MenopausePhase 4HERBRAVEHEARTNCT07732452
Hormone thERapy Effects on BRAin-HEART Health During the Menopausal Transition
A Phase 4 study testing Transdermal estradiol in people with Menopause and Perimenopause, run by McGill University Health Centre/Research Institute of the McGill University Health Centre.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older, women only
- Conditions the study is for
- Menopause, Perimenopause, Vasomotor Symptoms
- What is being tested?
- Transdermal estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Jan 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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).
- Current smoking.
- First-degree family history of premature cardiovascular disease, defined as myocardial infarction, stroke, or documented coronary artery disease occurring before age 55 years in a male relative or before age 65 years in a female relative.
- Eligible for systemic MHT (i.e., no formal contraindication to MHT).
- Able and willing to undergo research CMR and attend the 12-month follow-up assessment.
- Able to provide written informed consent.
- Not currently using systemic MHT at baseline, or willing to discontinue systemic MHT prior to randomization and remain off systemic MHT until allocation and baseline assessments are complete.
Who cannot join
- 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.
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- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: HER BRAVE HEART Trial - Hormone thERapy Effects on BRAin-HEART Health During the Menopausal Transition: A Randomized Feasibility Study
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?
Read more
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
- Being tested
- Transdermal estradiol, Standard of care - non hormonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transdermal estradiolDrug
Also called Estrogel® (estradiol 0.06% gel), Divigel® (estradiol 0.1% gel), Estradot® (estradiol transdermal patch), Climara® (estradiol transdermal patch)
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
Standard of care - non hormonalDrug
Also called Fezolinetant, Gabapentin, Oxybutynin, Selective serotonin reuptake inhibitor (SSRI)
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.
| Study group | Role | What they receive |
|---|---|---|
| Non Hormonal Management of Vasomotor Symptoms | Active comparator | Non hormonal management of vasomotor symptoms Receives: Drug: Standard of care - non hormonal |
| Transdermal Menopausal Hormone Therapy | Experimental | Not described Receives: Drug: Transdermal estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment Rate
Proportion of eligible women approached who consent to randomization, Percentage (%)
Measured: At enrollment
12-Month Retention Rate
Proportion of randomized participants completing the 12-month follow-up visit, Percentage (%)
Measured: 12 months
CMR Completion Rate
Proportion of participants completing both baseline and 12-month CMR examinations, Percentage (%)
Measured: 12 months
Crossover Rate
Proportion of participants in the no-MHT group who initiate systemic MHT during follow-up, Percentage (%)
Measured: 12 months
Secondary outcomes (18)
Myocardial oxygenation reserve
Percent change in myocardial signal intensity (ΔSI%) during breath-hold at 30 seconds relative to rest, assessed by OS-CMR (B-MORE)
Measured: Baseline and 12 months
Aortic distensibility
assessed by CMR, mmHg-¹
Measured: Baseline and 12 months
Aortic cross-sectional area
assessed by CMR, cm²
Measured: Baseline and 12 months
Left ventricular ejection fraction (LVEF)
Assessed by CMR, Percentage (%)
Measured: Baseline and 12 months
Left ventricular end-diastolic volume (LVEDV)
Assessed by CMR, mL
Measured: Baseline and 12 months
Left ventricular end-systolic volume (LVESV)
Assessed by CMR, mL
Measured: Baseline and 12 months
Left ventricular mass (LVM)
Assessed by CMR, grams (g)
Measured: Baseline and 12 months
LV mass-to-volume ratio (concentricity)
Assessed by CMR, g/mL
Measured: Baseline and 12 months
Global longitudinal strain (GLS)
Assessed by CMR, Percentage (%)
Measured: Baseline and 12 months
Superficial retinal capillary plexus vessel density
Assessed by OCT-A, Percentage (%)
Measured: Baseline and 12 months
Deep retinal capillary plexus vessel density
Assessed by OCT-A, Percentage (%)
Measured: Baseline and 12 months
Foveal avascular zone (FAZ) area
Assessed by OCT-A, mm2
Measured: Baseline and 12 months
FAZ perimeter
Assessed by OCT-A, mm
Measured: Baseline and 12 months
PROMIS Cognitive Function Short Form 8a score
Patient-reported cognitive function; scores range 8-40, higher scores indicate better cognitive function
Measured: Baseline and 12 months
RBANS Total Scale Score
Objective neuropsychological assessment of global cognitive function; standardized score (mean 100, SD 15), higher scores indicate better performance
Measured: Baseline and 12 months
Global native myocardial T1 according to vasomotor symptom burden
Baseline native T1 (ms) assessed by CMR, compared between women with high vs. low vasomotor symptom burden at baseline, defined by HFRDIS score
Measured: Baseline
LVEF according to vasomotor symptom burden
Baseline LVEF assessed by CMR, compared between women with high vs. low vasomotor symptom burden at baseline, defined by HFRDIS score, Percentage (%)
Measured: Baseline
Multivariable regression analysis of baseline predictors of 12-month change in global native myocardial T1
Exploratory multivariable linear regression will be used to identify associations between baseline clinical, lifestyle, and menopause-related factors (including age, BMI, blood pressure, lipid levels, smoking status, time since menopause, and vasomotor symptom burden) and 12-month change in global native myocardial T1 assessed by CMR. This analysis aims to identify candidate predictors for future cardiovascular risk stratification. The dependent variable is change in global native T1 (ms) from baseline to 12 months.
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Judy Luu, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07732452
- Sponsor's protocol ID
- MP-37-2026-12489
- Acronym
- HERBRAVEHEART
- Status last verified
- Jul 2026
- First submitted
- 25 Jun 2026
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No