Download Effects of repeated whole-body cold exposures on serum

Cryobiology 58 (2009) 275–278
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Cryobiology
journal homepage: www.elsevier.com/locate/ycryo
Effects of repeated whole-body cold exposures on serum concentrations of
growth hormone, thyrotropin, prolactin and thyroid hormones in healthy women q
Juhani Smolander a,*, Juhani Leppäluoto b, Tarja Westerlund c, Juha Oksa d, Benoit Dugue e,
Marja Mikkelsson f, Aimo Ruokonen g
a
ORTON Orthopaedic Hospital, Tenholantie 10, FIN-00280 Helsinki, Finland
Department of Physiology, Institute of Biomedicine, University of Oulu, Oulu, Finland
c
Rheumatism Foundation Hospital, Heinola, Finland
d
Finnish Institute of Occupational Health, Oulu, Finland
e
Laboratory of Exercise-Induced Physiological Adaptations (EA3813), University of Poitiers, Poitiers, France
f
Päijät-Häme Central Hospital, Päijät-Häme Social and Health Care Group, Lahti, Finland
g
Department of Clinical Chemistry, University of Oulu, Oulu, Finland
b
a r t i c l e
i n f o
Article history:
Received 27 November 2008
Accepted 4 February 2009
Available online 12 February 2009
Keywords:
Growth hormone
Prolactin
Thyrotropin
Thyroid hormones
Winter swimming
Whole-body cryotherapy
Females
a b s t r a c t
Cold therapy is used to relieve pain and inflammatory symptoms. Humoral changes may account for the
pain alleviation related to the cold exposures. The aim of the present study was to examine the effects of
two types of cold therapy, winter swimming in ice-cold water (WS) and whole body cryotherapy (WBC),
on the serum levels of the growth hormone, prolactin, thyrotropin and free fractions of thyroid hormones
(fT3, fT4). One group of healthy females (n = 6) was exposed to WS (water 0–2 °C) for 20 s and another
group (n = 6) to WBC (air 110 °C) for 2 min, three times a week for 12 weeks. Blood samples used for
the hormone measurements were taken on weeks 1, 4 and 12 before and 35 min after the cold exposures
and on the days of the respective weeks, when the cold exposures were not performed. During the WS
treatments, serum thyrotropin increased significantly at 35 min on weeks 1 (p < 0.01) and 4 (p < 0.05),
but the responses were within the health-related reference interval. During the WS, the serum prolactin
measured at 35 min on week 12 was lower than during the control treatment, and no changes in fT3 or
fT4 were observed. During the WBC, no changes in the serum levels of the studied hormones were
observed during the 12 weeks. In conclusion, repeated WS and WBC treatments for healthy females do
not lead to disorders related to altered secretions of the growth hormone, prolactin, thyrotropin, or thyroid hormones.
Ó 2009 Elsevier Inc. All rights reserved.
Whole-body cryotherapy (WBC) is one mode of cold therapy,
during which patients are exposed to very cold air (1–3 min,
110 °C), while dressed in minimal clothing (a bathing suit and a
cap, gloves, socks, shoes, and a face mask). It is mainly used to alleviate inflammation and pain related to arthritis, osteoarthritis,
fibromyalgia or ankylosing spondylitis [1,5,19]. Several hospitals
in Japan and Europe have special climate chambers for producing
WBC. The WBC treatment has been observed to lead to a decrease
in pain ratings and to increase the movement of joints for over 24 h
[1,5,8,16].
q
This study was supported by the Rheumatism Foundation Hospital’s PATU
development project, co-financed by the European Social Fund of the European
Commission, the provincial State Office of Southern Finland as well as the City of
Heinola. Also, support was received from the Juho Vainio Foundation.
* Corresponding author. Fax: +358 9 2418408.
E-mail address: juhani.smolander@orton.fi (J. Smolander).
