Aromatase and estrogen receptor α deficiency

Fertil Steril. 2014 Feb;101(2):323-9. doi: 10.1016/j.fertnstert.2013.12.022.


Studies on the phenotypes of women and men with mutations disrupting estrogen biosynthesis and action have significantly advanced our knowledge of the physiologic roles of estrogen in humans. Aromatase deficiency results from autosomal recessive inheritance of mutations in the CYP19A1 gene. It gives rise to ambiguous genitalia in 46,XX fetuses. At puberty, affected girls have hypergonadotropic hypogonadism, do not develop secondary sexual characteristics, and exhibit progressive virilization. The affected 46,XY men have normal male sexual differentiation and pubertal maturation. These men, however, are extremely tall and have eunucoid proportions with continued linear growth into adulthood, severely delayed epiphyseal closure, and osteoporosis due to estrogen deficiency. Although estrogen has been shown to be essential for normal sperm production and function in mice, its role in fertility is not clear in men. Thus far, one man and an unrelated woman with estrogen resistance due to mutations in the estrogen receptor α (ESR1) gene have been described. Their clinical presentations are similar to that of aromatase-deficient men and women.

Keywords: Aromatase deficiency; estrogen receptor-alpha; estrogen resistance; mutation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 46, XX Disorders of Sex Development / diagnosis
  • 46, XX Disorders of Sex Development / genetics*
  • 46, XX Disorders of Sex Development / metabolism*
  • Animals
  • Aromatase / deficiency*
  • Aromatase / genetics
  • Aromatase / metabolism
  • Estrogen Receptor alpha / deficiency*
  • Estrogen Receptor alpha / genetics*
  • Female
  • Genes, Recessive
  • Gynecomastia / diagnosis
  • Gynecomastia / genetics*
  • Gynecomastia / metabolism*
  • Humans
  • Infertility, Male / diagnosis
  • Infertility, Male / genetics*
  • Infertility, Male / metabolism*
  • Male
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / metabolism*
  • Mutation / genetics


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Aromatase

Supplementary concepts

  • Aromatase deficiency