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Estrogen resistance syndrome(ESTRR)

MedGen UID:
815580
Concept ID:
C3809250
Disease or Syndrome
Synonyms: ESTROGEN INSENSITIVITY; Estrogen resistance
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ESR1 (6q25.1-25.2)
 
Monarch Initiative: MONDO:0014148
OMIM®: 615363
Orphanet: ORPHA785

Definition

Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994). [from OMIM]

Clinical features

From HPO
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.
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Uterine hypoplasia
MedGen UID:
120575
Concept ID:
C0266399
Congenital Abnormality
Underdevelopment of the uterus.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Acne
MedGen UID:
152379
Concept ID:
C0702166
Disease or Syndrome
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Impaired glucose tolerance
MedGen UID:
852424
Concept ID:
C0151671
Finding
An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Elevated alkaline phosphatase of bone origin
MedGen UID:
318930
Concept ID:
C1833667
Finding
An abnormally increased level of bone isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
An increased concentration of insulin in the blood.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Increased serum estradiol
MedGen UID:
717742
Concept ID:
C1295643
Finding
An elevation above normal limits of the concentration of estradiol in the circulation.
Increased circulating osteocalcin level
MedGen UID:
1621520
Concept ID:
C4531126
Finding
An elevated level of osteocalcin in the blood.
Breast aplasia
MedGen UID:
539633
Concept ID:
C0266009
Congenital Abnormality
Failure to develop and congenital absence of the breast.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEstrogen resistance syndrome

Professional guidelines

PubMed

Bednarz K, Kowalczyk K, Cwynar M, Czapla D, Czarkowski W, Kmita D, Nowak A, Madej P
Int J Mol Sci 2022 Apr 14;23(8) doi: 10.3390/ijms23084334. PMID: 35457152Free PMC Article
Rabijewski M, Papierska L, Binkowska M, Maksym R, Jankowska K, Skrzypulec-Plinta W, Zgliczynski W
Ginekol Pol 2020;91(9):554-562. doi: 10.5603/GP.2020.0091. PMID: 33030737
Schorr M, Miller KK
Nat Rev Endocrinol 2017 Mar;13(3):174-186. Epub 2016 Nov 4 doi: 10.1038/nrendo.2016.175. PMID: 27811940Free PMC Article

Recent clinical studies

Etiology

Bizzarri M, Monti N, Piombarolo A, Angeloni A, Verna R
Nutrients 2023 Apr 13;15(8) doi: 10.3390/nu15081875. PMID: 37111094Free PMC Article
Baker FC, Lee KA
Sleep Med Clin 2022 Jun;17(2):283-294. Epub 2022 Apr 22 doi: 10.1016/j.jsmc.2022.02.004. PMID: 35659080
De Paoli M, Zakharia A, Werstuck GH
Am J Pathol 2021 Sep;191(9):1490-1498. Epub 2021 Jun 5 doi: 10.1016/j.ajpath.2021.05.011. PMID: 34102108
He Y, Lu Y, Zhu Q, Wang Y, Lindheim SR, Qi J, Li X, Ding Y, Shi Y, Wei D, Chen ZJ, Sun Y
Am J Obstet Gynecol 2019 Aug;221(2):138.e1-138.e12. Epub 2019 Mar 22 doi: 10.1016/j.ajog.2019.03.011. PMID: 30910544
Caretto M, Giannini A, Russo E, Simoncini T
Maturitas 2017 May;99:43-46. Epub 2017 Feb 7 doi: 10.1016/j.maturitas.2017.02.004. PMID: 28364867

Diagnosis

Yang J, Chen C
J Endocrinol 2024 Apr 1;261(1) Epub 2024 Feb 15 doi: 10.1530/JOE-23-0342. PMID: 38285626
Ko SH, Kim HS
Nutrients 2020 Jan 13;12(1) doi: 10.3390/nu12010202. PMID: 31941004Free PMC Article
He Y, Lu Y, Zhu Q, Wang Y, Lindheim SR, Qi J, Li X, Ding Y, Shi Y, Wei D, Chen ZJ, Sun Y
Am J Obstet Gynecol 2019 Aug;221(2):138.e1-138.e12. Epub 2019 Mar 22 doi: 10.1016/j.ajog.2019.03.011. PMID: 30910544
Schorr M, Miller KK
Nat Rev Endocrinol 2017 Mar;13(3):174-186. Epub 2016 Nov 4 doi: 10.1038/nrendo.2016.175. PMID: 27811940Free PMC Article
Katoh M, Nakagama H
Med Res Rev 2014 Mar;34(2):280-300. Epub 2013 May 21 doi: 10.1002/med.21288. PMID: 23696246

