Menopause, Menopause Hot Flashes, Menopause Related Conditions, Cardiovascular
Conditions
Brief summary
What if midlife women, who are inherently at an increased risk for future cardiometabolic disease due to transitioning into menopause, had access to a suite of evidence-based health interventions? Could these interventions reduce menopause-related inflammation, restore a healthier cardiometabolic profile, reverse epigenetic aging, and reduce bothersome menopausal symptoms? The ultimate goal of this work is to attenuate future disease and enhance women's quality of life, extend healthspan and increase productivity.
Interventions
DRUGMetformin
Metformin will be given to participants who have a elevated HbA1c and also for weightloss.
DRUGsemaglutide
Overweight women and women with obesity will take Semaglutide for weight-loss
DRUGAnti-hypertensives
a. Antihypertensives, with the goal of maintaining blood pressure at 130/80 or lower per ACC guidelines19. Per current clinical guidelines and standard of care, hypertension will be treated first with monotherapy using either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a calcium channel blocker, or a thiazide diuretic provided that are no contraindications.
. First line agents will be generic statin medications (atorvastatin or rosuvastatin)whichever is covered by the participant's health insurance), barring contraindication to their use.
BEHAVIORALLife style intervention
will simply be followed and given preventive advice (maintenance of a normal BMI and physical activity, moderation in salt intake, and no more than 1 alcoholic drink per day). They will be provided with a wearable activity monitor. This advice will be based on guidelines by the American Heart Association and the Menopause Society.
DRUGFezolinetant
Women with menopausal symptoms will be treated with hormone therapy (estrogen and progesterone) if appropriate, or with a neurokinin receptor antagonist (Fezolinetant). This can be treatment for women in any arm of the study as well as an arm by its self.
DRUGHormonal therapy
Participants will be treated with estrogen and/or progesterone for treatment of hot flashes in women during the study.
Sponsors
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be placed into treatment interventions based on their health and screening tests.
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* aged 45-55 * In the late menopausal transition, defined as 60 days of amenorrhea but less than 365 days of amenorrhea18 * No current use of hormone therapy or hormonal contraception * Presence of a uterus and at least one ovary in order to track menstrual patterns * Have a smartphone and broadband access adequate to accept telehealth appointments
Exclusion criteria
* Lack of broadband access (activity and survey data will be collected electronically whenever possible and some visits will be via telehealth) * Lack of regular menstrual periods in mid-reproductive life (ages 25-38) when not on hormones or not pregnant. * Pregnancy or actively trying to get pregnant * Inability to adhere to study protocol schedule * Untreated alcoholism * Un- Diagnosed abnormal uterine bleeding * Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN 2) for participants with a BMI\> 30 kg/m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epigenetic aging measurements of "PhenoAge" | Up to 2 years | Change in epigenetic aging, as assessed by PhenoAge. PhenoAge calculates a biological age score based on key biomarkers circulating in the bloodstream. A lower PhenoAge score suggests slower biological aging, while a higher score indicates accelerated aging. |
| Epigenetic aging measurements of "GrimAge" | Up to 2 years | Epigenetic aging, as assessed by GrimAge. GrimAge assesses lifespan from examining DNA Methylation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IL-1 | Up to 2 years | Inflammatory IL-1 serum levels, examined to determine a person's inflammatory state. Higher levels of IL-1 can indicate more inflammation. Being in an "inflamed state" can have detrimental effects on a woman's health. |
| TNF-alpha | Up to 2 years | Serum inflammatory marker TNF-alpha. Higher levels of TNF-alpha can indicate more inflammation. TNF-alpha is examined to determine a person's inflammatory state. |
| IL-6 | Up to 2 years | Serum IL-6 levels. IL-6 is examined to determine a person's inflammatory state. Higher levels of IL-6 indicate more inflammation. Being in an "inflamed state" can have detrimental effects on a women's health. |
| IL-8 | Up to 2 years | IL-8 serum levels. IL-8 is examined to determine a person's inflammatory state. Higher levelf of IL-8 indicate more inflammation. Being in an "inflamed state" can have detrimental effects on a women's health. |
| Flow-mediated dilation | Up to 2 years | Flow-mediated dilation measures the diameter of vascular and endothelial cell function and predicts cardiovascular event risk. The diameter of the target artery is measured by high-resolution external vascular ultrasound in response to an increase in blood flow. |
| Serum Marker for Ovarian Aging | Up to 2 years | Anti-mullerian hormones (AMH) serum levels will be analyzed. AMH is an indicator of ovarian aging and reflects egg supply. Lower levels of AMH indicate a lower egg supply. |
| MENQOL survey | Up to 2 years | Menopause-specific Quality of Life (MENQOL) measures quality of life in menopausal women. It is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor, psychosocial, physical, and sexual. There will be a overall score and we are examining if there is a change in response to treatment. |
| Eaotoxin levels | Up to 2 years | Eaotoxin is a inflammatory marker that increases when there is an inflammed state in a woman. Serum Eaotoxin will be measured before, during and at the end of the study. |
Countries
United States
Contacts
CONTACTCarrie Hsu, BA
CONTACTNalia Naushad
PRINCIPAL_INVESTIGATORNanette Santoro, MD
University of Colorado, Denver
Outcome results
None listed