Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women
Overview
- Phase
- Not Applicable
- Intervention
- Blood tests
- Conditions
- Hypertension
- Sponsor
- University of Minnesota
- Enrollment
- 160
- Locations
- 1
- Primary Endpoint
- Heart Rate (beats/min)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This is a cross-sectional study in which the investigators will determine the impact of premature/early menopause on MSNA, BP and baroreflex sensitivity in younger (≤49 yr old) and older (≥50 yr old) women. Specifically, aim one will determine mechanisms driving autonomic dysregulation of BP in premature and early menopausal women and aim two will determine mechanisms driving autonomic dysregulation of BP in older menopausal women. The study design outlined below will permit testing of aim one and aim two.
Detailed Description
Aim One: Determine mechanisms driving autonomic dysregulation of blood pressure (BP) in premature and early menopausal women. Because sympathetic activity and baroreflex function are important contributors for autonomic support of BP regulation, these two mechanisms will be assessed in premature and early menopausal women who are ≤49 yr old. To specifically identify the influence of menopause, these women will be compared to age-matched premenopausal women. The primary hypothesis is that there is greater resting sympathetic activity and blunted baroreflex function in premature and early menopausal women compared with age-matched premenopausal women. The secondary hypothesis is that BP and sympathetic reactivity will be greater in premature and early menopausal compared with age-matched premenopausal women when the sympathetic nervous system is challenged with a stressor. Aim Two: Determine mechanisms driving autonomic dysregulation of BP in older menopausal women. Because older age contributes to risk of CVD, it is imperative to assess the long-term effects of premature and early menopause in older (≥50 yr) women. To determine the impact of the premature loss of sex hormones on cardiovascular physiology, women whom have lived without functioning ovaries for \>10 yr will be compared to age-matched women who entered menopause at a typical age. The primary hypothesis is that resting sympathetic activity is greater and baroreflex function is attenuated in women who experience premature or early menopause compared with typically-aged menopausal women. The secondary hypothesis is that BP and sympathetic reactivity will be greater in premature and early compared with typically-aged menopausal women when the sympathetic nervous system is challenged with a stressor.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged 35-49 or 50-70 years of age who experienced premature (\<40) or early (≤45) menopause
- •Premenopausal 35-49 years of age
- •Typical-age menopause (i.e., after 45 years of age), who are between 50-70 years old
- •Menopause will be confirmed by subject report of amenorrhea for 12 months and serum FSH of \>30 mIU/mL
Exclusion Criteria
- •Current nicotine/tobacco use within the past six months
- •Are diabetic or asthmatic
- •Have diagnosed significant carotid stenosis
- •Have a history of significant autonomic dysfunction, heart disease, respiratory disease or a severe neurologic condition such as stroke or traumatic brain injury.
- •Have existing metabolic or endocrine abnormities
- •Take any heart/blood pressure medications that are determined to interfere with study outcomes
- •IF the participant is premenopausal AND currently taking OC or other exogenous steroids that are determined to interfere with study outcomes
- •Females who classify as having early or premature menopause AND are not willing to discontinue OC or MHT in order to complete the study
- •Are pregnant or breastfeeding
Arms & Interventions
Aim 2: Typical-Age Menopause
Participants in this group are women who experienced menopause at a typical age.
Intervention: Blood tests
Aim 1: Postmenopausal Women
Participants in this group are postmenopausal women.
Intervention: Microneurography to measure muscle sympathetic nerve activity (MSNA)
Aim 1: Postmenopausal Women
Participants in this group are postmenopausal women.
Intervention: Baroreflex sensitivity testing
Aim 1: Postmenopausal Women
Participants in this group are postmenopausal women.
Intervention: Sympathoexcitatory Maneuvers
Aim 1: Postmenopausal Women
Participants in this group are postmenopausal women.
Intervention: Blood tests
Aim 1: Premenopausal Women
Participants in this group are premenopausal women.
Intervention: Microneurography to measure muscle sympathetic nerve activity (MSNA)
Aim 1: Premenopausal Women
Participants in this group are premenopausal women.
Intervention: Baroreflex sensitivity testing
Aim 1: Premenopausal Women
Participants in this group are premenopausal women.
