Estrogen insensitivity syndrome

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Estrogen insensitivity syndrome
Classification and external resources
OMIM 133430

The estrogen insensitivity syndrome (EIS) or estrogen resistance is a form of congenital estrogen deficiency[1] caused by a defective estrogen receptor (ER). Thus, estrogens cannot be recognized and initiate their biological action.[2]

In humans, the condition is very rare and only one case has been described. A reported male with EIS was tall as estrogens were unable to act to close the epiphyseal line, at risk for osteoporosis, and sterile (suggesting that in humans estrogens are necessary for reproduction).[3]

ERKO mice[edit]

Estrogen insensitivity syndrome can be experimentally induced in animals, typically mice, by knocking out the estrogen receptor. In so-called ERKO mice different estrogens receptors can be disabled allowing to study the role of such receptors.[4] ERKO mice show development of the respective female or male reproductive systems, and male and female alpha ERKO mice are infertile, beta ERKO males are fertile while females are subfertile, male and female double alpha and beta ERKO mice are sterile. The hypoplastic uterus does not respond to exogenous stimulation by estrogens. Males are infertile with atrophy in the testes. Bones age is delayed and bones are more brittle. Variations in these patterns can be achieved by selectively disabling the alpha or beta ERs.


In contrast to EIS, the androgen insensitivity syndrome (AIS) where the androgen receptor is defective is relatively common. This can be explained by the genetics of each syndrome. AIS is a X-linked recessive condition and thus carried over, by females, into future generations. EIS is not compatible with reproduction, thus each occurrence in humans would have to be a de-novo mutation and is not transmitted to offspring.

Congenital estrogen deficiency can also be caused by a defect in the aromatizing enzyme.[5]


  1. ^ Rochira V; Balestrieri A; Madeo B et al. (June 2001). "Congenital estrogen deficiency: in search of the estrogen role in human male reproduction". Mol. Cell. Endocrinol. 178 (1–2): 107–15. doi:10.1016/S0303-7207(01)00432-4. PMID 11403900. 
  2. ^ Smith EP; Boyd J; Frank GR et al. (October 1994). "Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man". N. Engl. J. Med. 331 (16): 1056–61. doi:10.1056/NEJM199410203311604. PMID 8090165. 
  3. ^ Korach, KS; Couse, JF; Curtis, SW; Washburn, TF; Lindzey, J; Kimbro, KS; Eddy, EM; Migliaccio, S; Snedeker, SM (1996). "Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes". Recent progress in hormone research 51: 159–86; discussion 186–8. PMID 8701078. 
  4. ^ Couse, JF; Korach, KS (1999). "Estrogen receptor null mice: what have we learned and where will they lead us?". Endocrine Reviews 20 (3): 358–417. doi:10.1210/er.20.3.358. PMID 10368776. 
  5. ^ Rochira, V; Balestrieri, A; Madeo, B; Spaggiari, A; Carani, C (2002). "Congenital estrogen deficiency in men: a new syndrome with different phenotypes; clinical and therapeutic implications in men". Molecular and cellular endocrinology 193 (1–2): 19–28. doi:10.1016/S0303-7207(02)00092-8. PMID 12160998.