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Biophysics and Biomedical Modeling Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts 01760-5007
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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Effects of the
menstrual cycle on heat loss and heat production
(M) and core and skin temperature
responses to cold were studied in six unacclimatized female nonsmokers
(18-29 yr of age). Each woman, resting supine, was exposed to a
cold transient (ambient temperature = mean radiant temperature = 20 to
5°C at 0.32°C/min, relative humidity = 50 ± 2%, wind speed = 1 m/s) in the follicular (F) phase
(days 2-6) and midluteal (L)
phase (days 19-23) of her menstrual cycle. Clothed in each of two ensembles with different thermal resistances, women performed multiple experiments in the F and
L phases. Thermal resistance was 0.2 and 0.4 m2 · K · W
1
for ensembles A and
B, respectively. Esophageal
temperature (Tes), mean weighted
skin temperature
(
sk),
finger temperature (Tfing), and
area-weighted heat flux were recorded continuously. Rate of heat debt
(S) and integrated mean body
temperature
(b,i)
were calculated by partitional calorimetry throughout the cold ramp. Extensive peripheral vasoconstriction in the F phase during early periods of the ramp elevated Tes
above thermoneutral levels. Shivering thermogenesis
(
M = M Mbasal,
W /m2) was highly correlated with
declines in
sk and
Tfing
(P <0.0001). There was a reduced
slope in M as a function of
b,i in
the L phase with ensembles A
(P < 0.02) and
B (P < 0.01). Heat flux was higher and
S was less in the L phases with
ensemble A
(P < 0.05). An analytic model
revealed that
sk and
Tes contribute as additive inputs
and Tfing has a multiplicative
effect on the total control of M
during cold transients
(R2 = 0.9).
Endogenous hormonal levels at each menstrual cycle phase, core
temperature and
sk
inputs, vascular responses, and variations in body heat balance must be
considered in quantifying thermoregulatory responses in women during
cold stress.
clothing; regional heat flux; thermoregulatory model
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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THE REPRODUCTIVE SYSTEM has a clear and important role in altering thermoregulation in women, particularly when internal body temperature becomes elevated during the luteal phase compared with the follicular phase of the menstrual cycle. In the luteal phase, thermoregulatory responses of women are characterized by alterations in core temperature (Tc) thresholds affecting the onset of specific physiological effector responses during exercise, heat exposure, and cold exposure (17, 20, 24, 27). Elevated Tc thresholds controlling the onset of sweating and skin blood responses are consistent with a higher internal body temperature reference point evident in the luteal phase, which may compromise thermoregulation during prolonged exercise or warm exposures in the luteal phase (20, 24, 27). Several studies (17, 19, 20, 27) carried out in warm conditions during exercise show that when Tc and skin temperature (Tsk) are elevated, heat loss mechanisms become activated, and sudomotor drive and blood flow to the skin surface increase in the mid- to late luteal phase of some eumenorrheic women.
Few data exist quantifying female responses to cold stress. During cold
stress, shivering by gross muscular contraction may or may not be
sufficient to maintain Tc.
Tc and
Tsk interact in a unique fashion
as constant temperature multipliers or in a summative fashion to
increase metabolism (5, 15). Other than limited studies (1, 17, 28),
information on the role of reproductive hormones during various stages
of a woman's menstrual cycle is scarce. Also there are few studies on
how various stages of the menstrual cycle influence thermoregulatory
responses to cold. This thermosensitivity may be described by a change
in slope to a decreasing internal temperature or
Tsk affecting a given heat loss
response or an M response. The
integrated mean body temperature (b,i)
or core thermosensitivity of a thermoregulatory response is defined
here as the amount of change in the specific dependent response for
each unit change in
b,i
during cooling. The change in slopes of the respective dependent
response curves above a given reference
b,i
describes the various thermosensitivities. The shivering response is
generally determined by a plot of excess shivering vs.
Tsk or
Tc (2, 4, 15, 17). Peripheral
thermosensitivity is described as the shivering thermogenesis
influenced by skin surface temperature decreases solely (4, 5, 15).
Various studies (2, 4, 15) have revealed an interaction of hypothalamic temperature with skin and deep-body temperatures in the initiation and control of various thermoregulatory responses. Skin cooling has been shown to alter the hypothalamic thermosensitivity driving increases in metabolic heat production and cutaneous vasoconstriction (15, 17, 28). Fluctuations of estradiol and progesterone levels and changes in their relative ratios during a woman's menstrual cycle also participate in mediating cutaneous vascular responses during cold challenges (1, 17).
When Tc is offset to a higher
temperature level in a woman's midluteal phase, there may exist
competitive inhibition in the processing of thermal information in the
thermoregulatory system (4, 8). This competition of thermal afferent
information from central and peripheral receptors may blunt the
shivering response to cold stress at a given mean
Tsk
(sk)
(17). Additionally, there is strong evidence that hypothalamic neurons
show changes in their local hypothalamic thermosensitivity during
displacements in cutaneous temperature that closely parallel whole body
thermoregulatory responses (5). That is, the highest slope (e.g.,
"gain") in a shivering response (2, 15) occurs when cold
Tc is combined with cold
Tsk and their combined rate of
change is rapid.
