RELATIONSHIP BETWEEN CIRCULATING CORTISOL AND TESTOSTERONE: INFLUENCE
OF PHYSICAL EXERCISE
Section - Applied Physiology Laboratory, Department of Exercise & Sport
2Department of Nutrition - School of Public Health, University
of North Carolina, Chapel Hill, NC, USA
07 October 2004
© Journal of Sports Science
and Medicine (2005) 4, 76 - 83
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research has shown the administration of cortisol into the circulation
at rest will result in reduced blood testosterone levels. Many researchers
have used these results to imply that physical exercise induced cortisol
increases would perhaps result in subsequent reductions in circulating
testosterone levels. Our purpose was to examine this concept and determine
what, if any, relationship exists between circulating cortisol (C)
and testosterone (T) in men (n = 45, 26.3 3.8 yr) at rest and after
exercise. Blood samples were collect at rest (10 hour post-prandial;
denoted as 'Resting'; n = 45) and again on the same day at 1.0 hr
into recovery from intensive exercise (denoted as 'Exercise Recovery';
n = 45). Approximately 48-96 hr after this initial (Trial # 1) blood
collection protocol the subjects replicated the exact procedures again
and provided a second Resting and Exercise Recovery set of blood samples
(Trial # 2). Blood samples from Trial # 1and Trial # 2 were pooled
(Resting, n = 90; Exercise Recovery, n = 90). The blood samples were
analyzed by radioimmunoassay for C, total T (TT), and free T (fT).
Pearson correlation coefficients for the Resting samples ([TT vs.
C] r < +0.01; [fT vs. C] r = +0.06) were not significant (p >
0.05). For the Exercise Recovery samples ([TT vs. C] r = -0.53; [fT
vs. C] r = +0.21) correlation coefficients were significant (p <
0.05). The findings indicate that exercise does allow the development
of a significant negative relationship between C and TT. Interestingly,
a significant positive relationship developed between C and fT following
exercise; possibly due to an adrenal cortex contribution of fT or
disassociation of fT from sex hormone binding globulin. The detected
in vivo relationships between C and T, however, were associative
and not causal in nature and were small to moderate at best in strength.
WORDS: Glucocorticoids, androgens, exercise.
the main glucocorticoid form in humans, is a catabolic hormone secreted
from the adrenal cortex in response to physical and psychological
stress. Exercise at 60% or more of an individual's maximal oxygen
uptake (VO2max) is one of the physical stressors that
can cause an increase in the secretion of cortisol (Bloom et al.,
Davies and Few, 1973).
While cortisol increases during exercise, most of the changes and
perhaps effects of this hormone occur after exercise during the
early recovery (Daly et al., 2004;
Hackney and Viru, 1999;
McMurray and Hackney, 2000).
Cortisol's release affects metabolism by attempting to help maintain
blood glucose levels during physical exercise; it does this in part
by acting upon skeletal muscle and adipose tissue to increase amino
acid and lipid mobilization (Galbo, 2001;
Cortisol also aids this process by stimulating the liver to produce
enzymes involved in the gluconeogenic and glycogenetic pathways
allowing conversion of amino acids and glycerol into glucose and
glycogen (Galbo, 2001;
Testosterone is considered a key anabolic hormone with multiple
physiological functions in the human body. In males, testosterone
is mainly produced and secreted from the Leydig cells of the testes.
With respect to exercise, testosterone is especially important in
the growth and maintenance of skeletal muscle, bone, and red blood
cells (Zitzmann and Nieschlag, 2001).
Somewhat similar to cortisol, testosterone increases linearly in
response to exercise once a specific intensity threshold is reached
with peak concentrations usually occurring at the end of exercise
(Wilkerson et al., 1980).
It should be noted; however, even low intensity exercise if prolonged
enough in duration can result in significant elevations in testosterone
(Galbo et al., 1977;
[the same is true for cortisol, Väänänen et al., 2002]).
