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?

This trial explores how hormone replacement therapy (HRT) can assist adolescents with premature ovarian insufficiency (POI), a condition causing irregular periods, infertility, and early menopause symptoms. The study aims to determine the optimal doses and delivery methods for HRT, including estrogen patches and progesterone pills. Girls aged 11 to 19 with a POI diagnosis, along with healthy volunteers, are needed for participation. As an Early Phase 1 trial, this research seeks to understand how HRT functions in individuals, providing participants the chance to contribute to groundbreaking insights.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that hormone replacement therapy (HRT) is usually well-tolerated by adult women with premature ovarian insufficiency (POI). Studies have found that higher doses of estrogen can improve health without causing major side effects. For instance, applying 17β-estradiol (a type of estrogen) to the skin is effective and safe, and it works better for hormone levels and feminization than taking estrogen pills.

HRT also helps lower the risk of issues like osteoporosis (weak bones) and heart disease, which are concerns for women with POI. While HRT can have some side effects, it is generally safe when monitored by healthcare professionals.

The current trial is in an early stage, so although there is some evidence of safety in adults, researchers are still studying its effects on adolescents. This phase is crucial to understand how well teenagers handle the treatment and to determine the best doses and schedules for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about hormone replacement therapy (HRT) for premature ovarian failure because it uses a specific combination of transdermal 17 beta-estradiol and oral micronized progesterone. Unlike typical oral hormone therapies, the transdermal delivery method offers a more consistent release of hormones, potentially leading to fewer side effects and better symptom control. This approach aims to closely mimic the natural hormone cycles, which could improve overall effectiveness and quality of life for patients compared to existing treatments.

What evidence suggests that hormone replacement therapy might be an effective treatment for premature ovarian insufficiency?

Research has shown that hormone replacement therapy (HRT) helps women with premature ovarian insufficiency (POI) maintain strong bones. In this trial, POI patients will receive transdermal 17 beta-estradiol and oral micronized progesterone as part of their HRT regimen. Studies have found that both skin patches and pills for hormone therapy support bone health. Higher amounts of estrogen, a key hormone in HRT, are linked to improved quality of life and relief from symptoms caused by low estrogen levels. Additionally, increasing estrogen doses can help maintain healthy arteries, benefiting heart health. These findings suggest that HRT can effectively manage POI symptoms in teenagers. ^{1 4 5 6 7}

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40627723/

Transdermal versus oral hormone therapy in premature ... Conclusions: Both oral and transdermal hormone therapies effectively help maintain bone mineral density in women with premature ovarian insufficiency, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05737329

Efficacy, Safety, and Tolerability of Higher Doses Estrogen ... The goal of this study is to assess the effects of higher doses versus standard hormone therapy on quality of life (QoL), symptoms due to estrogen ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1807593225001644

Premature ovarian insufficiency: Updated concepts in ... POI affects up to 3.5 % of women under 40-years of age and is associated with significant physical and psychological repercussions due to early hypoestrogenism.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6276684/

HRT for women with premature ovarian insufficiency It was shown that increasing doses of estrogen (4 mg of 17β-estradiol versus 1 and 2 mg) resulted in a reduction in intima media thickness in ...

5. gremjournal.com gremjournal.com/journal/03-2021/different-approaches-to-hormone-replacement-therapy-in-women-with-premature-ovarian-insufficiency/

Different Approaches to Hormone Replacement Therapy in ... This article summarizes the current recommendations on hormonal treatment of POI, discusses pros and cons of the various hormone preparations.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01023178

Comparison of Transdermal and Oral Estrogens in ... Treatment with transdermal 17beta(17β) estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen ...

7. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

Hormone Therapy in Primary Ovarian Insufficiency Hormone therapy is indicated to reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve the quality of life of women ...