Topical Estrogen for Menopause

Recruiting in Baltimore (>99 mi)

Overseen By Audra Stinchcomb, PhD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Estrogens, Antihistamines, Corticosteroids, others

Disqualifiers: Smoking, Skin disorders, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 hours

4 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of the present study is to determine if two products can deliver bioequivalent amounts of estrogen (estradiol, estriol, and estrone).

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

Yes, you may need to stop certain medications. The trial excludes those who have used medications for menopausal symptoms within the last 30 days or during the study, and some chronic prescription medications within 30 days before the study. However, certain medications like thyroid medications, non-steroidal anti-inflammatory drugs, and cholesterol-lowering drugs may be allowed.

What data supports the effectiveness of the drug Topical Estrogen Product for menopause?

Research shows that transdermal estradiol, a form of estrogen applied to the skin, is effective in relieving menopausal symptoms like hot flashes and is well-tolerated by patients. It is considered as effective as oral estrogen treatments, with the added benefit of better patient compliance and fewer side effects. ^{1 2 3 4 5}

Is topical estrogen safe for use in humans?

Topical estrogen, such as transdermal estradiol, is generally considered safe for treating menopausal symptoms. Some mild skin irritation may occur, but serious side effects are rare. Studies show that these products have a good safety profile when used as directed. ^{5 6 7 8 9}

How does the topical estrogen drug for menopause differ from other treatments?

The topical estrogen drug for menopause is unique because it is applied directly to the skin, targeting skin-related symptoms of menopause like dryness and fine wrinkling, unlike oral or patch forms that primarily address systemic symptoms. This method can be more convenient and may have fewer systemic side effects, offering a cosmetic-like application that some patients find preferable. ^{8 10 11 12 13}

Research Team

Audra Stinchcomb, PhD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for postmenopausal women aged 45-65, of any ethnicity, with healthy major organs and no drug abuse history. Participants must have thighs at least 42 cm in circumference to apply the topical estrogen product and be deemed healthy by a medical professional.

Inclusion Criteria

Volunteer has mid thighs of at least 42 cm (16.5 in) in circumference to accommodate the products to be tested at an area of 400 cm2 per thigh

Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP)

I am a postmenopausal woman aged 45 to 65.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either EstroGel® 0.06% or Biest cream to determine bioequivalence

12 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Topical Estrogen Product

Trial Overview The study is testing whether two different topical estrogen products can deliver equivalent amounts of estradiol, estriol, and estrone to postmenopausal women when applied to their thighs.

Participant Groups

Group I: EstroGel® 0.06% Active Control 1 Intervention

EstroGel® 0.06% (1.25 g of gel)

Group II: Biest cream Active Control 1 Intervention

Biest cream (equivalent dose to EstroGel®)

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

In a six-month study of 460 post-menopausal women, transdermal estradiol was found to be as effective as oral conjugated equine estrogens for managing menopausal symptoms, with similar effects on the endometrium.

Patients using transdermal estradiol demonstrated better compliance and fewer drop-outs, and reported more physiological menstrual bleeding compared to those taking oral estrogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes. Polvani, F., Zichella, L., Bocci, A., et al.[2020]

Seventeen-beta-estradiol, delivered through the skin (transdermally), effectively alleviates menopausal symptoms, showing significant efficacy.

The treatment was well-tolerated by patients, indicating a favorable safety profile for this method of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. Grio, R., Piacentino, R., Abbondanza, M., et al.[2013]

Estradiol gel 0.1% significantly reduced the frequency and severity of moderate to severe vasomotor symptoms in postmenopausal women, regardless of their age, uterine status, or ovarian status, based on a reanalysis of a phase III clinical trial.