0011-2240/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.cryobiol.2009.02.001
Winter swimming in ice-cold water (WS), another form of cold
therapy, has been used as a treatment method for rheumatic diseases or as a recreational pastime in countries where waters freeze
during the wintertime. For instance, ca. 120,000 people are regular
WS enthusiasts in Finland. The process has been claimed to improve subjective well-being and to reduce pain in muscles and
joints, although there is a lack of objective findings.
The long-lasting effects of cold exposures have attracted attention to the humoral factors that may be therapeutically involved in
the outcome of the WBC treatments. Plasma levels of ACTH, betaendorphin and cortisol have been measured after single [2,15] or
repeated [15] WS or WBC exposures and no changes have usually
been observed. The same concerns plasma adrenalin levels,
whereas plasma noradrenaline levels have been shown to increase
after WS or WBC exposures [9–12,15], which may have a role in
the pain alleviation at a spinal cord level [15].
Besides the stress hormones, cold exposures also have effects on
other hormones, such as the pituitary hormones, growth hormone
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J. Smolander et al. / Cryobiology 58 (2009) 275–278
(GH), prolactin (PRL), thyrotropin (TSH), and the thyroid hormones.
Previously, the serum TSH was shown to have increased after a single or repeated WS exposure, while neither the serum GH nor PRL
experience any changes [6]. On the contrary, in laboratory conditions, the exposures to cold air had no effect on the serum TSH
or thyroid hormones, but the GH and PRL decreased [7,14]. However, a single and intense cold water exposure has been found to
lead to an increase in the serum TSH [13]. Previous information
in regards to the circulating levels of the GH, PRL, TSH or thyroid
hormones after WBC treatments appears to be lacking.
Thus, in the present study, we exposed healthy females to repeated WBC for three months and measured the serum levels of
the GH, PRL, TSH, and thyroid hormones at weeks 1, 4 and 12.
While the duration of a single WBC or WS exposure is short, the
heat loss may by greater in regards to the WS than with the
WBC exposure, as judged from the decreases in the mean skin temperatures during the WBC [15,20], and from the high thermal conductance of ice-cold water. Therefore, we exposed another group of
subjects to repeated WS treatments and compared the results with
those obtained during the WBC treatments.
New York) and the GH was analyzed by fluoroimmunoassay (PerkinElmer, Turku, Finland).
The intra- and inter-assay coefficients of the variation and reference intervals were 3.6% and 7.0% and 0.4–4.5 mU/l for TSH, 2.3%
and 3.0% and 10.2–21 pmol/l for fT4, 2.4% and 2.9% and 3.2–
6.5 pmol/l for fT3, 2.3% and 3.1% and less than 320/530 mU/l
(men/women) for PRL and 5.1% and 5.6% and less than 4.4 lg/l
for GH.
Materials and methods
Results
Subjects
The serum TSH, GH and PRL concentrations were measured during weeks 1, 4 and 12 before (0 min) and after (35 min) the control
exposures (room temperature), and similarly before and after the
WS and WBC treatments (Table 1). There were no significant
changes in the basal levels (0 min) of the serum TSH, GH or PRL
during weeks 1, 4 or 12 of the WBC or WS experiments. Serum
TSH only showed a significant increase at 35 min, compared with
0 min in week 1 (from 1.3 to 1.7 mU/l, p < 0.01) and 4 (from 1.3
to 1.6 mU/l, p < 0.05), only in the WS experiments. Serums GH
and PRL did not change significantly between 0 to 35 min during
the 12 weeks control and WS or WBC treatments. Serum PRL
was, during week 12 at 35 min in the WS treatment, significantly
lower than in the control treatment.
The basal serum levels (0 min) of the fT3 and fT4 did not show
any significant change between the weeks 1, 4 and 12 during the
control and WS or WBC treatments (Table 2).
Our original study sample [15] comprised 20 healthy women,
who were divided into 10 similar pairs and randomised into 2
groups, one participating in the WBC and the other in the WS. Since
the stress hormone (ACTH, beta-endorphin, cortisol, and cathecholamines) responses did not differ between the groups [15],
we included only the first 6 pairs (total n = 12) for the present
study. The mean age (SD) and body mass index were 38 (3) years
and 24 (3) for the WBC group, and 40 (2) years and 24 (3) for the
WS group, respectively. None of the subjects used oral contraceptives and three subjects in each group had intrauterine devices.
