A Phase 3 interventional study of Progesterone and Estrogen Patch in Premature Ovarian Insufficiency, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Recruiting at 1 site in United States. Open to female participants aged 11 Years to 19 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-29.
Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Phase 3, Interventional, and Treatment
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.
Study Description:
This is a study of adolescents with premature ovarian insufficiency (POI) and their response to hormone replacement therapy (HRT).
Objectives:
Primary:
To identify the phenotype and associated genotype of adolescents with POI at the time of diagnosis, including assessment of overall bone health of participants pre- and post-HRT treatment with respect to bone mineral density (BMD) and other skeletal endpoints.
Bone Health:
-Follow patients with POI for bone health assessments:
Secondary:
Bone Health
-Follow patients with POI for bone health assessments:
Metabolic Phenotype:
Follow patients with POI for metabolic assessment:
Muscle Phenotype:
-Follow patients with POI for muscle function assessment:
Cardiovascular Health
-Follow patients with POI for a cardiovascular evaluation:
Genetic profiling:
-If obtained, assess the baseline genotype of patients with POI to correlate with BMD and other health outcomes
--If subjects are co-enrolled on NIAID protocol 17I0122, utilize that genetic sequencing data to associate with genotype and response of multiple health outcomes to HRT.
Quality of Life:
-Follow patients with POI for evaluation of an individual s perception of their life quality and health:
Psychological health:
-Follow patients with POI for evaluation of an individual s mood and well-being:
Menopause profile:
-Follow patients with POI for determining signs and symptoms of menopause:
Hormone Replacement Therapy:
-Follow patients with POI longitudinally to determine the most effective HRT management:
Endpoints:
Primary:
Longitudinal evaluation of BMD of the central skeleton (lumbar spine).
As secondary 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.
Secondary:
181 studies on the registry are indexed under Primary Ovarian Insufficiency; 48 are open to participants now.
This study's planned enrollment of 185 is above the median of 48 across 113 interventional studies indexed under Primary Ovarian Insufficiency.
Browse Primary Ovarian Insufficiency studies →Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 422 studies on the registry; 24 are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 11 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria for POI Participants
To be eligible to participate in this study, an individual must meet all the following criteria:
Inclusion Criteria for Healthy Volunteers:
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:
Exclusion Criteria for Healthy Volunteers:
For healthy volunteers, all exclusion criteria will apply as for POI participants except for number 1.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Healthy Control Participants
POI patients will be receiving transdermal 17 beta-estradiol and oral micronized progesterone.
Drug: Progesterone · Drug: Estrogen Patch
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.
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).
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.
Time frame: 2 years
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.
Time frame: 2 years
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.
Time frame: 2 years
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.
Time frame: 2 years
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.
Time frame: 2 years
Compare the genetic background of participants with POI to healthy controls using whole genome sequencing.
Genetic profiling - Compare the genetic background of participants with POI to healthy controls using whole genome sequencing.
Time frame: 2 years
Assess quality of life using COPM and Interest Checklist questionnaires.
Quality of Life - Assess quality of life using COPM and Interest Checklist questionnaires.
Time frame: 2 years
Evaluate psychological health using the Beck Depression Inventory and Spielberger State/Trait Anxiety Inventory.
Psychological Health - Evaluate psychological health using the Beck Depression Inventory and Spielberger State/Trait Anxiety Inventory.
Time frame: 2 years
Compare menopausal profile, including ovarian hormone levels and responses to the Menopause Rating Scale, between participants with POI and healthy controls.
Menopausal profile - Compare menopausal profile, including ovarian hormone levels and responses to the Menopause Rating Scale, between participants with POI and healthy controls.
Time frame: 2 years
Assess health effects of a typical clinical HRT regimen over two years.
Hormone Replacement Therapy - Assess health effects of a typical clinical HRT regimen over two years.
Time frame: 2 years
Plan to share: Yes — All IPD that underlie results in a publication will be deposited into a data repository in line with NIH regulations.
Supporting information: Statistical analysis plan, 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.
Started Jul 2025 (actual). Primary completion is estimated for Dec 2031, 76 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Progesterone · Estrogens
Primary Ovarian Insufficiency →
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) →