Estradiol Patches for Female Infertility

Recruiting at 1 trial location

Overseen By Katherine Kuhn

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Reproductive hormones

Disqualifiers: Diabetes, Smoker, Venous thromboembolism, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 7-10 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how an estradiol patch (a hormone therapy) might aid in understanding fertility issues in women, particularly how obesity affects hormone responses related to reproduction. The study tests whether hormone responses differ between women of normal weight and those with a higher BMI. Women with regular menstrual cycles who haven't recently used hormone treatments may be suitable candidates, especially if they have a BMI over 30 and are interested in fertility solutions. Participants will wear a hormone patch for a week to observe its effects on their body's fertility signals. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant fertility research.

Will I have to stop taking my current medications?

The trial requires that you have not used reproductive hormones in the past 3 months and that you do not use medications that interact with reproductive hormones. If you are on such medications, you may need to stop taking them to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that estradiol patches often help alleviate menopause symptoms, such as hot flashes, and are generally well-tolerated. However, studies like the Women's Health Initiative have identified potential risks, including an increased chance of heart attack, stroke, and certain types of cancer.

This study is currently in its second phase, indicating that while basic safety has been established, further information is needed to confirm its safety for treating infertility. Although estradiol patches have been used safely in the past, participants should be aware of these potential risks and discuss them with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for infertility?

Researchers are excited about the use of estradiol patches for female infertility because they offer a novel, non-invasive delivery method that could improve hormonal regulation. Unlike traditional fertility treatments, which often involve oral medications or injections, these patches simplify the process by delivering the hormone directly through the skin. This could result in a more consistent and steady release of estradiol, potentially leading to better timing of ovulation and increased chances of conception. Additionally, tailoring the patches for different body types, such as normal weight and high BMI women, allows for more personalized treatment, potentially enhancing effectiveness.

What evidence suggests that estradiol patches might be an effective treatment for female infertility?

Research has shown that estradiol patches prepare the uterus for embryo attachment, which is crucial for increasing pregnancy chances. Estradiol, in various forms, supports fertility treatments and improves pregnancy outcomes. In this trial, participants will be divided into two groups: normal-weight women and women with a high BMI, both using estradiol patches. One study found that estradiol patches helped women with early ovarian issues ovulate more regularly. These findings suggest that estradiol patches may assist with fertility challenges, particularly when hormonal balance is a concern. ^{6 7 8 9 10}

Who Is on the Research Team?

Nanette Santoro, MD

Principal Investigator

University of Colorado School of Medicine

Are You a Good Fit for This Trial?

This trial is for women who are dealing with obesity and infertility. Participants should have a body mass index (BMI) that classifies them as obese and be experiencing difficulties in conceiving. Specific details about inclusion or exclusion criteria were not provided, so interested individuals should contact the study organizers for more information.

Inclusion Criteria

I haven't used any hormonal birth control or hormone replacement therapy in the last 3 months.

No history of chronic disease impacting reproductive hormones

Negative pregnancy test

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 weeks

Treatment

Participants wear estradiol patches for up to 7 days and collect daily morning urine to determine LH surge

7-10 days

1 visit (in-person) for blood draw on day 3

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 trial is investigating how obesity affects the response to estradiol, a form of estrogen, at the brain level. It will look at whether overweight impacts hormone surges related to fertility using estradiol patches and testing their effect on hormone release in obese women.

How Is the Trial Designed?

Group I: Estradiol Patch- Women with high BMI Experimental Treatment 1 Intervention

Women with a BMI greater than 30 kg/m2 will wear a Transdermal estradiol patch for 7 days and collect urine to determine LH surge.

Group II: Estradiol Patch- Normal Weight women Experimental Treatment 1 Intervention

Normal weight women (NWW) will wear a Transdermal estradiol patch for 7 days and collect urine to determine LH surge.

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 Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Colorado Clinical & Translational Sciences Institute

Collaborator

Trials

21

Recruited

1,400+

Published Research Related to This Trial

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 a once-weekly transdermal estradiol patch applied to either the buttocks or abdomen, the buttock application resulted in significantly higher estradiol levels, with a 125.1% peak concentration compared to the abdomen.

