Hormone Replacement Therapy for Premature Ovarian Failure

Overseen By Catherine M Gordon, M.D.

Age: < 65

Sex: Female

Trial Phase: Phase < 1

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

Must be taking: Estrogen, Progesterone

Must not be taking: Bone metabolism drugs

Disqualifiers: Turner syndrome, Celiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

Duration: 2 years

185 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are taking any medications that affect bone metabolism, you will need to stop them at least 3 months before joining the trial. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

Is hormone replacement therapy safe for women with premature ovarian failure?

Current research on hormone replacement therapy for premature ovarian failure is ongoing, and while it aims to address safety concerns, there is not yet robust data available to fully inform clinical recommendations. Studies are being conducted to evaluate its effects on bone health and cardiovascular markers, which will help determine its safety profile. ^{1 2 3 4 5}

How does hormone replacement therapy differ from other treatments for premature ovarian failure?

Hormone replacement therapy (HRT) for premature ovarian failure is unique because it helps manage symptoms by replacing hormones that the ovaries no longer produce, improving overall health and reducing symptoms like hot flashes. However, it is not typically associated with restoring fertility, although there are rare cases where women have conceived while on HRT. ^{5 6 7 8 9}

What data supports the effectiveness of the treatment Hormone Replacement Therapy for Premature Ovarian Failure?

Research shows that hormone replacement therapy can help women with premature ovarian failure by improving their quality of life and reducing risks of conditions like heart disease and osteoporosis. Some women have even been able to conceive and have healthy babies after receiving estrogen therapy. ^{5 6 10 11 12}

Who Is on the Research Team?

Catherine M Gordon, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for female adolescents aged 11 to 19 with Premature Ovarian Insufficiency (POI), as well as healthy volunteers. Participants will undergo various tests and receive Hormone Replacement Therapy (HRT) using estrogen patches and progesterone pills.

Inclusion Criteria

I am a female aged 11-19 with premature ovarian insufficiency and have had two high FSH tests.

I am a female aged 11-19, not pregnant, and do not have chronic diseases.

Exclusion Criteria

Exclusion Criteria for Healthy Volunteers: Same as for POI participants except for POI in the setting of Turner syndrome.

I am not a male and not pregnant, as required for this study.

I do not have Turner syndrome, celiac disease, recent bone medication use, or other bone health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants with POI receive hormone replacement therapy with transdermal 17 beta-estradiol and oral micronized progesterone

2 years

Clinic visits every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of bone density, metabolic, cardiovascular, and psychological health

2 years

Clinic visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Hormone Replacement Therapy

Trial Overview The study aims to determine effective doses and regimens of HRT in young women with POI. It involves clinic visits every six months for two years, where participants will have heart function tests, blood vessel stiffness measurements, grip strength assessments, bone density scans, skin pigmentation tests, and an optional vaginal exam.

How Is the Trial Designed?

Group I: POI Patients Experimental Treatment 2 Interventions

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

Group II: Healthy Participants Active Control 1 Intervention

Healthy Control Participants

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Estrogen treatment and subsequent pregnancy in two patients with severe hypergonadotropic ovarian failure. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Spontaneous pregnancy in a woman with premature ovarian failure: a case report. [2010]

3. Poland pubmed.ncbi.nlm.nih.gov

Premature ovarian insufficiency - hormone replacement therapy and management of long-term consequences. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Hormone Replacement Therapy Versus the Combined Oral Contraceptive Pill in Premature Ovarian Failure: A Randomized Controlled Trial of the Effects on Bone Mineral Density. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

OVARIAN FAILURE AND THE MENOPAUSE. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Premature ovarian insufficiency: the need for evidence on the effectiveness of hormonal therapy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Treatment of premature ovarian failure trial: description of an ongoing clinical trial. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Impact of hormone therapy on the bone density of women with premature ovarian insufficiency: A systematic review. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Long-term health of women with genetic POI due to FSH-resistant ovaries. [2022]

10. Singapore pubmed.ncbi.nlm.nih.gov

Pregnancy in a patient with premature ovarian failure. [2020]

11. Singapore pubmed.ncbi.nlm.nih.gov

Premature ovarian failure: diagnosis and treatment. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Adipose-derived stem cells promote the repair of chemotherapy-induced premature ovarian failure by inhibiting granulosa cells apoptosis and senescence. [2023]