Therapy

Manouchehri A, Abbaszadeh S, Ahmadi M, Nejad FK, Bahmani M, Dastyar N
JBRA Assist Reprod 2023 Mar 30;27(1):85-91. doi: 10.5935/1518-0557.20220024. PMID: 35916457Free PMC Article
Gambioli R, Forte G, Aragona C, Bevilacqua A, Bizzarri M, Unfer V
Eur Rev Med Pharmacol Sci 2021 Jan;25(1):438-446. doi: 10.26355/eurrev_202101_24412. PMID: 33506934
Caretto M, Giannini A, Russo E, Simoncini T
Maturitas 2017 May;99:43-46. Epub 2017 Feb 7 doi: 10.1016/j.maturitas.2017.02.004. PMID: 28364867
Nguyen PL, Alibhai SM, Basaria S, D'Amico AV, Kantoff PW, Keating NL, Penson DF, Rosario DJ, Tombal B, Smith MR
Eur Urol 2015 May;67(5):825-36. Epub 2014 Aug 2 doi: 10.1016/j.eururo.2014.07.010. PMID: 25097095
Katoh M, Nakagama H
Med Res Rev 2014 Mar;34(2):280-300. Epub 2013 May 21 doi: 10.1002/med.21288. PMID: 23696246

Prognosis

Zheng R, Shen H, Li J, Zhao J, Lu L, Hu M, Lin Z, Ma H, Tan H, Hu M, Li J
J Ethnopharmacol 2023 Jan 30;301:115824. Epub 2022 Oct 20 doi: 10.1016/j.jep.2022.115824. PMID: 36273747
Pandurevic S, Macut D, Fanelli F, Pagotto U, Gambineri A
Biomolecules 2021 Sep 12;11(9) doi: 10.3390/biom11091350. PMID: 34572562Free PMC Article
Caretto M, Giannini A, Russo E, Simoncini T
Maturitas 2017 May;99:43-46. Epub 2017 Feb 7 doi: 10.1016/j.maturitas.2017.02.004. PMID: 28364867
Allan CA
Asian J Androl 2014 Mar-Apr;16(2):232-8. doi: 10.4103/1008-682X.122589. PMID: 24457840Free PMC Article
Wild RA
Steroids 2012 Mar 10;77(4):295-9. Epub 2011 Dec 14 doi: 10.1016/j.steroids.2011.12.002. PMID: 22197663

Clinical prediction guides

Zheng R, Shen H, Li J, Zhao J, Lu L, Hu M, Lin Z, Ma H, Tan H, Hu M, Li J
J Ethnopharmacol 2023 Jan 30;301:115824. Epub 2022 Oct 20 doi: 10.1016/j.jep.2022.115824. PMID: 36273747
Cincione RI, Losavio F, Ciolli F, Valenzano A, Cibelli G, Messina G, Polito R
Int J Environ Res Public Health 2021 Nov 27;18(23) doi: 10.3390/ijerph182312490. PMID: 34886216Free PMC Article
Magri V, Boltri M, Cai T, Colombo R, Cuzzocrea S, De Visschere P, Giuberti R, Granatieri CM, Latino MA, Larganà G, Leli C, Maierna G, Marchese V, Massa E, Matteelli A, Montanari E, Morgia G, Naber KG, Papadouli V, Perletti G, Rekleiti N, Russo GI, Sensini A, Stamatiou K, Trinchieri A, Wagenlehner FME
Arch Ital Urol Androl 2019 Jan 18;90(4):227-248. doi: 10.4081/aiua.2018.4.227. PMID: 30655633
Nguyen PL, Alibhai SM, Basaria S, D'Amico AV, Kantoff PW, Keating NL, Penson DF, Rosario DJ, Tombal B, Smith MR
Eur Urol 2015 May;67(5):825-36. Epub 2014 Aug 2 doi: 10.1016/j.eururo.2014.07.010. PMID: 25097095
Wild RA
Steroids 2012 Mar 10;77(4):295-9. Epub 2011 Dec 14 doi: 10.1016/j.steroids.2011.12.002. PMID: 22197663

Recent systematic reviews

Manouchehri A, Abbaszadeh S, Ahmadi M, Nejad FK, Bahmani M, Dastyar N
JBRA Assist Reprod 2023 Mar 30;27(1):85-91. doi: 10.5935/1518-0557.20220024. PMID: 35916457Free PMC Article
Rong A, Ta N, E L, Meng W
Front Endocrinol (Lausanne) 2022;13:995106. Epub 2023 Apr 18 doi: 10.3389/fendo.2022.995106. PMID: 37143960Free PMC Article
Nasimi Doost Azgomi R, Moini Jazani A, Karimi A, Pourreza S
Eur J Pharmacol 2022 Oct 15;933:175275. Epub 2022 Sep 13 doi: 10.1016/j.ejphar.2022.175275. PMID: 36108737
Zeng L, Yang K
Endocrine 2018 Jan;59(1):30-38. Epub 2017 Oct 19 doi: 10.1007/s12020-017-1442-y. PMID: 29052180
Tempfer CB, Bentz EK, Leodolter S, Tscherne G, Reuss F, Cross HS, Huber JC
Fertil Steril 2007 Jun;87(6):1243-9. Epub 2007 May 9 doi: 10.1016/j.fertnstert.2007.01.120. PMID: 17490659

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