Estradiol for Perimenopause

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Delaware

Must not be taking: Blood pressure meds

Disqualifiers: Cardiovascular disease, Stroke, Cancer, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies how estradiol, a form of estrogen, affects blood vessel health in peri-menopausal women. The goal is to see if estradiol can improve the function of cells lining the blood vessels, potentially reducing the risk of cardiovascular disease. Estradiol has been shown to reduce cardiovascular disease by direct and indirect effects on the cardiovascular system, with recent evidence suggesting beneficial actions of its metabolites.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used hormones like birth control or hormone replacement in the past 3 months.

What evidence supports the effectiveness of the drug Estradiol for perimenopause?

Research shows that hormone replacement therapy (HRT) with estradiol can improve menopausal symptoms like hot flashes and mood swings, and may also help with bone health and cholesterol levels. A study found that a low-dose estrogen contraceptive relieved symptoms in perimenopausal women, suggesting that estradiol could be effective for similar issues. ^{1 2 3 4 5}

Is estradiol generally safe for use in perimenopausal women?

Hormonal methods, including those with estradiol, are considered safer than initially thought, especially with lower-dose formulations. They can be used safely for healthy women without risk factors during perimenopause, and they offer additional health benefits beyond contraception. ^{1 6 7 8 9}

How does the drug Estradiol differ from other treatments for perimenopause?

Estradiol is unique because it can be administered in various forms such as patches, gels, or tablets, allowing flexibility in treatment. It directly supplements estrogen levels, which can help alleviate menopausal symptoms like hot flashes and mood swings, and is often combined with progestogens to prevent endometrial issues. This versatility and direct hormone replacement make it a distinct option compared to other treatments. ^{1 2 4 10 11}

Eligibility Criteria

This trial is for peri-menopausal women aged 40-58 living in Delaware, experiencing changes in their menstrual cycles or short-term amenorrhea. It's not open to those with cardiovascular disease, blood clots, stroke, cancer, liver disease, extreme body weights (BMI <18 or >30), tobacco users, pregnant/breastfeeding women, high blood pressure patients not controlled without medication.

Inclusion Criteria

Live in Delaware

I am a woman aged 40-58 experiencing irregular periods or a pause in my menstrual cycle.

Exclusion Criteria

I have a history of heart disease, blood clots, stroke, cancer, or liver disease.

I am a woman with high blood pressure, diagnosed or on medication.

Women who are pregnant, planning on becoming pregnant, or are breast feeding;

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transdermal estradiol or placebo for 7 days to assess changes in endothelial function

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Estradiol (Hormone Therapy)

Trial Overview The study tests the effects of Estradiol patches on vascular endothelial function in peri-menopausal women. Participants will either receive the Estradiol patch or a placebo to compare outcomes and understand how advancing reproductive age affects vascular health.

Participant Groups

Group I: Estradiol Experimental Treatment 1 Intervention

Transdermal estradiol (0.1mg/day patch)

Group II: Placebo Placebo Group 1 Intervention

Placebo

Estradiol is already approved in Canada for the following indications:

Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Who Is Running the Clinical Trial?

University of Delaware

Lead Sponsor

Trials

167

Recruited

25,700+

Harry Jiannan Wang

University of Delaware

Chief Executive Officer since 2023

PhD in Business Administration from Pennsylvania State University

Dr. Kenneth Gene Yancey

University of Delaware

Chief Medical Officer

MD from Harvard Medical School

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

A new oral contraceptive containing 20 micrograms of ethinyl estradiol and 150 micrograms of desogestrel effectively relieved climacteric syndrome symptoms in perimenopausal women over a 6-month treatment period, with no atypical endometrial hyperplasia observed.

The treatment led to a significant reduction in serum cholesterol levels and an increase in HDL-cholesterol, suggesting a potentially beneficial cardiovascular effect, while maintaining contraceptive properties that may appeal to women seeking fertility control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low estrogen-desogestrel contraceptive in perimenopausal hormonal replacement. Porcile, A., Gallardo, E., Onetto, P., et al.[2019]

In a study of 40 perimenopausal women over one year, both estrogen-progestogen regimens effectively reduced climacteric symptoms, but the intrauterine device (IUD) group experienced significantly fewer bleeding disturbances, with 15 out of 18 women becoming amenorrheic by the end of the study.

The use of a levonorgestrel-releasing IUD combined with oral estradiol not only diminished symptoms but also prevented endometrial proliferation, suggesting it is a safe and effective alternative for hormone replacement therapy in perimenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrauterine release of levonorgestrel--a new way of adding progestogen in hormone replacement therapy. Andersson, K., Mattsson, LA., Rybo, G., et al.[2013]

Oral contraceptives are beneficial for perimenopausal women by managing symptoms like hot flashes, preventing pregnancy, and offering economic savings.

