Background:
Premature ovarian insufficiency (POI) is a condition in which women under the age of 40 years have absent or irregular menstrual cycles. POI can cause infertility, signs of menopause, osteoporosis, and other symptoms. Hormone replacement therapy (HRT) is a treatment that gives women extra hormones, such as estrogen and progesterone. HRT works well in adult women. Researchers want to find the most effective doses and regimens for adolescents.
Objective:
To monitor the effects of HRT on adolescents with POI.
Eligibility:
Female adolescents aged 11 to 19 years diagnosed with POI. Healthy volunteers are also needed.
Design:
All participants will have clinic visits every 6 months for 2 years. Each visit may last 2 days. Each visit may include:
Blood and urine tests.
A test of their heart function.
A test to measure the stiffness of their blood vessels. Participants will lie flat with a blood pressure cuff on a leg and a meter on the neck while the cuff inflates.
A test of their grip strength. Participants will squeeze a handheld device as hard as they can.
Two scans to measure bone density. For one, participants will lie on a table while a scanner passes along their body. For the other, participants will sit in a chair and insert their forearm, then their lower leg, into a scanner.
A test to measure skin pigmentation. Participants' skin will be touched lightly with a device.
An optional visual exam of the vagina. Some vaginal fluid may also be collected with a cotton swab/cytobrush.
Participants with POI will receive HRT. They will be given estrogen patches and progesterone pills.
Individuals aged 11-19 years, inclusive, at the time of enrollment.
Diagnosis of premature ovarian insufficiency.
Documentation of one elevated serum FSH measurement greater than the testing laboratory's upper reference range (for age/Tanner stage).
Identify as female (i.e., sex assigned at birth)
POI in the setting of Turner syndrome.
Patients who screened positive for celiac disease.
Receipt of any medications including HRT determined by the investigator to affect bone metabolism 3 months prior to enrollment.
Any medical condition determined by the investigator to affect bone health will be excluded.
Parallel
Progesterone
DrugOral micronized progesterone will be added (100 mg/day for 12 days/month) in the event of spontaneous vaginal bleeding and/or at 12 months over the 2-year protocol.
Estrogen Patch
Drugparticipants with POI (n=85) will receive transdermal 17 beta-estradiol (beginning at a dose of 25 microgram/patch applied weekly), with the dose increased at 3 months to 50 microgram, and thereafter every 6 months to 75 and 100 microgram/patch for pubertal induction or estrogen replacement (with 100 microgram/patch representing a full adolescent or young adult estradiol dose). The continued escalation of the estradiol dose and patch strength will be guided by the clinical presentation and physical examination (by the PI or designated AI).
Longitudinal evaluation of BMD of the central skeleton (lumbar spine).
measures of bone health, dual-energy x-ray absorptiometry (DXA) measures of skeletal sites other than the spine (DXA - hip/total body) will be evaluated longitudinally in POI participants and their BMD compared to healthy control participants. Using DXA, vertebral fractures assessment (VFA) will be performed in POI participants and compared to healthy control participants. In addition, BMD will be evaluated with respect to skin pigmentation and muscle grip strength.
Evaluate bone density and strength of the radius and tibia in participants with POI and compare with healthy controls.
Bone Health - Evaluate bone density and strength of the radius and tibia in participants with POI and compare with healthy controls.
Compare metabolic and cardiovascular parameters between participants with POI and healthy controls.
Metabolic Phenotype - Compare metabolic and cardiovascular parameters between participants with POI and healthy controls.
Assess muscle strength and lean body mass in participants with POI compared to healthy controls.
Muscle Phenotype - Assess muscle strength and lean body mass in participants with POI compared to healthy controls.
Analyze heart repolarization, arterial stiffness, and coagulation parameters in participants with POI versus healthy controls.
Cardiovascular Health - Analyze heart repolarization, arterial stiffness, and coagulation parameters in participants with POI versus healthy controls.
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