What should be included in the differential diagnoses of amenorrhea with normal puberty?

Answer

Amenorrhea with normal puberty

Frequently, pubertal development occurs at a normal rate, but primary amenorrhea may occur and may be associated with hirsutism. These individuals are eugonadal. The most common cause in this setting is polycystic ovarian syndrome (PCOS), which is characterized by anovulation, oligo-ovulation, androgen excess (clinical or biochemical), ultrasonographic demonstration of increased ovarian stroma and accumulation of antral follicles (polycystic appearance), and obesity.^[43]

Ovarian hyperthecosis results in hyperandrogenicity, which is evident by signs of hirsutism, acne, and obesity and can be associated with type 2 diabetes mellitus and acanthosis nigricans. Hyperthecosis can also cause virilization, which manifests as clitoromegaly, temporal balding, and deepened voice change. See Polycystic Ovarian Syndrome for an in-depth discussion of this entity.

Another cause of hirsutism is the rare late-onset 21-hydroxylase deficiency, which is caused by mutations in the 21-hydroxylase gene that result in excessive 17-hydroxyprogesterone levels. This deficiency is also termed non classic congenital adrenal hyperplasia and can occur in 1-10% of women with hirsutism.

Rarely, patients with hypothalamic amenorrhea may have hyperandrogenic/polycystic ovaries. Wang et al explored the coexistence of these 2 disorders in women with hypothalamic amenorrhea/PCOS, and found that over time, these patients may fluctuate between symptoms of hypothalamic amenorrhea and polycystic ovarian syndrome, depending on the status of their hypothalamic activity.^[44]

Other causes of hyperandrogenism include Cushing disease, ovarian stromal hypertrophy, and androgen-producing tumors of the ovary and adrenal glands. Exogenous anabolic steroid use should be considered in the differential for hyperandrogenic amenorrhea.

Anovulation remains the most common cause of amenorrhea in the setting of nonvirilization. Anovulation is caused by dysfunction of the hypothalamic-pituitary-ovarian axis, which can be apparent after discontinuation of various hormonal contraception medications and can result in loss of menses for several months. It is often associated with a hypothalamic hypogonadotropic etiology.

Premature ovarian failure can be idiopathic, secondary to chemotherapy or radiation therapy, or autoimmune in origin. The idiopathic form occurs in 1% of women younger than 40 years.

Premature ovarian failure is more accurately termed primary ovarian insufficiency (POI) because women with spontaneous POI may have intermittent ovarian function, and, as a group, demonstrate a pregnancy rate of 5-10%.^[45](For an in-depth discussion, see Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure].)

Prodromal POI is a state of ovarian insufficiency in which FSH levels are elevated and menses are irregular but not to the degree required to make a diagnosis of overt POI. This is likely on a continuum with diminished ovarian reserve (a state in which women respond poorly to exogenous gonadotropin stimulation) and overt POI (a state of drastically reduced fertility).

Hyperprolactinemia is a pituitary cause of amenorrhea in the presence of normal puberty. Hyperprolactinemia can occur as a consequence of breastfeeding, microadenomas of the pituitary, and use of psychoactive medications (eg, haloperidol, phenothiazines, amitriptyline, benzodiazepines, cocaine, marijuana) and metoclopramide (Reglan).

Amenorrhea may be caused by thyroid disorders, including hyperthyroidism and hypothyroidism. Hypogonadotropic hypogonadism can occur from the same causes as delayed puberty. In addition, Sheehan syndrome, which results from panhypopituitarism after pituitary infarction from postpartum hemorrhage or shock, can manifest as pubertal amenorrhea.

Amenorrhea that results from genital tract anomalies can arise from the absence of reproductive organs. Mayer-Rokitansky-Hauser syndrome is an anomaly of the genital tract characterized by vaginal agenesis. The uterus is usually absent, and the vagina is foreshortened.

Because the ovaries function normally and produce E₂, breasts are normal in shape and contour. Pubarche is also normal in this patient population; therefore, pubic hair remains normal. Mayer-Rokitansky-Hauser syndrome accounts for 15% of primary amenorrhea cases and is second to Turner syndrome as the most common cause of primary amenorrhea.

Androgen insensitivity syndrome (previously termed testicular feminization) is present in 10% of patients with amenorrhea. Androgen insensitivity syndrome is caused by an abnormality of the androgen receptor. The gonads are testicles producing testosterone; however, testosterone has no effect because the androgen receptor is nonfunctional.

The phenotypic appearance in patients with this condition is female, but the circulating hormonal pattern is male. Androgen insensitivity syndrome is a maternal X-linked recessive disease in which the testes remain intra-abdominal or partially descended, and pubic hair is sparse.

