Hormone Therapy for Menopause-Related Irritability

Overseen By Kayla Jensen

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Psychotropics, Hormonal preparations

Disqualifiers: Psychosis, Bipolar, Cardiovascular, 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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial uses an estradiol patch to help perimenopausal women with irritability by stabilizing their hormone levels. These patches have been used in various studies to treat menopausal symptoms, including hot flushes and depression, and are known for their convenience and effectiveness.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any psychotropic agents, hormonal preparations, or herbal supplements (other than multivitamins) that are believed to affect mood or menopausal symptoms.

Is hormone therapy for menopause-related irritability safe for humans?

Research shows that transdermal estradiol patches, used for hormone therapy, are generally safe for humans. They have a low incidence of side effects, such as skin irritation, and do not cause significant adverse changes in liver function or other safety variables. ^{1 2 3 4 5}

How does the drug for menopause-related irritability differ from other treatments?

This treatment uses a transdermal patch to deliver estradiol, which avoids liver metabolism and may reduce side effects compared to oral estrogen. It also includes progesterone, which is important for women who have not had a hysterectomy to prevent endometrial issues. ^{2 3 5 6 7}

What data supports the effectiveness of the drug Estradiol Patch for menopause-related irritability?

Research shows that transdermal estradiol patches are effective in reducing menopausal symptoms like hot flushes, depression, and sleep disturbances, which can contribute to irritability. Studies indicate that these patches are well-tolerated and preferred by many women over oral therapies. ^{1 2 3 8 9}

Who Is on the Research Team?

Susan Girdler, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Elizabeth Andersen, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for healthy women aged 45-59 in early menopause with variable menstrual cycles, increased irritability, and a BMI of 18-45. They must have had a stressful event recently and no history of heart disease, certain cancers, liver disease, severe hypertension, or mental health conditions requiring treatment.

Inclusion Criteria

Negative mammogram within the past two years

BMI between 18 - 45 kg/m^2

Have experienced 1+ very stressful life event (e.g. divorce, death of family member) within the past 6 months

Exclusion Criteria

I have a history of heart or blood vessel diseases.

I have experienced unexplained bleeding from my genital area.

I have had gallbladder problems in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either transdermal estradiol or placebo patch for 3 weeks

3 weeks

Weekly visits for monitoring and EEG assessments

Washout

Participants undergo a washout period to clear the effects of the first treatment

3 weeks

Treatment Phase 2

Participants receive the alternate treatment (placebo or estradiol) for 3 weeks

3 weeks

Weekly visits for monitoring and EEG assessments

Progesterone Treatment

All participants receive 200 mg/day of progesterone for 10 days

1.5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release
• Placebo
• Progesterone 200 mg

Trial Overview The study tests if an Estradiol Patch (hormone therapy) can stabilize mood changes related to estrogen fluctuations during perimenopause. Women will be randomly given either the hormone patch or a placebo along with Progesterone to see how it affects irritability.

How Is the Trial Designed?

Group I: Placebo, Then Estradiol Experimental Treatment 3 Interventions

Participants will first receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. After a washout period of 3 weeks, participants will then receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.

Group II: Estradiol, Then Placebo Experimental Treatment 3 Interventions

Participants will first receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. After a washout period of 3 weeks, participants will then receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 205 menopausal women, both Menorest 50 and the reservoir transdermal estradiol patch significantly reduced the mean number of hot flushes from baseline, showing similar efficacy in treating menopausal symptoms over 12 weeks.

Menorest 50 demonstrated better local tolerability with fewer topical adverse events like erythema and pruritus compared to the reservoir patch, making it a potentially more comfortable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of Menorest 50 compared with Estraderm TTS 50 in the treatment of postmenopausal symptoms. A randomized, multicenter, parallel group study. Pornel, B., Genazzani, AR., Costes, D., et al.[2019]

In a study involving 208 healthy postmenopausal women, the Estradot transdermal estrogen patch caused significantly less skin irritation and had better adhesion compared to the Menorest patch after 72 hours of use.

Estradot also showed a lower rate of patch loss than Menorest, indicating it may be a more effective option for delivering estrogen therapy with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of irritation and sensitisation of two 50 microg/day oestrogen patches. Toole, J., Silagy, S., Maric, A., et al.[2019]

The transdermal therapeutic system of estrogen (Estraderm) is effective in relieving hot flushes and vaginal atrophy, showing similar efficacy to oral estrogen treatments while maintaining bone health.

The patch is well tolerated with minimal side effects, such as low incidence of endometrial hyperplasia and breast tenderness, and patients generally prefer this method over oral administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with transdermal estradiol in the treatment of the climacteric. Utian, WH.[2013]

Citations

1. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of Menorest 50 compared with Estraderm TTS 50 in the treatment of postmenopausal symptoms. A randomized, multicenter, parallel group study. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Basic principles of hormone replacement therapy in the postmenopause]. [2016]

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

A randomized study to compare the effectiveness, tolerability, and acceptability of two different transdermal estradiol replacement therapies. The Transdermal HRT Investigators Group. [2013]

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

Transdermal estrogens in the changing landscape of hormone replacement therapy. [2017]

5. Ireland pubmed.ncbi.nlm.nih.gov

Transdermal oestrogen replacement therapy in a Finnish population. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Evaluation of irritation and sensitisation of two 50 microg/day oestrogen patches. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with transdermal estradiol in the treatment of the climacteric. [2013]

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

Transdermal hormonal contraception: benefits and risks. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and local tolerability of estradiol metered-dose transdermal spray to estradiol patch in a network meta-analysis. [2017]