Clinical trial NCT04439370: Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women
Official title: Autonomic Regulation of Blood Pressure in Premature and Early Menopausal Women
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertension
Menopause, Premature
Menopause
Blood Pressure
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2020-06-19
Enrollment: 160
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Two scenarios of recruiting and enrolling premature/early menopausal females have been determined. 1) Enroll participants prior to starting MHT and/or 2) for patients already taking prescribed MHT, a standard protocol has been developed with Dr. Torkelson on guidelines for enrolling these participants. This includes a baseline estradiol (E2) blood draw, then in coordination with the participant and their physician, the participant will stop taking MHT. Estradiol will be tested every two weeks, up to 3 times (6 weeks). When estradiol is \<30 pg/ml for two weeks, participants will be enrolled in the study and can commence MHT immediately upon completion of study visit.

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.

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

Primary outcomes:
measure: Muscle Sympathetic Nerve Activity (MSNA) (bursts per minute)
timeFrame: 3 hours
measure: Muscle Sympathetic Nerve Activity (MSNA) (bursts/100 heart beats)
timeFrame: 3 hours
measure: Cardiac baroreflex sensitivity
timeFrame: 3 hours
measure: Sympathetic baroreflex sensitivity
timeFrame: 3 hours
measure: Systolic Blood Pressure (mmHg)
timeFrame: 3 hours
measure: Diastolic Blood Pressure (mmHg)
timeFrame: 3 hours
measure: Mean Arterial Blood Pressure (mmHg)
timeFrame: 3 hours
measure: Heart Rate (beats/min)
timeFrame: 3 hours
Secondary outcomes:
measure: Respiratory Rate (breaths/min)
timeFrame: 3 hours
measure: Heart Rate Variability (frequency)
timeFrame: 3 hours
measure: Heart Rate Variability (time)
timeFrame: 3 hours
measure: Borg Rating of Perceived Exertion
timeFrame: 3 hours
measure: Numerical Pain Scale Rating
timeFrame: 3 hours
measure: Blood Levels: Estrogens-E1
timeFrame: 75 minutes
measure: Blood Levels: Estrogen-E2
timeFrame: 75 minutes
measure: Blood Levels: Progesterone
timeFrame: 75 minutes
measure: Blood Levels: Testosterone
timeFrame: 75 minutes
measure: Blood Levels: Follicle-Stimulating Hormone (FSH)
timeFrame: 75 minutes
measure: Upper extremity fatiguing contraction with post exercise circulatory occlusion (PECO)
timeFrame: 3 hours
measure: Cold Pressor Test
timeFrame: 3 hours
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
References: