Hormone replacement for adolescents with premature ovarian insufficiency

Hormone Replacement Therapy in Adolescents With Premature Ovarian Insufficiency

This study will test estrogen patches plus progesterone in girls and young women aged 11–19 with premature ovarian insufficiency to see if hormone replacement improves bone density, metabolic markers, muscle strength, and cardiovascular health.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 185 (estimated)
• Ages: 11 Years to 19 Years
• Sex: Female
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06851754 on ClinicalTrials.gov

What this trial studies

This phase 3 interventional trial enrolls female adolescents aged 11–19 with premature ovarian insufficiency and a group of healthy female volunteers for comparison. Participants receive hormone replacement therapy (estrogen patch with progesterone) and attend clinic visits every six months for two years with blood and urine tests, cardiovascular and vascular stiffness testing, and imaging. Primary outcomes focus on bone health including central and peripheral bone mineral density by DXA, vertebral fracture assessment, body composition, and correlation with phenotype and genotype; secondary outcomes include bone microarchitecture by HR-pQCT, metabolic panels, lipid profiles, insulin resistance, muscle strength, and other cardiovascular measures. All testing and imaging are conducted at the NIH Clinical Center with pre- and post-treatment comparisons over the follow-up period.

Who should consider this trial

Good fit: Ideal candidates are individuals assigned female at birth aged 11–19 with documented premature ovarian insufficiency (plus healthy female volunteers 11–19 for comparison), all with negative pregnancy tests.

Not a fit: People who are male, pregnant, outside the 11–19 age range, or who have contraindications to estrogen/progestin therapy or other excluded chronic conditions are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, the trial could identify hormone regimens that improve bone density, lower future fracture risk, and improve metabolic and cardiovascular markers in adolescents with POI.

How similar studies have performed: Hormone replacement is an established beneficial treatment in adult women with POI, but rigorous long-term trials specifically in adolescents are limited, making this pediatric application relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

Inclusion Criteria for POI Participants

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 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)
* Negative pregnancy test.

Inclusion Criteria for Healthy Volunteers:

* Individuals aged 11-19 years.
* Identify as female (i.e., sex assigned at birth)
* Negative pregnancy test.
* Absence of known chronic disease

EXCLUSION CRITERIA:

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.

Exclusion Criteria for POI participants:

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.

Exclusion Criteria for Healthy Volunteers:

For healthy volunteers, all exclusion criteria will apply as for POI participants except for number 1.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Catherine M Gordon, M.D. — Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Study coordinator: Catherine M Gordon, M.D.

Conditions: Premature Ovarian Insufficiency, Hormone Replacement Therapy, Adolescents, Bone Health