Hormone thERapy Effects on BRAin-HEART Health During the Menopausal Transition

NCT07732452 | Not Yet Recruiting Phase 4

• 1 other identifier: MP-37-2026-12489
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn whether it is feasible to conduct a larger study comparing transdermal menopausal hormone therapy (MHT) versus no hormone therapy in menopausal women with vasomotor symptoms (hot flashes and night sweats) and at least one cardiovascular risk factor. The main questions it aims to answer are:

• What proportion of eligible women agree to be randomly assigned to either receive MHT or not?
• How many participants complete the 12-month follow-up, including repeat heart imaging?
• Does transdermal MHT affect early changes in heart muscle tissue as measured by cardiac MRI? Researchers will compare immediate initiation of transdermal estradiol (a skin gel or patch) to a no-hormone therapy strategy to see if MHT influences early cardiovascular and brain-vascular changes over 12 months. Participants will:
• Be randomly assigned to start transdermal MHT within 2 weeks, or to use no hormone therapy for at least the first 3 months
• Undergo a cardiac MRI and retinal eye imaging at the start of the study and again at 12 months
• Complete cognitive testing and questionnaires about symptoms, sleep, and stress at both visits
• Provide a blood sample for storage and future analysis of heart and brain health markers
• Receive follow-up phone calls at 3, 6, and 9 months to review symptoms, medications, and any health changes

Conditions

Menopause; Perimenopause; Vasomotor Symptoms; Cardiovascular Disease Risk Factor; Menopausal Hormone Therapy; Cardiac Remodeling; Myocardial Fibrosis; Microvascular Dysfunction; Cognitive Function Assessment

Outcome Measures

Primary Outcomes (4)

• Recruitment Rate

  Proportion of eligible women approached who consent to randomization, Percentage (%)

  At enrollment

• 12-Month Retention Rate

  Proportion of randomized participants completing the 12-month follow-up visit, Percentage (%)

  12 months

• CMR Completion Rate

  Proportion of participants completing both baseline and 12-month CMR examinations, Percentage (%)

  12 months

• Crossover Rate

  Proportion of participants in the no-MHT group who initiate systemic MHT during follow-up, Percentage (%)

  12 months

Secondary Outcomes (18)

• Myocardial oxygenation reserve

  Baseline and 12 months

• Aortic distensibility

  Baseline and 12 months

• Aortic cross-sectional area

  Baseline and 12 months

• Left ventricular ejection fraction (LVEF)

  Baseline and 12 months

• Left ventricular end-diastolic volume (LVEDV)

  Baseline and 12 months

Study Arms (2)

Non Hormonal Management of Vasomotor Symptoms

ACTIVE COMPARATOR

Non hormonal management of vasomotor symptoms

Drug: Standard of care - non hormonal

Transdermal Menopausal Hormone Therapy

EXPERIMENTAL

Drug: Transdermal estradiol

Interventions

Transdermal estradiol DRUG

Participants randomized to this arm will initiate systemic transdermal estradiol within 2 weeks of the baseline visit. The specific formulation and dose will be selected through shared decision-making between the participant and her physician based on individual clinical factors, tolerability, and patient preference. Permitted formulations include: Estrogel® (0.06% estradiol gel): 1 pump (0.75 mg) to 2 pumps (1.5 mg) applied daily Divigel® (0.1% estradiol gel): 1.0 mg sachet applied once daily Estradot® (estradiol patch): 25, 37.5, or 50 mcg, changed twice weekly Climara® (estradiol patch): 25, 37.5, or 50 mcg, changed once weekly Participants with a uterus will receive endometrial protection. First-line therapy is micronized progesterone (Prometrium® 100 mg orally once daily, continuous regimen). Alternative progestogens (medroxyprogesterone acetate 2.5 mg orally once daily or a levonorgestrel-releasing intrauterine device) may be used if clinically indicated or not tolerated. Dose ad

Also known as: Estrogel® (estradiol 0.06% gel), Divigel® (estradiol 0.1% gel), Estradot® (estradiol transdermal patch), Climara® (estradiol transdermal patch)