Previous research has established that under certain circumstances
a negative relationship exists between the hormones cortisol and
testosterone. Bambino and Hsueh (1981)
showed a direct inhibitory effect of high doses of glucocorticoids
upon testicular Leydig cell function in rats, which resulted in
a decrease in the production of testosterone. Cumming et al. (1983)
found a similar relationship in humans, using pharmacological doses
of cortisol to induce a decrease in testosterone production. These
latter researchers speculated cortisol disrupted the testicular
testosterone production process (i.e., via disruption of the hormone's
While this previous research has identified this inverse, negative
relationship between cortisol and testosterone, studies thus far
have apparently not statistically examined this point closely or
have done so with inadequate sample sizes. Also, while pharmacological
doses of cortisol appear to have a strong effect on circulating
testosterone concentrations in humans, the strength of the in vivo
relationship at rest and in recovery from exercise has not been
thoroughly determined. This last point is important as many published
exercise physiology studies have inferred that observed testosterone
reductions following certain forms of physical exercise are caused
by cortisol elevations in response to the exercise. Therefore, the
purpose of this study was to determine what, if any, relationship
exists between physiological levels of cortisol and testosterone
(both in total and free forms) in men at rest and in recovery from
physical exercise. We approached this research question using a
simple correlative design, which would allow us to examine whether
a relationship existed between the hormones. This approach, however,
only permitted us to determine if the relationship was of an associative
nature and not a "cause and effect".
of 45 healthy, physically active men (4-5 d·wk-1, >60
min·d-1, ≥5 yr) participated in this study. Their
physical characteristics were as follows: age, 26.3 ± 3.8 years
[mean ± SD]; height, 1.77 ± 0.06 meters; and body mass, 77.2 ± 7.8
kilograms (kg). All subjects gave voluntary, written informed consent
prior to participation in the study in accordance with the Helsinki
These men were all participants in several resting and exercise
based research ancillary-studies which involved giving multiple
blood samples. From each subject blood samples were collected at
rest in a 10 hour post-prandial state (denoted as 'Resting'; n =
45) and again on the same day at 1.0 hr (0.75 - 1.25 hr, range)
into recovery from intensive exercise (denoted as 'Exercise Recovery';
n = 45). The recovery sample time was based upon research by Daly
et al. (2004) in which recommendations were made concerning sampling
time for obtaining peak cortisol responses. Approximately 48-96
hr after this initial (Trial # 1) blood collection protocol the
subjects replicated the preceding procedures providing a second
(Trial # 2) Resting and Exercise Recovery set of blood samples.
In the time between the collection of the Resting and Exercise Recovery
blood specimens in both Trial # 1 and Trial # 2 only water was consumed
(ad lib). These overall procedures are depicted in Figure
All blood samples were collected by the veni-puncture technique
(~3 mL blood), a procedure all the subjects were familiar with from
previous research participation. All blood samples were collected
in the mid-morning time frame (9:00-11:30 AM), and the Resting and
Exercise Recovery blood collections times for Trial # 1 and Trial
# 2 were replicated (within ± 0.25 hr, range). The exercise protocols
performed by the subjects varied dependent upon the focus of each
ancillary study in which they were participants. The modes of exercise
involved running, rowing, and cycling, which were all of an intensity
(~65% to 75% VO2max) and duration (60 - 90 minutes) sufficient
to cause a significant increase in cortisol secretion (see Table
1; Davies and Few, 1973;
McMurray and Hackney, 2000).
Additionally, the mode, intensity and duration of the exercise at
Trial # 1 and Trail # 2 were replicated.
Once collected, blood specimens were placed on ice until centrifuged
at 4oC (3000 x g - 15 min) to separate the serum. The
sera were in turn stored frozen at -80o C until later
analysis. Hormonal analysis was conducted by using single-antibody
solid phase radioimmunoassay procedures using commercially available
I125 kits for the determination
of cortisol, total testosterone, and free testosterone (DPC Inc,
Los Angles, CA, USA). The within assay coefficients of variance
ranged from 5.9% to 8.1% while the between assay coefficients of
variance ranged from 6.5% to 9.8%.