The local ethics committee of the hospital district approved the
protocol, and informed consents were obtained from each subject.
Procedures
In the WBC group, the subjects had three exposures in a temperature controlled unit (Zimmer, Elektromedizin, Germany), for
a period of 2 minutes (110 °C) per week for 3 months In the
WS group, the subjects had three head-out water immersions in
a pond nearby the hospital, for a period of 20 s per week for 3
winter months. The water temperature was between 0 and 2 °C.
Three blood samples were taken twice a week during weeks 1,
2, 4, 8 and 12. The specimens were taken at 0, 5 and 35 min in
the week and day, when no cold exposure occurred (control).
During the same week, the second series of samples were drawn
before the cold exposure (time 0), as well as 5 and 35 min after
the cold exposure. For the procedural details, see [15]. For the
present study, samples taken at 0 and 35 min during weeks 1,
4, and 12 were used to analyze the GH, PRL and TSH. Baseline
samples (time 0) during weeks 1, 4 and 12 were used to analyze
the changes in the fT3 and fT4 during the three-month
interventions.
Biochemical analyses
Blood samples were collected into glass tubes, kept cool, centrifuged for 60 min, and stored at a temperature of 70 °C.
Serum concentrations of the TSH, free thyroxine (fT4), free triiodothyronine (fT3) and PRL were analyzed using an automated
chemiluminescence system (Advia Centaur, Bayer Corporation,
Statistical analyses
The results are expressed as means and the standard error of
the means (SE). The changes in the GH, PRL and TSH during the
experiments were analyzed by a mixed-model ANOVA for repeated
measures (group, week, day, and time). Post hoc comparisons of
interest were analyzed by Fisher’s LSD test. Changes in the fT3
and fT4 were analyzed by a 2-way ANOVA for repeated measures
(time and treatment as factors). Post hoc comparisons were made
by the Student–Newman–Keuls procedure. The results were considered to be statistically significant, when p < 0.05.
Discussion
The results of the present study showed that the serum TSH did
not change significantly during the 12 weeks of the WBC treatments. Although there are no earlier studies in regards to the
TSH secretion during WBC treatments, this finding is in line with
several other studies, where single or repeated cold-air exposures
have not been observed to lead to any significant changes in TSH
concentrations [7,14]. However, in our WS treatments, the serum
TSH increased significantly at 35 min during weeks 1 and 4, but
not later. In a previous WS study, the serum TSH increased significantly at 30 min during months 1 and 2.5 [6]. Therefore, the increases in the serum TSH that we saw in weeks 1 and 4 agree
with those presented in the aforementioned WS study [6]. The reason why we did not observe any significant changes in the serum
TSH in week 12, as the other authors did, may be due to longer cold
water exposures (1.5 min vs. 20 s). It should also be noted that
clearly longer cold-water exposures in laboratory conditions have
been found to result in an increase in the serum TSH levels within
5–15 min [13]. However, a habituation to cold stimulus may have
occurred over the course of our study.
The differing responses in TSH between the WBC and WS treatments may be caused by differences in heat loss during the exposures. During the WBC, the mean skin temperature decreases
within 1–2 min to a minimum of circa 15 °C and then returns to
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Table 1
SerumTSH, PRL, and GH (presented as the mean and SE in parentheses) in female subjects participating in winter swimming or whole-body cryotherapy. The concentrations at
rest, and after 35 min of exposure (and the corresponding times for the control session) during weeks 1, 4 and 12 are presented. The number of subjects was 6 in each session.
