181
Mnturitas. 14 (1992) 181-188 Elsevier Scientific Publishers Ireland
Ltd
MAT 00668
Effect of fever on menopausal hot flashes Ruth M. Barnarda, “School
of Nursing,
Medicine,
College
(Received
University
of Michigan.
of Physicians
August
Some women report
Fredi Kronenbergb Ann
and Surgeons,
27, 1991; revision
received
Arbor, Columbia
November
and John A. Downeyb
MI
48109
and hDepartment
University,
New
York,
25, 1991; accepted
NY
of Rehabilitation 10032 ( U.S. A. )
December
12. 1991)
that they have fewer hot flashes when they have a fever. This is the tirst case of
physiological monitoring of hot flashes during fever in a subject with a well documented pattern of frequent hot flashes when afebrile. During fever, there were fewer hot flashes than during afebrile periods. and these hot flashes also tended to be less intense. For most of the period of reduced hot flashes. internal (core) temperature was elevated, above 375°C. When the fever broke, hot flashes resumed in a pattern similar to that of afebrile periods. Possible explanations for the reduction in hot flashes during a fever include: (I) a hot flash is triggered, but the characteristic physiological changes do not occur due to competing thennoregulatory drives, (2) the febrile core temperature inhibits whatever it is that triggers a hot flash; or (3) some product of the fever process inhibits the hot flash trigger or masks the physiological changes
that occur during
Key wordr: monitoring
hot flash;
hot flashes.
hot flush; fever; menopause;
body
temperature;
thermoregulation;
ambulatory
Introduction
Hot flashes are experienced by 75% of women around the time of menopause, and about 15% of these women experience severe hot flashes that significantly decrease their quality of life [ 11.A hot flash is a transient event during which there is a sudden feeling of intense heat, flushing and sweating, sometimes followed by a chill. Core temperature typically drops, reflecting the loss of heat due to the vasodilation and sweating. These patterns of physiological changes during a hot flash are similar to those which occur when a fever breaks. Fever is an elevation of core temperature resulting from an upward shift in the thermoregulatory set-point [2-41. When the set-point returns to normal, the fever breaks, with characteristic sweating and flushing, as the body acts to return internal temperature to normal. The analogy between a hot flash and fever has led to the hypothesis that a hot flash, like a fever, involves a perturbation of the thermoregulatory system, but in the opposite direction. That is, a transient lowering of the thermoregulatory set-point occurs during a hot flash [5,6]. The hypothesis that a hot flash is a thermoregulatory event is furCorrespondence
Surgeons,
to: F. Kronenberg,
Columbia
University,
Department of Rehabilitation New York, NY 10032, U.S.A.
0378-5122/92/$05.00 0 1992 Elsevier Printed and Published in Ireland
Scientific
Publishers
Ireland
Medicine,
Ltd
College of Physicians
and
182
ther strengthened by the results of a recent study that showed that ambient temperature, which is known to affect thermoregulation, also influences the frequency and intensity of hot flashes, with fewer hot flashes occurring at the cooler ambient temperature [7]. In addition, some of our subjects recalled that their hot flashes decreased or stopped completely when they had a fever. Perhaps fever, which alters normal thermoregulatory processes, also affects hot flashes. Our goal was to document objectively what had previously been reported by women, that is, the suppression of hot flashes during fever. We wanted to see whether hot flashes were actually suppressed during fever, or whether they occurred during fever but were not distinguishable from the feverish feeling. We report here on the documentation of the reduction in the frequency and reported intensity of hot flashes in a post-menopausal woman during fever. Subjects and Methods Subjects
Subjects with frequent hot flashes (IO+/day) who participated in our laboratory studies were asked to notify us if they ever developed a fever. One subject experienced two spontaneous fevers within a l-year period. During these fever episodes, she agreed to be monitored in her home. This subject was 53 years old at the time of the first fever, and had experienced menopause about 6 years earlier. She had been experiencing hot flashes for more than 11 years, and recalled that her hot flashes had been less frequent and intense when she had been febrile with a cold or flu. Because she had been a subject for the past 2 years in several of our laboratory studies, we had extensive documentation of her hot flashes when she was afebrile. Measurements
All physiological variables were recorded at 30-s intervals on a Squirrel Physiological Monitor (Science Electronics, Dayton, OH). The Squirrel is a portable microprocessor data logger with a computer interface. Heart rate was measured using standard single-use EKG electrodes. Skin temperatures were measured on the chest and the dorsal surface of the index or ring finger of the non-dominant hand using disc thermistors (YSI, Models 421 and 409A) attached to the skin with tape and collodion. Internal (core) temperature was measured using a flexible vinylcovered disposable thermistor (YSI Model 491A) taped to a tampon and inserted vaginally by the subject. Ambient temperature was measured using a thermistor (YSI Model 421) situated on a carrying case worn around the waist or placed beside the subject. Skin resistance, used as an index of local sweating activity, was recorded using silver silver-chloride electrodes (SensorMedics), placed approximately 2 cm apart on the chest over the upper sternum (first fever episode) or on the index and middle fingers of the non-dominant hand (second fever episode). Subjective report
The subject was instructed to record in a hot flash diary the beginning and ending times of each hot flash, as well as activities such as eating, drinking and sleeping.
