Estradiol Patch for Menopause

(LILAC Trial)

Overseen By Kerrie Moreau, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Estrogen patch

Must not be taking: Antihypertensives, Lipid lowering

Disqualifiers: Diabetes, High BMI, Cardiac disease, 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: 12

Duration: 20 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how changes in estrogen levels during menopause affect artery health and belly fat, which can increase heart disease risk as women age. Researchers are testing whether low estrogen levels impact artery function and belly fat, potentially linked to a pathway influencing aging. Participants will receive either a medication to lower estrogen (Degarelix), an estrogen patch (Transdermal Estradiol Patch), or a placebo patch. This trial suits premenopausal women with regular menstrual cycles who are not on hormonal birth control and exercise less than twice a week. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, offering participants a chance to contribute to understanding how these treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial requires participants to stop using medications that might affect blood vessel function, such as blood pressure medications, cholesterol-lowering drugs, and blood thinners. Additionally, participants must stop using antioxidant supplements and chronic NSAIDs (non-steroidal anti-inflammatory drugs) for 4 weeks before joining the study.

What is the safety track record for these treatments?

Studies have shown that the estradiol patch, applied to the skin, is generally well-tolerated and helps relieve menopausal symptoms. Research indicates that estradiol can alleviate hot flashes, support bone health, and might reduce belly fat gain. However, limited information exists on its long-term effects on heart health.

Degarelix, often used to treat endometriosis or fibroids, is generally safe and works by lowering estrogen levels.

Both treatments have been used before, but their combination in this trial is new. Monitoring their combined effectiveness is important. Always discuss potential side effects with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for menopause because they offer a fresh approach to managing symptoms. Unlike traditional hormone replacement therapies, which often involve oral pills or other forms of estrogen, these treatments use a transdermal estradiol patch. This delivery method can provide a steady release of hormones, potentially leading to more consistent symptom relief with fewer side effects. Additionally, one arm of the study combines the estradiol patch with degarelix, a drug typically used in prostate cancer treatment, which could offer a novel way to manage menopause symptoms by targeting hormone pathways differently. This combination might offer new hope for those who haven't found relief with standard therapies.

What evidence suggests that this trial's treatments could be effective for menopause?

Research has shown that skin patches containing estradiol effectively treat menopausal symptoms. Studies have found that these patches can reduce hot flashes by up to 84% and work as well as hormone pills. By raising estrogen levels, the patches can improve heart health and reduce belly fat, which is crucial since menopause often lowers estrogen and increases health risks like heart disease. Additionally, estradiol patches are well-tolerated and provide a steady release of hormones, making them a reliable option for many women. Participants in this trial may receive a transdermal estradiol patch combined with Degarelix or a transdermal placebo patch with Degarelix to evaluate the effectiveness of these treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Kerrie L Moreau, PhD

Principal Investigator

University of Colorado Denver Anschutz Medical Campus

Are You a Good Fit for This Trial?

This trial is for premenopausal women who are experiencing the transition to menopause, which may affect their artery health and increase belly fat. Participants should be generally healthy but concerned about obesity, low estrogen levels due to aging or menopause.

Inclusion Criteria

Not lactating in the last 3 months

Serum FSH <10 IU/L measured during days 1-10 of the menstrual cycle

Not on hormonal contraception in the last 3 months

Exclusion Criteria

Known hypersensitivity to study medications

Diabetic or fasted glucose >126 mg/dL

Body mass index (BMI) >35 kg/m2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (virtual or in-person)

Treatment

Participants receive either a low estrogen condition (GnRHant plus placebo patch) or a high estrogen condition (GnRHant plus estrogen patch) for 20 weeks

20 weeks

Weekly patch changes, with additional visits at weeks 9 and 17 for MPA administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Degarelix
• Transdermal Estradiol Patch
• Transdermal Placebo Patch

Trial Overview The study tests how estrogen affects artery function and abdominal fat gain in aging women. It involves a medication called Degarelix to lower estrogen levels, an Estradiol Patch to raise them in some participants, and a placebo patch with no active hormone for comparison over 20 weeks.

How Is the Trial Designed?

Group I: Degarelix plus transdermal placebo Experimental Treatment 2 Interventions

At baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus Placebo transdermal patch (applied twice per week)

Group II: Degarelix plus transdermal estradiol Experimental Treatment 2 Interventions

At baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus 0.075mg estradiol transdermal patch (applied twice per week)

Degarelix is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Firmagon for:

• Advanced hormone-dependent prostate cancer

Approved in United States as Firmagon for:

• Advanced prostate cancer

Approved in Canada as Firmagon for:

• Hormone-sensitive prostate cancer

Approved in Japan as Firmagon for:

• Prostate cancer

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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]

Menorest is a new transdermal patch that delivers 17 beta-estradiol in a microfine suspension, making it thinner and more cosmetically appealing than older patches.