Ability to tolerate cold stress is also affected by use of extra clothing (e.g., thermal resistance added to a fixed tissue resistance). Here, effect of added clothing is considered an extrinsic factor that only functions as part of the passive means in the regulation of energy exchange between the body and the environment (12).
The present experiments were designed to perturb the thermoregulatory system by employing a controlled decrease in ambient temperature (Ta) (14). The technique allows quantification of dynamic Tsk responses and provides information characterizing cold reactions in women. The purposes of this study were 1) to determine the heat exchange responses during cold transients at two stages of the menstrual cycle in women clothed in two different clothing systems, 2) to ascertain whether heat loss responses are influenced by dynamic changes in Tsk and internal body temperature during a cold transient at two stages of a woman's menstrual cycle, and 3) to establish effective model parameters in the control of shivering thermogenesis during cold transients. First, it was hypothesized that a constant level of thermal resistance affects heat loss but should not alter thermoregulatory mechanisms within each menstrual cycle phase. Second, it was hypothesized that the cold stress would principally stimulate skin thermoreceptors rather than central Tc driving the shivering responses. Finally, it was hypothesized that control of thermoregulatory responses (shivering and heat loss) activated by peak levels of estradiol and progesterone in the luteal phase should have significant effects on the Tc reference point (20, 27) but not the slope of shivering thermogenesis.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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Six highly motivated women, recruited from the military test subject pool, volunteered to participate in the study after being informed of the risks and purpose of the study and after giving their written, informed consent. The protocol was approval by the US Army Research Institute of Environmental Medicine Human Use Review Committee (HURC). The women completed a questionnaire that incorporated various signs and symptoms related to their menstrual cycle. A complete medical examination was done on each woman before any experimentation. Each woman had no history of cardiovascular or respiratory disease or complications from irregular menstruation. Before any testing began, each subject had a blood scan to ensure the absence of anemia and a pregnancy test, which was verified as negative.
Each woman completed all experiments. The characteristics of the subjects were as follows (means ± SD): age = 21.2 ± 3.9 yr, height = 1.65 ± 0.10 m, weight = 60.9 ± 7.9 kg, body surface area = 1.66 ± 0.12 m2, and body fat = 23.9 ± 2.5%. Experiments on each subject were done in the late fall, winter, and early spring between 0700 and 0900 to control for circadian variation in temperature regulation. The women were normal early risers. Each of the six women displayed a normal menstrual cycle as defined by regular periodicity (~28- to 30-day cycles) kept in a daily log book, and no subject was taking oral contraceptives. To verify that ovulation had taken place in a given month, each subject recorded her daily basal body temperature on awakening for the month throughout the experimental study. Oral temperature was measured twice while the subject rested at the same time each morning (with mouth completely shut) with a calibrated, fast-responding, automated oral thermometer. Data from an entire menstrual cycle were collected and graphed before the study to determine whether oral temperature increased after ovulation (18). Although basal body temperature monitoring is not a wholly sufficient method to predict ovulation time, higher basal internal temperature is closely correlated with the higher plasma progesterone concentration evident in the luteal phase of the menstrual cycle (9) and directly applicable to our resting study.
Testing in the luteal phase occurred only on days when the resting Tc was elevated (approximately days 19-23). Testing in the early follicular phase occurred on days 2-6 (day 1 = 1st day of menstrual flow). The calendar dates initially chosen to correspond with a given stage of the menstrual cycle of the woman were verified by post hoc blood analyses of estradiol and progesterone levels. Hormonal data, basal body temperature records, and subject logs were matched for proper cycle phase at the end of the total study protocol. Experimental data authenticated with the respective hormonal data from each woman were used in the statistical analyses. Hormonal data were culled according to appropriate phase and test day to determine mean differences in precision of measurement by ANOVA (e.g., interassay variability) for the two separate test samples from each woman. Percent differences between test days are shown in Table 1, along with the mean concentrations of the reproductive hormones at each cycle phase.
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Clothing Ensembles
The women dressed in each of two clothing ensembles devised to add two constant, fixed resistances to their skin surface layer. Ensemble A consisted of the US Army-issue physical training shorts and underwear plus the US Army T-shirt worn under a temperate battle dress uniform. Ensemble B consisted of a US Army battle dress overgarment worn over ensemble A. The clothing insulation values were evaluated separately at three different wind speeds to establish effective clothing heat and water vapor transfer coefficients employed in partitional calorimetric analysis. These heat transfer coefficients were estimated using a regional copper manikin resting supine on a wood-framed cot supported by parachute nylon webbing, which simulated the conditions of the human experiments. The total thermal resistance of ensemble A measured at chamber wind speed of 1 m/s (paralleling the human experiments) was 0.21 m2 · K · W1
(1.33 clo). The clothing resistance of ensemble
A is equivalent to normal civilian trousers and shirt.
The thermal resistance of ensemble B,
also tested at a wind speed of 1 m/s, was 0.4 m2 · K · W1
(2.58 clo).