Analytes
TSH (mU/L)
Treatment
Winter swimming
Cryotherapy
PRL (mU/L)
Winter swimming
Cryotherapy
GH (lg/L)
Winter swimming
Cryotherapy
*
**
§
Day
Week 1
Control day
Exposure day
Control day
Exposure day
Control day
Exposure day
Control day
Exposure day
Control day
Exposure day
Control day
Exposure day
Week 4
Week 12
Basal value
After 35 min
Basal value
After 35 min
Basal value
After 35 min
1.2 (0.1)
1.3 (0.1)
1.5 (0.3)
1.3 (0.2)
133 (20)
168 (30)
248 (84)
142 (10)
0.7 (0.3)
1.4 (1.0)
2.0 (1.0)
2.0 (1.0)
1.1 (0.1)
1.7** (0.2)
1.3 (0.3)
1.3 (0.2)
138 (23)
177 (37)
221 (57)
119 (10)
2.0 (0.7)
1.1 (0.6)
1.5 (0.8)
2.1 (1.2)
1.1 (0.1)
1.3 (0.2)
1.1 (0.2)
1.0 (0.2)
176 (44)
156 (27)
131 (16)
108 (17)
1.4 (0.7)
2.4 (1.0)
3.2 (1.4)
1.5 (0.6)
1.0 (0.1)
1.6* (0.2)
1.1 (0.2)
1.1 (0.2)
163 (48)
167 (35)
135 (16)
101 (16)
1.4 (0.8)
2.5 (0.9)
4.7 (1.9)
2.7 (1.9)
1.0 (0.1)
1.1 (0.2)
1.1 (0.2)
1.0 (0.2)
180 (35)
134 (22)
156 (27)
130 (18)
1.1 (0.4)
2.5 (1.1)
1.5 (0.7)
3.7 (1.7)
1.0 (0.1)
1.2 (0.2)
1.1 (0.2)
1.1 (0.1)
234 (63)
130§ (22)
164 (27)
116 (21)
0.7 (0.4)
1.8 (0.5)
2.5 (1.5)
1.3 (0.7)
p < 0.05 from the 0 min values.
p < 0.01.
Denotes p < 0.05 from the respective control day value.
Table 2
Free fractions of serum T3 and T4 (presented as the mean and SE in parentheses) in
female subjects participating in winter swimming or whole-body cryotherapy. The
values were measured at the baseline (time 0) before the treatments during weeks 1,
4 and 12.
Analytes
Treatment
Week 1
Week 4
Week 12
fT3 (pmol/l)
Winter swimming
Cryotherapy
Winter swimming
Cryotherapy
4.8
4.8
16.2
14.6
4.8
4.7
15.9
15.1
4.6
4.4
14.6
14.8
fT4 (pmol/l)
(0.1)
(0.2)
(0.6)
(0.7)
(0.1)
(0.1)
(0.5)
(0.8)
(0.2)
(0.2)
(0.9)
(0.9)
20–25 °C, representing a heat loss of about 13 kJ/kg of body weight
[15,20]. The heat loss is similar to those observed during previous
studies utilizing cold-air exposures [14,17]. In the present WS
treatments, the mean skin temperature (not measured) probably
approached the water temperature of 0–2 °C. This assumption represents an approximate heat loss of ca. 26 kJ/kg maximally, which
is two times greater than during the WBC treatments. This may be
one reason why the serum TSH increased after the WS, but not
after the WBC treatments. Another reason could be that all of our
subjects were of the female gender. Previous studies have shown
that the responses of ACTH, cortisol, GH, PRL and noradrenaline
to WS or other types of cold exposures are greater in women than
in men [4,11].
We observed that the basal (0 min) serum GH and PRL concentrations remained at the same levels during the 12 week period of
WS and WBC treatments. In a study by Hermanussen and his coworkers, the basal GH did not change but the basal PRL increased
almost 2-fold during the 2.5 month of WS treatments [6]. The reason for the increase in the basal PRL levels in the previous mentioned study is unknown and we did not observe any such
changes in our study. In another study, no seasonal changes in
plasma PRL were observed either [3]. In our present WS and
WBC treatments, we found no significant changes in the PRL between the 0 and 35 min levels during the 12 weeks. These findings
are similar to those presented in the aforementioned WS study [6].