Spontaneous testicular regression is a rare disorder of genetic males that results in a female phenotype with an absent uterus. In addition, certain enzyme deficiencies affecting androgen production can result in male pseudohermaphrodites. All disorders that are pheno typically female but chromosomally male (XY) require that the gonads be removed to avert cancerous changes.

Primary amenorrhea can result from an imperforate hymen, which presents as a boggy uterus and cyclic abdominal pain. Asherman syndrome occurs after an overzealous curettage of the endometrial lining, which results in adhesions or synechiae that prevent the endometrium from responding to estradiol. The diagnosis is suggested by absence of endometrial stripe on uterine ultrasonography and confirmed by hysteroscopy evaluation or by absence of bleeding after cyclic therapy with estrogen and later progestin for several weeks.

A case report has been published of a woman in whom persistent secondary amenorrhea developed due to intrauterine adhesions after selective embolization of the uterine arteries for control of refractory primary postpartum hemorrhage. Adverse effects of these new lifesaving technologies remain to be evaluated long term.^[46]

Clinically significant infections that destroy the endometrial lining can also result in primary or secondary amenorrhea.

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Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril. 2004 Sep. 82(Suppl 1):S33-9. [Medline].
Pletcher JR, Slap GB. Menstrual disorders. Amenorrhea. Pediatr Clin North Am. 1999 Jun. 46(3):505-18. [Medline].
Gardner DG, Shoback D, eds. Greenspan's Basic and Clinical Endocrinology. 9th ed. New York: McGraw-Hill; 2011.
Santoro N, Filicori M, Crowley WF Jr. Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone. Endocr Rev. 1986 Feb. 7(1):11-23. [Medline].
Current evaluation of amenorrhea. Fertil Steril. 2004 Sep. 82 Suppl 1:S33-9. [Medline].
Trarbach EB, Baptista MT, Garmes HM, Hackel C. Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients. J Endocrinol. 2005 Dec. 187(3):361-8. [Medline].
Dodé C, Rondard P. PROK2/PROKR2 Signaling and Kallmann Syndrome. Front Endocrinol (Lausanne). 2013. 4:19. [Medline]. [Full Text].
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. 2009 Nov 26. [Medline].
Committee on Adolescent Health Care. Committee Opinion No.702: Female Athlete Triad. Obstet Gynecol. 2017 Jun. 129 (6):e160-e167. [Medline].
Miller KK, Grinspoon SK, Ciampa J, et al. Medical findings in outpatients with anorexia nervosa. Arch Intern Med. 2005 Mar 14. 165(5):561-6. [Medline].
Kawano Y, Kamihigashi S, Nakamura S, et al. Delayed puberty associated with hyperprolactinemia caused by pituitary microadenoma. Arch Gynecol Obstet. 2000 Sep. 264(2):90-2. [Medline].
Crosignani PG. Current treatment issues in female hyperprolactinaemia. Eur J Obstet Gynecol Reprod Biol. 2006 Apr 1. 125(2):152-64. [Medline].
Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986 Apr. 67(4):604-6. [Medline].
Sherman SL. Premature ovarian failure among fragile X premutation carriers: parent-of-origin effect?. Am J Hum Genet. 2000 Jul. 67(1):11-3. [Medline].
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. 2002 Aug. 17(8):2096-100. [Medline].
Morcel K, Camborieux L, , Guerrier D. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet J Rare Dis. 2007. 2:13. [Medline].
Hughes IA, Deeb A. Androgen resistance. Best Pract Res Clin Endocrinol Metab. 2006 Dec. 20(4):577-98. [Medline].
Huhtaniemi I, Alevizaki M. Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab. 2006 Dec. 20(4):561-76. [Medline].
Jones ME, Boon WC, McInnes K, Maffei L, Carani C, Simpson ER. Recognizing rare disorders: aromatase deficiency. Nat Clin Pract Endocrinol Metab. 2007 May. 3(5):414-21. [Medline].
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.
Current evaluation of amenorrhea. Fertil Steril. 2006 Nov. 86(5 Suppl 1):S148-55. [Medline].
Professional Guide to Diseases (Professional Guide Series). 8th ed. Lippincott Williams & Wilkins; 2005.
Pandey S, Bhattacharya S. Impact of obesity on gynecology. Womens Health (Lond Engl). 2010 Jan. 6(1):107-17. [Medline].
Phillips KP, Foster WG. Key developments in endocrine disrupter research and human health. J Toxicol Environ Health B Crit Rev. 2008 Mar. 11(3-4):322-44. [Medline].
Adams Hillard PJ, Nelson LM. Adolescent girls, the menstrual cycle, and bone health. J Pediatr Endocrinol Metab. 2003 May. 16 Suppl 3:673-81. [Medline].
Diaz A, Laufer MR, Breech LL. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006 Nov. 118(5):2245-50. [Medline].
Moran L, Teede H. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum Reprod Update. 2009 Jul-Aug. 15(4):477-88. [Medline].
Iatrakis G, Zervoudis S, Saviolakis A, et al. Women younger than 50 years with endometrial cancer. Eur J Gynaecol Oncol. 2006. 27(4):399-400. [Medline].
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan. 81(1):19-25. [Medline].
Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb. 91(2):456-88. [Medline].
Cartwright MM. Eating disorder emergencies: understanding the medical complexities of the hospitalized eating disordered patient. Crit Care Nurs Clin North Am. 2004 Dec. 16(4):515-30. [Medline].
Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003 May 31. 361(9372):1881-93. [Medline].
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. 2010 Feb. 162(2):377-84. [Medline].
Blüher S, Shah S, Mantzoros CS. Leptin deficiency: clinical implications and opportunities for therapeutic interventions. J Investig Med. 2009 Oct. 57(7):784-8. [Medline].
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. 2004 Sep 2. 351(10):987-97. [Medline].
Kyriakidis M, Caetano L, Anastasiadou N, Karasu T, Lashen H. Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice - systematic review. Eur J Obstet Gynecol Reprod Biol. 2016 Mar. 198:131-7. [Medline].
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. 2009 Nov. 94(11):4315-23. [Medline].
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. 2008 Dec. 21(6):361-70. [Medline].
Karabulut A, Balci Y, Demirlenk S, Semiz S. Gonadal dysfunction and pelvic sonographic findings in females with thalassaemia major. Gynecol Endocrinol. 2010 Apr. 26(4):307-10. [Medline].