It effectively maintains plasma estradiol levels at or above the target of 40 pg/ml for the entire 80-hour dosing period, demonstrating consistent and reliable hormone delivery across various doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New trends in transdermal technologies: development of the skin patch, Menorest. Marty, JP.[2016]

The 5-cm² transdermal patch (Estradot) caused less skin irritation compared to the larger 12.5-cm² patch (Climara), with a lower incidence of erythema (21.4% vs. 32.3%).

Adherence to the 5-cm² patch was slightly better, with 87.5% of patches remaining adhered compared to 82.0% for the 12.5-cm² patch, indicating it may be a more user-friendly option for estradiol delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study to evaluate skin irritation and adhesion of Estradot and Climara in healthy postmenopausal women. Ibarra de Palacios, P., Schmidt, G., Sergejew, T., et al.[2019]

The 7-day estradiol transdermal patch (Climara) effectively reduces hot flushes in women, with a mean decline of 74.6% for the higher dose compared to 64.5% for the lower dose, showing comparable efficacy to traditional hormone therapies.

The Climara patch is well tolerated, with a low withdrawal rate due to adverse events (8.9%), primarily related to skin reactions, and it demonstrated better adhesion compared to other patches, making it a practical option for estrogen replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy. Gordon, SF.[2019]

In a study involving 33 postmenopausal women, the Alora transdermal patch delivered a higher and more consistent level of estradiol compared to the Evorel patch, despite both being labeled to deliver the same amount of the hormone.

The Evorel patch showed a significantly higher fluctuation index and a lower overall estradiol exposure, indicating that Alora may provide a more stable hormone delivery, which could be important for effective hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems. Buch, AB., Shen, LZ., Kelly, SC., et al.[2019]

The study demonstrated that the test patch delivering 17 beta-estradiol (E2) at varying rates (37.5, 50, and 75 micrograms/day) produced consistent plasma E2 levels in postmenopausal women over a 4-day period, indicating effective transdermal delivery.

The systemic bioavailability of the test patch at 37.5 micrograms/day was comparable to that of a reference patch at 50 micrograms/day, suggesting that lower doses can achieve similar therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma profiles of transdermal 17 beta-estradiol delivered by two different matrix patches. A four-way cross-over study in postmenopausal women. Rohr, UD., Ehrly, AM., Kuhl, H.[2013]

In a study involving 208 healthy postmenopausal women, the Estradot transdermal estrogen patch caused significantly less skin irritation and had better adhesion compared to the Menorest patch after 72 hours of use.

Estradot also showed a lower rate of patch loss than Menorest, indicating it may be a more effective option for delivering estrogen therapy with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of irritation and sensitisation of two 50 microg/day oestrogen patches. Toole, J., Silagy, S., Maric, A., et al.[2019]

In a study of 205 menopausal women, both Menorest 50 and the reservoir transdermal estradiol patch significantly reduced the mean number of hot flushes from baseline, showing similar efficacy in treating menopausal symptoms over 12 weeks.

Menorest 50 demonstrated better local tolerability with fewer topical adverse events like erythema and pruritus compared to the reservoir patch, making it a potentially more comfortable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of Menorest 50 compared with Estraderm TTS 50 in the treatment of postmenopausal symptoms. A randomized, multicenter, parallel group study. Pornel, B., Genazzani, AR., Costes, D., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06264882

Cardiometabolic Consequences of the Loss of Ovarian ... The menopause transition is associated with a decrease in artery health and an increased risk for weight gain in storing fat in the stomach area which may ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10147786/

Effects of transdermal versus oral hormone replacement ... Transdermal estrogen preparations are considered as effective for treating menopausal symptoms [63] as the oral administration route [64]. However, the ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37942806/

Changes in menopausal symptoms comparing oral ... This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and ...

4. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2025/RD0073-MHT_Rapid_Review-final.pdf

Comparative Evidence Between Transdermal and Oral ... Hormone therapy may be prescribed to support individuals experiencing symptoms of menopause due to a decline in estrogen in the body.

5. dovepress.com dovepress.com/clinical-efficacy-of-estradiol-transdermal-system-in-the-treatment-of--peer-reviewed-fulltext-article-RRTD

Clinical efficacy of estradiol transdermal system in the ... The frequency of hot flashes was reduced in up to 84% of cases using doses as low as 0.025 mg/day. There were no significant differences between ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28622476/

The Effect of Transdermal Estrogen Patch Use on ... The transdermal estrogen patch provides relief from menopausal symptoms. However, there are limited data on mortality and cardiovascular ...

7. erc.bioscientifica.com erc.bioscientifica.com/view/journals/erc/24/8/ERC-17-0153.xml

Estradiol for the mitigation of adverse effects of androgen ... Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation and maintenance, and prevention of fat accumulation.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/206685Orig1s000Lbl.pdf

This label may not be the latest approved by FDA. For current ... There have been no efficacy and safety trials conducted with estradiol transdermal system. (twice-weekly). ... The estradiol transdermal system (twice-weekly) ...