An observational study in Androgen Insensitivity Syndrome, Metabolic Parameters in AIS, CAIS, PAIS and MAIS and Tumor Formation in AIS, CAIS, PAIS and MAIS, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Recruiting at 1 site in United States. Open to participants aged 8 Years to 99 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-13.
Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Observational
Background:
Androgen effects in humans are usually (but not always) mediated by the androgen receptor which is coded for by the androgen receptor gene (AR gene). Androgen Insensitivity Syndrome (AIS) is a rare condition in which the body cannot sense the male hormones in the blood or tissue. Both women and men can be affected by AIS. Researchers want to learn more about the health of people with AIS over time.
With a natural history study in individuals with AIS, data and tests may provide information regarding health risks (including the risks and benefits of gonadectomy and best ways to monitor for tumor) and optimal management of individuals with AIS as well as elucidate the role of the androgen receptor in human health. This study does not involve any interventions and we can provide clinical care while collecting data.
Objective:
The objective of this natural history study is to describe and define a comprehensive phenotype (characteristic) of patients with AIS based on confirmed androgen receptor (AR) gene difference. We will evaluate hormones, bone density and markers, cardiovascular and metabolic parameters, as well as quality of life and tumor formation risk and evaluation. The purpose is to obtain a better understanding of the overall health issues that people with AIS may have through the study procedures listed.
Eligibility:
People ages 8-99 with AIS and their adult relatives
Design:
Participants will go through a series of study procedures for data and specimen collection. This will be done to understand how AIS affects individuals since the androgen receptor is found in many tissues in the body including skin, bone, muscle, and the neurologic, immune and metabolic systems. All tests will be performed by skilled and trained study professionals.
Participants will be screened with:
Medical history
Physical exam
Medical record review
Lab tests.
Participants will have physical exams. Their body measurements will be taken. They will have blood and urine tests. They will have electrocardiograms to check heart health. They may complete questionnaires. They may have an Oral Glucose Tolerance Test.
Participants may have x-rays and HRpQCT scans taken of the hand, wrist, and other bones.
Participants will have body scans to measure bone thickness.
Participants will have magnetic resonance imaging (MRI) or sonogram of the pelvis. For MRI, they may get a contrast agent via intravenous (IV) catheter.
Adult participants may have the following:
MR elastography. It uses MRI and low-frequency vibrations to map stiffness of body tissues.
MR spectroscopy. It uses MRI to take pictures of chemicals in the liver and body fat.
Cardiac computed tomography scan. It uses x-rays to make pictures of the heart. Participants may get a contrast agent via IV.
Optional genital exam.
Optional one-time vaginal swab.
Participants will have visits every 1-2 years. Participation lasts indefinitely.
Adult relatives will also be invited to participate but will have only 1 visit. It will include some of the above tests.
Study Description: This is a natural history study of individuals with androgen receptor gene abnormalities.
Objectives:
Primary Objectives:
To define and describe a comprehensive phenotype of patients with androgen insensitivity (based on confirmed androgen receptor
(AR) gene difference), including hormonal, metabolic, immunologic, and cardiovascular aspects of AIS, as well as quality life and tumor formation risk and evaluation.
Secondary Objectives:
Bone Health:
- Follow a large population of patients with androgen receptor abnormalities for:
Studies to determine bone geometry, strength and shape,
Metabolic and Immune Abnormalities:
- Follow a large population of patients with androgen receptor abnormalities for studies of metabolic abnormalities and auto-immune disease screening
Metabolic syndrome,
Testicular Tumor Risk and Monitoring:
- Follow a large population of patients with androgen receptor abnormalities in order to:
-- Describe the typical and atypical appearance of testes on ultrasound and magnetic resonance imaging (MRI) in young individual with
CAIS.
Evaluate gonadal tumor markers as a tool to assess for gonadal tumor.
- When individuals with androgen receptor abnormalities decide to undergo gonadectomy, perform tissue evaluation in order to:
Quality of Life:
similar ages.
Hormone Replacement:
- Evaluate different types and delivery of hormone replacement therapy on quality of life, sexual function, bone health and metabolic parameters in individual who have undergone gonadectomy
Follow a large population of patients with AIS for referral to future treatment studies.
Endpoints:
Primary Endpoint: Longitudinal evaluation of 500 individuals with AIS.
Secondary:
We will enroll and evaluate 500 patients with confirmed androgen receptor mutations. We will enroll 50 female relatives who are carriers of the AR gene difference and 50 female relatives who are not carriers of the AR gene and 50 healthy male relatives.
Inclusion Criteria for AIS Subjects
In order to be eligible to participate in this study, an individual must meet all the following criteria:
Inclusion Criteria for Relative of AIS Subjects
1) Adult Relatives of patients with AIS
EXCLUSION CRITERIA:
Exclusion Criteria for AIS Subjects
Exclusion Criteria for Relative of AIS Subjects
1) Patients with significant non-endocrine medical conditions.
We will enroll 50 female subjects relatives AIS subjects who are carriers of the AR gene difference
We will enroll 50 female subjects relatives of AIS subjects who are not carriers of the AR gene.
We will enroll 50 healthy male subjects of AIS relative subjects
500 Subjects with confirmed androgen receptor mutations
To define and describe a comprehensive phenotype in 500 patients with androgen insensitivity
Primary Objectives: To define and describe a comprehensive phenotype of patients with androgen insensitivity (based on confirmed androgen receptor (AR) gene difference), including hormonal, metabolic, immunologic, and cardiovascular aspects of the disease, as well as quality life and tumor formation risk and evaluation
Time frame: End of study
Effects of hormone therapy in individuals with Androgen Insensitivity
Evaluate different types and delivery of hormone replacement therapy on quality of life, sexual function, bone health and metabolic parameters in individuals who have undergone gonadectomy
Time frame: End of study
Quality of life measures (QoL) in individuals with Androgen Insensitivity
Quality of life questionnaires will be administered during each patient visit
Time frame: End of study
Gonadal Tumor evaluation in individuals with Androgen Insensitivity
A) MRI and Ultrasound imaging will be performed to describe the typical appearance of testes on ultrasound and magnetic resonance imaging (MRI) in young individuals with CAIS. B) Evaluate gonadal tumor markers as a tool to assess for gonadal tumor C) Gonadectomy tissue evaluation in order to: Investigate the histology and pathophysiology of gonadal tumor formation and assess the state of spermatogenesis in testis of individuals with androgen receptor abnormalities
Time frame: End of study
Metabolic assessment in individuals with Androgen Insensitivity
Metabolic parameters including laboratory evaluation as well as novel endometabolic imaging will be performed. Imaging will include MR spectography of liver fat and body composition, MR elastography for fibrosis assessment, and coronary wall imaging using CT angiography, and MRI evaluation of endothelial function to evaluate for artherosclerosis
Time frame: End of study
Evaluate Bone Health in individuals with Androgen Insensitivity
DEXA and HRpQCT scans and bone metabolism markers will be evaluated longitudinally in all individuals with AIS and family members. Comparison between family members who are carriers and non-carriers of the AR gene difference, those with mild, partial and complete androgen insensitivity will allow for evaluation of the effect of androgen receptor abnormalities on bone mineral density and growth as well as develop normative data for DEXA and HRpQCT scan interpretation in this population. Physiatry measurements will allow evaluation of muscle skeletal unit inferences.
Time frame: End of study
Plan to share: Undecided
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Androgen-Insensitivity Syndrome
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)