183
In the same hot flash diary, she recorded the peak intensity of each hot flash on a scale of l-10, with 1 being a very mild hot flash, and 10 being the most intense hot flash she had experienced. Procedure
After the onset of each fever, the subject reported to the laboratory and was instrumented with the Squirrel. She inserted the vaginal thermistor and the investigators attached the remaining leads. The subject returned to her home where data collection continued. She removed the electrodes prior to showering each morning, and returned to the laboratory for reattachment of the leads and resetting of the Squirrel. (She lived within 10 min of the laboratory). Fever I (9/25-27/89)
The subject awoke with a fever and reported to the laboratory at about 1O:OOh. Physiological recording was initiated and continued for 48 h, through the breaking of the fever. Fever 2 (4/26-30/90)
The second fever occurred about 7 months after the first episode. The subject awoke with a fever and reported to the laboratory at about 14:OOh. Physiological data were recorded for 3 days: the first, second and fourth days of her fever. On the third day the subject did not feel well enough to be instrumented. On day two of this fever, the subject took Tylenol@ (500 mg) every 4 h for three doses. On the fourth day of the fever the subject took aspirin (650 mg) twice about 10 h apart (at approximately 14:OOh and 24:00 h) Analysis
For analysis purposes, 1 day during a fever was defined as the 24-h period from 12 noon of one day until 12 noon of the next day. During fever, skin resistance was the best measure of hot flash occurrence. This is in accordance with what has been demonstrated by others for objective monitoring of hot flashes [8]. Skin temperature and heart rate, which typically increase during a hot flash, were already high during the fevers, leaving less scope for further increase during a hot flash. Therefore, they could not provide as clear an indicator of a hot flash as could skin resistance. During a hot flash, skin resistance shows a characteristic pattern of change: a sharp, almost instantaneous drop and a relatively rapid return to normal. Therefore, hot flashes were assessed physiologically by the occurrence of the characteristic pattern of skin resistance change. There were four other occasions during which the subject, when afebrile, kept a record of the hot flashes that she perceived for 24-h periods (l/29/89, 5/18- 19/89, 11/18-19/90, 1l/19-20/90). On the first two of these days, hot flashes were also measured physiologically. These sessions were used for comparison with the fever days. If hot flashes were identified physiologically from the skin resistance record, but were not reported by the subject, they were labeled ‘unreported’ hot flashes.
184
FEVER 1 $3
Q/25/89
#54
I
12
14
16
LL
18
‘I
20
24
22
4
2
6
- Q/26/89 8
10
12
v - 1400
k? 3 k?‘-?j
39 r
Y
7
-
38 -
oki OQ,
37.
> P
36
\
39 38
- 37 12
14
I. 16
/
18
I 20
I, 22 TIME
24 OF DAY
I.,, 2
4
I.,, 6
36 8
10
12
(hours)
Fig. 1. Febrile: hot flashes, skin resistance, and core temperature for a 24-h period during Fever I. v = reported hot flash; V = unreported hot flash (9125-26189).
