Neurovascular Responses to Hot Flashes
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Mayo Clinic
Must not be taking: Cardiovascular medications
Disqualifiers: Smoking, Obesity, Cardiovascular disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Women who experience hot flashes are at greater risk for hypertension and other cardiovascular disease. Neurovascular control mechanisms are likely to play an important role in this relationship. As such, these studies are designed to provide a major step forward in understanding the link between hot flashes and neurovascular dysfunction and, by extension, cardiovascular disease in women.
Will I have to stop taking my current medications?
Yes, you will need to stop taking any medications that influence cardiovascular function to participate in this trial.
What data supports the effectiveness of the drugs used in the clinical trial for treating hot flashes?
The research indicates that hot flashes are associated with changes in catecholamine levels, such as norepinephrine, which is one of the drugs being studied. This suggests that targeting these changes with norepinephrine-related treatments could potentially help manage hot flashes.
12345How does the drug norepinephrine differ from other treatments for hot flashes?
Norepinephrine is unique because it targets the thermoregulatory processes in the brain, specifically affecting the hypothalamic preoptic area, which is involved in heat dissipation. This approach is different from other treatments like estrogen, which works through unknown mechanisms, or clonidine, which reduces central sympathetic activation to widen the thermoneutral zone.
16789Eligibility Criteria
This trial is for non-obese women who are not on cardiovascular medications, have at least one ovary, do not smoke, and are free from cardiovascular diseases. It aims to understand the connection between hot flashes during menopause and risks of hypertension.Inclusion Criteria
I am not on any medications that affect heart function.
I do not have any heart diseases.
Non-obese
+2 more
Exclusion Criteria
N/A
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Study Visits
Participants undergo assessments of hot flash frequency, microvascular function, and autonomic function
1-2 visits
1-2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after study visits
4 weeks
Participant Groups
The study tests how substances like Norepinephrine affect blood vessels and heart function in women with hot flashes. It looks at body responses to stressors and drugs that influence blood pressure and flow during menopausal changes.
1Treatment groups
Experimental Treatment
Group I: Experimental: Healthy Women VolunteersExperimental Treatment5 Interventions
Hot Flash frequency will be assessed in the study subjects during a screening period. Participants can then chose to participate 1 or 2 study visits- Protocol 1: Microvascular function and/or Protocol 2: Autonomic function
Norepinephrine is already approved in United States, Canada, European Union for the following indications:
πΊπΈ Approved in United States as Levophed for:
- Severe, acute hypotension
- Cardiac arrest
π¨π¦ Approved in Canada as Norepinephrine Bitartrate for:
- Severe, acute hypotension
- Cardiac arrest
πͺπΊ Approved in European Union as Noradrenaline for:
- Severe, acute hypotension
- Cardiac arrest
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Institutes of Health (NIH)Collaborator
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Menopausal hot flashes: thermoregulatory, cardiovascular, and circulating catecholamine and LH changes. [2019]Thermoregulatory, cardiovascular and endocrine changes were simultaneously monitored in 11 post-menopausal women with frequent hot flashes (catecholamine and LH levels were measured in 5 and 6 subjects respectively). Plasma samples were obtained at 1- and 5-min intervals. Hot flashes were accompanied by abrupt increases in plasma epinephrine (about 150%) and concomitant decreases in norepinephrine (about 40%). Increased luteinizing hormone was associated with most hot flashes. A detailed sequence of hot flash-associated changes was established. An aura preceded the onset of the hot flash by several seconds. HR and FBF increased just before the onset of the flash and reached peak levels of 10-20 beats/min and 30-fold respectively. Coincident with vasodilation and sweating, finger temperature increased an average of 3.9 degrees C and esophageal temperature fell 0.2-0.6 degrees C. Flashes of both discrete and prolonged intervals were observed. Sensation was a reliable index of flash occurrence and intensity as measured physiologically. Our observations are consistent with the hypothesis that hot flashes are due to a change in the thermoregulatory set point. Furthermore, the changes in catecholamine levels are consistent with the cardiovascular changes accompanying hot flashes.
Association between vasomotor hot flashes and heart rate variability in recently postmenopausal women. [2010]The aim of this study was to investigate whether cardiovascular autonomic reactivity and risk profile are associated with the frequency and severity of hot flashes in recently postmenopausal women.
Cardiovascular autonomic responsiveness in postmenopausal women with and without hot flushes. [2013]During menopausal transition autonomic balance is known to shift towards sympathetic dominance, but the role of vasomotor hot flushes in this phenomenon is not understood. We compared cardiovascular autonomic responsiveness between women with and without hot flushes.
