Arch Gynecol Obstet. Sep 2000;264(2):90-2. [Medline].

  9. Crosignani PG. Current treatment issues in female hyperprolactinaemia. Eur J Obstet Gynecol Reprod Biol. Apr 1 2006;125(2):152-64. [Medline].

  10. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. Apr 1986;67(4):604-6. [Medline].

  11. Sherman SL. Premature ovarian failure among fragile X premutation carriers: parent-of-origin effect?. Am J Hum Genet. Jul 2000;67(1):11-3. [Medline].

  12. Bakalov VK, Vanderhoof VH, Bondy CA, Nelson LM. Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure. Hum Reprod. Aug 2002;17(8):2096-100. [Medline].

  13. Morcel K, Camborieux L, , Guerrier D. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet J Rare Dis. 2007;2:13. [Medline].

  14. Huhtaniemi I, Alevizaki M. Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab. Dec 2006;20(4):561-76. [Medline].

  15. Jones ME, Boon WC, McInnes K, Maffei L, Carani C, Simpson ER. Recognizing rare disorders: aromatase deficiency. Nat Clin Pract Endocrinol Metab. May 2007;3(5):414-21. [Medline].

  16. Reindollar RH, Tho SPT, McDonough PG. Delayed Puberty: an updated study of 326 patients. Transactions of the Gynecological and Obstetrical Society. 1989;8:146-62.

  17. Current evaluation of amenorrhea. Fertil Steril. Nov 2006;86(5 Suppl 1):S148-55. [Medline].

  18. Professional Guide to Diseases (Professional Guide Series). 8th ed. Lippincott Williams & Wilkins; 2005.

  19. Pandey S, Bhattacharya S. Impact of obesity on gynecology. Womens Health (Lond Engl). Jan 2010;6(1):107-17. [Medline].

  20. Phillips KP, Foster WG. Key developments in endocrine disrupter research and human health. J Toxicol Environ Health B Crit Rev. Mar 2008;11(3-4):322-44. [Medline].

  21. Adams Hillard PJ, Nelson LM. Adolescent girls, the menstrual cycle, and bone health. J Pediatr Endocrinol Metab. May 2003;16 Suppl 3:673-81. [Medline].

  22. Diaz A, Laufer MR, Breech LL. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. Nov 2006;118(5):2245-50. [Medline].

  23. Cartwright MM. Eating disorder emergencies: understanding the medical complexities of the hospitalized eating disordered patient. Crit Care Nurs Clin North Am. Dec 2004;16(4):515-30. [Medline].

  24. Eldar-Geva T, Hirsch HJ, Benarroch F, Rubinstein O, Gross-Tsur V. Hypogonadism in females with Prader-Willi syndrome from infancy to adulthood: variable combinations of a primary gonadal defect and hypothalamic dysfunction. Eur J Endocrinol. Feb 2010;162(2):377-84. [Medline].

  25. Blüher S, Shah S, Mantzoros CS. Leptin deficiency: clinical implications and opportunities for therapeutic interventions. J Investig Med. Oct 2009;57(7):784-8. [Medline].

  26. Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. Sep 2 2004;351(10):987-97. [Medline].

  27. Jayasena CN, Nijher GM, Chaudhri OB, Murphy KG, Ranger A, Lim A, et al. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab. Nov 2009;94(11):4315-23. [Medline].

  28. Erb TM, Gerschultz K, Gold MA, Sanfilippo JS. Primary amenorrhea in a young adult with sickle cell disease: a case report and brief literature review on adolescent reproductive health and sickle cell disease. J Pediatr Adolesc Gynecol. Dec 2008;21(6):361-70. [Medline].

  29. Karabulut A, Balci Y, Demirlenk S, Semiz S. Gonadal dysfunction and pelvic sonographic findings in females with thalassaemia major. Gynecol Endocrinol. Apr 2010;26(4):307-10. [Medline].

  30. Livshits A, Seidman DS. Fertility issues in women with diabetes. Womens Health (Lond Engl). Nov 2009;5(6):701-7. [Medline].

  31. Bauer J, Cooper-Mahkorn D. Reproductive dysfunction in women with epilepsy: menstrual cycle abnormalities, fertility, and polycystic ovary syndrome. Int Rev Neurobiol. 2008;83:135-55. [Medline].