During all experiments, subjects wore a standard US Army light-duty
work glove with a five-finger woolen insert, which added a constant
thermal resistance to the hands. The glove was separately evaluated on
the US Army Research Institute for Environmental Medicine copper hand
model and had a thermal resistance of 0.13 m2 · K · W1
(0.86 clo). During all experiments a standard-issue US Army black boot
and US Army cushion-sole socks were worn on the feet with each clothing
system. The thermal insulation of the boot with a sock was analyzed
(1.8 clo, thermal resistance = 0.28 m2 · K · W1)
using a regionally heated copper foot in our laboratory. During all
experiments, subjects were not allowed to open or ventilate their
garments by opening closures or zippers or by excessive movement,
thereby serving to control against disparate changes in skin surface
temperatures and heat flow.
Before the beginning of the study, volunteers were thoroughly familiarized with all experimental techniques, and their standing height was measured. During these training sessions, body weights were measured so that on the four test days (twice in ensemble A and twice in ensemble B), preexperiment body weights could be easily traced back within 1% of the mean body weight measured during preliminary testing to control for possible effects of hypohydration.
Experimental Testing
On arriving at the laboratory each morning, the subject rested on a chair for 30 min, and a 10-ml blood sample was taken by venipuncture for the measurement of serum 17
-estradiol and progesterone concentrations (by RIA; Coat-a-Count, Diagnostic Products, Los Angeles,
CA) to accurately define menstrual cycle phases in each woman (Table
1). Blood samples were quickly processed when taken and frozen. Samples
from all women were analyzed in the same batch assay (in duplicate) to
obviate potential interassay variability, as pointed out previously.
After blood was drawn, the previously trained subject inserted through
the nostril a polyethylene-encased thermocouple channeled through the
pharynx into the esophagus to a depth ~25% of her height (in cm).
Exact placement of the thermocouple at the midheart level was verified
by following a real-time thermal recording on a computer screen as she
slightly inserted and retracted the thermocouple into the esophagus
past the initial "hot" spot demarcating a correct heart-level
point (27). The women were asked to avoid swallowing by spitting saliva into a cup during the experiments to obviate spurious recordings. Any
inadvertent swallows, shown by immediate dips on the computer monitor
scan, were later smoothed in the data file by using an exponential
smoothing of esophageal temperature
(Tes) to predict a value based
on the forecast for the immediately preceding 15-s period.
Surface thermistors with calibrated heat flow disks (Concept
Engineering, Old Saybrook, CT) were placed at six skin surface sites
(midchest, midthigh, lateral calf, upper hand, upper arm, and
midforearm) and area weighted to estimate
sk
(23). Separate 28-gauge copper-constantan thermocouples were also
placed in the middle fingernail bed and big toenail bed. The calibrated
heat flow disk surrounding each embedded thermistor element determined heat flux from each of the skin sites. Weighted heat flux
(W /m2) was calculated from each
respective skin site area weighting (10, 23).
Environmental temperatures, Tes
and Tsk, and heat flow data were
recorded every 15 s with a personal computer. Wind speed in the chamber
was controlled at 1 m/s. O2 uptake
(
O2, l/min) was measured by
2-min collection of all expired gases into a Douglas bag
sampled every 20th min of the transient and twice at 20°C, once
before the decrease of Ta and once
after ~10-15 min at ~10°C. Heat production
(W /m2) was calculated from the
expired respiratory parameters obtained, the caloric equivalent of 1 liter of O2, and the DuBois
surface area equation (12). Subjects were exposed to the lowest air temperature (10°C) for an additional ~10-15 min.
Experiments ceased if a woman voluntarily withdrew or if she was
withdrawn because fingertip Tsk
(Tfing) reached 
5°C or
Tes plummeted toward 35°C.
These lower limits were advisory guidelines set by our HURC for removal
of a given subject from the test for that day.
Heart rates were obtained and recorded every 5 min from the electrocardiogram measured continuously using chest electrodes (CM5 placement) interfaced to a telemetry system (models 78510A and B, Hewlett-Packard).
The subjects were to refrain from active exercise and were not to consume food, caffeine, and medication (including aspirin or any analgesic-antipyretic compounds) ~10 h before the experimental testing. If the subject had unintentionally taken any medication, an experiment was rescheduled for the next appropriate calendar day. Body weight and composition were determined by repeated nude weighings and skin-fold measurements (27).
Steady-State and Transient Exposure
All subjects rested supine on a specially designed wooden cot for 15 min of baseline data collection at 20°C air temperature. After complete instrumentation, an additional resting period began; it lasted ~20-30 min, until equilibration occurred, i.e., the woman's Tsk and Tc remained constant within ±0.1°C for 10-15 min. After the initial equilibration period, each subject was exposed to the thermal transient by decreasing the environmental chamber Ta (Ta =r = To, where
r is
mean radiant temperature and To is
operative temperature) (12) in a controlled downward ramp [for
the 24 runs: To = 17.5 0.316 · (min) + 1.088e3 · (min)2,
R2 = 0.98, SE of
estimate ±1.2°C]. To
is the critical variable describing the ambient environment when
clothing is worn (12). Dew point temperature was allowed to fall
passively during the room temperature decreases. The cooling phase at
the lowest target To typically continued for 80-120 min (the latter time point when the subject was dressed in ensemble B) at a
constant decreased exponential ramping rate of 0.32°C/min. A
final exposure time of 10-20 min at
To of 5 to 10°C
was completed before the experiments were ended by a subject's request
or in conformity with our HURC recommendations. All data were truncated
to an 80-min time point to facilitate statistical analyses.