Statistical analyses were performed using the Statistica software
(version 6.0) program (Statsoft, Tulsa, OK, USA). Descriptive statistics
were determined for all subject characteristics, including age,
height, and weight, as well as for hormone concentrations. The hormonal
data from Trial # 1and Trial # 2 were pooled so that the Resting
and Exercise Recovery comparison involved 90 data points each. Repeated
measures ANOVA were applied to the 'Resting' versus the 'Exercise
Recovery' to examine for concentration differences within each respective
hormone. Relationships between hormone concentrations were analyzed
using Pearson correlations, and Hotelling statistics were used to
test for significant difference between the correlation coefficients
Statistical significance was set at p ≤ 0.05.
results of the hormone concentrations for the Resting and Exercise
Recovery samples are displayed in Table
2. All hormonal values within each set of samples were normal
and within acceptable clinical ranges for the conditions under which
they were collected (McMurray and Hackney, 2000;
Cortisol and free testosterone concentrations were found to be significantly
greater in the Exercise Recovery samples than the Resting samples
(p < 0.01) in agreement with previous literature (Bonifazi et
Davies and Few, 1973;
Kivlighan et al., 2005;
Vogel et al., 1985).
correlations were used to analyze the relationship between cortisol
versus total testosterone and free testosterone. Of the four correlations
generated, two were significant, although the magnitude of effect
size was small to moderate for these coefficients (Cohen, 1988).
Cortisol versus total testosterone was negatively related in the
Exercise Recovery samples (r = -0.53, p<0.001, see Figure
2). The Resting samples showed no relationship for cortisol
versus total testosterone (r < 0.01, p > 0.05). The cortisol
versus free testosterone was positively related in the Exercise
Recovery samples (r = 0.21, p < 0.05, See Figure
3). The Resting samples showed no relationship for cortisol
versus free testosterone (r = 0.06, p > 0.05).
For the cortisol versus total testosterone relationship, the Exercise
Recovery coefficient was significantly greater than the Resting
coefficient (r = -0.53 vs. r < 0.01, respectively; Hotelling
statistic, p < 0.01). Likewise, for the cortisol versus free
testosterone the Exercise Recovery coefficient was significantly
greater than the Resting coefficient (r = 0.21 vs. r = 0.06, respectively;
Hotelling statistic, p < 0.01).
purpose of this study was to determine what, if any, relationship
exists between cortisol and testosterone (both in total and free
forms) in physically active men at rest and in the recovery from
physical exercise. Previous research had found that pharmacologically
manipulated levels of cortisol had resulted in reductions in circulating
testosterone (i.e., a negative relationship) (Bambino and Hsueh,
Cumming et al., 1983).
We hypothesized that this negative relationship would exist between
circulating cortisol and testosterone, specifically after exercise
when cortisol was at the high end of the normal physiological range.
A correlation relationship was found in this study that was in concordance
with previous literature, and supportive of our hypothesis. That
is, a significant negative relationship between cortisol and total
testosterone was found in the Exercise Recovery samples; however,
there was no relationship between the hormones in the Resting samples.
This finding of a relationship when cortisol is elevated (~160%
above Resting) suggests that perhaps that some critical level of
cortisol must be reached in order to substantially influence circulating
testosterone levels (see mechanism discussion below concerning pharmacological
dosages). This notion, however, is in need of further examination
in future research.
This negative association between testosterone and cortisol has
been reported in a few other exercise related studies (Hoogeveen
and Zonderland, 1996;
Nindl et al., 2001;
However, these studies have suffered from use of very small samples
sizes (thus limiting their external validity) or they reported the
relationship only on an observational basis and did not test the
association statistically. To our knowledge, our study is the first
to examine this issue in an exercise-based study with adequate subject
numbers to allow a statistical analysis of the relationship. It
is recognized, however, that the issue of blood collection timing
in the present study is a limitation within our data. Ideally, the
blood sampling times should have been precisely identical and standardized
in Trial #1 and # 2 as has been recommended by others (Daly et al.,
Nevertheless, the Exercise Recovery data for cortisol and total
testosterone in the present study reveal similar relationships as
reported by the Daly et al. study (Daly et al., 2005).
The specific physiological basis for a negative relationship between
cortisol and total testosterone can not be determined from our data,
but several postulates have been put forth by other investigators.
Cumming et al., (1983)
examined the response of luteinizing hormone (LH), prolactin, and
total testosterone to cortisol administration (i.e., pharmacological
levels). They found that while circulating testosterone was decreased,
there were no changes in LH or prolactin, suggesting that the effect
of cortisol on testosterone production was in the testes and not
the central endocrine regulatory components (i.e., hypothalamus-pituitary;
[The authors, however, did not measure LH pulse frequency or amplitude,
thus a central component influence can not be totally discounted]).
Cumming and associates speculated that cortisol disrupted the testicular
steroidogenic process in the Leydig cells perhaps by enzymatic inhibition.