Transdermal Menopausal Hormone Therapy

Standard of care - non hormonal DRUG

Participants randomized to this arm will not initiate systemic menopausal hormone therapy for at least the first 3 months following randomization. Non-hormonal management of vasomotor symptoms is permitted at the discretion of the treating physician, and may include lifestyle interventions, supplements, and/or guideline-recommended non-hormonal pharmacologic therapies such as SSRIs/SNRIs, gabapentin, oxybutynin, or fezolinetant. If participants experience persistent or intolerable vasomotor symptoms despite non-hormonal management, initiation of systemic MHT may be proposed after 3 months based on shared decision-making between the participant and her treating physician. All crossovers will be documented including timing, reason, and regimen. Participants will remain analyzed in their originally assigned group for intention-to-treat analyses.

Also known as: Fezolinetant, Gabapentin, Oxybutynin, Selective serotonin reuptake inhibitor (SSRI)

Non Hormonal Management of Vasomotor Symptoms

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged ≥ 45 years.
• Perimenopausal or postmenopausal, defined as at least one of the following:
• Perimenopause, defined as menstrual cycle irregularity (changes in cycle length, skipped cycles, or amenorrhea ≥ 60 days) accompanied by vasomotor symptoms consistent with the menopausal transition.
• Postmenopause, defined as at least one of:
• ≥ 12 months of spontaneous amenorrhea, or
• bilateral oophorectomy, or
• hysterectomy with FSH \> 40 IU/L when menstrual history is unavailable.
• Vasomotor symptoms with a negative impact on quality of life, defined as :
• Recurrent hot flashes (sudden sensations of heat, typically involving the face, neck, or chest, often associated with flushing and/or sweating), and/or
• Night sweats (episodes of excessive sweating during sleep), With associated interference in daily functioning, sleep, or overall quality of life, such that the participant would be an appropriate candidate for systemic menopausal hormone therapy in clinical practice.
• Presence of at least one cardiovascular risk factor, defined as either:
• Hypertension (diagnosed hypertension, use of antihypertensive medication, or blood pressure ≥ 140/90 mmHg on screening).
• Dyslipidemia (diagnosed dyslipidemia, use of lipid-lowering therapy, LDL ≥ 3.0 mmol/L, or total cholesterol ≥ 5.2 mmol/L).
• Type 2 diabetes mellitus, defined as HbA1c ≥ 6.5%, fasting plasma glucose ≥ 7.0 mmol/L, or use of glucose-lowering medication.
• Obesity (body mass index ≥ 30 kg/m²).

You may not qualify if:

• Prior cardiovascular event or established cardiovascular disease, including myocardial infarction, stroke or TIA, coronary artery disease, heart failure, cardiomyopathy, or clinically significant valvular heart disease.
• Uncontrolled hypertension or other unstable cardiovascular condition (e.g., unstable angina, decompensated heart failure, uncontrolled arrhythmia).
• Formal contraindication to systemic menopausal hormone therapy, including estrogen-dependent cancer, unexplained vaginal bleeding, active severe liver disease, severe thrombophilia, antiphospholipid syndrome, prior or active VTE.
• Standard contraindications to MRI (e.g., MRI-incompatible pacemakers or intracardiac devices, certain metallic implants, metallic foreign bodies in the eye, or severe claustrophobia not manageable).
• Pregnant.
• Active cancer on ongoing cardiotoxic chemotherapy.
• Current use of systemic hormonal therapy outside the study strategy, including systemic menopausal hormone therapy, combined hormonal contraception, or systemic progestin-only contraception, with unwillingness or inability to discontinue prior to baseline and randomization.
• Ten years or more since menopause, defined as ≥10 years from the final menstrual period or from bilateral oophorectomy
• Participants currently using combined hormonal contraception or systemic progestin-only contraception who are willing to discontinue must complete a washout period of at least 4 weeks prior to the baseline visit and randomization

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

MeSH Terms

Interventions

Estradiol; Gels; fezolinetant; Gabapentin; oxybutynin; Selective Serotonin Reuptake Inhibitors

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Central Study Contacts

Amytis HEIM, MD

CONTACT

12633813556; amytis.heim@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD/PhD, FRCPC

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share