Heat Exchange Variables
Partitional calorimetric analyses (12, 30) were conducted at 20-min intervals with each avenue of heat exchange from the heat balance equation (e.g., respiratory and convective heat loss responses combining all respective clothing and heat transfer coefficients) taken into account, in which
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(1) |
S is heat debt);
M is metabolic heat production
calculated from each 20-min
O2 interval;
Esk is
evaporation or insensible (wet) heat exchange, which is set by the
clothing moisture properties
(im/clo, where
im is an evaporative constant) (12) and evaporative heat transfer coefficients determined from parallel copper manikin evaluations of the garments, the
Tsk-Ta
gradient
(sk To), and the change in
body weight loss and respiratory heat loss;
R is radiation;
C is convection; and
K is conduction.
R and
C combine as sensible (dry) heat
exchange, which was determined by the environment, thermal conductance,
and insulative properties of the ensembles and their respective heat
transfer coefficients.
Details of the analysis to ascertain integrated mean body temperature from partitional calorimetry are addressed in the APPENDIX.
Statistical Methods
Values are means ± SD. For the baseline equilibration periods, mean values of Tes and Tsk, Tc and Tsk changes from neutral (Tes,
sk,
and Tfing), and metabolic
heat production were analyzed by univariate ANOVA techniques with
repeated measures. Whenever a significant
F-ratio was found, Tukey's critical
difference was employed for post hoc analysis (
= 0.05) (25).
Mean data of Tes,
sk,
heat content (kJ), and heat flux as a function of time during the
thermal transient were analyzed by two-way (ensemble × menstrual
phase and time × menstrual phase) or three-way (time × ensemble × menstrual phase) ANOVA for repeated measures. When the
ANOVA indicated significant main or interactive effects, Tukey's
studentized range, honestly significant difference (HSD) was used to
compare means and locate minimum significant differences ( = 0.05)
between factors and among repeated measurements (25).
Regression methods.
Regression analyses of metabolic heat production vs.
sk and
Tfing were determined using a
linear regression for repeated measures, with between-subjects
differences taken into account (13, 25). Dummy variables were used to
encode the different subjects, and all the data were pooled to estimate
a single regression equation (13, 25).
M = M M0,
where M0 is the basal metabolic rate) as a
function of integrated mean body temperature. Each regression
coefficient (slope) and threshold point were examined by ANOVA for
repeated measures and Tukey's post hoc test, as described above (6, 25).
Parameter model estimation.
Maximum-likelihood parameter estimation (MLE) was used to determine the
respective control coefficients (parameters) derived by independent
effects of Tc and
Tsk likely to be considered
influencing shivering thermogenesis
(M = L). This technique was
chosen as an ideal method of describing
M = L on the basis of the estimates of
three principal control variables:
Tes,
sk, and
Tfing (15, 28) driving the
shivering response throughout the cold transient. It was assumed that
the product of a parameter value times a given variable
(Tes,
sk,
and Tfing) in the
data set are independent terms that equally weight the final
likelihood function (M = L). Also assumed was an initial
model statement that shivering thermogenesis is based on proportional
control (13) by summed linear effects or multiplicative (28) effects
from the three variables. In the MLE analysis, starting values of
control parameters (P1,
P2, and
P3) and their respective
constants
(Tsk,x1, Tes,x2,
and
Tfing,x3)
are first set to default values on the basis of a given model
statement. Each subsequent iteration seeks to find the minimum sum of
squares residual (SSR) by a quasi-Newtonian derivative procedure. This is done by differentiating with respect to a given parameter and equating each derivative to zero (e.g., 
log
L/P1 = log
L/P2 = ... log
L/Pn = 0). Iterations terminate when the values of the parameter estimates
in the iteration procedure fail to change. This yields the
maximum-likelihood estimator of all the parameters. The method also
generates R2 = (1 residual SSR/total SSR) of each model equation.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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Tsk and Tes Responses
Extensive peripheral vasoconstriction and rate of fall in Tsk (
sk/t)
of about 0.1°C/min occurred during all thermal transient runs. During the initial thermoneutral equilibration periods, sk was
not significantly different between phases for a given ensemble. Final
sk in
both phases was lower in ensemble A
than in ensemble B experiments (23.2 ± 0.6 and 27.4 ± 0.3°C,
P < 0.05).
In ensemble A experiments a higher
Tes was evident in the luteal
phase than in the follicular phase (36.9 ± 0.05 vs. 36.6 ± 0.16°C, P < 0.01) during the
basal resting period (at 30 min). During the initial phases of
the transient the drops in
sk were associated with elevations in Tes.
Figure 1 shows that
Tes initially rose in the early
time periods of the transients with ensemble A. Tes was
elevated higher at 50, 70, and 80 min of the transient in the
follicular phase than in the luteal phase
(P < 0.05).
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In experiments with ensemble B,
Tes was higher
(P < 0.05) during the
follicular phase than during the luteal phase at 70 and 80 min of the
transient. Toward the final time points (70-80 min)
Tes began to decline markedly
with the cold stress.
