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.
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.
Study Type
OBSERVATIONAL
Enrollment
160
Microneurography is a direct measurement of electrical activity of peripheral sympathetic nerves
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.
Cold Pressor Test (CPT) and Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO) will be performed
Serum FSH, estrogen, progesterone, and testosterone will be measured
University of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGMuscle Sympathetic Nerve Activity (MSNA) (bursts per minute)
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.
Time frame: 3 hours
Muscle Sympathetic Nerve Activity (MSNA) (bursts/100 heart beats)
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.
Time frame: 3 hours
Cardiac baroreflex sensitivity
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.
Time frame: 3 hours
Sympathetic baroreflex sensitivity
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.
Time frame: 3 hours
Systolic Blood Pressure (mmHg)
Blood pressure is measured using a non-invasive blood pressure cuff secured to the middle or ring finger and reported in units of mmHg.
Time frame: 3 hours
Diastolic Blood Pressure (mmHg)
Blood pressure is measured using a non-invasive blood pressure cuff secured to the middle or ring finger and reported in units of mmHg.
Time frame: 3 hours
Mean Arterial Blood Pressure (mmHg)
Blood pressure is measured using a non-invasive blood pressure cuff secured to the middle or ring finger and reported in units of mmHg.
Time frame: 3 hours
Heart Rate (beats/min)
Heart rate will be measured with a three-lead electrocardiogram (ECG) and reported in units of beats/min.
Time frame: 3 hours
Respiratory Rate (breaths/min)
Respiratory rate will be measured with a belt placed around the stomach and reported in units of breaths-per-minute.
Time frame: 3 hours
Heart Rate Variability (frequency)
Heart rate variability will be measured using electrocardiogram and reported in units of Hertz.
Time frame: 3 hours
Heart Rate Variability (time)
Heart rate variability will be measured using electrocardiogram and reported in units of milliseconds.
Time frame: 3 hours
Borg Rating of Perceived Exertion
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.
Time frame: 3 hours
Numerical Pain Scale Rating
Participants will be asked to rate pain on a scale from 0 to 10. Higher scores indicate greater pain.
Time frame: 3 hours
Blood Levels: Estrogens-E1
Serum concentration of estrogen-E1 will be reported in units of ng/ml.
Time frame: 75 minutes
Blood Levels: Estrogen-E2
Serum concentration of estrogen-E2 will be reported in units of ng/ml.
Time frame: 75 minutes
Blood Levels: Progesterone
Serum concentration of progesterone will be reported in units of ng/ml.
Time frame: 75 minutes
Blood Levels: Testosterone
Serum concentration of testosterone will be reported in units of ng/ml.
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Time frame: 75 minutes
Blood Levels: Follicle-Stimulating Hormone (FSH)
Serum concentration of FSH will be reported in units of IU/L.
Time frame: 75 minutes
Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO)
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.
Time frame: 3 hours
Cold Pressor Test
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.
Time frame: 3 hours