The buttocks provided better bioavailability of estradiol, which may benefit women experiencing menopausal symptoms, as it maintained higher hormone levels throughout the week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). Taggart, W., Dandekar, K., Ellman, H., et al.[2019]

A comprehensive safety review of Estratest and Estratest HS, based on over 1 million woman-years of exposure from 1989 to 1996, found no significant safety concerns, with only 863 adverse events reported, which is relatively low given the extensive use.

The most common adverse events were typical of estrogen and androgen therapies, such as weight gain and headaches, and serious adverse events were rare, indicating that these medications are safe when used as directed, with manageable risks associated with their androgen component.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States. Phillips, E., Bauman, C.[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]

New hormonal contraceptive methods, such as the norelgestromin-ethinyl estradiol patch and etonogestrel-ethinyl estradiol vaginal ring, aim to improve compliance and reduce side effects compared to traditional oral contraceptives, which are taken daily.

Despite their different administration methods, these new contraceptives maintain similar efficacy and adverse effect profiles to oral contraceptives, making them viable alternatives for women who may struggle with daily pill adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New hormonal contraceptives: a comprehensive review of the literature. Forinash, AB., Evans, SL.[2019]

In a study involving 200 postmenopausal women, the topical micellar nanoparticle estradiol emulsion (MNPEE) significantly reduced the frequency of moderate to severe hot flushes, with a mean reduction of 11.1 hot flushes per day by week 12 compared to placebo.

MNPEE was found to be safe and well tolerated, demonstrating significant improvements in both the frequency and severity of vasomotor symptoms over a 12-week treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol in micellar nanoparticles: the efficacy and safety of a novel transdermal drug-delivery technology in the management of moderate to severe vasomotor symptoms. Simon, JA.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4842240/

A Comparison of the Effects of Transdermal Estradiol and ... This study showed no significant differences in implantation, biochemical and clinical pregnancy rates between the two examined groups. However, it provided ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00370019

Effects of an Estrogen Replacement Therapy Skin Patch on ... This study will determine whether giving estrogen replacement therapy through an estradiol patch can improve ovulation rates in women with spontaneous premature ...

3. withpower.com withpower.com/trial/estradiol-patches-for-female-infertility-59b0a

Estradiol Patches for Female Infertility Research shows that estradiol, used in various forms like patches and tablets, is effective in preparing the endometrium (lining of the uterus) for embryo ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/0002937895902503

Clinical experience with a seven-day estradiol transdermal ... The combined data also showed that the onset of efficacy is within 1 to 2 weeks after the start of therapy and that efficacy is fully sustained during the 7-day ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8022087/

Effect of transdermal estrogen dose regimen for ... There was no difference in clinical pregnancy rate (28.9% vs 28.2%, P =.837) and live birth rate (17.3% vs 21.4%, P =.201) between the ID and CD groups.

6. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-transdermal-route/description/drg-20075306

Estradiol (transdermal route) - Side effects & dosage Estradiol transdermal gel, patch, and spray are used to treat moderate to severe symptoms of menopause (eg, feelings of warmth in the face, neck, and chest)

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/020375s026lbl.pdf

Climara (Estradiol Transdermal System) - accessdata.fda.gov The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein.

8. medsafe.govt.nz medsafe.govt.nz/Profs/Datasheet/e/Estradiolpatch.pdf

Data Sheet – Estradiol Transdermal Patches Women should be advised that Estradiol Transdermal Patches is not a contraceptive nor will it restore fertility. During treatment, periodic ...

9. goodrx.com goodrx.com/climara/what-is?srsltid=AfmBOopt7kYYYWmAPGfblVya8PZHxKIe01EW5I9ulEH3w_c5VqeoCGXZ

Climara (estradiol patch): Uses, Side Effects, Dosage & ... The Climara (estradiol patch) is a once-weekly hormonal patch that relieves menopause symptoms and treats low estrogen levels.

10. novartis.com novartis.com/us-en/sites/novartis_us/files/Vivelle_DOT.pdf

Vivelle-Dot® (estradiol transdermal system) Pregnancy. Risk Summary. Vivelle-Dot is not indicated for use in pregnancy. There are no data with the use of Vivelle-Dot in pregnant women; however ...