Metabolic Heat Production
Steady-state metabolic heat production was not significantly different during equilibration time periods (30 min) when the women wore
ensemble A or
B in the follicular and luteal phases: 47.16 ± 5.11 and 47.28 ± 4.69 (SD)
W /m2 in the follicular and luteal
phases, respectively, with ensemble A
and 44.2 ± 5.13 and 45.9 ± 6.2 W /m2 in the follicular and
luteal phases, respectively, with
ensemble B. These values, which ranged
from 5 to 13%, are not significantly different from the basal heat
production values (41.85 W /m2)
reported for 25-yr-old women (17).
Figures 2 and 3 show that
total heat production was closely correlated
(P < 0.0001) with the reduced
sk and
Tfing in all the cold transient
experiments.
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Shivering thermogenesis (i.e., M Mbasal,
W /m2) was determined from each
woman's response to the cold ramp and plotted as a function of
integrated mean body temperature
(b,i),
as described in the APPENDIX, to
derive regression coefficients (6). Table 2
shows the mean results.
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The slope of shivering thermogenesis response to
b,i
(M/b,i)
in the luteal phase of the menstrual cycle in each woman was attenuated
during experiments with ensemble A
(P < 0.02) and ensemble B
(P < 0.01). The
b,i
threshold
(b,i,0)
was not significantly different between phases or ensembles.
Heat Flux
Figure 4 shows the weighted heat flux data plotted at 20-min intervals from all the experiments. During the 12-13 min of the cold ramp with ensemble A in the luteal phase, the heat flux through the garment was not significantly different from values observed in the follicular phase. Into the 20th min (To
12 ± 1°C) and throughout the cold transient, heat flux was displaced toward a higher
level in the luteal phase than in the follicular phase (P < 0.05). During experiments with
ensemble B, heat flux values were
increased by 60-70% (P < 0.05)
above basal values, but mean heat flux at each time point of the
transient was not significantly different between phases.
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Three-way ANOVA (time × phase × ensemble) followed by Tukey's HSD indicated that mean weighted heat flow values were higher at each time point and cycle phase with ensemble A (P < 0.05).
Rate of Heat Debt
Figure 5 shows the results of whole body rate of heat debt calculated for each 20-min period of the transient. Heat debt was determined by partitional calorimetric analyses, with each woman's metabolic heat production, body weight, percent body fat and surface area, Tes, andsk
taken into account, as explained in the
APPENDIX.
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ANOVA revealed significant differences in rate of heat debt from basal time periods. The women in the follicular phase with ensemble A exhibited a higher rate of heat debt at 40 and 60 min and final time points (P < 0.05) than at similar time points in the luteal phase. In experiments with ensemble B the rate of heat debt was greater than values at basal time points (P < 0.05), but there were no phase differences throughout the transient.
Prediction Equations for Shivering Thermogenesis
The variables Tes,Tes,
sk, and
Tfing were shown to be independent
factors influencing the shivering response (Figs. 1-3). For this
reason, an attempt was made to develop a unifying algorithm to describe
shivering thermogenesis as a function of the respective Tsk and
Tc thresholds and control
constants. Because shivering thermogenesis was highest in the
experiments with ensemble A, this data
set was examined for distinct differences possibly related to cycle
phase. All data were analyzed by an iteration procedure employing MLE,
as explained in METHODS. An acceptable
criterion for a model equation based on summative or multiplicative
construct of the independent variables was a derived
R2 
0.9 from
the lowest SSR (3).
Threshold values initiating excess heat production due to shivering
thermogenesis were generated from the data set. In the follicular
phase, thresholds were 26.5 ± 0.3°C for
Tfing
(Tfing,0) and 32.5 ± 0.2°C for
sk(sk,0).
In the luteal phase, thresholds were 21.5 ± 0.3°C for Tfing,0 and 31 ± 0.9°C for
sk,0.
These values were found to be offset to lower temperatures
(P < 0.002). Tes,0 thresholds were not
significantly different between phases (36.9 ± 0.1°C).
Prediction equations established by MLE
are
![&Dgr;<IT>M</IT><SUB>F</SUB> = [P<SUB>1,F</SUB> · (<OVL>T</OVL><SUB>sk</SUB> − 32.5) + P<SUB>2,F</SUB> · (T<SUB>es</SUB> − 36.9)]](/content/vol85/issue2/fulltext/543/img007.gif)
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(2) |
M
(MF) 0, and
![&Dgr;<IT>M</IT><SUB>L</SUB> = [P<SUB>1,L</SUB> · (<OVL>T</OVL><SUB>sk</SUB> − 31.0) + P<SUB>2,L</SUB> · (T<SUB>es</SUB> − 36.9)]](/content/vol85/issue2/fulltext/543/img011.gif)
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(3) |
M
(ML) 0.
The analyses indicate that
Tes/sk
thermal sensitivity (P2,F > P1,F) governing the
shivering responses was 2.42 W · m2 · °C1
in the follicular phase and 3.5 W · m2 · °C1
in the luteal phase (increase of ~44.6%). That is, sensitivity to a
lowering of Tc is still a stronger
factor in the control of the shivering response than
Tsk alone (Fig. 1).
Tfing was shown to be a
significant peripheral multiplier to the summed effects of core and
skin thermal inputs affecting shivering thermogenesis in both phases.