Livshits A, Seidman DS. Fertility issues in women with diabetes. Womens Health (Lond Engl). 2009 Nov. 5(6):701-7. [Medline].
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].
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. 2000 Jul. 58(1):331-5. [Medline].
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan. 19(1):41-7. [Medline].
Wang JG, Lobo RA. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 Apr. 93(4):1394-7. [Medline].
Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol (Oxf). 2008 Apr. 68(4):499-509. [Medline].
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. 2006 Jul. 127(1):140-2. [Medline].
Iglesias EA, Coupey SM. Menstrual cycle abnormalities: diagnosis and management. Adolesc Med. 1999 Jun. 10(2):255-73. [Medline].
Aloi JA. Evaluation of amenorrhea. Compr Ther. 1995 Oct. 21(10):575-8. [Medline].
Speroff L, Glass RH, Kase NG. Amenorrhea. Speroff L, Glass RH, Kase NG, eds. Clinical Gynecologic Endocrinology and Infertility. 6th ed. Baltimore, Md: Williams & Wilkins; 1999. 422-85.
Iliodromiti S, Kelsey TW, Anderson RA, et al. Can anti-Mullerian hormone predict the diagnosis of polycystic ovary syndrome? A systematic review and meta-analysis of extracted data. J Clin Endocrinol Metab. 2013 Aug. 98(8):3332-40. [Medline].
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.
Thelen MH, Farmer J, Wonderlich S, Smith M. A revision of the bulimia test: the BULIT-R. Psychol Assess. 1991. 3:119-24.
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. 2000 Jan. 15(1):197-202. [Medline].
Sharma ST, Nestler JE. Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. Best Pract Res Clin Endocrinol Metab. 2006 Jun. 20(2):245-60. [Medline].
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. 2002 Feb. 77(2):209-15. [Medline].
Teede HJ, Meyer C, Norman RJ. Insulin-sensitisers in the treatment of polycystic ovary syndrome. Expert Opin Pharmacother. 2005 Nov. 6(14):2419-27. [Medline].
Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2012 May 16. 5:CD003053. [Medline].
Norman RJ, Homan G, Moran L, Noakes M. Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome. Endocrine. 2006 Aug. 30(1):35-43. [Medline].
Kreipe RE, Yussman SM. The role of the primary care practitioner in the treatment of eating disorders. Adolesc Med. 2003 Feb. 14(1):133-47. [Medline].
Golden NH, Jacobson MS, Schebendach J, Solanto MV, Hertz SM, Shenker IR. Resumption of menses in anorexia nervosa. Arch Pediatr Adolesc Med. 1997 Jan. 151(1):16-21. [Medline].
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. 2006 Mar. 11(1):e20-6. [Medline].
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. 2003 Jun 15. 118(3):249-57. [Medline].
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. 1999 Jun. 84(6):2049-55. [Medline].
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. 2006 Aug. 91(8):2931-7. [Medline].
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. 2004 Oct. 35(4):836-41. [Medline].
Rickenlund A, Eriksson MJ, Schenck-Gustafsson K, Hirschberg AL. Oral contraceptives improve endothelial function in amenorrheic athletes. J Clin Endocrinol Metab. 2005 Jun. 90(6):3162-7. [Medline].
Gidwani GP. Amenorrhea in the athlete. Adolesc Med. 1999 Jun. 10(2):275-90, vii. [Medline].
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. 2001 Sep. 30(3):611-29. [Medline].
Falsetti L, Gambera A, Barbetti L, Specchia C. Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors. J Clin Endocrinol Metab. 2002 Feb. 87(2):500-5. [Medline].
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. 1976 Feb 1. 124(3):293-300. [Medline].
Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007 Jan. 92(1):10-25. [Medline].
Adhikary AK, Banik U, Numaga J, Suzuki E, Inada T, Okabe N. Heterogeneity of the fibre sequence in subgenus C adenoviruses. J Clin Pathol. 2004 Jun. 57(6):612-7. [Medline]. [Full Text].
Laml T, Preyer O, Umek W, Hengstschlager M, Hanzal H. Genetic disorders in premature ovarian failure. Hum Reprod Update. 2002 Sep-Oct. 8(5):483-91. [Medline].
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. 2005 Oct. 84(4):958-65. [Medline].
Gordon CM, Ackerman KE, Berga SL, et al. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017. 102:1-27.
Frellick M. Endocrine Society Issues Hypothalamic Amenorrhea Guideline. Medscape Medical News. Available at http://www.medscape.com/viewarticle/877950. March 30, 2017; Accessed: March 31, 2017.
Davis SR. Premature ovarian failure. Maturitas. 1996 Feb. 23(1):1-8. [Medline].
DiPiro JT TRYG. Hormone therapy in women. Pharmacotherapy. A Pathophysiologic Approach. 6th ed. New York: McGraw-Hill; 2005. 1493-513.
Davis SR. The therapeutic use of androgens in women. J Steroid Biochem Mol Biol. 1999 Apr-Jun. 69(1-6):177-84. [Medline].
Albarel F, Gaudy C, Castinetti F, Carré T, Morange I, Conte-Devolx B, et al. Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. Eur J Endocrin. 2015 Feb. 172(2):195-204. [Medline]. [Full Text].
Carmina E, Fruzzetti F, Lobo RA. Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea. Am J Obstet Gynecol. 2016 Jan 6. [Medline].
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].
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. 2011 Feb. 7(1):72-5. [Medline].
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. 2007 May. 109(5):1111-5. [Medline].
[Guideline] Identifying and treating eating disorders. Pediatrics. 2003 Jan. 111(1):204-11. [Medline].
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. 2009 Feb. 22(2):181-5. [Medline].
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. 1996 Feb 7. 275(5):370-5. [Medline].
Lomniczi A, Ojeda SR. The Emerging Role of Epigenetics in the Regulation of Female Puberty. Endocrin Dev. 2015 Dec 17. 29:1-16:1-16. [Medline]. [Full Text].
Hamner M. The effects of atypical antipsychotics on serum prolactin levels. Ann Clinical Psychiatry. Sept 2002. 14(3):163-173. [Medline]. [Full Text].
Ackerman KE, Singhal V, Baskaran C, Slattery M, Campoverde Reyes KJ, Toth A, et al. Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial. Br J Sports Med. 2018 Oct 9. [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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Author

