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

Trial Summary

What is the purpose of this trial?

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 increase the risk for heart disease. The purpose of this research is to study how the decrease in estrogen at menopause changes artery health and fat gain, and risk of disease in women as they age. The first aim in this study will determine whether short term and long term low estrogen levels in premenopausal women decreases artery function and whether this is related to an increase in fat in the stomach area. The second aim will determine whether the changes in artery health and body fat are related to changes in a pathway that breaks down an important amino acid called tryptophan. This pathway is thought to play a role in regulating the aging process. Therefore, the investigators will determine whether the decrease in artery health and the increase in body fat in the stomach region with low estrogen is related to changes in this pathway in the blood, in vascular cells and fat tissue. Because estrogen levels fluctuate in premenopausal women, the investigators will use an approach (intervention) that controls estrogen levels to address these aims. The investigators will use a medication that is typically used to treat endometriosis or uterine fibroids to lower estrogen levels and an estrogen patch to increase estrogen in some women. Some women will receive a patch that has no estrogen (called a placebo patch). The intervention period will be 20 weeks. The study will provide us with new knowledge on how low estrogen with menopause affects artery health and fat gain estrogen.

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 data supports the effectiveness of the drug Estradiol Patch for menopause?

Research shows that transdermal estradiol patches, like Menorest 50 and Estraderm, significantly reduce hot flushes and improve menopausal symptoms such as vasomotor, psychiatric, and urogenital symptoms. These patches are effective in lowering the number of hot flushes from around 6.5 per day to less than 0.5 per day over 12 weeks. ^{1 2 3 4 5}

Is the estradiol patch safe for use in humans?

Research shows that estradiol patches, like Climara and Estradot, are generally well-tolerated in humans, with good skin adhesion and minimal irritation. Studies indicate that these patches are safe for use in hormone replacement therapy, with similar tolerance levels to other estrogen treatments. ^{1 2 3 4 6}

What makes the Estradiol Patch for Menopause treatment unique?

The Estradiol Patch for Menopause is unique because it uses a transdermal (through the skin) delivery system, which can provide a consistent release of estradiol, potentially reducing skin irritation and improving adhesion compared to other patches. This method may offer a more stable hormone level and is less invasive than oral treatments. ^{1 3 4 7 8}

Research Team

Kerrie L Moreau, PhD

Principal Investigator

University of Colorado Denver Anschutz Medical Campus

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative study to evaluate skin irritation and adhesion of Estradot and Climara in healthy postmenopausal women. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems. [2019]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. Ireland 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. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Evaluation of irritation and sensitisation of two 50 microg/day oestrogen patches. [2019]

7. Germany 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. [2013]

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

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