Intervention: Sympathoexcitatory Maneuvers
Aim 1: Premenopausal Women
Participants in this group are premenopausal women.
Intervention: Blood tests
Aim 2: Premature/Early Menopause
Participants in this group women who experienced premature or early menopause.
Intervention: Microneurography to measure muscle sympathetic nerve activity (MSNA)
Aim 2: Premature/Early Menopause
Participants in this group women who experienced premature or early menopause.
Intervention: Baroreflex sensitivity testing
Aim 2: Premature/Early Menopause
Participants in this group women who experienced premature or early menopause.
Intervention: Sympathoexcitatory Maneuvers
Aim 2: Premature/Early Menopause
Participants in this group women who experienced premature or early menopause.
Intervention: Blood tests
Aim 2: Typical-Age Menopause
Participants in this group are women who experienced menopause at a typical age.
Intervention: Microneurography to measure muscle sympathetic nerve activity (MSNA)
Aim 2: Typical-Age Menopause
Participants in this group are women who experienced menopause at a typical age.
Intervention: Baroreflex sensitivity testing
Aim 2: Typical-Age Menopause
Participants in this group are women who experienced menopause at a typical age.
Intervention: Sympathoexcitatory Maneuvers
Outcomes
Primary Outcomes
Heart Rate (beats/min)
Time Frame: 3 hours
Heart rate will be measured with a three-lead electrocardiogram (ECG) and reported in units of beats/min.
Muscle Sympathetic Nerve Activity (MSNA) (bursts/100 heart beats)
Time Frame: 3 hours
Muscle sympathetic nerve activity (MSNA) is a measurement of sympathetic activity. This is measured by two small needles are inserted behind or on the side of the knee, one needle is an acupuncture needle and one needle is a small recording microelectrode (same size as the acupuncture needle). Outcome will be reported in units of bursts per 100 heart beats.
Cardiac baroreflex sensitivity
Time Frame: 3 hours
Baroreflex sensitivity will be derived from electrocardiogram measurements and blood pressure measurements during the baseline rest period and by performing a modified valsalva maneuver which involves exhaling against 30-40 mmHg of pressure over 15 seconds after a normal inhalation. Outcome will be reported in units as ms/mmHg.
Sympathetic baroreflex sensitivity
Time Frame: 3 hours
Baroreflex sensitivity will be derived from electrocardiogram measurements and blood pressure measurements during the baseline rest period and by performing a modified valsalva maneuver which involves exhaling against 30-40 mmHg of pressure over 15 seconds after a normal inhalation. Outcome will be reported in units of MSNA bursts/mmHg.
Mean Arterial Blood Pressure (mmHg)
Time Frame: 3 hours
Blood pressure is measured using a non-invasive blood pressure cuff secured to the middle or ring finger and reported in units of mmHg.
Diastolic Blood Pressure (mmHg)
Time Frame: 3 hours
Blood pressure is measured using a non-invasive blood pressure cuff secured to the middle or ring finger and reported in units of mmHg.
Muscle Sympathetic Nerve Activity (MSNA) (bursts per minute)
Time Frame: 3 hours
Muscle sympathetic nerve activity (MSNA) is a measurement of sympathetic activity. This is measured by two small needles are inserted behind or on the side of the knee, one needle is an acupuncture needle and one needle is a small recording microelectrode (same size as the acupuncture needle). Outcome will be reported in units of bursts per minute.
Systolic Blood Pressure (mmHg)
Time Frame: 3 hours
Blood pressure is measured using a non-invasive blood pressure cuff secured to the middle or ring finger and reported in units of mmHg.
Secondary Outcomes
- Blood Levels: Testosterone(75 minutes)
- Numerical Pain Scale Rating(3 hours)
- Blood Levels: Estrogens-E1(75 minutes)
- Blood Levels: Follicle-Stimulating Hormone (FSH)(75 minutes)
- Cold Pressor Test(3 hours)
- Respiratory Rate (breaths/min)(3 hours)
- Borg Rating of Perceived Exertion(3 hours)
- Blood Levels: Estrogen-E2(75 minutes)
- Blood Levels: Progesterone(75 minutes)
- Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO)(3 hours)
- Heart Rate Variability (frequency)(3 hours)
- Heart Rate Variability (time)(3 hours)