Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women

Overview

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.

Interventions

• Diagnostic test Microneurography to measure muscle sympathetic nerve activity (MSNA)
  Microneurography is a direct measurement of electrical activity of peripheral sympathetic nerves
• Diagnostic test Baroreflex sensitivity testing
  Two arms of the baroreflex that will be tested in this study are sympathetic and cardiovagal. Static baroreflex is tested during baseline resting conditions and dynamic baroreflex is tested during Valsalva maneuvers.
• Diagnostic test Sympathoexcitatory Maneuvers
  Cold Pressor Test (CPT) and Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO) will be performed
• Diagnostic test Blood tests
  Serum FSH, estrogen, progesterone, and testosterone will be measured

Primary outcome measures

• Muscle Sympathetic Nerve Activity (MSNA) (bursts per minute) [Time frame: 3 hours]
• Muscle Sympathetic Nerve Activity (MSNA) (bursts/100 heart beats) [Time frame: 3 hours]
• Cardiac baroreflex sensitivity [Time frame: 3 hours]
• Sympathetic baroreflex sensitivity [Time frame: 3 hours]
• Systolic Blood Pressure (mmHg) [Time frame: 3 hours]
• Diastolic Blood Pressure (mmHg) [Time frame: 3 hours]
• Mean Arterial Blood Pressure (mmHg) [Time frame: 3 hours]
• Heart Rate (beats/min) [Time frame: 3 hours]

Secondary outcome measures (12)

• Respiratory Rate (breaths/min) [Time frame: 3 hours]
• Heart Rate Variability (frequency) [Time frame: 3 hours]
• Heart Rate Variability (time) [Time frame: 3 hours]
• Borg Rating of Perceived Exertion [Time frame: 3 hours]
• Numerical Pain Scale Rating [Time frame: 3 hours]
• Blood Levels: Estrogens-E1 [Time frame: 75 minutes]
• Blood Levels: Estrogen-E2 [Time frame: 75 minutes]
• Blood Levels: Progesterone [Time frame: 75 minutes]
• Blood Levels: Testosterone [Time frame: 75 minutes]
• Blood Levels: Follicle-Stimulating Hormone (FSH) [Time frame: 75 minutes]
• Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO) [Time frame: 3 hours]
• Cold Pressor Test [Time frame: 3 hours]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• University of Minnesota — Minneapolis

Identifiers

NCT: NCT04439370 · PT-2018-27097

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