Subjective and objective measures of hot flashes. [2013]Up to 75% of women in the US report having experienced hot flashes during the menopausal transition. The purpose of this review is to describe the physiology of hot flashes, and the ways in which hot flashes have been examined by subjective report and by objective measurement. Hot flashes occur because of an activation of the heat dissipation response, possibly triggered by a hypothalamic mechanism within the context of declining estrogen levels. There is cross-population variation in the frequency of self-reported hot flashes, although cross-study comparisons are problematic because of incompatibilities in study design. Diaries are a good way to collect information on the time and severity of hot flashes, and body diagrams allow researchers to study the pattern of heat and sweating. Hot flashes can be objectively measured by increases in heart rate, finger blood flow, respiratory exchange ratio, skin temperature, and core body temperature. Sternal skin conductance is the method most highly correlated with subjective hot flash report. In a laboratory, concordance between subjective report and sternal skin conductance can approach 100%. Ambulatory monitoring allows for the tracking of hot flashes during a woman's daily routine or sleep; however, concordance is much lower with ambulatory, compared to laboratory, monitoring. The study of hot flashes at menopause provides a model for the study of any experience that can be assessed by both self-report and biometric measurement.
Moclobemide in the treatment of hot flashes in postmenopausal women. [2019]This randomized, prospective, double-blind study evaluated the efficacy and tolerability of moclobemide, a reversible, selective inhibitor of monoamine oxidase-A, in reducing the frequency and severity of hot flashes. Thirty postmenopausal women were enrolled, and 28 were allocated to 5 weeks of treatment with moclobemide 150 mg (group 1, n = 10), moclobemide 300 mg (group 2, n = 11), or placebo (group 3, n = 9). Data on hot flashes were recorded in a daily diary. Mean reductions in the hot flash severity score were 24.4% in the placebo group, 69.8% in group 1, and 35.0% in group 2. This large difference suggests that the beneficial effects were not due to a placebo effect. Moclobemide may be a new nonhormonal option for reducing the incidence, severity, and duration of hot flashes in postmenopausal women who do not wish to take estrogen or have contraindications to its use.
Clonidine raises the sweating threshold in symptomatic but not in asymptomatic postmenopausal women. [2019]To determine the effects of clonidine, which reduces central sympathetic activation, on the sweating threshold in postmenopausal women with and without hot flashes.
Physiology of hot flashes. [2013]Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.
Changes in TRPV1 expression in the POA of ovariectomized rats regulated by NE-dependent Ξ±2-ADR may be involved in hot flashes. [2021]Hot flashes (HF) caused by low estrogen in menopause result from changes in thermoregulatory processes in the hypothalamic preoptic area (POA). In the POA, transient receptor potential vanilloid 1 (TRPV1) participates in heat dissipation processes. Studies suggest that TRPV1 expression may be regulated by norepinephrine (NE)-activated Ξ±2-adrenergic receptors (Ξ±2-ADR) in the dorsal root ganglia. The goal of this study was to investigate the relationship between NE-regulated TRPV1 expression in the POA of ovariectomized rats and the development of HF.
Norepinephrine modulation of heat dissipation in female rats lacking estrogen. [2022]Postmenopausal hot flushes are caused by lack of estradiol (E2) but their neuroendocrine basis is still poorly understood. Here, we investigated the interrelationship between norepinephrine and hypothalamic neurons, with emphasis on kisspeptin neurons in the arcuate nucleus (ARC), as a regulatory pathway in the vasomotor effects of E2. Ovariectomized (OVX) rats displayed increased tail skin temperature (TST), and this increase was prevented in OVX rats treated with E2 (OVX + E2). Expression of Fos in the hypothalamus and the number of ARC kisspeptin neurons coexpressing Fos were increased in OVX rats. Likewise, brainstem norepinephrine neurons of OVX rats displayed higher Fos immunoreactivity associated with the increase in TST. In the ARC, the density of dopamine-Γ-hydroxylase (DBH)-immunoreactive (ir) fibers was not altered by E2 but, importantly, DBH-ir terminals were found in close apposition to kisspeptin cells, revealing norepinephrine inputs to ARC kisspeptin neurons. Intracerebroventricular injection of the Ξ±2-adrenergic agonist clonidine (CLO) was used to reduce central norepinephrine release, confirmed by the decreased 3-methoxy-4-hydroxyphenylglycol/norepinephrine ratio in the preoptic area and ARC. Accordingly, CLO treatment in OVX rats reduced ARC Kiss1 mRNA levels and TST to the values of OVX + E2 rats. Conversely, CLO stimulated Kiss1 expression in the anteroventral periventricular nucleus (AVPV) and increased luteinizing hormone secretion. These findings provide evidence that augmented heat dissipation in OVX rats involves the increase in central norepinephrine that modulates hypothalamic areas related to thermoregulation, including ARC kisspeptin neurons. This neuronal network is suppressed by E2 and its imbalance may be implicated in the vasomotor symptoms of postmenopausal hot flushes.