Amenorrhea Clinical Presentation

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

History

An adequate history includes childhood growth and development and other areas, including height and weight charts and age at thelarche and menarche. Ascertaining the age at menarche of the patient's mother and sisters is advisable because the age at menarche in family members can occur within a year of the age in others. The duration and flow of menses, cycle days, day and date of last menstrual period, presence or absence of molimina (breast soreness and mood change immediately before menses) are necessary pieces of information.

Any history of chronic illness, trauma, surgery, and medications is also important. A sexual history should be obtained in a confidential manner. Information regarding substance use, exercise, diet, home and school situations, and psychosocial issues should be elicited. A comprehensive review of symptoms should include vasomotor symptoms, hot flashes, virilizing changes, galactorrhea, headache, fatigue, palpitations, nervousness, hearing loss, and visual changes.

Primary amenorrhea

Assessment of the adolescent patient requires a sensitive, age-appropriate approach. Clinicians need to consider the psychosocial age and emotional maturity of the patient, rather than simply the chronological age, when examining the adolescent. The physician should find out how much the patient knows by asking her about her understanding of why she is being seen and what she has been told. The subsequent step is to find out how much the patient wants to know by asking about her concerns and letting questions emerge.

Absence of spontaneous menstruation before age 16 years is an indication for a careful review of systems. The menstrual cycle should be viewed as a vital sign. Inquiring about other aspects of growth and pubertal development is important. An absence of any breast development or pubertal growth spurt by age 13-14 years in girls is distinctly abnormal and requires investigation.

Breast development, pubertal growth spurt, and adrenarche are delayed or absent in girls with hypothalamic pituitary failure. A distinguishing factor in the case of isolated ovarian insufficiency or failure is that adrenarche occurs normally, while estrogen-dependent breast development and the pubertal growth spurt are absent or delayed.

Pregnancy could be the cause for primary amenorrhea. Determining whether the patient is sexually active and whether she is using contraceptive methods is important.

Secondary amenorrhea

Loss of menstrual regularity is an indication for a careful review of systems. The menstrual cycle should be viewed as a vital sign. Loss of menstrual regularity may be the first clear symptom heralding the onset of a major illness or systemic disease. Viewing the menstrual cycle as a vital sign may lead to earlier diagnosis of, and intervention for, several potentially life-threatening disorders. The clinician need not wait for an arbitrarily defined duration of amenorrhea to pass before taking corrective action.

Amenorrhea can be due to pregnancy, anatomic defects of the outflow tract, ovarian disorders, and pituitary or hypothalamic disorders. In some cases, the cause is functional, meaning that the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator has shut down the reproductive system in its role as an integrator of metabolic and psychogenic stress.

Attributing the loss of menstrual regularity to a recent stressful life event is tempting; however, this approach can delay the detection of significant pathology that can have long-term health consequences. One study has shown that one third of women in a control group report a significant stressful life event in the preceding year.

Pregnancy is the most common cause of amenorrhea. Determining whether the patient is sexually active and whether she is using contraceptive methods is important. In some cases, hormonal contraception itself may be the cause of the amenorrhea.

Taking a careful patient history is paramount in deciphering potential etiologies of secondary amenorrhea. Often, time constraints do not permit practitioners to obtain a thorough history and review of symptoms on the first visit. Scheduling a repeat visit to permit a more thorough evaluation may be necessary.

Another option is to use standardized history-taking instruments to collect this information in preparation for a return visit. In other cases, patients may be asked to keep a menstrual calendar and return in 3 months for reassessment. The importance of the ovary as an endocrine organ that helps maintain bone density should be stressed to the patient to help ensure proper follow-up.

Disorders of the outflow tract

A history of otherwise normal growth and pubertal development and cyclic pelvic pain in association with primary amenorrhea suggests the possibility of a congenital outflow tract abnormality such as imperforate hymen or agenesis of the vagina, cervix, or uterus. These findings are also compatible with the complete androgen resistance syndrome.

Prior history of a surgical procedure involving the endometrial cavity, especially if performed in the presence of infection, raises the possibility of uterine synechiae (Asherman syndrome).

Ovarian disorders

Symptoms of vaginal dryness, hot flashes, night sweats, or disordered sleep may be a sign of ovarian insufficiency or premature ovarian failure. The presence of these symptoms in young women demands further evaluation in a timely manner. A prior history of chemotherapy or radiation therapy may be associated with ovarian failure.

Autoimmune oophoritis may be associated with autoimmune adrenal insufficiency, a potentially fatal condition that often manifests as vague and nonspecific symptoms. Loss of menstrual regularity may be the first clear symptom indicating a need for further evaluation to detect this condition.

Hypothalamic/pituitary disorders

Associated galactorrhea, headaches, or reduced peripheral vision could be a sign of an anterior pituitary adenoma. These symptoms require immediate further evaluation. However, secondary amenorrhea may be the only overt symptom of a small prolactinoma.