P3 was higher in the follicular
than in the luteal phase (by ~53%).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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The general results of this study suggest that a woman's metabolic
response to a lowered Tsk and a
lowered
b,i
becomes significantly attenuated during the midluteal phase of her
menstrual cycle when endogenous levels of estradiol and progesterone
become elevated. The mechanism that determines the level of shivering
per change in
b,i
during a woman's luteal phase may be associated with a reduced
requirement of heat production but enhanced skin blood flow to the
cutaneous sites (16, 17, 19). It is possible to infer from our study's
heat balance results that elevated reproductive hormones induce a
warmer central core (Tc),
resulting in a lower rate of heat debt, which would extend tolerance
times during cold transients.
The general effect of the added clothing insulation in combination with enhanced central warming in the luteal phase is that, for a given decrease in Tsk, less heat production is required to maintain deep body temperature and rate of heat debt is diminished as a function of time of the cold stress. The practical application is that women during their midluteal phases are able to tolerate lower Tc during cold transient exposures.
Clothing Resistance
We hypothesized that intrinsic thermoregulatory mechanisms activated by the hormonal changes appearing during the two menstrual cycle phases would probably not become modified during cold stress by addition of clothing. This hypothesis was confirmed by the heat flux and rate of heat debt alterations evident during the thermal transients (Figs. 4 and 5). The higher thermal resistance of ensemble B significantly decreased sensible heat loss from the skin surface to the ambient. Additionally, the added clothing resistance diminished heat debt by adjusting the lower critical temperature (e.g., Ta where net metabolic heat production rises) necessary for shivering thermogenesis. Adding a finite thermal resistance to the skin layer by clothing blunts somewhat the heat exchange properties but not the consequences of thermoregulatory effector responses (shivering, vasoconstrictor activity). Changes in heat production and heat loss responses remained controlled by alterations in Tc and Tsk during the two stages of the menstrual cycle.Shivering Responses
Because the Tes of the women in each phase was elevated in the cold transients, more so in the follicular phase with ensemble A, it would appear that the stimulus for increased heat production was, to a large extent, peripheral in origin. The hypothesis was confirmed that a strong peripheral drive becomes active in controlling shivering thermogenesis during supine rest in the women. The results suggest that as long as the Tes remains near thermoneutral levels (orTes
from basal is approximately ±0.15°C), the summed effect of
shivering thermogenesis is highly correlated with a combined effect of
sk
(weighted without fingers and toes) and temperature of cold acral sites
(Tfing). As evident in Figs. 2
and 3, absolute heat production was strongly correlated with the
decreases in sk and
Tfing during the cold transient.
The reciprocal response of a rise in
Tc to skin cooling has been
frequently displayed in small animals and humans, in which the heat
capacitance is limited due to small surface area-to-volume ratio (2,
15, 17, 30). Hessemer and Brück (17) found that a reciprocal
effect of Tc to
Tsk decreases in women exposed to
cold temperature step changes. Our study showed that the rise in
Tes was most clearly apparent
during the follicular phase when the women were clothed in
ensemble A, which has the lower
thermal resistance (Fig. 1). Rises in
Tes accompanying
Tsk cooling were less
(P < 0.05) during experiments in the
luteal phase with ensemble A than
during experiments in the follicular phase at 40-80 min of the
transient.
This study also revealed important new information regarding the
effectiveness of a change in Tc
relative to a change in
sk in
producing alterations in shivering response during the two stages of
the menstrual cycle. Previously, Hessemer and Brück (17) found,
in unclothed women exposed to a step change of room temperature from 32 to 12°C, that the shivering response was strongly altered by
Tc and
Tsk, and the threshold for
shivering shifted to a higher level in the luteal phase. They
attributed the shift in threshold for the initiation of shivering to an
increase in basal metabolic heat production. They revealed that a
decreased electromyogram response to cold stress also occurs in the
luteal phase. Unresolved from their study was whether the slope of the shivering response to Tsk or
Tc becomes modified as a
consequence of the hormonal changes during the luteal phase.
The present study confirmed the results of the study of Hessemer and
Brück (17), in which shivering responses were strongly correlated
with Tsk. However, our results
indicate that, in the luteal phase, decreases in the shivering
thermogenesis are strongly affected by decreasing
b,i
determined from summed heat balance. Unlike Hessemer and Brück,
we found that, during the luteal phase, basal metabolic heat production
was unaltered and there was no statistically significant shift in the
b,i
reference point controlling the initiation of shivering. This latter
result was contrary to our initial hypothesis.
In past studies using animal models to study shivering, it was found
that hypothalamic warming reduces or even suppresses shivering in a
cold environment (4, 5, 15). Boulant and Gonzalez (5) showed in rabbits
that heating the preoptic/anterior hypothalamic area decreased the
hypothalamic thermosensitivity, inducing the shivering thermogenesis
when colonic temperature and Tsk
were warm. Preoptic cooling, however, increased the hypothalamic thermosensitivity when Tc and
Tsk were very cold. Our study
showed that shivering response to a given
b,i
signal was reduced in the luteal phase of the women when the warming
activity on the hypothalamus would be most likely prevalent. In
response to cold skin calling for increased metabolic heat production,
the greater weighted influence of deep body thermoreceptors, possibly
acting within a warmed hypothalamic area during the midluteal phase, could have a dominant role in inhibition of the shivering response. The
mechanisms for the diminished
M/Tb,i
and lack of any
b,i reference shift suggest a readjustment of overall heat balance during
the luteal phase possibly influenced by the thermogenic activity of
peak hormonal levels of estradiol and progesterone or other mediators
(8, 24, 26).
