Topical Estrogen for Menopause

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if two different topical estrogen products deliver similar amounts of estrogen to the body. The focus is on postmenopausal women using a gel or cream to manage menopause symptoms. Women who are naturally postmenopausal and have been without periods for at least a year may be suitable candidates. The study seeks women with no significant skin conditions who are comfortable applying the treatment to their thighs. As an Early Phase 1 trial, this research explores how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that EstroGel, a gel containing estrogen applied to the skin, is generally safe. Many women use it to relieve menopause symptoms like hot flashes and vaginal dryness. Common side effects include skin irritation and breast tenderness. However, using it without another hormone to balance it can increase the risk of cancer in the lining of the uterus.

Biest cream, another estrogen product applied to the skin, lacks official FDA approval for safety. It can cause side effects such as headaches, skin changes, and breast tenderness. Some reports suggest it might pose less risk than estradiol regarding breast cancer.

Both treatments have been used safely under a doctor's guidance, but Biest cream has less official support. Always consult a doctor to understand the benefits and risks before starting any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these menopause treatments because they offer new ways to deliver estrogen. While traditional options like oral estrogen pills and patches are common, EstroGel® 0.06% and Biest cream are both topical products, allowing estrogen to be absorbed directly through the skin, potentially reducing side effects associated with oral delivery. EstroGel® provides a controlled dose of estrogen in a gel form, while Biest cream uses a combination of two types of estrogen, aiming to mimic the body's natural hormone balance more closely. These innovative delivery methods could provide more personalized and potentially safer options for women experiencing menopause symptoms.

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

This trial will compare two treatments for menopause symptoms: EstroGel and Biest cream. Research has shown that EstroGel, a gel applied to the skin, effectively reduces the frequency and severity of moderate to severe hot flashes in menopausal women. Many women using EstroGel report high satisfaction with the treatment. Studies also indicate that it helps maintain bone health and supports other body functions affected by menopause.

Conversely, Biest cream, another treatment option in this trial, is a custom-made hormone therapy that has shown significant improvements in mood and hot flashes in menopausal women. However, it provides lower estrogen levels compared to standard treatments. Both treatments aim to relieve menopause symptoms by increasing estrogen levels in the body. ^{6 7 8 9 10}

Who Is on the Research Team?

Audra Stinchcomb, PhD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

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)

Provide written informed consent before initiation of any of the study procedures

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3131235/

Effectiveness of Compounded Bioidentical Hormone ...

Significant improvements or resolution of vasomotor symptoms were seen at 4 months in P4-treated patients compared to placebo (83% vs 19%; p < ...

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK562865/

The Safety and Effectiveness of Compounded Bioidentical ...

Estradiol has been shown to be one of the most effective hormone therapies for reducing vasomotor symptoms. ... Given that the effectiveness of estrogens is ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0378512213000194

A pharmacokinetic evaluation in a randomized clinical trial

This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the standard-dose estradiol ...

4.

liebertpub.com

liebertpub.com/doi/10.1089/jwh.2014.4770

Risks and Effectiveness of Compounded Bioidentical ...

Statistically significant improvements in mood symptoms (irritability, emotional lability, anxiety) were observed following initiation of ...

5.

acog.org

acog.org/clinical/clinical-guidance/clinical-consensus/articles/2023/11/compounded-bioidentical-menopausal-hormone-therapy

Compounded Bioidentical Menopausal Hormone Therapy

There are good data to support that some formulations of androgen therapy improve symptoms in postmenopausal women with sexual interest and arousal disorders, ...

6.

dailymed.nlm.nih.gov

dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c4d3860f-c211-b18c-e053-2a95a90a4474

Label: BIEST 5.0 ESTROGEN CREAM- estriol,estradiol cream

DISCLAIMER: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about ...

7.

uspharmacist.com

uspharmacist.com/article/biest-80-20-cream

Bi-Est 80/20 Cream

Common adverse effects of Bi-Est include fatigue, skin changes, headache, breast tenderness, and nausea.2,4. E3 (C18H24O3, MW 288.4) is a ...

8.

empowerpharmacy.com

empowerpharmacy.com/compounding-pharmacy/bi-est-cream/

Compounded Bi-est Cream

Common adverse events include breast tenderness, headache, vaginal discharge, and localized erythema at the application site; most are dose-dependent and ...

9.

gethealthspan.com

gethealthspan.com/treatments/bi-est-cream?srsltid=AfmBOopHGfEh5v2sgYdh2WIDpOUOP36-z-X0CWVPc7PIQxKgOniY2Q7k

Bi-Est 50/50 Cream | Bioidentical Estrogen for Menopause ...

When prescribed and monitored by licensed clinicians, bioidentical estrogen therapy is considered safe and effective for symptom relief in midlife. Healthspan ...

10.

journals.sagepub.com

journals.sagepub.com/doi/10.2217/17455057.4.2.163

Bioidentical Hormones for Menopausal Therapy

Animal data suggested that estriol-containing compounds may be safer than those containing estradiol with respect to causing breast cancer, so ...