An impaired sense of smell in association with primary amenorrhea and failure of normal pubertal development may be related to isolated gonadotropin deficiency, as is observed in persons with Kallmann syndrome.

Neurosarcoidosis can infiltrate the hypothalamus and/or pituitary and cause hypogonadotropic hypogonadism, leading to disrupted menses. Sarcoidosis can manifest insidiously, with development of mild fatigue, malaise, anorexia, weight loss, and fever. Because 90% of patients with sarcoidosis have pulmonary involvement at some stage of the disorder, cough and dyspnea may be present.

Hemachromatosis may manifest as weakness, lassitude, weight loss, and a change in skin color.

A history of hemorrhage after childbirth with subsequent failure of regular menses to return may be an indication of postpartum pituitary necrosis (Sheehan syndrome). Failure of lactation is an even earlier sign. Detecting this condition early is important because of the possible development of associated central adrenal insufficiency, a potentially fatal condition.

Functional hypothalamic impairment

Dieting with excessive restriction of energy intake, especially fat restriction, may lead to amenorrhea and associated bone loss. In extreme cases, the process may advance to anorexia nervosa, a potentially fatal condition. Associated symptoms are an intense fear of fatness and a body image that is heavier than observed. Eating disorders can be restrictive in nature or can be of a binge-eating/purging type.

Orthorexia is characterized by obsession with eating healthy or organic foods, often to the detriment of a patient’s health. This is currently classified as an “eating disorder not otherwise specified” in the DSM-IV-TR. Patients with orthorexia may also restrict specific nutrients and calories from their diet and develop amenorrhea and its long-term health consequences, namely, low bone mineral density.[23]

Major psychiatric disorders such as depression, obsessive-compulsive, or schizophrenia may cause amenorrhea. Symptoms associated with these conditions may be detected upon review of systems. In these cases, secondary amenorrhea may be due to the psychiatric disorder itself, as these are chronic disease states, or amenorrhea may be related to necessary medications, such as antipsychotic or antiepileptic drugs.

Autoimmune adrenal insufficiency, a potentially fatal condition, often manifests as vague and nonspecific symptoms. Amenorrhea may be the first clear symptom indicating a need for further evaluation to detect this condition.

Amenorrhea may herald the onset of other autoimmune endocrine disorders such as hyperthyroidism, hypothyroidism, or autoimmune lymphocytic hypophysitis. The same is true for other endocrine disorders such as Cushing syndrome or pheochromocytoma. A careful review of symptoms may help uncover these disorders.

Strenuous exercise related to a wide variety of athletic activities can be associated with the development of amenorrhea. Elicit a history regarding the type of exercise activity and its duration per week.

Both extreme thinness or rapid weight loss and morbid obesity or rapid weight gain may result in amenorrhea by altering pulsatile GnRH release.

History of excessive food intake may be due to Prader-Wili syndrome[24] or leptin deficiency,[25] both of which cause both extreme obesity and amenorrhea.

Women with hypothalamic amenorrhea have lower serum leptin concentrations, which may contribute to their low gonadotropin secretion. Leptin administration resulted in improvement of the reproductive axis in one study of women with functional hypothalamic amenorrhea.[26]

Kisspeptin, a neural signal that acts directly on GnRH neurons to stimulate neuronal firing, and which may act downstream from leptin as an integrator of metabolic cues to the GnRH pulse generator, is also downregulated in cases of hypothalamic amenorrhea. Interestingly, exogenous administration of kisspeptin to women with hypothalamic amenorrhea acutely stimulates gonadotropin secretion, an effect similar to what is seen with leptin administration.[27]

Drugs

When taking the medication history, consider the following:

  • Abuse of drugs such as cocaine and opioids have central effects that may disrupt the menstrual cycle
  • Use of antiepileptics is associated with amenorrhea
  • Use of birth control pills or other hormonal therapies may be associated with disordered menses

Chronic diseases

Malnutrition and cirrhosis associated with alcoholism may cause loss of menstrual regularity. AIDS, HIV disease, or other types of immune-deficiency states may induce systemic infection, lipodystrophy, or other chronic health complications, leading to loss of menstrual regularity.

Occult malignancy with progressive weight loss and a catabolic state may lead to loss of menstrual regularity. A careful review of systems may help uncover such a disorder.

Sickle cell disease[28] and thalassemia[29] are associated with amenorrhea.

