Estrogen insensitivity syndrome

Structure of the estrogen receptor alpha (ESR1) protein.

Estrogen Insensitivity Syndrome is a rare genetic condition characterized by the body's inability to respond to estrogen, a key hormone in the development and regulation of the female reproductive system and secondary sexual characteristics. This condition is caused by mutations in the estrogen receptor gene, leading to a non-functional receptor that cannot bind estrogen effectively.

Pathophysiology

The syndrome results from mutations in the ESR1 gene, which encodes the estrogen receptor alpha. This receptor is crucial for mediating the effects of estrogen in various tissues, including the breast, uterus, and bone. In individuals with estrogen insensitivity syndrome, the receptor is unable to bind estrogen, leading to a lack of estrogenic effects in the body.

Clinical Presentation

Individuals with estrogen insensitivity syndrome typically present with symptoms of estrogen deficiency despite normal or elevated levels of circulating estrogen. In females, this may include:

• Lack of breast development
• Primary amenorrhea
• Infertility
• Osteoporosis

In males, the condition may present with:

• Lack of pubertal development
• Gynecomastia
• Infertility

Diagnosis

Diagnosis of estrogen insensitivity syndrome involves a combination of clinical evaluation, hormonal assays, and genetic testing. Elevated levels of circulating estrogen with a lack of expected physiological response suggest the condition. Genetic testing can confirm mutations in the ESR1 gene.

Management

Management of estrogen insensitivity syndrome is primarily supportive and symptomatic. Hormone replacement therapy may be considered, although its effectiveness is limited due to the receptor's insensitivity. Management of osteoporosis and other complications is crucial.

Related Pages

• Estrogen receptor
• Hormone resistance
• Genetic disorders