However, previous studies performed in laboratory conditions
have shown that exposures to cold water for 20 min or to cold
air for 120 min result in decreased levels of GH and PRL
[13,14,17]. Our present results support the findings that cold exposures lead to a decreased secretion of the PRL, since we observed
that in the 12 weeks the serum prolactin level was lower after
WS than after the control. These decreases are evidently mediated
by the increased release of dopamine from hypothalamic neurons
induced by the cold, leading to a decreased secretion of the PRL
from the pituitary lactotrophs [14]. It appears that the intensity
and/or duration of our WBC treatments have not been sufficient
to lead to a suppression of the GH or PRL.
We measured the levels of free fractions of the serums T3 and
T4 during the WS and WBC treatments. Since the TSH responses increased in the WS treatments during weeks 1 and 4, changes to the
thyroid hormone levels could be expected. However, the basal
(0 min) levels of the free T3 and T4 did not show any significant
changes during or between the WS or WBC treatments. It has been
previously observed that the total and free serum T3 decreases
after 80 exposures to cold air or 40 exposures of feet to cold water
[7,18]. Our cold exposures were of a shorter duration than in those
studies, and therefore we presumably observed no changes. The
TSH responses that we observed in the WS treatments were small
and the serum TSH remained within the reference interval of
healthy subjects, which may also explain why the fT3 and fT4
did not change.
It is noteworthy that although the WS and WBC treatments are
of short duration both have found to reduce pain for over 24 h [8].
Our previous study demonstrated that noradrenaline was the only
stress hormone that responded to our WS and WBC treatments and
that the sustained noradrenaline stimulation could have a role in
pain alleviation [15]. During the present study, we did not observe
any significant changes in the basal or cold stimulated levels of the
serum TSH, GH, PRL or thyroid hormones during the 12 weeks of
WBC treatment. These findings suggest that repeated WBC treatments over three months do not lead to disorders related to altered
secretions of these hormones. The same evidently concerns WS
treatments, as the observed TSH responses at weeks 1 and 4 were
within the health-related reference intervals and no changes in the
free fractions of thyroid hormones were observed.
References
[1] G. Birwe, R. Fricke, R. Hartmann, Ganzkörperkältetherapie: Beeinflussung der
subjektiven Beschwerenlinderung und der Gelenkenfunktion, Z. Phys. Med.
Baln. Med. Klim. 18 (1989) 11–15.
[2] L. Fricke, R. Fricke, W. Wiegelman, Beeinflussung hormoneller Reaktionen
durch Ganzkörperkältetherapie, Z. Phys. Med. Baln. Med. Klim. 17 (1988) 363–
364.
[3] R.R. Gala, C. Van De Valle, W.H. Hoffman, D.M. Lawson, D.R. Pieper, S.W. Smith,
M.G. Subramanian, Lack of circannual cycle of daytime serum prolactin in man
and monkey, Acta Endocrinol. 86 (1977) 257–262.
[4] G. Gerra, R. Volpi, R. Delsignore, L. Maninetti, R. Caccavari, S. Vouma, D.
Maestri, P. Chiodera, G. Ugolotti, V. Coiro, Sex-related responses of betaendorphin, ACTH, GH and prolactin to cold exposure in humans, Acta
Endocrinol. 126 (1992) 24–28.
278
J. Smolander et al. / Cryobiology 58 (2009) 275–278
[5] C. Gutenbrunner, G. Englert, M. Neues-Lahusen, A. Gehrke, Kontrollierte Studie
über Wirkungen von Kältekammerexpositionen bei Fibromyalgiesyndrom, Akt
Rheumatol. 24 (1999) 93–100.
[6] M. Hermanussen, F. Jensen, N. Hirsch, K. Friedel, B. Kröger, R. Lang, S. Just, J.
Ulmer, M. Schaff, P. Ahnert, K. Heyne, H.J. Zeisel, Acute and chronic effects of
winter swimming on LH, FSH, prolactin, growth hormone, TSH, cortisol, serum
glucose and insulin, Arct. Med. Res. 54 (1995) 45–51.