In vitro animal model research supports this conjecture on
their part. For example, Bambino and Hsueh (1981)
found a direct inhibitory effect of infused pharmacological dosages
of cortisol on the LH receptor activity and content of the testes
in rats. Specifically, they proposed that that increased concentrations
of glucocorticoids (cortisol) disrupt the binding of LH on the testes
and thus steroidogenesis process. Later work by these same authors
expanded on this point and suggested that perhaps testicular cAMP
production and the activity of the 17α-hydroxylase enzyme were
somehow suppressed by glucocorticoids (Welsh et al., 1982).
Other researchers have reached similar conclusions; i.e., the steroidogentic
enzymatic activity for testosterone synthesis within the testis
is disrupted (Castro and Matt, 1997).
We acknowledge also that other factors could be affecting cortisol
and total testosterone in an independent fashion, and thus the observation
we report could be the result of such factors and the cortisol and
testosterone in our subjects are not directly affecting one another.
A negative relationship was not found between cortisol and free
testosterone, but rather the opposite occurred - a positive relationship
existed in the Exercise Recovery samples. This finding has been
previously reported in the literature (Daly et al., 2005).
The physiological explanation for this finding is uncertain, but
several possibilities exist. First, it is possible that the increased
concentration of free testosterone is a result of an increased adrenal
contribution of testosterone to the circulation. In response to
physical stress such as exercise, the adrenal gland is stimulated
through a cascade of reactions to produce cortisol. Cortisol and
testosterone are formed in the same cascade of reactions at the
adrenal gland (Kroboth et al., 1999).
Therefore when the adrenal gland is stimulated to produce cortisol,
it is possible that some free testosterone is produced and secreted
concurrently, leading to increased circulating concentrations of
both hormones. Secondly, testosterone can be transported in the
blood bound to sex hormone binding globulin and other carrier proteins
(e.g., albumin), while cortisol can be transported somewhat by the
latter and cortisol binding globulin (Rosner, 1990).
Since, cortisol and testosterone are formed from the same precursor,
they are structurally very similar. Thus the possibility exists
that an increased concentration of cortisol in circulation could
cause some dissociation of free testosterone from its carrier proteins
as the two hormones compete for binding sites (Rosner, 1990).
Additionally, binding protein affinity changes can happen in response
to the pH and temperature changes occurring with exercise which
could result in overall less carrier protein uptake of hormone thereby
increasing the free hormonal portion (Obminiski and Stupnicki, 1996;
Whether any of these events occurred to influence the hormones and
resulted in the positive relationship observed is uncertain and
speculation on our part; further research is necessary to examine
this phenomena and elucidate the mechanism.
conclusion, there are statistically significant relationships between
cortisol and testosterone in humans in the recovery from physical
exercise. Previous results demonstrate pharmacological levels of
cortisol have a highly significant negative effect on circulating
testosterone concentrations (Bambino and Hsueh, 1981;
Cumming et al.,1983).
Exercise appears to allow for the development of a similar negative
relationship between cortisol and total testosterone (although not
an extremely robust association). This finding would seem to support
the notion that the observed testosterone reductions following certain
forms of physical exercise could be related to cortisol elevations
in response to that exercise. But, this is speculative on our part
as the current data only indicate the existence of an associative
relationship between the hormones and does not indicate a cause
and effect relationship. Further research is necessary to fully
address this question. Additionally, it is important for researchers
to distinguish between the forms of testosterone being examined
when addressing the testosterone-cortisol relationship following
exercise, as free testosterone has an opposite relationship with
cortisol to that of total testosterone.
Pharmacologically increased levels of cortisol have a significant
negative effect on circulating testosterone
certain types of physical exercise a negative statistical associative
relationship exist between cortisol and total testosterone
Kaye K. BROWNLEE
Employment: A research associate at the U.S. Army Environmental
Laboratory at Natick, MA, USA.
Degree: BS, MA
Research interests: Hormones, Androgens
Alex W. MOORE
Employment: A biology instructor and laboratory manager
at Westmont College in Santa Barbara CA, USA.
Degree: BA, MA
Research interests: Human Performance - cycling
Anthony C. HACKNEY
Employment: Professor and faculty member at the University
of North Carolina, Chapel Hill, NC, USA.
Degree: BA, MA, PhD, GCPH
Research interests: Endocrinology