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Amenorrhea

MedGen UID:
8016
Concept ID:
C0002453
Finding
Synonyms: Abnormal absence of menstruation; Absence of menstruation; absence of menstruation; amenia; amenorrhea; amenorrhea (disease)
SNOMED CT: Amenorrhea (14302001); Absence of menstruation (14302001)
 
HPO: HP:0000141
Monarch Initiative: MONDO:0001836

Definition

Absence of menses for an interval of time equivalent to a total of more than (or equal to) 3 previous cycles or 6 months. [from HPO]

Conditions with this feature

Polycystic ovaries
MedGen UID:
10836
Concept ID:
C0032460
Disease or Syndrome
Polycystic ovary syndrome is a condition that affects women in their child-bearing years and alters the levels of multiple hormones, resulting in problems affecting many body systems.\n\nMost women with polycystic ovary syndrome produce excess male sex hormones (androgens), a condition called hyperandrogenism. Having too much of these hormones typically leads to excessive body hair growth (hirsutism), acne, and male pattern baldness.\n\nHyperandrogenism and abnormal levels of other sex hormones prevent normal release of egg cells from the ovaries (ovulation) and regular menstrual periods, leading to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility). For those who achieve pregnancy, there is an increased risk of complications and pregnancy loss. Due to irregular and infrequent menstruation and hormone abnormalities, affected women have an increased risk of cancer of the uterine lining (endometrial cancer).\n\nIn polycystic ovary syndrome, one or both ovaries can contain multiple small, immature ovarian follicles that can appear as cysts on medical imaging. Normally, ovarian follicles contain egg cells, which are released during ovulation. In polycystic ovary syndrome, abnormal hormone levels prevent follicles from growing and maturing to release egg cells. Instead, these immature follicles accumulate in the ovaries. Affected women can have 12 or more of these follicles. The number of these follicles usually decreases with age.\n\nAbout half of all women with polycystic ovary syndrome are overweight or have obesity and are at increased risk of a fatty liver. Additionally, many women with polycystic ovary syndrome have elevated levels of insulin, which is a hormone that helps control levels of blood glucose, also called blood sugar. By age 40, about 10 percent of overweight women with polycystic ovary syndrome develop abnormally high blood glucose levels (type 2 diabetes), and up to 35 percent develop prediabetes (higher-than-normal blood glucose levels that do not reach the cutoff for diabetes). Obesity and increased insulin levels (hyperinsulinemia) further increase the production of androgens in polycystic ovary syndrome.\n\nWomen with polycystic ovary syndrome are also at increased risk for developing metabolic syndrome, which is a group of conditions that include high blood pressure (hypertension), increased belly fat, high levels of unhealthy fats and low levels of healthy fats in the blood, and high blood glucose levels. About 20 percent of affected adults experience pauses in breathing during sleep (sleep apnea). Women with polycystic ovary syndrome are more likely than women in the general popluation to have mood disorders such as depression.
Blepharophimosis, ptosis, and epicanthus inversus syndrome
MedGen UID:
66312
Concept ID:
C0220663
Disease or Syndrome
Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is defined by a complex eyelid malformation characterized by four major features, all present at birth: blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES type I includes the four major features and primary ovarian insufficiency; BPES type II includes only the four major features. Other ophthalmic manifestations that can be associated with BPES include dysplastic eyelids, lacrimal duct anomalies, strabismus, refractive errors, and amblyopia. Other craniofacial features may include a broad nasal bridge and low-set ears.
Rokitansky sequence
MedGen UID:
140915
Concept ID:
C0431648
Congenital Abnormality
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by uterovaginal atresia in an otherwise phenotypically normal female with a normal 46,XX karyotype. Anomalies of the genital tract range from upper vaginal atresia to total mullerian agenesis with urinary tract abnormalities. It has an incidence of approximately 1 in 5,000 newborn girls (Cheroki et al., 2006). The abnormality of sexual development in MRKH syndrome is the same as that in the MURCS association (601076), in which cervicothoracic somite anomalies, unilateral renal agenesis, and conductive deafness are also seen. Mullerian aplasia and hyperandrogenism (158330) is caused by mutation in the WNT4 gene (603490). Familial cases of unilateral or bilateral renal agenesis in combination with mullerian anomalies have also been reported (see urogenital adysplasia, 191830).
Satoyoshi syndrome
MedGen UID:
318882
Concept ID:
C1833454
Disease or Syndrome
Satoyoshi syndrome is a rare disorder characterized by progressive, painful, intermittent muscle spasms, diarrhea or unusual malabsorption, endocrinopathy with amenorrhea, and secondary skeletal abnormalities. The disorder is also called komuragaeri disease by the Japanese; in Japanese 'komura' means calf and 'gaeri' means 'turnover' or spasm. All cases have apparently been sporadic, even when occurring in large families (Ehlayel and Lacassie, 1995).
DNA ligase IV deficiency
MedGen UID:
339855
Concept ID:
C1847827
Disease or Syndrome