  32. Weisinger JR, Gonzalez L, Alvarez H, Hernandez E, Carlini RG, Capriles F, et al. Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women. Kidney Int. Jul 2000;58(1):331-5. [Medline].

  33. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. Jan 2004;19(1):41-7. [Medline].

  34. Wang JG, Lobo RA. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome. J Clin Endocrinol Metab. Apr 2008;93(4):1394-7. [Medline].

  35. Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol (Oxf). Apr 2008;68(4):499-509. [Medline].

  36. Chitrit Y, Zafy S, Pelage JP, Ledref O, Khoury R, Caubel P. Amenorrhea due to partial uterine necrosis after uterine artery embolization for control of refractory postpartum hemorrhage. Eur J Obstet Gynecol Reprod Biol. Jul 2006;127(1):140-2. [Medline].

  37. Iglesias EA, Coupey SM. Menstrual cycle abnormalities: diagnosis and management. Adolesc Med. Jun 1999;10(2):255-73. [Medline].

  38. Aloi JA. Evaluation of amenorrhea. Compr Ther. Oct 1995;21(10):575-8. [Medline].

  39. Speroff L, Glass RH, Kase NG. Amenorrhea. In: Speroff L, Glass RH, Kase NG, eds. Clinical Gynecologic Endocrinology and Infertility. 6th ed. Baltimore, Md: Williams & Wilkins; 1999:422-85.

  40. Garner DM, Olmsted MP, Polivy J. Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia. Int J Eating Disorders. 1983;2:15-34.

  41. Thelen MH, Farmer J, Wonderlich S, Smith M. A revision of the bulimia test: the BULIT-R. Psychol Assess. 1991;3:119-24.

  42. Marozzi A, Vegetti W, Manfredini E, Tibiletti MG, Testa G, Crosignani PG, et al. Association between idiopathic premature ovarian failure and fragile X premutation. Hum Reprod. Jan 2000;15(1):197-202. [Medline].

  43. Sharma ST, Nestler JE. Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. Best Pract Res Clin Endocrinol Metab. Jun 2006;20(2):245-60. [Medline].

  44. Nestler JE, Stovall D, Akhter N, Iuorno MJ, Jakubowicz DJ. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril. Feb 2002;77(2):209-15. [Medline].

  45. Teede HJ, Meyer C, Norman RJ. Insulin-sensitisers in the treatment of polycystic ovary syndrome. Expert Opin Pharmacother. Nov 2005;6(14):2419-27. [Medline].

  46. Norman RJ, Homan G, Moran L, Noakes M. Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome. Endocrine. Aug 2006;30(1):35-43. [Medline].

  47. Kreipe RE, Yussman SM. The role of the primary care practitioner in the treatment of eating disorders. Adolesc Med. Feb 2003;14(1):133-47. [Medline].

  48. Golden NH, Jacobson MS, Schebendach J, Solanto MV, Hertz SM, Shenker IR. Resumption of menses in anorexia nervosa. Arch Pediatr Adolesc Med. Jan 1997;151(1):16-21. [Medline].

  49. Jacoangeli F, Masala S, Staar Mezzasalma F, Fiori R, Martinetti A, Ficoneri C, et al. Amenorrhea after weight recover in anorexia nervosa: role of body composition and endocrine abnormalities. Eat Weight Disord. Mar 2006;11(1):e20-6. [Medline].

  50. Brambilla F, Monteleone P, Bortolotti F, Dalle Grave R, Todisco P, Favaro A, et al. Persistent amenorrhoea in weight-recovered anorexics: psychological and biological aspects. Psychiatry Res. Jun 15 2003;118(3):249-57. [Medline].

  51. Grinspoon S, Miller K, Coyle C, Krempin J, Armstrong C, Pitts S, et al. Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea. J Clin Endocrinol Metab. Jun 1999;84(6):2049-55. [Medline].

  52. Miller KK, Lee EE, Lawson EA, Misra M, Minihan J, Grinspoon SK, et al. Determinants of skeletal loss and recovery in anorexia nervosa. J Clin Endocrinol Metab. Aug 2006;91(8):2931-7. [Medline].

