Estradiol Products 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: 4

Duration: 1 week

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using medications for menopausal symptoms and certain other medications within 30 days before the study. However, some medications like thyroid medications, non-steroidal anti-inflammatory drugs, and cholesterol-lowering drugs are allowed.

What data supports the effectiveness of the drug for menopause?

Research shows that estradiol gels like Divigel and Estrogel are effective in reducing moderate to severe vasomotor symptoms (hot flashes and night sweats) in postmenopausal women. Studies have demonstrated that these gels can decrease the frequency and severity of these symptoms, providing relief for women experiencing menopause. ^{1 2 3 4 5}

Is estradiol gel safe for humans?

Research shows that estradiol gels like Divigel and Estrogel are generally safe for treating menopausal symptoms, with studies focusing on their safety and effectiveness in reducing symptoms like hot flashes. ^{1 2 3 4 6}

How does the drug for menopause differ from other treatments?

The estradiol products for menopause, such as compounded estradiol gel and Estrogel, are unique because they are applied topically, allowing for direct absorption through the skin, which can provide a more consistent release of the hormone compared to oral medications. This method can also reduce the risk of liver metabolism and potentially lower the risk of certain side effects associated with oral hormone therapy. ^{1 3 5 7 8}

What is the purpose of this trial?

The purpose is to determine if the two estradiol products can deliver similar amounts of estradiol after single and multiple dosing.

Research Team

Audra Stinchcomb, PhD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for postmenopausal women aged 45-65 with healthy organ function and no drug abuse history. Participants must have legs long enough to apply the gel over a specific area and be comfortable with it. They should not be on any medication that could affect the study outcome.

Inclusion Criteria

Have normal screening laboratories for urine protein and urine glucose

Able to adhere to the study restrictions and study schedule

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

Exclusion Criteria

Participation in any ongoing clinical drug trial/study

Positive urine drug screening test

I have not donated or lost more than one pint of blood in the last 60 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Divigel 0.1% or a compounded estradiol product to evaluate serum concentrations over four consecutive days

1 week

Daily visits for 4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Compounded estradiol gel
• Estradiol
• Estrogel 0.06 % Topical Gel

Trial Overview The trial is testing two types of estradiol gels: Estrogel and a compounded version, to see if they deliver similar amounts of hormone after being applied once or multiple times.

Participant Groups

Group I: Divigel 0.1% Active Control 1 Intervention

Divigel 0.1% (1.25 g of gel/dose)

Group II: Compounded estradiol product Active Control 1 Intervention

Compounded estradiol product (equivalent to Divigel/dose)

Compounded estradiol gel is already approved in United States, Canada, European Union for the following indications:

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
• Palliation therapy for breast cancer
• Palliation therapy for androgen-dependent prostate cancer

Approved in Canada 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

Approved in European Union 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

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

Divigel 1.0 mg was found to be the most effective treatment for reducing hot flush frequency in postmenopausal women, significantly outperforming all other estradiol gel doses, including Estrogel 1.5 mg, which had the least efficacy.

While Divigel 1.0 mg showed the best efficacy, it also had a higher risk of treatment-related adverse events compared to placebo, indicating a trade-off between effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women: an indirect comparison meta-analysis. Derzko, C., Sergerie, M., Siliman, G., et al.[2018]

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]

In a 12-week study involving 488 postmenopausal women, estradiol gel 0.1% significantly reduced the frequency and severity of vasomotor symptoms, showing effects as early as Week 2 compared to placebo.

All three doses of estradiol gel 0.1% also improved signs of vulvar and vaginal atrophy, making it an effective treatment option with flexible dosing for managing menopause symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women. Hedrick, RE., Ackerman, RT., Koltun, WD., et al.[2013]

In a 12-month study involving 395 postmenopausal women, transdermal estradiol gel combined with either monthly or quarterly oral progestogen effectively reduced climacteric symptoms like hot flushes and vaginal dryness, with over 87% of participants completing the study.

Both treatment regimens showed similar bleeding patterns and endometrial safety, with only 0.3% of women experiencing endometrial hyperplasia, and 97% of participants found the gel to be acceptable or convenient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of an estradiol gel with monthly or quarterly progestogen on menopausal symptoms and bleeding. Hirvonen, E., Crona, N., Wahlström, T., 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]

In a study of 425 women undergoing in vitro fertilization, transdermal estradiol hemihydrate (Divigel) resulted in a comparable increase in endometrial thickness to oral estradiol valerate, while requiring significantly lower doses and shorter treatment duration.

Both treatment groups had similar pregnancy and 'take home baby' rates, indicating that transdermal estrogens are effective for improving endometrial conditions without increasing the total estrogen exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thin endometrium problem in IVF programs. Vartanyan, E., Tsaturova, K., Devyatova, E.[2021]

Oesclim, a new estradiol transdermal delivery system, demonstrated comparable pharmacokinetics to Vivelle 0.05 in delivering estradiol, with similar absorption rates and maximum serum concentrations in a study of 24 postmenopausal women.

Oesclim 50 showed better skin tolerance and adhesion compared to Vivelle 0.05, with no reports of skin intolerance for Oesclim 50, while skin issues were more common with the higher dose Oesclim 100 and Vivelle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacokinetics of 17 beta-estradiol after a single 4-day application of Oesclim 50, Oesclim 100, and Vivelle 0.05 (Menorest 50) transdermal delivery systems. Guichard, JP., Sauron, R., Jones, AB.[2019]

In a 12-week study involving 273 postmenopausal women, the estradiol transdermal delivery system significantly reduced the frequency of moderate-to-severe hot flushes compared to placebo, with effects noticeable as early as 2 weeks for the 100-microgram/d dose and 3 weeks for the 50-microgram/d dose.

While the treatment was effective, there were some estrogen-related side effects, such as breast pain and breakthrough bleeding, which were more common in the active treatment groups than in the placebo group, indicating a need for monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-masked, multicenter study of an estradiol matrix transdermal delivery system (Alora) versus placebo in postmenopausal women experiencing menopausal symptoms. Alora Study Group. Good, WR., John, VA., Ramirez, M., et al.[2019]

References

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

Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women: an indirect comparison meta-analysis. [2018]

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

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

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

Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women. [2013]

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

Effect of an estradiol gel with monthly or quarterly progestogen on menopausal symptoms and bleeding. [2019]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Thin endometrium problem in IVF programs. [2021]

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

Comparison of the pharmacokinetics of 17 beta-estradiol after a single 4-day application of Oesclim 50, Oesclim 100, and Vivelle 0.05 (Menorest 50) transdermal delivery systems. [2019]

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

Double-masked, multicenter study of an estradiol matrix transdermal delivery system (Alora) versus placebo in postmenopausal women experiencing menopausal symptoms. Alora Study Group. [2019]