Estrogen for Bone Health in Amenorrhea

MM
Overseen ByMadhusmita Misra, MD, MPH
Age: < 65
Sex: Female
Trial Phase: Phase 2
Sponsor: University of Virginia
Must be taking: Estrogen, Progesterone
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether different types of estrogen can improve bone strength in young women with few or no menstrual periods. Participants will either use a skin patch or take a pill with natural estrogen (17-beta estradiol) or use a birth control patch with synthetic estrogen (ethinyl estradiol). The goal is to determine which method best supports bone health over a year. Women aged 14-25 who have had fewer than three periods in the last six months and are otherwise healthy may be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings on bone health.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications known to affect bone metabolism within 3 months before starting the study. If you're on such medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both natural and synthetic forms of estrogen can be safe to use, though they may have different effects and comfort levels.

For the synthetic form, ethinyl estradiol in a patch, studies have found it effective in preventing pregnancy and generally easy to tolerate. Some women, however, might experience irregular bleeding or no periods. There is also a possible risk of slower bone growth in young people using these hormones.

For the natural form, 17-beta estradiol, available as a patch and in pill form, studies suggest it is generally well-tolerated. The patch form may help improve bone strength, especially in postmenopausal women. One study found that only about 5.5% of participants stopped using it due to side effects over three years, indicating it is quite tolerable for most. There is less specific data for the pill form, but it is considered similarly safe.

These findings suggest that estrogen treatments in this trial are likely safe for most people. However, individual experiences may vary, and discussing personal health concerns with a healthcare provider is always advisable.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for amenorrhea because they offer fresh approaches to enhancing bone health. Unlike typical oral contraceptives, which are the standard treatment, these investigational treatments use 17-beta estradiol and ethinyl estradiol, but with unique delivery methods. The transdermal options, such as the patches for both 17-beta estradiol and ethinyl estradiol, provide a direct and potentially more stable hormone delivery, which might improve bone health more effectively. Additionally, the incorporation of cyclic progestin in the treatment regimen could offer a more balanced hormonal approach, which is particularly promising for maintaining or improving bone density.

What evidence suggests that this trial's treatments could be effective for improving bone strength in amenorrhea?

This trial will compare different forms of estrogen treatments for bone health in amenorrhea. Research has shown that 17-beta estradiol, a natural form of estrogen, can improve bone health, particularly in postmenopausal women. Studies have found that this estrogen type can increase bone mineral density (BMD) and help maintain bone strength over time. Participants in this trial may receive 17-beta estradiol either transdermally or orally, both with cyclic progestin. Taking 17-beta estradiol in pill form also offers benefits, with some studies showing it can reduce signs of bone breakdown. However, the exact effects of oral estrogen on bone health remain less understood. Another treatment arm in this trial involves transdermal ethinyl estradiol with LNG. Synthetic estrogen, like ethinyl estradiol, often found in birth control pills, has been associated with less positive effects on bones. Overall, natural estrogen, especially when applied to the skin, appears promising for improving bone health.15678

Who Is on the Research Team?

MM

Madhusmita Misra, MD, MPH

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for females aged 14-25 with bone maturity and fewer than three menstrual cycles in the past six months. They must not be pregnant, planning pregnancy soon, or have conditions like PCOS affecting menstruation. Participants should not smoke heavily or have a BMI over 25 and must use non-hormonal contraception if sexually active.

Inclusion Criteria

I am a female aged 14-25 with almost no growth left in my bones.
Biochemical criteria: negative βHCG (pregnancy test), normal TSH, prolactin, potassium, ALT ≤3 times upper limit of normal, LDL ≤190 mg/dl
I am using non-hormonal birth control or a progestin IUD if I am of childbearing age and sexually active.
See 1 more

Exclusion Criteria

Pregnant, planning to become pregnant within 12 months of the end of treatment and/or breastfeeding
I currently smoke more than 10 cigarettes a day.
I have high blood pressure or I am taking medication for it.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive estrogen treatment for 12 months, either as a transdermal patch or oral pill, with additional calcium and vitamin D supplements.

12 months
4 visits (in-person) over 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • 17-beta estradiol
  • ethinyl estradiol
Trial Overview The study compares three estrogen treatments on bone strength: natural estrogen (17β-E2) as an oral pill or skin patch with cyclic progestin, and synthetic estrogen (ethinyl estradiol) as a birth control patch. The treatment method will be randomly assigned to participants who also take calcium and vitamin D supplements.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: transdermal EE+LNGExperimental Treatment1 Intervention
Group II: transdermal 17β-E2 with cyclic progestinExperimental Treatment1 Intervention
Group III: oral 17β-E2 with cyclic progestinExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials
802
Recruited
1,342,000+

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

Collaborator

Trials
2,103
Recruited
2,760,000+

Citations

Role of Estrogen on Skeletal Outcomes in FHAWhile combined oral contraceptive pills containing EE are not effective in improving bone outcomes, it is not clear whether oral 17β-E2 (a physiologic form ...
Effect of oral and transdermal oestrogen therapy on bone ...Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake. To systematically review the ...
3.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/16278618/
Oral hormone therapy with 17beta-estradiol and ...Compared with placebo, women receiving active treatment experienced greater reductions in bone resorption markers. The effects were evident by 6 months and ...
Effects of Estrogen Replacement on Bone Geometry and ...In young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol–containing ...
The effect of low-dose cyclic 17-ß-estradiol administration ...Cyclic 17-β-estradiol administration resulted in higher bone formation over time compared to continuous standard-dose administration.
EFFECT OF ORAL CONTRACEPTIVES ON BONE MINERAL ...Combined Oral Contraceptives (COCs) may be detrimental to the BMD of adolescents. However, low-dose are more protective than ultra-low-dose COCs.
Hormonal Contraception and Bone Health in AdolescentsUse of these medications has been associated with slower accrual of bone mineral density (BMD) and increased fracture risk in some studies. Far ...
Full article: A combined, bioidentical, oral, 17β-estradiol ...Cumulative amenorrhea rates from cycle 1 to 13 ranged from 56.1% (1 mg E2/100 mg P4 group, p < 0.001 versus placebo) to 73.1% in the 0.25 mg E2/50 mg P4 group (
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