Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
Condition: Early Menopause; Menopause
MeSH terms: Menopause, Premature; Primary Ovarian Insufficiency
Study type: Interventional

Summary: 
      Women who enter menopause early are at a greater risk for developing cardiovascular disease
      later in life as compared to women with normal onset of menopause. This increased risk may be
      due to a prolonged length of time with decreased hormone levels post-menopause; however, this
      health risk remains understudied. The current study plan to study why women with early
      menopause are at higher risk for cardiovascular disease by evaluating their sympathetic
      nervous system and heart-blood vessel function. In addition, there is lack of promising
      treatment plans for cardiovascular disease in post-menopausal women. Therefore, the current
      study will also test the impact of dietary nitrate on post-menopausal women to determine if
      it might serve as a potential treatment to reduce risk of cardiovascular disease in older
      women.
    

Detailed description: 
      The current study is recruiting two groups of women aged between 60-70 years old; 1) women
      who had early natural/non-surgical menopause (age 40-44 yrs) and 2) women who had normal
      natural/non-surgical menopause (age 50-54). The investigators are recruiting women who do not
      have any cardiovascular disease, hypertension, diabetes, and other major health issue.

      The main hypothesis of the project is that early menopause negatively impacts the heart,
      blood vessel and nerve system due to the increased length of time with reduced hormone
      levels; which could explain the relationship between early menopause and greater risk of
      cardiovascular disease in later life. Sympathetic nerve system and cardiovascular functions
      will be evaluated in both groups to compare the impact of prolonged hormone deficiency. In
      addition, current study will examine the impact of inorganic nitrate supplementation (beet
      root juice) to see if there are any favorable changes after 2 weeks of beet root juice
      intake. There are 2 main test visits in the current study.

      Visit 1. Nerve system test (maximally take about 5 hours): Participants will rest in the
      supine position for ≥ 20 mins. Resting heart rate, breathing rate, finger blood pressure will
      be monitored. Cardiac output will be assessed using the acetylene gas rebreathing technique
      (1 hour). IV will be inserted for blood draw. Nerve signal search will be performed using a
      thin needle behind knee to find a signal from a specific nerve. At the same time,
      transcranial Doppler probe will be placed on the head to look at brain blood flow using soft
      head gear (1-2 hour). After acceptable signals are obtained, baseline data collection will
      begin. It will be followed by handgrip exercise and hand immersion to cold water to examine
      neural sympathetic response to different stimuli (30 mins). After this, to evaluate nerve
      response to different degrees of passive standings, a bed will be tilted to 30° and 60° for 8
      mins each. Blood samples will be obtained in the supine resting position and at the end of
      60° tilt (45 mins).

      Visit 2. Heart and vessel function assessment (Proximately take 2 hours): All measurements
      are non-invasive for this visit. Participants will rest in the supine position for ≥ 20 mins.
      Resting heart function will be assessed by ultrasound echocardiography (30mins). Vascular
      stiffness measurement will be performed using a probe placed on wrist, neck and leg groin
      area (30 mins). Vascular endothelial function will be measured using flow-mediated dilation
      and followed by smooth muscle responsiveness test will be performed by measuring brachial
      artery diameter changes for 10 min following 0.4 mg sublingual nitroglycerin administration
      (1 hour).

      After Visit 1-2, participant will be asked to drink either dietary nitrate supplementation or
      placebo for 2 weeks (randomly assigned). After 2 weeks intervention, participant will come
      back for post-intervention tests which are identical to visit 1 and 2.

      After completion of the first intervention, participants will have at least 2 weeks of
      wash-out period. After 2 weeks participant will be back to the lab and repeat the visit 1 and
      2, as well as 2 weeks of dietary nitrate supplementation or placebo. (For those who received
      2 weeks of nitrate supplementation for the first intervention, it will be a placebo for this
      intervention. For those who received placebo for the first intervention, it will be a nitrate
      supplementation for this intervention). After intervention participants will repeat the visit
      1 and 2 again.
    

Intervention name(s): Nitrate supplementation; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Subjects will drink 70 ml of beet root juice twice a day for 2 weeks.; Subjects will drink 70 ml of nitrate depleted placebo juice twice a day for 2 weeks.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 2 groups of women (early and normal menopause transition) will be enrolled to crossover design study in a fashion of randomized and double-blinded.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Neural control; Cardiovascular function; Inorganic nitrate supplementation