LIG4 syndrome is an autosomal recessive severe combined immunodeficiency with features of radiosensitivity, chromosomal instability, pancytopenia, and developmental and growth delay. Leukemia and dysmorphic facial features have been reported in some patients (summary by van der Burg et al., 2006).
Fuhrmann syndrome
MedGen UID:
346429
Concept ID:
C1856728
Disease or Syndrome
This syndrome has main characteristics of bowing of the femora, aplasia or hypoplasia of the fibulae and poly, oligo and syndactyly. It has been reported in 11 patients. Most of the patients also had a hypoplastic pelvis and hypoplasia of the fingers and fingernails. Some had congenital dislocation of the hip, absence or fusion of tarsal bones, absence of various metatarsals and hypoplasia and aplasia of the toes. The syndrome is caused by a partial loss of WNT7A function (gene mapped to 3p25).
Hemochromatosis type 3
MedGen UID:
388114
Concept ID:
C1858664
Disease or Syndrome
TFR2-related hereditary hemochromatosis (TFR2-HHC) is characterized by increased intestinal iron absorption resulting in iron accumulation in the liver, heart, pancreas, and endocrine organs. Age of onset is earlier than in HFE-HHC. The majority of individuals present with signs and symptoms of iron overload in the third decade (e.g., weakness, fatigue, abdominal pain, hepatomegaly, arthritis, arthralgia, progressive increase in skin pigmentation). Others present as young adults with nonspecific symptoms and abnormal serum iron studies or as adults with abnormal serum iron studies and signs of organ involvement including cirrhosis, diabetes mellitus, and arthropathy.
Hemochromatosis type 2A
MedGen UID:
356321
Concept ID:
C1865614
Disease or Syndrome
Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life. Males and females are equally affected. Prominent clinical features include hypogonadotropic hypogonadism, cardiomyopathy, glucose intolerance and diabetes, arthropathy, and liver fibrosis or cirrhosis. Hepatocellular cancer has been reported occasionally. The main cause of death is cardiac disease. If juvenile hemochromatosis is detected early enough and if blood is removed regularly through the process of phlebotomy to achieve iron depletion, morbidity and mortality are greatly reduced.
Hemochromatosis type 1
MedGen UID:
854011
Concept ID:
C3469186
Disease or Syndrome
HFE hemochromatosis is characterized by inappropriately high absorption of iron by the small intestinal mucosa. The phenotypic spectrum of HFE hemochromatosis includes: Persons with clinical HFE hemochromatosis, in whom manifestations of end-organ damage secondary to iron overload are present; Individuals with biochemical HFE hemochromatosis, in whom transferrin-iron saturation is increased and the only evidence of iron overload is increased serum ferritin concentration; and Non-expressing p.Cys282Tyr homozygotes, in whom neither clinical manifestations of HFE hemochromatosis nor iron overload are present. Clinical HFE hemochromatosis is characterized by excessive storage of iron in the liver, skin, pancreas, heart, joints, and anterior pituitary gland. In untreated individuals, early symptoms include: abdominal pain, weakness, lethargy, weight loss, arthralgias, diabetes mellitus; and increased risk of cirrhosis when the serum ferritin is higher than 1,000 ng/mL. Other findings may include progressive increase in skin pigmentation, congestive heart failure, and/or arrhythmias, arthritis, and hypogonadism. Clinical HFE hemochromatosis is more common in men than women.
Perrault syndrome 2
MedGen UID:
767019
Concept ID:
C3554105
Disease or Syndrome
Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy.
Premature ovarian failure 9
MedGen UID:
816706
Concept ID:
C3810376
Disease or Syndrome
Nonsyndromic primary ovarian insufficiency, which is characterized by amenorrhea with elevated gonadotropin levels, is observed in 1% of otherwise healthy women under the age of 40 years (summary by Wang et al., 2014). For a general phenotypic description and discussion of the genetic heterogeneity of premature ovarian failure, see POF1 (311360).
Premature ovarian failure 13
MedGen UID:
1393321
Concept ID:
C4479510
Disease or Syndrome
Premature ovarian failure-13 (POF13) is characterized by female infertility due to secondary amenorrhea in the third decade of life. Patients exhibit atrophic ovaries devoid of follicles (Guo et al., 2017). For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360).
Mitochondrial dna depletion syndrome 16B (neuroophthalmic type)
MedGen UID:
1780329
Concept ID:
C5543632
Disease or Syndrome
Mitochondrial DNA depletion syndrome-16B (MTDPS16B) is an autosomal recessive childhood-onset and progressive neuroophthalmic mtDNA depletion disorder characterized by optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia, and generalized chorea (Dosekova et al., 2020).
Oocyte/zygote/embryo maturation arrest 17
MedGen UID:
1841054
Concept ID:
C5830418
Disease or Syndrome
Oocyte/zygote/embryo maturation arrest-17 (OZEMA17) is characterized by female infertility due to arrest of the embryo after the first rounds of cleavage or failure to establish pregnancy after implantation (Wang et al., 2023). For a discussion of genetic heterogeneity of OZEMA, see 615774.
Oocyte/zygote/embryo maturation arrest 20
MedGen UID:
1841175
Concept ID:
C5830539
Disease or Syndrome
Oocyte/zygote/embryo maturation arrest-20 (OZEMA20) is characterized by early embryonic arrest with fragmentation. Extrusion of a large polar body 1 is observed in some patients (Zhang et al., 2021; Zhang et al., 2022). For a discussion of genetic heterogeneity of OZEMA, see 615774.

Professional guidelines

PubMed

Passos IMPE, Britto RL
Taiwan J Obstet Gynecol 2020 Mar;59(2):183-188. doi: 10.1016/j.tjog.2020.01.003. PMID: 32127135
Klein DA, Paradise SL, Reeder RM
Am Fam Physician 2019 Jul 1;100(1):39-48. PMID: 31259490
Molitch ME
JAMA 2017 Feb 7;317(5):516-524. doi: 10.1001/jama.2016.19699. PMID: 28170483

Recent clinical studies

Etiology

Huhmann K
Clin Ther 2020 Mar;42(3):401-407. Epub 2020 Mar 2 doi: 10.1016/j.clinthera.2020.01.016. PMID: 32139174
Klein DA, Paradise SL, Reeder RM
Am Fam Physician 2019 Jul 1;100(1):39-48. PMID: 31259490
Shufelt CL, Torbati T, Dutra E
Semin Reprod Med 2017 May;35(3):256-262. Epub 2017 Jun 28 doi: 10.1055/s-0037-1603581. PMID: 28658709Free PMC Article
Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, Murad MH, Santoro NF, Warren MP
J Clin Endocrinol Metab 2017 May 1;102(5):1413-1439. doi: 10.1210/jc.2017-00131. PMID: 28368518
Klein DA, Poth MA
Am Fam Physician 2013 Jun 1;87(11):781-8. PMID: 23939500

Diagnosis

Seppä S, Kuiri-Hänninen T, Holopainen E, Voutilainen R
Eur J Endocrinol 2021 May 4;184(6):R225-R242. doi: 10.1530/EJE-20-1487. PMID: 33687345
Sophie Gibson ME, Fleming N, Zuijdwijk C, Dumont T
J Clin Res Pediatr Endocrinol 2020 Feb 6;12(Suppl 1):18-27. doi: 10.4274/jcrpe.galenos.2019.2019.S0178. PMID: 32041389Free PMC Article
Klein DA, Paradise SL, Reeder RM
Am Fam Physician 2019 Jul 1;100(1):39-48. PMID: 31259490
Klein DA, Poth MA
Am Fam Physician 2013 Jun 1;87(11):781-8. PMID: 23939500
Practice Committee of American Society for Reproductive Medicine
Fertil Steril 2008 Nov;90(5 Suppl):S219-25. doi: 10.1016/j.fertnstert.2008.08.038. PMID: 19007635

Therapy

Donnez J, Taylor HS, Taylor RN, Akin MD, Tatarchuk TF, Wilk K, Gotteland JP, Lecomte V, Bestel E
Fertil Steril 2020 Jul;114(1):44-55. Epub 2020 Jun 4 doi: 10.1016/j.fertnstert.2020.02.114. PMID: 32505383
Carvalho N, Margatho D, Cursino K, Benetti-Pinto CL, Bahamondes L
Fertil Steril 2018 Nov;110(6):1129-1136. doi: 10.1016/j.fertnstert.2018.07.003. PMID: 30396557
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Prognosis

Triana P, López-Gutierrez JC
Pediatr Blood Cancer 2021 Mar;68(3):e28867. Epub 2020 Dec 27 doi: 10.1002/pbc.28867. PMID: 33369022
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Clinical prediction guides

Indirli R, Lanzi V, Mantovani G, Arosio M, Ferrante E
Front Endocrinol (Lausanne) 2022;13:946695. Epub 2022 Oct 11 doi: 10.3389/fendo.2022.946695. PMID: 36303862Free PMC Article
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Recent systematic reviews

Walsh BT, Hagan KE, Lockwood C
Int J Eat Disord 2023 Apr;56(4):798-820. Epub 2022 Dec 12 doi: 10.1002/eat.23856. PMID: 36508318
de Souza Pinto LP, Ferrari G, Dos Santos IK, de Mello Roesler CR, de Mello Gindri I
Arch Gynecol Obstet 2023 Jan;307(1):21-37. Epub 2022 Nov 24 doi: 10.1007/s00404-022-06846-0. PMID: 36434439
Bofill Rodriguez M, Dias S, Jordan V, Lethaby A, Lensen SF, Wise MR, Wilkinson J, Brown J, Farquhar C
Cochrane Database Syst Rev 2022 May 31;5(5):CD013180. doi: 10.1002/14651858.CD013180.pub2. PMID: 35638592Free PMC Article
Chowdhury R, Sinha B, Sankar MJ, Taneja S, Bhandari N, Rollins N, Bahl R, Martines J
Acta Paediatr 2015 Dec;104(467):96-113. doi: 10.1111/apa.13102. PMID: 26172878Free PMC Article
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