Type 1 and type 2 diabetes may both be associated with disordered menses.[30]

Epilepsy itself, as well as antiepileptic medications, are associated with reproductive dysfunction in women. The etiology of menstrual cycle abnormalities in epileptic females may vary and includes polycystic ovarian syndrome (PCOS), hypothalamic amenorrhea, and hyperprolactinemia.[31]

Chronic kidney disease requiring hemodialysis is associated with loss of menstrual cyclicity and vitamin D deficiency, putting patients at high risk of bone mineral density loss.[32]

Next

Physical Examination

In the case of primary amenorrhea, before physical examination, the clinician should engage the adolescent in a discussion to assess her emotional maturity and establish a relationship. As questions emerge, the clinician should share age-appropriate information about the condition, giving the opportunity to respond to the patient’s emotions. After careful preparation and with privacy, the physical and pelvic examination should come later in the assessment

General physical examination

A general physical examination may identify features of many of the disorders that underlie amenorrhea. In addition, it may uncover unexpected findings that are indirectly related to the loss of menstrual regularity (eg, discovery of hepatosplenomegaly, which may lead to detection of a chronic systemic disease).

Physical examination should begin with an overall assessment of sexual development, nutritional status, and general health. Measure height and weight and seek evidence for chronic disease, cachexia, or obesity.

In anorexia nervosa, hypothermia, bradycardia, hypotension, and reduced subcutaneous fat may be observed. Other findings include yellow skin (carotenemia) and a body mass index (BMI) of less than 18 kg/m2. In cases of frequent vomiting, look for possible dental erosion, reduced gag reflex, trauma to the palate, subconjunctival hemorrhage, and metacarpophalangeal calluses or bruises.

Examine the skin for evidence of androgen excess, such as hirsutism, hair loss, and acne. Acanthosis nigricans may be present in association with androgen excess related to insulin resistance (eg, diabetes, polycystic ovarian syndrome (PCOS). A BMI of more than 30 kg/m2 is common.

Examine for stigmata of Turner syndrome (short stature, webbed neck, low-set hairline and/or ears, pubertal delay, cubitus valgus, nail hypoplasia, short fourth metacarpal, high-arched palate, chronic otitis media, cardiac abnormalities).

Skin examination findings can also give clues to other endocrine disorders. Vitiligo or increased pigmentation of the palmar creases may herald primary adrenal insufficiency. Thin, parchmentlike skin, wide purplish striae, and evidence of easy bruising may be signs of Cushing syndrome. Warm, moist skin radiating excessive heat may be a sign of hyperthyroidism.

Large pituitary tumors can cause visual-field cuts by impinging on the optic tract. In some cases, these visual-field cuts can be detected by simple confrontational testing.

Examine for the presence of axillary and pubic hair. These are a marker of adrenal and ovarian androgen secretion. In cases of panhypopituitarism, sources of androgen are low and pubic and axillary hair is sparse.

Also, some women develop the combination of autoimmune premature ovarian failure and autoimmune primary adrenal insufficiency. These women are also markedly androgen deficient and have scant axillary and pubic hair. The same is true for persons with androgen insensitivity syndrome (testicular feminization), 17-hydroxylase deficiency, and 17,20-desmolase deficiency.

Breast examination

Assess the state of breast development. Delayed puberty results in underdeveloped breasts with sparse pubic hair, whereas gonadal dysgenesis (eg, Turner syndrome) results in undeveloped breasts with normal growth of pubic hair.

Also examine the breasts for galactorrhea. In some cases, breast discharge can be expressed, yet the condition is not true galactorrhea. If the discharge is indeed milk, this can be confirmed by finding fat globules in the fluid using low-power microscopy.

Pelvic examination

In cases of primary amenorrhea with otherwise normal pubertal development, pelvic examination may help detect imperforate hymen, a transverse vaginal septum, or cervical or uterine aplasia. If the uterus is enlarged, pregnancy must be excluded.

Pelvic examination findings can provide physical evidence indicating the adequacy of estrogen production. Thin and pale vaginal mucosa with absent rugae is evidence of estrogen deficiency.

The presence of cervical mucus with spinnbarkeit is good evidence of estrogen effect. However, evidence of estrogen effect detected on physical examination findings can be misleading in some cases because estrogen is being produced as a result of higher-than-normal follicle-stimulating hormone (FSH) levels (compensated ovarian insufficiency). Women with well-established premature ovarian failure often have intermittent ovarian follicle function that produces enough estrogen to have vaginal and cervical effects.

Measuring the clitoris is an effective method for determining the degree of androgen effect. The clitoral index is the product of the sagittal and transverse diameters of the glans of the clitoris in the anteroposterior and transverse diameter. A clitoral index greater than 35 mm2 is evidence of increased androgen effect. A clitoral index greater than 100 mm2 is evidence of virilization.

Ovarian enlargement may be found upon pelvic examination in cases of autoimmune oophoritis, 17-hydroxylase deficiency, or 17,20-desmolase deficiency. In these disorders, inadequate negative feedback supplied by the ovary permits excessive gonadotropin stimulation that may cause ovarian enlargement with multiple follicular cysts. In some cases, these disorders manifest with an acute onset of pain related to ovarian torsion.

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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].

 
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Hypothalamus, pituitary and ovaries form a functional endocrine axis, known as HPO axis with hormonal regulations and feedback loops.
Primary amenorrhea flowchart.
 
 
 
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