  53. Hartard M, Kleinmond C, Kirchbichler A, Jeschke D, Wiseman M, Weissenbacher ER, et al. Age at first oral contraceptive use as a major determinant of vertebral bone mass in female endurance athletes. Bone. Oct 2004;35(4):836-41. [Medline].

  54. Rickenlund A, Eriksson MJ, Schenck-Gustafsson K, Hirschberg AL. Oral contraceptives improve endothelial function in amenorrheic athletes. J Clin Endocrinol Metab. Jun 2005;90(6):3162-7. [Medline].

  55. Gidwani GP. Amenorrhea in the athlete. Adolesc Med. Jun 1999;10(2):275-90, vii. [Medline].

  56. Warren MP, Fried JL. Hypothalamic amenorrhea. The effects of environmental stresses on the reproductive system: a central effect of the central nervous system. Endocrinol Metab Clin North Am. Sep 2001;30(3):611-29. [Medline].

  57. Falsetti L, Gambera A, Barbetti L, Specchia C. Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors. J Clin Endocrinol Metab. Feb 2002;87(2):500-5. [Medline].

  58. Manuel M, Katayama PK, Jones HW Jr. The age of occurrence of gonadal tumors in intersex patients with a Y chromosome. Am J Obstet Gynecol. Feb 1 1976;124(3):293-300. [Medline].

  59. Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. Jan 2007;92(1):10-25. [Medline].

  60. Adhikary AK, Banik U, Numaga J, Suzuki E, Inada T, Okabe N. Heterogeneity of the fibre sequence in subgenus C adenoviruses. J Clin Pathol. Jun 2004;57(6):612-7. [Medline]. [Full Text].

  61. Laml T, Preyer O, Umek W, Hengstschlager M, Hanzal H. Genetic disorders in premature ovarian failure. Hum Reprod Update. Sep-Oct 2002;8(5):483-91. [Medline].

  62. Bakalov VK, Anasti JN, Calis KA, Vanderhoof VH, Premkumar A, Chen S, et al. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril. Oct 2005;84(4):958-65. [Medline].

  63. Davis SR. Premature ovarian failure. Maturitas. Feb 1996;23(1):1-8. [Medline].

  64. DiPiro JT TRYG. Hormone therapy in women. Pharmacotherapy. In: A Pathophysiologic Approach. 6th ed. New York: McGraw-Hill; 2005:1493-513.

  65. Davis SR. The therapeutic use of androgens in women. J Steroid Biochem Mol Biol. Apr-Jun 1999;69(1-6):177-84. [Medline].

  66. Arnhold IJ, Lofrano-Porto A, Latronico AC. Inactivating mutations of luteinizing hormone beta-subunit or luteinizing hormone receptor cause oligo-amenorrhea and infertility in women. Horm Res. 2009;71(2):75-82. [Medline].

  67. Capito C, Leclair MD, Arnaud A, David A, Baron S, Corradini N, et al. 46,XY pure gonadal dysgenesis: clinical presentations and management of the tumor risk. J Pediatr Urol. Feb 2011;7(1):72-5. [Medline].

  68. Fedele L, Bianchi S, Frontino G, Ciappina N, Fontana E, Borruto F. Laparoscopic findings and pelvic anatomy in Mayer-Rokitansky-Küster-Hauser syndrome. Obstet Gynecol. May 2007;109(5):1111-5. [Medline].

  69. [Guideline] Identifying and treating eating disorders. Pediatrics. Jan 2003;111(1):204-11. [Medline].

  70. Quintos JB, Krotz S, Vogiatzi MG, Kralickova M, New MI. Partial hypogonadotropic hypogonadism associated with the Leu266Arg and Gln106Arg mutation of the gonadotropin-releasing hormone receptor. J Pediatr Endocrinol Metab. Feb 2009;22(2):181-5. [Medline].

  71. The Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. Feb 7 1996;275(5):370-5. [Medline].

 
Previous
Next
 
Hypothalamus, pituitary and ovaries form a functional endocrine axis, known as HPO axis with hormonal regulations and feedback loops.
Primary amenorrhea flowchart.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.