Hormone Replacement Therapy in Adolescents With Premature Ovarian Insufficiency

NCT06851754 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: 10002141002141-CH
• Study Type: interventional
• Target: 185
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Premature Ovarian Insufficiency

Keywords

Premature Ovarian Insufficiency; Hormone Replacement Therapy; Adolescents; Bone Health

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (9)

• Evaluate bone density and strength of the radius and tibia in participants with POI and compare with healthy controls.

  2 years

• Compare metabolic and cardiovascular parameters between participants with POI and healthy controls.

  2 years

• Assess muscle strength and lean body mass in participants with POI compared to healthy controls.

  2 years

• Analyze heart repolarization, arterial stiffness, and coagulation parameters in participants with POI versus healthy controls.

  2 years

• Compare the genetic background of participants with POI to healthy controls using whole genome sequencing.

  2 years

Study Arms (2)

Healthy Participants

NO INTERVENTION

Healthy Control Participants

POI Patients

EXPERIMENTAL

POI patients will be receiving transdermal 17 beta-estradiol and oral micronized progesterone.

Drug: Progesterone; Drug: Estrogen Patch

Interventions

Progesterone DRUG

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.

POI Patients

Estrogen Patch DRUG

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).

POI Patients

Eligibility Criteria

• Age: 11 Years - 19 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Primary Ovarian Insufficiency

Interventions

Progesterone

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Catherine M Gordon, M.D.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine M Gordon, M.D.

CONTACT

(301) 827-5449; catherine.gordon@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: February 28, 2025
• Study Start: July 17, 2025
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: April 22, 2026

Record last verified: 2026-04-17

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: In line with publication of results.
• Access Criteria: De-identified datasets used to generate results presented in manuscripts will be deposited into a repository that can be publicly accessible in line with NIH regulations. In compliance with ethical standards and institutional policies, other access to individual participant data will be governed by a structured data-sharing framework to ensure participant privacy and confidentiality. Access to IPD will be granted under a Data Use Agreement that specifies permissible uses, prohibits re-identification or further data sharing, and requires secure storage and handling of data. Access will be restricted to de-identified or coded datasets, with direct identifiers removed.

Locations

US (1)