Overview
Estrogen resistance syndrome is an extremely rare genetic condition where the body cannot properly respond to estrogen, one of the main female sex hormones. Even though estrogen is produced in normal or even high amounts, the body's cells cannot 'read' the estrogen signal because the receptor — the protein that normally receives and acts on estrogen — does not work correctly. This is caused by changes (mutations) in the ESR1 gene, which provides instructions for making the estrogen receptor. In people assigned female at birth, this condition typically causes delayed or absent puberty, lack of menstrual periods, infertility, and bones that do not develop properly (low bone density), leading to a higher risk of fractures. Interestingly, blood estrogen levels are often very high because the body keeps trying to compensate. In people assigned male at birth, the condition can cause tall stature, continued bone growth into adulthood, and reduced bone density. Both sexes may have metabolic changes affecting cholesterol and blood sugar. Treatment is challenging because standard estrogen therapy does not work well when the receptor itself is faulty. Management focuses on protecting bone health, addressing metabolic issues, and supporting quality of life. This condition is also sometimes called 'estrogen insensitivity syndrome' or 'estrogen receptor deficiency.' Because fewer than 10 cases have been reported worldwide, much is still being learned about the best ways to manage it.
Key symptoms:
Delayed or absent puberty in femalesNo menstrual periods (primary amenorrhea)InfertilityVery low bone density, leading to fragile bonesUnusually tall height due to continued bone growthHigh estrogen levels in the blood despite the body not responding to itUnderdeveloped uterus and ovaries in femalesEnlarged ovaries with multiple cysts (similar to polycystic ovary syndrome)Abnormal cholesterol levelsInsulin resistance or blood sugar problemsContinued growth of long bones past normal age in malesBreast tissue that does not develop normally in females
Clinical phenotype terms (24)— hover any for plain English
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Variable
Can begin at different ages, from infancy through adulthood
Treatments
No FDA-approved treatments are currently listed for Estrogen resistance syndrome.
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Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to Estrogen resistance syndrome.
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Caregiver Resources
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Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.What is my current bone density, and what is the best plan to protect my bones long-term?,Are there any hormone therapies that might partially work for me given that my estrogen receptor is not functioning normally?,What are my options regarding fertility, and should I see a reproductive specialist?,How often should I have blood tests to monitor my hormone and metabolic levels?,Are there any clinical trials or research studies I could participate in?,What signs or symptoms should prompt me to seek urgent medical care?,Should other family members be tested for the ESR1 gene mutation?
Common questions about Estrogen resistance syndrome
What is Estrogen resistance syndrome?
Estrogen resistance syndrome is an extremely rare genetic condition where the body cannot properly respond to estrogen, one of the main female sex hormones. Even though estrogen is produced in normal or even high amounts, the body's cells cannot 'read' the estrogen signal because the receptor — the protein that normally receives and acts on estrogen — does not work correctly. This is caused by changes (mutations) in the ESR1 gene, which provides instructions for making the estrogen receptor. In people assigned female at birth, this condition typically causes delayed or absent puberty, lack of
How is Estrogen resistance syndrome inherited?
Estrogen resistance syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
Which specialists treat Estrogen resistance syndrome?
3 specialists and care centers treating Estrogen resistance syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.