Estradiol for Perimenopause

Overseen By Kathy Masso, BS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Delaware

Must not be taking: Blood pressure meds

Disqualifiers: Cardiovascular disease, Stroke, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how estradiol, a hormone, affects blood vessel health in women experiencing perimenopause. The goal is to understand why blood vessel issues occur as women age and how estradiol might help. Participants will receive either an estradiol patch or a placebo (a dummy treatment). Women with changing menstrual cycles for over two years may be suitable for this study. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, offering participants the chance to contribute to understanding its benefits for more patients.

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 is the safety track record for estradiol?

Research has shown that estradiol, a type of estrogen, is generally safe when used as directed. A large study from Finland found that estrogen did not increase the risk of breast problems. Additionally, studies indicate that topical forms of estrogen, such as creams, are well-tolerated by most healthy women. This suggests that using estradiol as a patch in this study should be safe for many women. However, some large studies have identified certain health risks associated with hormone therapy. Staying informed and discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike many current treatments for perimenopause, which often involve oral hormone therapy, this study explores transdermal estradiol, delivered through a patch. This method offers a unique advantage by providing a more steady release of hormones into the bloodstream, potentially minimizing fluctuations that can cause side effects. Additionally, transdermal delivery bypasses the liver, which may reduce the risk of certain side effects associated with oral hormone therapies. Researchers are excited about this approach because it could offer a safer and more consistent option for alleviating perimenopausal symptoms.

What is the effectiveness track record for estradiol in treating perimenopause?

Research has shown that estradiol effectively treats various menopause symptoms. In this trial, participants may receive transdermal estradiol, which studies have found can significantly reduce depression and overall discomfort during menopause. For instance, one study found that estradiol lowered the risk of depression in women going through menopause from 32% to 17%. Another study reported that 80% of patients experienced relief from menopause symptoms, such as hot flashes. Estradiol is a well-known treatment for menopause issues, suggesting it may also help improve heart and blood vessel health in women undergoing menopause. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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;

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol

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.

How Is the Trial Designed?

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 European Union, United States, Canada for the following indications:

Approved in European Union as Estradiol for:

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

Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

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+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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