[7] R.L. Hesslink Jr., M.M. D0 Alesandro, D.W. Armstrong III, H.L. Reed, Human cold
air habituation is independent of thyroxine and thyrotropin, J. Appl. Physiol. 72
(1992) 2134–2139.
[8] H. Hirvonen, M. Mikkelsson, H.P. Kautiainen, M. Leirisalo-Repo, Effectiveness of
different cryoptherapies on pain and disease activity in active rheumatoid
arthritis. A randomized single blinded controlled trial, Clin. Exp. Rheumatol. 24
(2006) 295–301.
[9] J. Hirvonen, S. Lindeman, S. Joukamaa, P. Huttunen, Plasma catecholamines,
serotonin and their metabolites and endorphin of winter swimmers during one
winter. Possible correlations to psychological traits, Int. J. Circumpolar Health
61 (2001) 363–372.
[10] P. Huttunen, N. Lando, V. Meshtsherryakov, V. Lutov, Effects of long-distance
swimming in cold water on temperature, blood pressure and stress hormones
in winter swimmers, J. Thermal Biol. 25 (2000) 171–174.
[11] P. Huttunen, J. Leppäluoto, Human endocrine responses to repeated cold water
exposures, in: B.K. Sharma (Ed.), Adaptation Biology and Medicine, Narosa
Publishing House, New Delhi, 1997, pp. 231–235.
[12] P. Huttunen, H. Rintamäki, J. Hirvonen, Effect of regular winter swimming on
the activity of the sympathoadrenal system before and after a single cold
water immersion, Int. J. Circumpolar Health 60 (2001) 400–406.
[13] J. Leppäluoto, H. Lybeck, P. Virkkunen, J. Partanen, T. Ranta, Effects of
immersion in cold water on the plasma ACTH, GH, LH and TSH
concentrations in man, in: B. Harvald, J.P. Hart-Hansen (Eds.), Circumpolar
Health 81, Strougaard Jensen, Copenhagen, 1982, pp. 601–602.
[14] J. Leppäluoto, I. Korhonen, P. Huttunen, J. Hassi, Serum levels of thyroid and
adrenal hormones, testosterone, TSH, LH, GH and prolactin in men after a 2-h
stay in a cold room, Acta Physiol. Scand. 132 (1988) 543–548.
[15] J. Leppäluoto, T. Westerlund, P. Huttunen, J. Oksa, J. Smolander, B. Dugué, M.
Mikkelsson, Effects of long-term whole-body cold exposures on plasma
concentrations of ACTH, beta-endorphin, cortisol, catecholamines and
cytokines in healthy females, Scan. J. Clin. Lab. Investigation 68 (2008) 145–
153.
[16] D. Metzger, C. Zwingmann, W. Protz, W. Jackel, Die bedeutung der
Ganzkörperkältetherapie im Rahmen der Rehabilitation bei Patienten mit
rheumatischen Erkrankungen, Rehabilitation 19 (2000) 93–100.
[17] D. Mills, D. Robertshaw, Response of plasma prolactin to changes in ambient
temperature and humidity in man, J. Clin. Endocrinol. 52 (1981) 279–283.
[18] G. Savourey, J.P. Caravel, B. Barnavol, J.H. Bittel, Thyroid hormone changes in
cold air environment after local cold acclimation, J. Appl. Physiol. 76 (1994)
1963–1967.
[19] T. Stratz, P. Schlegel, P. Mennet, W. Müller, Biochemische und hormonelle
Reaktionen unter der Ganzkörperkältetherapie, in: W. Müller (Ed.),
Generalisierte
Thendomyopathie
(Fibromyalgie),
Steinkopf
Verlag,
Darmstadt, 1991, pp. 299–306.
[20] T. Westerlund, J. Oksa, J. Smolander, M. Mikkelsson, Thermal responses during
and after whole-body cryotherapy (110 °C), J. Thermal Biol. 28 (2003) 601–
608.