A new hormone replacement therapy regimen using constant estrogen and intermittent progestin may enhance treatment adherence and reduce side effects due to its lower progestin dose and continuous effect on the endometrium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing the transition from oral contraceptives to hormone replacement therapy. Burkman, RT.[2005]

In a 48-week observational study, ERr 731 demonstrated long-term efficacy in reducing menopausal symptoms in perimenopausal women, with participants experiencing a significant decrease in symptoms over time.

The study found no clinically relevant safety concerns or adverse events associated with the long-term use of ERr 731, indicating it is a safe option for managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Hasper, I., Ventskovskiy, BM., Rettenberger, R., et al.[2015]

A study involving 37 patients using estradiol gel for hormone replacement therapy revealed that 70% did not use the gel as prescribed, indicating a significant issue with patient adherence.

Pharmacists play a crucial role in improving adherence by providing clear instructions and education about HRT, as proper use is essential for maximizing benefits like symptom relief and overall quality of life during menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The investigation of understanding and comfort of patients taking Divigel(®) 1 mg]. Soda, M., Ogawa, K., Harada, Y., et al.[2019]

Copper intrauterine devices (IUDs) are highly effective and safe for contraception in perimenopausal women, offering additional protection against endometrial cancer, although they may not be suitable for those with heavy menstrual bleeding.

Progestogen-based contraceptive methods are generally safe for most perimenopausal women due to their favorable cardiovascular profile, while combined hormonal contraceptives carry higher cardiovascular risks but provide significant health benefits, including protection against certain cancers and improvement of menstrual symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of perimenopausal contraception. Bitzer, J.[2020]

Many over-the-counter herbal and natural alternative medicines marketed for perimenopausal symptoms can have real physiological effects, including potential adverse effects and drug interactions.

Despite their popularity, these substances are largely untested and unregulated, raising concerns about their safety and efficacy compared to established treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of perimenopause: focus on alternative therapies. Thacker, HL., Booher, DL.[2019]

Hormonal contraceptive methods for perimenopausal women are safer than previously thought, especially with lower-dose formulations, and they also provide noncontraceptive health benefits.

Intrauterine devices (IUDs) are now recognized as very safe and effective, with infection risks mainly associated with the insertion process, while surgical sterilization remains the most popular choice among this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contraceptive Options for Perimenopausal Women. Plourd, DM.[2019]

During perimenopause, effective contraception is crucial to prevent unintended pregnancies, with hormonal methods and intrauterine devices (IUDs) being the most effective options.

Natural estrogen combined with a progestagen is a safe contraceptive alternative for perimenopausal women, and progestin-releasing IUDs can help reduce menstrual bleeding, addressing a common issue with traditional IUDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Contraception in the premenopause]. Rudolf, K.[2008]

In a study of 38 perimenopausal women, combined hormone therapy with transdermal estradiol and various oral progestogens effectively eliminated menopausal symptoms such as hot flashes and night sweats over a 6-month period.

The therapy also suppressed ovulation and hypothalamic-pituitary-ovarian function, indicating its potential to prevent unwanted pregnancies during the perimenopausal phase, while being well tolerated by participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women. De Leo, V., Lanzetta, D., Morgante, G., et al.[2019]

In a study of 100 patients with perimenopausal syndrome, those treated with estradiol valerate showed significant improvements in hormone levels, sleep quality, mood, and overall quality of life compared to the control group receiving conventional treatment.

The safety profile of estradiol valerate was found to be high, suggesting it is a promising option for clinical use in managing perimenopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Study of the Effect of Estradiol Valerate on Sleep Disorders, Negative Emotions, and Quality of Life in Perimenopausal Women. Zhang, J., Shao, S., Ye, C., et al.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Very low estrogen-desogestrel contraceptive in perimenopausal hormonal replacement. [2019]

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

Intrauterine release of levonorgestrel--a new way of adding progestogen in hormone replacement therapy. [2013]

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

Managing the transition from oral contraceptives to hormone replacement therapy. [2005]

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

Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. [2015]

5. Japan pubmed.ncbi.nlm.nih.gov

[The investigation of understanding and comfort of patients taking Divigel(®) 1 mg]. [2019]

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

Overview of perimenopausal contraception. [2020]

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

Management of perimenopause: focus on alternative therapies. [2019]

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

Contraceptive Options for Perimenopausal Women. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Contraception in the premenopause]. [2008]

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

Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women. [2019]

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

A Clinical Study of the Effect of Estradiol Valerate on Sleep Disorders, Negative Emotions, and Quality of Life in Perimenopausal Women. [2021]