Skin Heat Flux Responses
The weighted heat flux obtained in these experiments represents an independent assessment of cutaneous blood flow stemming from extremity (arms, thighs, and calf) and chest skin surface sites purported to be responsive to neural efferent drive controlling skin blood flow (10, 12). If cutaneous heat flux reflects a concomitant effect of augmented peripheral blood flow throughout the body's system, which we believe it certainly does, then the mean weighted heat flux responses found in the present study (Fig. 4) definitely concur with studies showing increased arm blood flow by direct vasodilatory action or attenuation of vasoconstrictor activity prevalent in the luteal phase of a woman's menstrual cycle (1, 16, 17, 20).During experiments in the luteal phase in which the women wore ensemble A, increases in mean weighted heat flux were initiated earlier and rose to a much higher level at 20-80 min of the cold transient (Fig. 4) than during the follicular phase (P < 0.05). Decreases in heat flux were evident with ensemble B during the cold transient. This lowered heat flux would be a requirement, owing to the summed effect of increased tissue resistance during vasoconstriction coupled with trapped heat within the extra layers of clothing. This trapped heat likely caused a reduction in the Tsk-Ta gradient, thereby constraining skin heat flow to the ambient.
The increased heat flux responses observed in the luteal phase with ensemble A are at variance with steady-state studies of unclothed women exposed to 90 min of a 28°C Ta showing decreased thermal conductance in the midluteal phase (11) and other resting studies showing reductions in thermal conductances (3). These latter studies proposed that the offset in Tc apparent in the luteal phases of women is the outcome of an increase in tissue thermal insulation. Our data suggest, on the other hand, that such observations of reliance on thermal insulation per se are probably not in effect when peripheral cold receptor activity (e.g., dynamic skin receptors) dominates in resting clothed women.
The elevated heat flux response displayed in the luteal phase with ensemble A suggests that the response results from augmented endogenous levels of estradiol and/or progesterone acting centrally (4, 5) or in peripheral vascular sites (1, 16). In our study it was not possible with our experimental techniques to deduce whether the heat flux response derives from a direct central nervous system response activating a peripheral vasodilatory response or occurs primarily via release of vasoconstrictor response at various peripheral vascular sites (1, 16).
Body Heat Debt
Analysis of rate of heat storage in the heat balance equation (in this case, heat debt) (12, 30) (Fig. 5) provided a highly valuable indicator of the summed effects of cold stress. Decreases in rate of heat debt were readily apparent after 40 min of the cold stress, when a marked rise in sensible heat loss accompanied the decreased shivering thermogenesis (Figs. 2 and 5). In the follicular phase with prolonged inactivity, sufficient heat cannot be generated to prevent excessive body cooling when an ensemble with thermal resistance equivalent to street clothing (ensemble A) is worn. With ensemble A, rate of heat debt was significantly less in the women in the luteal phase than in the follicular phase at 40-80 min of exposure. Body heat debt in the luteal phase was also less at 40, 60, and 80 min (P < 0.05, 3-way ANOVA with Tukey's HSD post hoc test) than in the follicular and luteal phases with ensemble B. However, ensemble B, with a higher thermal resistance than ensemble A, also has outer semipermeable layers that impede insensible heat loss. Vapor accumulation potentially causes condensation within the layers, lowering the intrinsic insulation and increasing skin wettedness (12). This vapor accumulation may have contributed to elevated heat debt evident with ensemble B during the final time points of the cold transient. During the luteal phase when the women were dressed in ensemble A, sensible heat loss was also impeded by the intrinsic insulation of the ensemble higher than bare skin. However, ensemble A is vapor permeable, and without moisture condensation, any trapped heat apparently was sufficient to prevent excessive body cooling during the transient.Control Mechanisms During Cold Transients
Another interesting finding from the parameter estimation analyses of data during both menstrual cycle phases is that there appears to be a separate contribution from Tsk, Tes, and Tfing (representing vasoconstriction in acral sites) (1) controlling the shivering response. Shivering responses have been shown to be predicted by linear dependency betweensk and
Tes or tympanic, spinal, or rectal
temperatures (2, 15, 28, 29). In various model schemes,
output of the thermocontroller (shivering thermogenesis) is described
as being proportional to the difference between the sensed value (skin
and core thermal signals), the controller variable (e.g., hypothalamic
temperature), and various thermal reference or "set" points (15,
28). Hammel (15) proposed that shivering thermogenesis could be
regulated by such a proportional control scheme with different thermal
sensitivities emanating from different thermal inputs. Several thermal
models predict metabolic response to cold with use of such a
proportional control scheme from measurements of
sk and
Tc in which there is a linear
dependence of these two variables (12, 15). Others (28, 29) have shown
that shivering thermogenesis is closely associated by a multiplication
of thermal signals from the body core and mean weighted skin sites and
heavily influenced by percent body fat.