The study found no interactions between the treatment and factors like age or surgical history, indicating that estradiol gel is effective across different demographics of postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol gel 0.1% relieves vasomotor symptoms independent of age, ovarian status, or uterine status. Hedrick, RE., Ackerman, RT., Koltun, WD., et al.[2013]

The study found that a low dose of 0.87 g/d of transdermal estradiol gel significantly reduced the frequency and severity of hot flushes in postmenopausal women, demonstrating its efficacy in managing menopausal symptoms.

This lowest effective dose also improved symptoms of vulvovaginal atrophy without unexpected adverse effects, indicating it is a safe option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial. Simon, JA., Bouchard, C., Waldbaum, A., et al.[2013]

Transdermal estrogen products have become the preferred method for menopausal hormone therapy due to their efficacy and superior safety profile compared to oral formulations, especially after concerns raised by the Women's Health Initiative.

FDA-approved transdermal estradiol is favored over custom compounded bioidentical products because of its consistent quality and adherence to safety standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal delivery of bioidentical estrogen in menopausal hormone therapy: a clinical review. Files, J., Kling, JM.[2020]

A transdermal estradiol gel with a dose of 0.75 mg significantly reduced the frequency and severity of moderate to severe hot flushes in postmenopausal women, demonstrating its efficacy in managing symptoms.

The 0.75 mg dose was identified as the lowest practical dose that improved vaginal maturation index (VMI) and was well tolerated, with no serious treatment-related adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. Archer, DF., Pickar, JH., MacAllister, DC., et al.[2013]

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]

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]

Micellar nanoparticle estradiol emulsion (MNPEE) is an effective and FDA-approved transdermal therapy for managing moderate to severe menopausal vasomotor symptoms, showing no significant adverse effects compared to placebo in clinical trials.

MNPEE offers advantages over traditional transdermal estrogen therapies by minimizing skin irritation and maintaining stable plasma estradiol levels, making it a safer option for hormone therapy in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle delivery for transdermal HRT. Valenzuela, P., Simon, JA.[2012]

Estrogen deficiency during menopause leads to significant skin changes, including dryness, atrophy, and increased wrinkling, highlighting the importance of estrogen for maintaining skin health.

Topical treatments, such as estrogens and soy-derived isoflavones, may offer alternatives to systemic estrogen therapy for alleviating skin aging symptoms in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen-deficient skin: The role of topical therapy. Rzepecki, AK., Murase, JE., Juran, R., et al.[2020]

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]

Research is ongoing to find the ideal preparation for estrogen replacement therapy, with over 40 new products currently in development, primarily focusing on transdermal patches due to their increasing acceptance among women.

Most new oral formulations combine estrogen with progestin, highlighting a trend towards combination therapies, which may offer different benefits and risks for women with existing medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging delivery systems for estrogen replacement: aspects of transdermal and oral delivery. Nachtigall, LE.[2019]

The novel micellar nanoparticle emulsion containing 17beta-estradiol significantly reduces hot flash frequency by 85% after 12 weeks of daily application, making it an effective treatment for moderate-to-severe menopausal symptoms.

Patients reported high satisfaction with this cosmetic-like delivery system, which had a low incidence of mild side effects, suggesting it may improve treatment compliance compared to traditional methods like transdermal patches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol topical emulsion for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. Simon, JA.[2016]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

[Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. [2013]

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

Estradiol gel 0.1% relieves vasomotor symptoms independent of age, ovarian status, or uterine status. [2013]

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

Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Transdermal delivery of bioidentical estrogen in menopausal hormone therapy: a clinical review. [2020]

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

Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. [2013]

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

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

8. Germany pubmed.ncbi.nlm.nih.gov

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

9. Ireland pubmed.ncbi.nlm.nih.gov

Nanoparticle delivery for transdermal HRT. [2012]

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

Estrogen-deficient skin: The role of topical therapy. [2020]

11. Australia pubmed.ncbi.nlm.nih.gov

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

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

Emerging delivery systems for estrogen replacement: aspects of transdermal and oral delivery. [2019]

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

Estradiol topical emulsion for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. [2016]