Fever 1
There were fewer, less intense hot flashes during the febrile period when core temperature was above 37.K (Fig. 1, Table I), than during a comparable afebrile period (Fig. 3). At the start of data collection (- 1190 h), core temperature was TABLE I FREQUENCY AND INTENSITY OF HOT FLASHES FEBRILE AND AFEBRILE PERIODS No. of reported HFs
Fever 1 Day 1 Day 2 Fever 2 Day 1 Day 2 Day 3 Day 4 Afebrile Day 1 Day 2 Day 3 Day 4
(Breaking fever)
1 6
Intensitya of of reported HFs
2.0 3.2 (f
0.74)
3.0 ( ?? O.oo)b 1.8 (* 0.37) 2.0 2.0 (f 0.00)
(Antipyretic) (Antipyretic)
‘Mean ( ?? S.E.) intensity for that day. bBased on two hot flashes. cBased on 12 hot flashes. na = not available.
(HFs) EXPERIENCED
16 16 15 14
7.5 (* 0.45) 5.4 ( ?? 0.5O)C na na
DURING
24-h
185
BREAKING FEVER 1 g/26/89
#54 12
+rn p4
14
16
18
20
LL
22 v
24
2
ov
4
- g/27/89
6 QIV
v
8 v
10
12
vr
TIME OF DAY (hours) Fig. 2. Breaking fever: hot flashes, skin resistance and core temperature 1. v = reported hot flash; V = unreported hot flash (9/26-27189).
for a 24-h period at end of Fever
38.3%. One hot flash was reported at - 16:00 h and no further hot flashes were reported for the next 29 h. During this 29-h period, one unreported hot flash was identified (Figs. 1 and 2). During sleep on night 1, core temperature exhibited an expected nighttime decline and dropped somewhat to 37.9”C; no hot flashes were reported by the subject or identified from the recording. At about 24:00 h on night 2, the fever broke. Core temperature fell, and between 24:00 and 02:OO h some sweating activity is indicated on the skin resistance record. By 04:OOh hot flashes had resumed (Fig. 2) in a pattern similar to that of an afebrile night (Fig. 3).
AFEBRILE #54 12
+& oq IJ E =F Z
Mnturitas. 14 (1992) 181-188 Elsevier Scientific Publishers Ireland
Ltd
MAT 00668
Effect of fever on menopausal hot flashes Ruth M. Barnarda, “School
of Nursing,
Medicine,
College
(Received
University
of Michigan.
of Physicians
August
Some women report
Fredi Kronenbergb Ann
and Surgeons,
27, 1991; revision
received
Arbor, Columbia
November
and John A. Downeyb
MI
48109
and hDepartment
University,
New
York,
25, 1991; accepted
NY
of Rehabilitation 10032 ( U.S. A. )
December
12. 1991)
that they have fewer hot flashes when they have a fever. This is the tirst case of
physiological monitoring of hot flashes during fever in a subject with a well documented pattern of frequent hot flashes when afebrile. During fever, there were fewer hot flashes than during afebrile periods. and these hot flashes also tended to be less intense. For most of the period of reduced hot flashes. internal (core) temperature was elevated, above 375°C. When the fever broke, hot flashes resumed in a pattern similar to that of afebrile periods. Possible explanations for the reduction in hot flashes during a fever include: (I) a hot flash is triggered, but the characteristic physiological changes do not occur due to competing thennoregulatory drives, (2) the febrile core temperature inhibits whatever it is that triggers a hot flash; or (3) some product of the fever process inhibits the hot flash trigger or masks the physiological changes
that occur during
Key wordr: monitoring
hot flash;
hot flashes.
hot flush; fever; menopause;
body
temperature;
thermoregulation;
ambulatory
Introduction
Hot flashes are experienced by 75% of women around the time of menopause, and about 15% of these women experience severe hot flashes that significantly decrease their quality of life [ 11.A hot flash is a transient event during which there is a sudden feeling of intense heat, flushing and sweating, sometimes followed by a chill. Core temperature typically drops, reflecting the loss of heat due to the vasodilation and sweating. These patterns of physiological changes during a hot flash are similar to those which occur when a fever breaks. Fever is an elevation of core temperature resulting from an upward shift in the thermoregulatory set-point [2-41. When the set-point returns to normal, the fever breaks, with characteristic sweating and flushing, as the body acts to return internal temperature to normal. The analogy between a hot flash and fever has led to the hypothesis that a hot flash, like a fever, involves a perturbation of the thermoregulatory system, but in the opposite direction. That is, a transient lowering of the thermoregulatory set-point occurs during a hot flash [5,6]. The hypothesis that a hot flash is a thermoregulatory event is furCorrespondence
Surgeons,
to: F. Kronenberg,
Columbia
University,
Department of Rehabilitation New York, NY 10032, U.S.A.
