Menopause
Conditions
Keywords
menopause, cognition, metabolism, estrogen, ketone, PET scan, estrogen receptor
Brief summary
This observational cross-sectional study aims to better understand how the menopausal transition affects brain energy metabolism and cognition. Menopause, a natural stage in a woman's life, is typically divided into three phases: premenopause, perimenopause, and postmenopause. This transition involves hormonal fluctuations and a decline in estrogen levels, which can impact physical, emotional, and cognitive well-being. Common symptoms include hot flashes, sleep disturbances, mood changes, and difficulties with memory and concentration. Emerging evidence suggests that the decline in estrogen may impair how the brain uses glucose, its primary energy source. This reduction in glucose metabolism is thought to contribute to cognitive difficulties reported during midlife. In contrast, the brain's capacity to use ketones-alternative energy substrates produced during fasting or low-carbohydrate intake-appears preserved during aging and hormonal changes. Increasing circulating ketones may offer a promising strategy to support brain energy and cognitive function. To explore these relationships, the study will employ advanced brain imaging (PET scans) to assess glucose and ketone uptake in the brain. Additional measures will include hormone levels, cognitive testing, continuous glucose monitoring, and MRI. PET tracers will also be used to evaluate estrogen receptor distribution, providing insight into how the brain responds to hormonal changes. A total of 45 women aged 35-60 will be enrolled and categorized into three groups (15 per group): premenopause, perimenopause, and postmenopause. Each participant will attend four study visits that include questionnaires, blood tests, cognitive assessments, metabolic measurements, and imaging procedures. The results may help identify early neurobiological and metabolic markers associated with the menopausal transition. These findings could inform new approaches to preserve brain health and prevent cognitive decline in aging women. Improving understanding of how the female brain adapts to hormonal shifts may ultimately support more targeted strategies for promoting healthy aging.
Interventions
None listed
Sponsors
Nestlé Health Science
Université de Sherbrooke
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Able to read and speak French * Capable of understanding and signing informed consent GROUP SPECIFIC INCLUSION CRITERIA Premenopause: • Women aged 35 to 55; No change in menstrual cycle regularity over the past 10 months (variation less than 7 days per cycle) Perimenopause: Women aged 40 to 60; Menstrual cycles varying by more than 7 days per cycle for at least 10 cycles, or no period for 3 to 11 months postmenopause: Women aged 45 to 65; No menstrual period for ≥ 12 months
Exclusion criteria
* Pregnancy, childbirth within the past 12 months, or breastfeeding * Use of hormone replacement therapy or hormonal contraceptives in the past 6 months * contraindications to MRI (e.g., presence of non-compatible metallic objects) * Claustrophobia * Type 1 diabetes * Adherence to a ketogenic intervention (e.g., ketone supplements, intermittent fasting, ketogenic diet) in the past 3 months * Engaging in intense physical activity 5 times per week or more * Any significant neurological disorder (e.g., dementia, brain tumor, seizure disorder, history of significant head trauma with persistent neurological deficits, known structural brain abnormalities) * History of oophorectomy or hysterectomy * Any significant psychiatric disorder (e.g., major depression within the past 2 years, bipolar disorder, schizophrenia) * Systemic diseases or unstable/uncontrolled medical conditions (e.g., cardiovascular disease, uncontrolled diabetes, kidney or liver disorders) * Any other condition that may interfere with participation, as judged by the study physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cerebral metabolic rates (μmol/100 g/min) measured by PET (11C-AcAc +18F-FDG) | 1 day at baseline | Brain energy metabolism will be quantified using two PET tracers: 11C-acetoacetate (for ketone use) and 18F-fluorodeoxyglucose (for glucose use). This will allow comparison of brain fuel usage between three menopausal groups (PRE, PERI, POST).Total Cerebral metabolic rates (μmol/100 g/min) (CMR tot= CMR acac + CMRglu) |
| Tracer influx rates (k) measured by PET (11C-AcAc +18F-FDG) | 1 day at baseline | Brain energy metabolism will be quantified using two PET tracers: 11C-acetoacetate (for ketone use) and 18F-fluorodeoxyglucose (for glucose use). This will allow comparison of brain fuel usage between three menopausal groups (PRE, PERI, POST). tracer influx rates (K values). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time in range | Over 5 days following sensor placement et stabilisation | Total minutes with glucose values within the standard glycemic range (3.9-10.0 mmol/L) over the 5 days monitoring period. (min) |
