Estradiol and Elagolix for Menopause

Overseen By Olivia K. Leach, MS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Penn State University

Must not be taking: Hormone therapy, Hormonal contraceptives

Disqualifiers: Chron's, Diverticulitis, Tobacco, others

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

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

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The frequency and severity of heat waves has increased in the last decades. Older adults (over 65 years) have impaired responses to heat stress making them at increased risk for adverse events. Previous heat waves report that women over 65 experience worse health outcomes than any other age group and age matched men. Aging and reproductive hormones, specifically estrogen, independently alter responses to heat stress. However, the combined effects of low estrogen following menopause and aging on the response to heat stress are unknown. In this study, the investigators will identify the role of estrogen in pre and post menopausal women on thermoregulatory responses to heat stress.

Do I need to stop my current medications for the trial?

The trial requires that participants are not using hormone therapy or hormonal contraceptives, so you would need to stop these medications if you are currently taking them.

What data supports the effectiveness of the drug Estradiol patch for menopause?

Research shows that the Estradiol patch is effective in reducing menopausal symptoms like hot flashes and improving quality of life. Studies have found it to be well-tolerated and convenient, with a low incidence of side effects. ^{1 2 3 4 5}

Is the estradiol patch safe for use in humans?

The estradiol patch has been generally well-tolerated in studies, with common side effects including breast tenderness, weight gain, and occasional skin irritation. It has been used safely in menopausal women, with few reported side effects, although some issues with patch adhesion were noted in warmer climates. ^{1 2 6 7 8}

How does the drug Estradiol patch differ from other menopause treatments?

The Estradiol patch is unique because it delivers hormones through the skin, which can be more consistent and better tolerated than oral options. It also offers flexibility in dosage and application site, potentially reducing side effects like skin irritation and improving adhesion compared to other patches. ^{2 4 7 8 9}

Research Team

W. Larry Kenney, Ph.D.

Principal Investigator

The Pennsylvania State University

Eligibility Criteria

This trial is for postmenopausal women over the age of 65 who are experiencing issues with body temperature regulation. Participants should not have any conditions that could interfere with hormone therapy or thermoregulation studies.

Inclusion Criteria

I am a woman aged between 42 and 64.

Exclusion Criteria

High-risk determined by the Atherosclerotic Cardiovascular Disease (CVD) Risk Factor Assessment

I am currently on hormone therapy.

I have a history of Crohn's disease or similar bowel conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Premenopausal women receive a GnRH antagonist to reduce estrogen, and postmenopausal women receive a transdermal estradiol patch to increase estrogen.

3 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Estradiol patch

Trial Overview The study tests how estrogen affects body heat management in older women. It involves an estradiol patch, which provides estrogen, and Elagolix Oral Tablet to counteract it, compared against placebo counterparts in a controlled environment.

Participant Groups

Group I: Premenopausal estrogen suppression Experimental Treatment 2 Interventions

Participants take a cellulose placebo tablet for 4 days prior to baseline testing and continue until experimental visits are complete. Following completion of placebo testing, participants begin taking 400 mg/day Elagolix for 4 days prior to testing and continue until experimental visits are complete.

Group II: Postmenopausal estrogen supplementation Experimental Treatment 2 Interventions

Participants wear a transdermal estradiol patch or placebo patch for 5 days prior to testing and continue until experimental visits are complete. After 48 hr washout, participants then wear the alternative treatment for 5 days prior to testing until experimental visits are complete.

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Findings from Research

The seven-day transdermal estradiol patch significantly reduced menopausal symptoms over six months, as indicated by a decrease in the average climacteric score from 27.18 at admission to 12.18 by the end of the study.

The patch demonstrated excellent adhesion with over 94% remaining securely in place, and it was generally well tolerated, with skin irritation being the most common side effect, primarily itching.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch for estrogen replacement therapy. Jarupanich, T., Lamlertkittikul, S., Chandeying, V.[2013]

The Women's Health Initiative (WHI) study raised safety concerns about hormone therapy, particularly focusing on a specific oral regimen of conjugated equine estrogen and medroxyprogesterone, which may not represent the broader population's response to hormone therapy.

In contrast, the once-weekly transdermal patch delivering 17beta-estradiol and levonorgestrel has been shown to effectively reduce vasomotor symptoms and improve quality of life without adverse effects like endometrial hyperplasia or negative impacts on cholesterol, making it a safer alternative for managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

17Beta-estradiol/levonorgestrel transdermal system for the management of the symptomatic menopausal woman. Shulman, LP.[2019]

In a study of 166 postmenopausal women, both a transdermal 17 beta-estradiol patch and oral estrogen therapy significantly reduced the average number of hot flashes from 6 per day to 1 per day over 12 weeks, showing similar efficacy between the two treatments.

The transdermal patch was associated with a greater reduction in other symptoms like sweating and difficulty concentrating, and had fewer skin-related side effects compared to oral estrogen, indicating it may be a safer alternative for managing postmenopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of transdermal with oral hormone substitution: a multicenter study with a new matrix patch]. Sajtos, B., Herold, J., Winkler, UH., et al.[2013]

In a study of 121 menopausal women using transdermal oestradiol patches for 3 months to 2.5 years, the patches were found to be effective in relieving menopausal symptoms, with most women preferring them over oral therapy.

The patches were generally well tolerated, with few side effects reported; however, some women experienced minor issues like breast tenderness and weight gain, and there were challenges with patch adhesiveness during hot weather.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Australian experience of transdermal oestradiol patches in a subtropical climate. O'Neill, S., Kirkegard, Y.[2019]

The new 7-day estrogen matrix patch (Climara) effectively alleviates climacteric symptoms in postmenopausal women, showing positive results in two 11-week placebo-controlled studies with good tolerance across different doses.

The 7-day patch demonstrated superior adhesion compared to the Estraderm patch, and absorption of estradiol was found to be higher and more consistent when applied to the buttock rather than the abdomen, indicating potential for optimized application sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a 7-day estrogen patch: principles and practice. Notelovitz, M.[2013]

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch for estrogen replacement therapy. [2013]

2. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints. [2019]

3. England pubmed.ncbi.nlm.nih.gov

17Beta-estradiol/levonorgestrel transdermal system for the management of the symptomatic menopausal woman. [2019]

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

A randomized study to compare the effectiveness, tolerability, and acceptability of two different transdermal estradiol replacement therapies. The Transdermal HRT Investigators Group. [2013]

5. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of Estraderm MX, a new estradiol matrix patch. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

[Comparison of transdermal with oral hormone substitution: a multicenter study with a new matrix patch]. [2013]

7. Australia pubmed.ncbi.nlm.nih.gov

An Australian experience of transdermal oestradiol patches in a subtropical climate. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Clinical experience with a 7-day estrogen patch: principles and practice. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of estradiol and of estrone during application of three strengths of an estradiol transdermal patch with active matrix. [2013]