Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05251324 |
| Other study ID # |
STUDY00013742 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2022 |
| Est. completion date |
March 30, 2024 |
Study information
| Verified date |
October 2023 |
| Source |
University of Minnesota |
| Contact |
Manda Keller-Ross, PhD, DPT, PT |
| Phone |
(612) 625-3175 |
| Email |
kell0529[@]umn.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The overall objective of this study is to examine the physiological responses that occur
during a hot flush in postmenopausal women. The following specific aims will be executed to
reach the overall objective of this study. Aim 1: To determine if hot flushes can be reliably
induced with a temperature-controlled, water- circulating (TCWC) heating pad. Based on
previous research, the investigators hypothesize that hot flushes will be inducible with the
TCWC in symptomatic women, but not in asymptomatic women. Aim 2: To determine if heat-induced
hot flushes in symptomatic women will cause reproducible cardiovascular and respiratory
responses. The investigators hypothesize that heat-induced hot flushes produce similar and
reproducible cardiovascular and respiratory responses to spontaneous hot flushes. Aim 3: To
determine if body fat percentage influences hot flush severity or frequency during
spontaneous or induced hot flushes. The investigators hypothesize that women with higher body
fat have reduced hot flash severity and frequency.
Description:
Cardiovascular disease (CVD) increases aggressively after menopause and is the leading cause
of mortality in women in the US. Autonomic dysregulation and high blood pressure (BP), often
demonstrated in postmenopausal women, are directly linked to CVD. Women who experience
vasomotor symptoms (VMS) of menopause, such as night sweats or hot flushes, are at an
increased CVD risk. For example, VMS were associated with endothelial dysfunction, elevated
blood pressure (BP) and cholesterol, suggesting that VMS may be a marker of adverse vascular
changes associated with CVD. Thus, the investigators have designed a pilot study to 1)
replicate the hot flush induction protocol and 2) determine if the cardiovascular responses
(increased blood pressure and heart rate) during hot flushes are altered. The investigators
hypothesize that VMS, and in particular, hot flushes, will cause elevated BP and HR compared
with asymptomatic women. These findings will provide important information to physiological
responses of VMS in women, which will provide mechanistic insight to the greater
cardiovascular risk observed in women who report these symptoms compared with asymptomatic
women.
Hot flushes are the most common symptom of climacteric and are reported as feelings of
intense warmth along with sweating, flushing and chills. Indeed, it is suggested that 50-80%
of women post-menopause will experience hot flushes. Hot flushes usually last for one to five
minutes but can last up to an hour. The median duration of symptoms is about four years, but
some can last as long as 20 years. Although estrogen withdrawal is necessary to produce a hot
flush, it is not sufficient to explain the occurrence of them as some women do not experience
them, but all women experience a deficit in estradiol and progesterone during menopause.
There are also no relationships between symptoms and plasma, urinary, or vaginal levels of
estrogens, nor are there differences in plasma levels between women with and without hot
flushes. The putative physiological trigger of hot flashes is core body temperature
elevations acting within a reduced thermoneutral zone. This reduction appears to be closely
related to increased central nervous levels of norepinephrine (NE), partly through alpha 2
-adrenergic receptors. The involvement of NE in central thermoregulation and the etiology of
hot flushes are supported by results from experimental and animal studies that demonstrate
increased central nervous system NE levels narrow the width of the thermoneutral zone. During
hot flushes, skin temperature increases in digits, face, arms, chest, abdomen, back and legs;
sweating often occurs; and heart rate increases. In previous research, measurable sweating
occurred in 90% of hot flushes. Sweat rate corresponds closely to skin conductance, the
electrical measure of sweating, during hot flushes. Indeed, sternal skin conductance and skin
temperature are the gold standard objective measurement of a hot flush.
Body weight and adiposity are increased by estrogen deficiency, thus estradiol may have a
protective role against increased body fat in aging women. In addition, fat mass increases as
a consequence of aging and menopause in females. However, aromatase, the rate limiting enzyme
of androgen to estradiol conversion, is mainly produce in adipocytes (fat cells), where it
becomes an important source for estradiol in the postmenopausal period. Thus, the varying
levels of estradiol could influence hot flushes in women. Thus, it is important to
characterize fat mass in postmenopausal women to determine if body fat percentage influences
the severity or frequency of VMS, either spontaneous or induced.
Hot flushes occur spontaneously, which can make it challenging to measure their etiology and
physiological responses to them. Because these vasomotor symptoms are strongly connected with
CVD, it is important to understand the mechanism by which these symptoms may lead to CVD.
Thus, being able to reliably induce a hot flush is key to understanding these mechanisms.
Previous research has demonstrated that hot flushes can be induced pharmacologically with
yohimbine, an alpha 2 -adrenergic antagonist, and with controlled heating to the torso in
symptomatic women, but not asymptomatic women. While measuring physiological responses to hot
flushes, the investigators will be able to determine factors that contribute to the greater
CVD risk in women who experience VMS.
Importantly, being able to compare the responses of hot flushes to the predictable and known
responses to the cold pressor test. The investigators' central hypothesis is that hot flushes
can be induced in symptomatic women with a temperature controlled, water heating pad and that
BP and HR will be elevated in these women compared with asymptomatic women. If these findings
prove to be true, it suggests that women who have vasomotor symptoms may also demonstrate
exaggerated responses to stress and this may be occurring frequently in women who experience
these debilitating menopausal symptoms.