0378-5122/92/$05.00 0 1992 Elsevier Printed and Published in Ireland
Scientific
Publishers
Ireland
Medicine,
Ltd
College of Physicians
and
182
ther strengthened by the results of a recent study that showed that ambient temperature, which is known to affect thermoregulation, also influences the frequency and intensity of hot flashes, with fewer hot flashes occurring at the cooler ambient temperature [7]. In addition, some of our subjects recalled that their hot flashes decreased or stopped completely when they had a fever. Perhaps fever, which alters normal thermoregulatory processes, also affects hot flashes. Our goal was to document objectively what had previously been reported by women, that is, the suppression of hot flashes during fever. We wanted to see whether hot flashes were actually suppressed during fever, or whether they occurred during fever but were not distinguishable from the feverish feeling. We report here on the documentation of the reduction in the frequency and reported intensity of hot flashes in a post-menopausal woman during fever. Subjects and Methods Subjects
Subjects with frequent hot flashes (IO+/day) who participated in our laboratory studies were asked to notify us if they ever developed a fever. One subject experienced two spontaneous fevers within a l-year period. During these fever episodes, she agreed to be monitored in her home. This subject was 53 years old at the time of the first fever, and had experienced menopause about 6 years earlier. She had been experiencing hot flashes for more than 11 years, and recalled that her hot flashes had been less frequent and intense when she had been febrile with a cold or flu. Because she had been a subject for the past 2 years in several of our laboratory studies, we had extensive documentation of her hot flashes when she was afebrile. Measurements
All physiological variables were recorded at 30-s intervals on a Squirrel Physiological Monitor (Science Electronics, Dayton, OH). The Squirrel is a portable microprocessor data logger with a computer interface. Heart rate was measured using standard single-use EKG electrodes. Skin temperatures were measured on the chest and the dorsal surface of the index or ring finger of the non-dominant hand using disc thermistors (YSI, Models 421 and 409A) attached to the skin with tape and collodion. Internal (core) temperature was measured using a flexible vinylcovered disposable thermistor (YSI Model 491A) taped to a tampon and inserted vaginally by the subject. Ambient temperature was measured using a thermistor (YSI Model 421) situated on a carrying case worn around the waist or placed beside the subject. Skin resistance, used as an index of local sweating activity, was recorded using silver silver-chloride electrodes (SensorMedics), placed approximately 2 cm apart on the chest over the upper sternum (first fever episode) or on the index and middle fingers of the non-dominant hand (second fever episode). Subjective report
The subject was instructed to record in a hot flash diary the beginning and ending times of each hot flash, as well as activities such as eating, drinking and sleeping.
