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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how hormone therapy can alleviate irritability in women experiencing menopause. It seeks to understand why some women become more irritable when their hormone levels change. Participants will use a real hormone patch (Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release) and a placebo (fake patch) to determine if the real patch reduces irritability. Women who have noticed increased irritability since their menstrual cycles began to change and have recently experienced a very stressful life event might be suitable for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, offering participants a chance to benefit from established therapy.

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.

What is the safety track record for these treatments?

Research shows that the estradiol patch, often used to relieve menopause symptoms, is generally well-tolerated. Common side effects include skin irritation at the application site, headaches, and breast tenderness. Some women might also experience bloating and increased vaginal discharge.

Similarly, progesterone, used in hormone therapy, is considered safe for treating menopause symptoms. However, it can cause sore breasts, light vaginal bleeding, and nausea. Some individuals might feel dizzy, sleepy, or notice mood changes.

Both treatments have FDA approval for managing menopause symptoms, indicating general safety. However, like any treatment, side effects can occur, and considering these is important when deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the hormone therapy involving an estradiol patch and progesterone for menopause-related irritability because it offers a targeted and potentially more balanced approach to managing symptoms. Unlike traditional oral hormone therapies, the estradiol patch delivers hormones through the skin, allowing for a steady release of medication and potentially reducing side effects. This method can provide a more consistent hormone level, which might lead to better symptom control. Additionally, the inclusion of progesterone following the estradiol treatment aims to balance hormone levels, potentially offering a more comprehensive and effective management of mood-related symptoms associated with menopause.

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

Research has shown that estradiol patches applied to the skin can reduce menopause symptoms such as hot flashes and sleep problems. This treatment also improves mood and lessens depression in menopausal women. In this trial, participants will receive estradiol patches in one of the treatment sequences. Studies have found that symptoms improve after using estrogen in forms like sprays or patches for three to six months.

Progesterone effectively addresses menopause symptoms. It can safely ease symptoms and improve sleep by reducing night sweats. In this trial, all participants will receive progesterone following the initial treatment sequences. In some cases, progesterone reduced menopause symptoms by 55%. Both treatments are strongly supported by medical research and are recommended for managing menopause symptoms. ^{6 7 8 9 10}

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11514567/

Hormone replacement therapy for menopausal mood ... The emotional state of treated menopausal women was also improved; the positive and negative affect scale score after three courses of therapy ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK614933/

Comparative Evidence Between Transdermal and Oral ... - NCBI In 1 RCT, oral estrogen was found to be as effective as, or sometimes more effective than, transdermal estrogen for relieving menopausal symptoms. However ...

3. gremjournal.com gremjournal.com/journal/04-2020/satisfaction-on-the-use-of-a-transdermal-spray-containing-1-53-mg-estradiol-for-the-treatment-of-symptoms-associated-with-menopause/

Satisfaction on the use of a transdermal spray containing ... CONCLUSION. Menopause-related symptoms improved both after 3 and after 6 months of estrogen application in the form of a transdermal spray. The ...

4. withpower.com withpower.com/trial/phase-4-menopause-4-2022-0555d

Hormone Therapy 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 ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/13697137.2024.2376185

Full article: Use of an estradiol transdermal spray in women ... Most patients in our cohort reported significant improvements in postmenopausal symptoms within 3 months of starting treatment with EMDTS and ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-transdermal-route/description/drg-20075306

Estradiol (transdermal route) - Side effects & dosage Estradiol transdermal gel, patch, and spray are used to treat moderate to severe symptoms of menopause (eg, feelings of warmth in the face, neck, and chest)

7. goodrx.com goodrx.com/estradiol/estradiol-patch-side-effects?srsltid=AfmBOorluiohMJHYoy9CBHED_b4KOqPTgy1Y3Rr8mRk5dWjMwzdfStzv

7 Common and Rare Estradiol Patch Side Effects Common estradiol patch side effects include skin irritation, headaches, and breast tenderness. Bloating and increased vaginal discharge are also ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/206685Orig1s000Lbl.pdf

This label may not be the latest approved by FDA. For current ... The interruption of treatment in women taking estradiol transdermal system (twice-weekly) might increase the likelihood of breakthrough bleeding, spotting and ...

9. webmd.com webmd.com/drugs/2/drug-177431/dotti-transdermal/details

Estradiol transdermal - Uses, Side Effects, and More When this happens, the vagina can become dry and irritated, bones can become weak and fragile, and you may have hot flashes or night sweats.

10. media.allergan.com media.allergan.com/actavis/actavis/media/allergan-pdf-documents/safety-data-sheets/ALORA-RM00008-AGHS-EN.pdf

SAFETY DATA SHEET Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females. Chemical Name. Medical Conditions Aggravated ...