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

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

Interventions

DRUG

Transdermal estradiol

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

DRUG

Standard of care - non hormonal

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.

Sponsors & Collaborators

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

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

45 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-11-30

Primary Completion

2028-11-30

Completion

2029-01-31