The general results of a decrease in shivering thermogenesis but increase in heat flux responses shown in the luteal phase are consonant with Boulant's (4) model and Hammel's concept (15) that activation of warm-sensitive neurons is accompanied by reciprocal inhibition of cold-sensitive neurons. Elevated levels of estradiol and/or progesterone functioning during a woman's luteal phase may possibly trigger heightened activity in warm-sensitive neurons in the preoptic/anterior hypothalamus during cold stress (4, 21). Activation of warm-sensitive neurons stimulating heat loss responses has been shown to cause a dampening of cold-sensitive neurons that stimulates shivering (4, 26). However, extensive interaction (and possible competition) between thermal inputs from skin and deep body thermoreceptors probably exists, tempering the final summed shivering responses in women as a function of the menstrual cycle (4, 5, 15).
In summary, during cold transient stress in resting women at two stages
of the menstrual cycle, 1) a
decreased slope in the luteal phase was observed when shivering
thermogenesis was plotted as a function of integrated mean body
temperature, 2) in the luteal phase,
women dressed in an ensemble equivalent to street clothing displayed an
increase in cutaneous heat flux, but rate of heat debt, assessed by
partitional calorimetry, was reduced, which extended cold tolerance,
and 3) the control of shivering
thermogenesis in both phases was found to be influenced by a linear
combination of Tc
(Tes) and
sk.
Tfing (e.g., thermal inputs from
acral areas) is multiplicative with other thermal signals influencing
total control of the shivering response.
| |
APPENDIX |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
|
|---|
Rate of heat storage and integrated mean body temperature.
In the cold, initial mean body temperature
('b,0)
is often calculated from a steady-state weighting ratio of
sk to rectal temperature
(sk/Tre)
of 1:2 (7). In the heat or during exercise the probable ratio varies
from 1:4 to 1:9 when Tes or Tre is used as a measure of
Tc (12, 28). During exercise or Ta transients when body
temperatures are in a non-steady state, coefficients for mean body
temperature change appreciably (12, 21). The calculation of the classic
Burton (7) mean body temperature by a simple weighting of
Tc and
Tsk is inaccurate during thermal
transients and probably not applicable in women, since time and
Ta, as well as
Tsk and
Tc, vary.
b/t). This form was used in the present study to quantify responses during
the cold ramps (12, 30), in which
|
(A1) |
is the specific heat of the body in
0.965W · h · °C1 · kg1
(or 3.49 kJ · °C1 · kg1),
mb is the body
weight in kg, and t is time in
hours.
For this study, during the resting period at
Ta of 20°C before
Ta drops,
'b,0
was first calculated by a 1:4 weighted average of
sk and
Tes.
b,i
(°C) was then determined as
|
(A2a) |
![= <OVL>T</OVL>′<SUB>b,0</SUB> + [(<IT>S</IT> · <IT>A</IT><SUB>D</SUB>)/(&lgr; · <IT>m</IT><SUB>b</SUB>)] · &Dgr;<IT>t</IT>](/content/vol85/issue2/fulltext/543/img017.gif)
|
(A2b) |
t is the time interval
(tx t0) of a run
taken at each
b
(min/60) in hours.
b,i at
each time point is evaluated by
![&Dgr;T′<SUB>b,i</SUB>/&Dgr;<IT>t</IT> = <FR><NU>[<IT>M</IT> − (<IT>W</IT>) − (<IT>R</IT> + <IT>C</IT>) − <IT>E</IT><SUB>sk</SUB>] · <IT>A</IT><SUB>D</SUB></NU><DE>&lgr; · <IT>m</IT><SUB>b</SUB></DE></FR> (°C)](/content/vol85/issue2/fulltext/543/img018.gif)
|
(A3) |
is the specific heat constant,
AD is the DuBois
surface area (in m2), and the
energy exchange terms in brackets (all in
W /m2) are evaluated by
partitional calorimetry (12, 30).
| |
ACKNOWLEDGEMENTS |
|---|
We thank the subjects for participation in the study; W. F. Allison, Nisha Charkoudian, Janet E. Staab, Michelle Mayo, and Jane P. Deluca for help with data collection, data reduction, graphical presentation, and general biochemical analyses; and especially Robert F. Wallace for statistical analyses and consultation.
| |
FOOTNOTES |
|---|
This study was funded, in part, by a Congressional Special Interest Medical Research Program Grant focused on Defense Women's Health.
Human subjects participated in these studies after giving their free and informed voluntary consent. US investigators adhered to US Army Medical Research and Materiel Command (USAMRMC) Regulation 70-25 on Use of Volunteers in Research. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other official documentation.
Address for reprint requests: R. R. Gonzalez, Biophysics and Biomedical Modeling Div., USARIEM, 5 Kansas St., Natick, MA 1760-5007.
Received 22 September 1997; accepted in final form 15 April 1998.
| |
REFERENCES |
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Abstract
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Methods
Results
Discussion
Appendix
References
|
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)
and luteal phase (Lut, 
). B:
ensemble B in follicular (
) and
luteal phase (
). Values are means ± SD; SD bars are plotted at
10-min intervals for clarity.
a Significant difference
between phases at each time point (P < 0.05).
and
during the cold ramp
