Estrogens regulate pubertal development and reproductive function in women, spermatogenesis in men, and bone turnover and metabolic conditions in individuals of both sexes. Estradiol, the major estrogen in humans, is synthesized from testosterone by the action of aromatase and exerts its effects though binding to estrogen receptors. Germline loss- and gain-of-function variants in CYP19A1, the gene encoding aromatase, lead to aromatase deficiency and aromatase excess syndrome, respectively. Germline loss-of-function variants in ESR1, the gene encoding estrogen receptor α, are known to cause of estrogen insensitivity/resistance. In addition, rare variants in ESR1 and ESR2 have been implicated in various disease phenotypes. Clinical studies on these rare endocrine disorders provided clues to understand the biological functions of estrogens in the human body. This review introduces the genetic basis, phenotypes, and current management procedures of congenital disorders in estrogen biosynthesis and action.

雌激素调节女性的青春期发育和生殖功能、男性的精子发生以及男女个体的骨转换和代谢状况。雌二醇是人体主要的雌激素，由睾酮通过芳香酶作用合成，通过与雌激素受体结合发挥作用。编码芳香酶的基因CYP19A1中的种系丧失和获得功能变体分别导致芳香酶缺乏和芳香酶过量综合征。已知ESR1 （编码雌激素受体 α 的基因）中的种系功能丧失变体会导致雌激素不敏感/抗性。此外，ESR1和ESR2中的罕见变异与多种疾病表型有关。对这些罕见内分泌疾病的临床研究为了解雌激素在人体内的生物学功能提供了线索。这篇综述介绍了雌激素生物合成和作用中先天性疾病的遗传基础、表型和当前管理程序。