Kristi A Tough DeSapri, MD Clinical Assistant Professor of Obstetrics and Gynecology, Director of Comprehensive Bone Center, University of Chicago Medicine Women's Care

Kristi A Tough DeSapri, MD is a member of the following medical societies: American Society for Colposcopy and Cervical Pathology, North American Menopause Society

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Amgen and AMAG pharmaceuticals.

Chief Editor

Richard Scott Lucidi, MD, FACOG Associate Professor of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Kenneth M Bielak, MD 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 Society for Colposcopy and Cervical Pathology, American College of Sports Medicine, American Medical Society for Sports Medicine

Disclosure: Nothing to disclose.

Gayla S Harris, MD Associate Professor, Department of Obstetrics and Gynecology, University of Tennessee Health Science Center Graduate School of Medicine

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

Disclosure: Nothing to disclose.

Acknowledgements

Elizabeth Alderman, MD Director of Fellowship Training Program, Director of Adolescent Ambulatory Service, Professor of 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

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.

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.

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.

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.

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.

Thomas Michael Price, MD Associate Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Director of Reproductive Endocrinology and Infertility Fellowship 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 Medical Association, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Endocrine Society, Phi Beta Kappa, Society for Gynecologic Investigation, Society for Reproductive Endocrinology and Infertility, and South Carolina Medical Association

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

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

Disclosure: Nothing to disclose.

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 Association of Clinical Endocrinologists, American Thyroid Association, and Endocrine Society

Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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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

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Somya Verma, MD, Fellow in Pediatric Endocrinology, National Institutes of Child Health and Human Development; Officer of United States Public Health Service Commissioned Corps

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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

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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

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What should be included in the differential diagnoses of amenorrhea with normal puberty?

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What should be included in the differential diagnoses of amenorrhea with normal puberty?

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