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

Trial Summary

What is the purpose of this trial?

Dr. Nanette Santoro proposes to test the specific question that obesity results in abnormal estradiol response at the level of the pituitary and hypothalamus. This will be shown in diminished pituitary sensitivity to gonadorelin releasing hormone with a reduced estradiol induced luteinizing hormone surge in obese women.

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.

What data supports the effectiveness of the drug Estradiol 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 transfer in fertility treatments. This suggests it may help improve conditions for pregnancy in women undergoing fertility procedures. ^{1 2 3 4 5}

Is the estradiol patch generally safe for use in humans?

Research on estradiol patches, like Climara, shows they are generally safe for use in humans. Common side effects include weight gain, headache, and nausea, which are typical for estrogen therapy. Serious side effects are rare and can be managed with proper monitoring. ^{1 3 5 6 7}

How does the drug Estradiol differ from other treatments for female infertility?

Estradiol patches offer a unique way to deliver hormones through the skin, providing steady hormone levels and avoiding the digestive system, which can improve patient compliance compared to daily oral medications. This method minimizes fluctuations in hormone levels and reduces the risk of gastrointestinal side effects. ^{3 7 8 9 10}

Research Team

Nanette Santoro, MD

Principal Investigator

University of Colorado School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

References

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

New hormonal contraceptives: a comprehensive review of the literature. [2019]

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

Comparison between oral and vaginal estrogen usage in inadequate endometrial patients for frozen-thawed blastocysts transfer. [2018]

3. United States 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). [2019]

4. United States 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. [2013]

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

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

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

Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

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

The transdermal contraceptive system. [2007]

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]

10. Belgium pubmed.ncbi.nlm.nih.gov

[Medication of the month. Evra: first contraceptive transdermal patch]. [2019]