What side effects are associated with this type of intervention?

Common treatments for menopause, such as hormone therapy with estradiol, can have several side effects. Combined hormone therapy (estrogen and progestin) has been associated with an increased risk of invasive breast cancer, coronary heart disease, stroke, and pulmonary embolism. Estrogen-alone therapy may reduce the risk of coronary heart disease and breast cancer but can increase the risk of stroke and pulmonary embolism. Both therapies can improve symptoms like hot flashes and may reduce the risk of osteoporosis-related fractures. Non-hormonal treatments and lifestyle changes are also options but may have variable efficacy and fewer side effects.

What prior FDA approvals exist?

The FDA has approved several hormone therapies for the treatment of menopausal symptoms, particularly focusing on estradiol and its combinations. Estradiol, a bioidentical hormone, is commonly used in various forms such as oral tablets, transdermal patches, and topical gels. Conjugated equine estrogens (CEE) combined with medroxyprogesterone acetate have also been approved for women with an intact uterus to prevent endometrial hyperplasia. Additionally, non-hormonal options like SSRIs (e.g., paroxetine) and SNRIs (e.g., venlafaxine) have been approved for managing hot flashes in women who cannot or prefer not to use hormone therapy.

What other types of research exist?

Promising alternatives to estradiol therapy for menopause patients include: 1) High-dose progestogens, such as depot medroxyprogesterone acetate, which have shown efficacy in reducing hot flash frequency and severity. 2) Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which can help manage mood instability and hot flashes. 3) Elagolix, an oral GnRH antagonist, which has been effective in treating endometriosis-associated pain and may offer benefits for menopausal symptoms. 4) Non-hormonal options like cognitive-behavioral therapy (CBT) and lifestyle modifications, which can help manage symptoms without the use of hormones.

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Hormone Therapy

Hormone Therapy for Menopause-Related Irritability

Phase 4

Recruiting

Led By Susan Girdler, PhD

Research Sponsored by University of North Carolina, Chapel Hill

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Healthy women 45 - 59 years of age

Moderate to severe irritability symptoms, as defined by IDAS ill-temper scale score >10

Must not have

Personal history of any cardiovascular disease including coronary artery disease, arteriosclerosis, heart attack, stroke

Undiagnosed abnormal genital bleeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to week 13

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include skin irritation at the patch site, headaches, breast tenderness or pain, abdominal cramps or bloating. There's also a risk of more serious issues like blood clots due to hormonal changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a healthy woman aged between 45 and 59.

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I often feel very irritable, more than usual.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of heart or blood vessel diseases.

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I have experienced unexplained bleeding from my genital area.

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I have had gallbladder problems in the past.

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I have Type I diabetes.

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I am receiving treatment for severe psychological symptoms.

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I have a history of blood clots.

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I have had migraines with aura recently.

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My family or I have a history of breast, ovarian, or endometrial cancer.

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I have liver disease or dysfunction.

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I am not allergic to Climara® or peanut oil in Prometrium®.

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I have had a tumor that grows in response to estrogen.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to week 13

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to week 13

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to week 13 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Mean IDAS Ill Temper Scale Score Over Time

Secondary study objectives

Beta Oscillatory Activity (13-30 Hz) In Response To Affective Posner Paradigm (probing Frustration) Over Time

Theta Oscillatory Activity (4-8 Hz) In Response To Dot Probe Task (Indexing Threat) Over Time

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Placebo, Then EstradiolExperimental Treatment3 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 PlaceboExperimental Treatment3 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for menopause, particularly estradiol therapy, work by stabilizing fluctuating hormone levels, specifically estradiol, which can alleviate symptoms such as hot flashes, irritability, and mood swings. Estradiol, a form of estrogen, helps to replenish the declining levels of this hormone in menopausal women, thereby reducing the frequency and severity of vasomotor symptoms and improving overall quality of life. This stabilization is crucial as it addresses the neurophysiologic basis of susceptibility to estradiol fluctuations, which is linked to affective symptoms like irritability. Additionally, hormone therapy can have protective effects on bone density and may reduce the risk of osteoporosis and fractures. Understanding these mechanisms is important for menopause patients as it helps them make informed decisions about managing their symptoms and improving their long-term health outcomes.

Estrogen therapy in postmenopausal women: effects on cognitive function and dementia.