183
In the same hot flash diary, she recorded the peak intensity of each hot flash on a scale of l-10, with 1 being a very mild hot flash, and 10 being the most intense hot flash she had experienced. Procedure
After the onset of each fever, the subject reported to the laboratory and was instrumented with the Squirrel. She inserted the vaginal thermistor and the investigators attached the remaining leads. The subject returned to her home where data collection continued. She removed the electrodes prior to showering each morning, and returned to the laboratory for reattachment of the leads and resetting of the Squirrel. (She lived within 10 min of the laboratory). Fever I (9/25-27/89)
The subject awoke with a fever and reported to the laboratory at about 1O:OOh. Physiological recording was initiated and continued for 48 h, through the breaking of the fever. Fever 2 (4/26-30/90)
The second fever occurred about 7 months after the first episode. The subject awoke with a fever and reported to the laboratory at about 14:OOh. Physiological data were recorded for 3 days: the first, second and fourth days of her fever. On the third day the subject did not feel well enough to be instrumented. On day two of this fever, the subject took Tylenol@ (500 mg) every 4 h for three doses. On the fourth day of the fever the subject took aspirin (650 mg) twice about 10 h apart (at approximately 14:OOh and 24:00 h) Analysis
For analysis purposes, 1 day during a fever was defined as the 24-h period from 12 noon of one day until 12 noon of the next day. During fever, skin resistance was the best measure of hot flash occurrence. This is in accordance with what has been demonstrated by others for objective monitoring of hot flashes [8]. Skin temperature and heart rate, which typically increase during a hot flash, were already high during the fevers, leaving less scope for further increase during a hot flash. Therefore, they could not provide as clear an indicator of a hot flash as could skin resistance. During a hot flash, skin resistance shows a characteristic pattern of change: a sharp, almost instantaneous drop and a relatively rapid return to normal. Therefore, hot flashes were assessed physiologically by the occurrence of the characteristic pattern of skin resistance change. There were four other occasions during which the subject, when afebrile, kept a record of the hot flashes that she perceived for 24-h periods (l/29/89, 5/18- 19/89, 11/18-19/90, 1l/19-20/90). On the first two of these days, hot flashes were also measured physiologically. These sessions were used for comparison with the fever days. If hot flashes were identified physiologically from the skin resistance record, but were not reported by the subject, they were labeled ‘unreported’ hot flashes.
184
FEVER 1 $3
Q/25/89
#54
I
12
14
16
LL
18
‘I
20
24
22
4
2
6
- Q/26/89 8
10
12
v - 1400
k? 3 k?‘-?j
39 r
Y
7
-
38 -
oki OQ,
37.
> P
36
\
39 38
- 37 12
14
I. 16
/
18
I 20
I, 22 TIME
24 OF DAY
I.,, 2
4
I.,, 6
36 8
10
12
(hours)
Fig. 1. Febrile: hot flashes, skin resistance, and core temperature for a 24-h period during Fever I. v = reported hot flash; V = unreported hot flash (9125-26189).
Fever 1
There were fewer, less intense hot flashes during the febrile period when core temperature was above 37.K (Fig. 1, Table I), than during a comparable afebrile period (Fig. 3). At the start of data collection (- 1190 h), core temperature was TABLE I FREQUENCY AND INTENSITY OF HOT FLASHES FEBRILE AND AFEBRILE PERIODS No. of reported HFs
Fever 1 Day 1 Day 2 Fever 2 Day 1 Day 2 Day 3 Day 4 Afebrile Day 1 Day 2 Day 3 Day 4
(Breaking fever)
1 6
Intensitya of of reported HFs
2.0 3.2 (f
0.74)
3.0 ( ?? O.oo)b 1.8 (* 0.37) 2.0 2.0 (f 0.00)
(Antipyretic) (Antipyretic)
‘Mean ( ?? S.E.) intensity for that day. bBased on two hot flashes. cBased on 12 hot flashes. na = not available.
(HFs) EXPERIENCED
16 16 15 14
7.5 (* 0.45) 5.4 ( ?? 0.5O)C na na
DURING
24-h
185
BREAKING FEVER 1 g/26/89
#54 12
+rn p4
14
16
18
20
LL
22 v
24
2
ov
4
- g/27/89
6 QIV
v
8 v
10
12
vr
TIME OF DAY (hours) Fig. 2. Breaking fever: hot flashes, skin resistance and core temperature 1. v = reported hot flash; V = unreported hot flash (9/26-27189).
for a 24-h period at end of Fever
38.3%. One hot flash was reported at - 16:00 h and no further hot flashes were reported for the next 29 h. During this 29-h period, one unreported hot flash was identified (Figs. 1 and 2). During sleep on night 1, core temperature exhibited an expected nighttime decline and dropped somewhat to 37.9”C; no hot flashes were reported by the subject or identified from the recording. At about 24:00 h on night 2, the fever broke. Core temperature fell, and between 24:00 and 02:OO h some sweating activity is indicated on the skin resistance record. By 04:OOh hot flashes had resumed (Fig. 2) in a pattern similar to that of an afebrile night (Fig. 3).
AFEBRILE #54 12
+& oq IJ E =F Z
