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NCT Number: NCT04439370

Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women

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.

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Key information

Conditions

Hypertension Adnexal Diseases Blood Pressure Cardiovascular Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Menopause Menopause, Premature Ovarian Diseases Urogenital Diseases Vascular Diseases

Age range

35 year–70 year

Sex eligibility

Female

Study type

Observational

Primary location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location status: Recruiting

Location contact

Manda Keller-Ross, PhD, DPT, PT

CONTACT

[email protected]

612-625-3175

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Microneurography to measure muscle sympathetic nerve activity (MSNA)

Diagnostic Test

Microneurography is a direct measurement of electrical activity of peripheral sympathetic nerves

Baroreflex sensitivity testing

Diagnostic Test

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.

Sympathoexcitatory Maneuvers

Diagnostic Test

Cold Pressor Test (CPT) and Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO) will be performed

Blood tests

Diagnostic Test

Serum FSH, estrogen, progesterone, and testosterone will be measured

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

Secondary outcomes

  1. Respiratory Rate (breaths/min)

    Time frame: 3 hours

    Respiratory rate will be measured with a belt placed around the stomach and reported in units of breaths-per-minute.

  2. Heart Rate Variability (frequency)

    Time frame: 3 hours

    Heart rate variability will be measured using electrocardiogram and reported in units of Hertz.

  3. Heart Rate Variability (time)

    Time frame: 3 hours

    Heart rate variability will be measured using electrocardiogram and reported in units of milliseconds.

  4. Borg Rating of Perceived Exertion

    Time frame: 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.

  5. Numerical Pain Scale Rating

    Time frame: 3 hours

    Participants will be asked to rate pain on a scale from 0 to 10. Higher scores indicate greater pain.

  6. Blood Levels: Estrogens-E1

    Time frame: 75 minutes

    Serum concentration of estrogen-E1 will be reported in units of ng/ml.

  7. Blood Levels: Estrogen-E2

    Time frame: 75 minutes

    Serum concentration of estrogen-E2 will be reported in units of ng/ml.

  8. Blood Levels: Progesterone

    Time frame: 75 minutes

    Serum concentration of progesterone will be reported in units of ng/ml.

  9. Blood Levels: Testosterone

    Time frame: 75 minutes

    Serum concentration of testosterone will be reported in units of ng/ml.

  10. Blood Levels: Follicle-Stimulating Hormone (FSH)

    Time frame: 75 minutes

    Serum concentration of FSH will be reported in units of IU/L.

  11. Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO)

    Time frame: 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.

  12. Cold Pressor Test

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Manda Keller-Ross, PhD, DPT, PT

CONTACT

[email protected]

612-625-3175

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Registry information

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Jun 19, 2020
Registry last updated
Jan 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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