Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women

Recruiting

• Conditions: Blood Pressure; Menopause, Premature; Menopause; Hypertension
• Interventions: Diagnostic Test: Microneurography to measure muscle sympathetic nerve activity (MSNA); Diagnostic Test: Baroreflex sensitivity testing; Diagnostic Test: Sympathoexcitatory Maneuvers; Diagnostic Test: Blood tests

• Registration Number: NCT04439370
• Lead Sponsor: University of Minnesota

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-10-01
• Study First Submitted: 2019-10-28
• Study First Submitted QC: 2020-06-17
• Study First Posted: 2020-06-19
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-12
• Last Update Posted: 2024-04-15
• Primary Completion: 2025-04-30
• Study Completion: 2025-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 160

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Aim 1: Premenopausal Women	Microneurography to measure muscle sympathetic nerve activity (MSNA)	Participants in this group are premenopausal women.
Aim 1: Premenopausal Women	Blood tests	Participants in this group are premenopausal women.
Aim 2: Premature/Early Menopause	Blood tests	Participants in this group women who experienced premature or early menopause.
Aim 1: Premenopausal Women	Sympathoexcitatory Maneuvers	Participants in this group are premenopausal women.
Aim 2: Premature/Early Menopause	Baroreflex sensitivity testing	Participants in this group women who experienced premature or early menopause.
Aim 1: Postmenopausal Women	Microneurography to measure muscle sympathetic nerve activity (MSNA)	Participants in this group are postmenopausal women.
Aim 1: Postmenopausal Women	Sympathoexcitatory Maneuvers	Participants in this group are postmenopausal women.
Aim 1: Postmenopausal Women	Baroreflex sensitivity testing	Participants in this group are postmenopausal women.
Aim 2: Premature/Early Menopause	Microneurography to measure muscle sympathetic nerve activity (MSNA)	Participants in this group women who experienced premature or early menopause.
Aim 1: Postmenopausal Women	Blood tests	Participants in this group are postmenopausal women.
Aim 2: Typical-Age Menopause	Baroreflex sensitivity testing	Participants in this group are women who experienced menopause at a typical age.
Aim 2: Typical-Age Menopause	Blood tests	Participants in this group are women who experienced menopause at a typical age.
Aim 1: Premenopausal Women	Baroreflex sensitivity testing	Participants in this group are premenopausal women.
Aim 2: Premature/Early Menopause	Sympathoexcitatory Maneuvers	Participants in this group women who experienced premature or early menopause.
Aim 2: Typical-Age Menopause	Microneurography to measure muscle sympathetic nerve activity (MSNA)	Participants in this group are women who experienced menopause at a typical age.
Aim 2: Typical-Age Menopause	Sympathoexcitatory Maneuvers	Participants in this group are women who experienced menopause at a typical age.

Primary Outcome Measures

Name	Time	Method
Heart Rate (beats/min)	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)	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	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	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)	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)	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)	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)	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 Outcome Measures

Name	Time	Method
Blood Levels: Progesterone	75 minutes	Serum concentration of progesterone will be reported in units of ng/ml.
Respiratory Rate (breaths/min)	3 hours	Respiratory rate will be measured with a belt placed around the stomach and reported in units of breaths-per-minute.
Blood Levels: Estrogens-E1	75 minutes	Serum concentration of estrogen-E1 will be reported in units of ng/ml.
Blood Levels: Follicle-Stimulating Hormone (FSH)	75 minutes	Serum concentration of FSH will be reported in units of IU/L.
Borg Rating of Perceived Exertion	3 hours	Participants will be asked to rate their perceived exertion using the Borg Rating of Perceived Exertion scale. Scores range from 6-20 with higher scores indicating greater exertion.
Numerical Pain Scale Rating	3 hours	Participants will be asked to rate pain on a scale from 0 to 10. Higher scores indicate greater pain.
Blood Levels: Testosterone	75 minutes	Serum concentration of testosterone will be reported in units of ng/ml.
Cold Pressor Test	3 hours	The cold pressor test is done by placing the participant's hand in a bucket of ice-cold water for 2 minutes. The outcome measurements are the total change in systolic, diastolic and mean blood pressure from rest as well as how much blood pressure changes every 15 seconds. The measurement units are the change in blood pressure in mmHg.
Blood Levels: Estrogen-E2	75 minutes	Serum concentration of estrogen-E2 will be reported in units of ng/ml.
Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO)	3 hours	This test involves holding a hand grip device at 30% of the participant's maximum hand grip strength until they fatigue. At the end of this test a blood pressure cuff is inflated for two minutes. The outcome measurements are the total change in systolic, diastolic and mean blood pressure from rest as well as how much blood pressure changes every 15 seconds. The measurement units are the change in blood pressure in mmHg.
Heart Rate Variability (frequency)	3 hours	Heart rate variability will be measured using electrocardiogram and reported in units of Hertz.
Heart Rate Variability (time)	3 hours	Heart rate variability will be measured using electrocardiogram and reported in units of milliseconds.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States