RecruitingPhase 3NCT06851754

Hormone Replacement Therapy in Adolescents With Premature Ovarian Insufficiency

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Enrollment

185 participants

Start Date

Jul 17, 2025

Study Type

INTERVENTIONAL

Conditions

Premature Ovarian Insufficiency

Summary

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.

Eligibility

Sex: FEMALEMin Age: 11 YearsMax Age: 19 Years

Inclusion Criteria10

To be eligible to participate in this study, an individual must meet all the following criteria:
Individuals aged 11-19 years, inclusive, at the time of enrollment.
Diagnosis of premature ovarian insufficiency.
Documentation of two elevated serum FSH measurements, at least month apart, greater than the testing laboratory s the upper reference range (for age/Tanner stage).
Identify as female (i.e., sex assigned at birth)
Negative pregnancy test.
Individuals aged 11-19 years.
Identify as female (i.e., sex assigned at birth)
Negative pregnancy test.
Absence of known chronic disease

Exclusion Criteria8

Male participants are excluded from both study groups (POI and Healthy Volunteers) as POI affects only the female reproductive system, while pregnant participants are not eligible to have DXA or HRpQCT imaging for safety reasons.
An individual who meets any of the following criteria will be excluded from participation in this study:
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.
Presence of a medical, psychiatric, or social condition which, in the opinion of the investigator, would place undue burden on the subject, NIH resources, or increase risk of participation.
Report of sexual activity but refusal to use a copper intrauterine device or double barrier forms of contraception during the study.

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Interventions

DRUGProgesterone

Oral 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.

DRUGEstrogen Patch

participants 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).