| Time-activity curves of the estrogen receptor in the brain (by 18F-4FMFES PET) | 1 day at baseline | Time-activity curves of the estrogen recept will be measured using 18F-4FMFES PET express as SUV (Standardized Uptake Value) |
| distribution volume ratio of the estrogen receptor in the brain (by 18F-4FMFES PET) | 1 day at baseline | distribution volume ratio of the estrogen receptor will be measured by kinetic modelisation using 18F-4FMFES PET. |
| Glucose variability (SD of glucose measured by continuous glucose monitoring) | Over 5 days following sensor placement et stabilisation | Continuous glucose monitoring (CGM) will track glucose levels over several days. Glycemic variability will be assessed by the standard deviation of glucose values over the 5 days monitoring period. (mmol/L) |
| Glucose average (mean of glucose measured by continuous glucose monitoring) | Over 5 days following sensor placement et stabilisation | Continuous glucose monitoring (CGM) will track glucose levels over several days. Average glucose concentration over the monitoring period.(mmol/L) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Boston naming tests (total answer) | 1 day at baseline | Measures language and word retrieval ability.Total correct responses (range: 0-60); higher scores are better |
| Symbol coding (score) | 1 day at baseline | Assesses processing speed.Score (higher = better) |
| Logical Memory Subtest of the Wechsler Memory Scale-IV | 1 day at baseline | Assesses elayed story recall. Score (0-25); higher scores indicate better memory |
| Fasting plasma glucose (mM) | 1 day at baseline | Blood samples will be used to assess the systemic metabolis plasma markers and will be compared across 3 groups |
| Fasting plasma insulin (mM) | 1 day at baseline | Blood samples will be used to assess the systemic metabolis plasma markers and will be compared across 3 groups |
| Fasting plasma HbA1c (%) | 1 day at baseline | Blood samples will be used to assess the systemic metabolis plasma markers and will be compared across 3 groups |
| Fasting plasma total ketone (uM) | 1 day at baseline | Blood samples will be used to assess the systemic metabolis plasma markers and will be compared across 3 groups. Total ketone = acetoacetate + beta-hydroxybutyrate |
| Estrogene levels (pmol/L) | 1 day at baseline | Blood samples will be used to assess sex hormone and will be compared across 3 group |
| follicule stimulating hormone levels (mIU/mL) | 1 day at baseline | Blood samples will be used to assess sex hormone and will be compared across 3 group |
| Progesterone (nmol/L) | 1 day at baseline | Blood samples will be used to assess sex hormone and will be compared across 3 group |
| hormone lutéinisante (mUI/mL) | 1 day at baseline | Blood samples will be used to assess sex hormone and will be compared across 3 group |
| Menopause-Specific Quality of Life Questionnaire | 1 day at baseline | Self-reported questionnaires. Self-reported symptom burden. Unit of Measure: Score (range: 0-44); higher = more severe symptoms |
| Menopause Rating Scale | 1 day at baseline | Self-reported symptom burden. Unit of Measure: Score (range: 0-44); higher = more severe symptoms |
| Pittsburgh Sleep Quality Index | 1 day at baseline | Self-reported questionnaire. Assesses sleep quality over the past month. Unit of Measure: Score (range: 0-21); higher = poorer sleep |
| Patient Health Questionnaire (PHQ-9) | 1 day at baseline | Depressive symptoms. Score (range: 0-27); higher = more severe depression |
| Subjective memory complain | 1 day at baseline | Self-reported memory or concentration issues. Unit of Measure: Score (range 62-372) ; higher scores indicate more complaints |
| International Physical Activity Questionnaire | 1 day at baseline | Physical activity over the past week. (MET-minutes/week) |
| Brain volume | 1 day at baseline | Will be measured by MRI - T1-weighted images and express in cm³ |
| Rey Auditory Verbal Learning Test (RAVLT) | 1 day at baseline | Assesses verbal memory. Total score (range: 0-75); higher scores indicate better performance |
| Stroop Color and Word test (Stroop Test) (secondes) | 1 day at baseline | Measures processing speed and executive function; outcome is time to completion. Unit of Measure: Seconds; lower scores indicate better performance |
| Trail making test (secondes) | 1 day at baseline | Assesses cognitive flexibility, visual attention, and processing speed. Unit of Measure: Seconds; lower scores indicate better performance |
| Montreal Cognitive Assessment (MoCA) score | 1 day at baseline | Global cognitive screening tool. Unit of Measure: Score (range: 0-30); higher scores indicate better cognition. |
Countries
Canada
Contacts
Primary ContactMelanie Fortier, M.Sc.
Outcome results
None listed