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Post-exercise hypertrophic adaptations: A re-examination of the hormone hypothesis and
its applicability to resistance training program design
Brad Schoenfeld
Department of Health Sciences
Program of Exercise Science
APEX Building, Room # 263
Lehman College, CUNY
250 Bedford Park Blvd West
Bronx, NY 10468
Email: brad@workout911.com
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Abstract
It has been well-documented in the literature that resistance training can promote marked
increases in skeletal muscle mass. Post-exercise hypertrophic adaptations are mediated by a
complex enzymatic cascade whereby mechanical tension is molecularly transduced into anabolic
and catabolic signals that ultimately leads to a compensatory response, shifting muscle protein
balance to favor synthesis over degradation. Myocellular signaling is influenced, in part, by the
endocrine system. Various hormones have been shown to alter the dynamic balance between
anabolic and catabolic stimuli in muscle, helping to mediate an increase or decrease in muscle
protein accretion. Resistance training can have an acute impact on the post-exercise secretion of
several of these hormones including insulin-like growth factor (IGF)-1, testosterone, and growth
hormone (GH). Studies show that hormonal spikes are magnified following hypertrophy-type
exercise that involves training at moderate intensities with shortened rest intervals as compared
to high-intensity strength-oriented training. The observed positive relationship between anabolic
hormones and hypertrophy-type training has led to the hormone hypothesis, which postulates
that acute post-exercise hormonal secretions mediate increases muscle size. Several researchers
have suggested that these transient hormonal elevations may be more critical to hypertrophic
adaptations than chronic changes in resting hormonal concentrations. Theoretically, high levels
of circulating hormones increase the likelihood of interaction with receptors, which may have
particular hypertrophic importance in the post-workout period when muscles are primed for
anabolism. Moreover, hormonal spikes may enhance intracellular signaling so that post-exercise
protein breakdown is rapidly attenuated and anabolic processes are heightened, thereby leading
to a greater supercompensatory response. While the hormone hypothesis has received
considerable support in the literature, however, several researchers have questioned its veracity,
with some speculating that the purpose of post-exercise hormonal elevations is to mobilize fuel
stores rather than promote tissue anabolism. Therefore, the purpose of this paper will be to
critically and objectively review the current literature, and then draw relevant conclusions as to
the potential role of acute systemic factors on muscle protein accretion.
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It has been well-documented in the literature that resistance training can promote marked
increases in skeletal muscle mass (68). Post-exercise hypertrophic adaptations are mediated by a
complex enzymatic cascade whereby mechanical tension is molecularly transduced into anabolic
and catabolic signals that ultimately lead to a compensatory response, shifting muscle protein
balance to favor synthesis over degradation. A number of signaling pathways involved in post-
exercise hypertrophic adaptations have been identified including phosphatidylinositol 3-kinase-
protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR), mitogen-activated protein
kinase (MAPK), and various calcium- (Ca2+) dependent pathways, amongst others. Although
these pathways may overlap at key regulatory steps, there is evidence that they may be
interactive rather than redundant (80).
Myocellular signaling is influenced, in part, by the endocrine system. Various hormones
have been shown to alter the dynamic balance between anabolic and catabolic stimuli in muscle,
helping to mediate an increase or decrease in muscle protein accretion (73). Resistance training
can have an acute impact on the during- and post-exercise elevation of several of these hormones
including insulin-like growth factor (IGF)-1, testosterone, and growth hormone (GH). Studies
generally show that hormonal spikes are magnified following hypertrophy-type exercise that
involves training at moderate intensities (~60 to 80% 1RM) with shortened rest intervals (~60 to
90 seconds between sets) and high volumes as compared to high-intensity strength-oriented
training (39). It is believed that high metabolic stress associated with such routines potentiates
post-exercise hormonal release. Although the exact mechanisms are not entirely clear, the
accumulation of metabolites (lactate, Pi, etc), a reduction in pH, and/or the effects of hypoxia
have been implicated as causative factors in the process. Studies involving restricted blood flow
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exercise seem to support this view, as low intensity occlusion training produces significant
increases in both metabolic stress and hormonal levels (18, 78, 79).
The observed positive relationship between anabolic hormones and hypertrophy-type
training has led to the hormone hypothesis, which postulates that acute post-exercise hormonal
elevations play a part in mediating increases in muscle size (22, 30). Several researchers have
suggested that these transient hormonal elevations may be more critical to hypertrophic
adaptations than chronic changes in resting hormonal concentrations because most studies have
failed to show changes in resting hormonal concentrations with the exception of significant
changes to the program or overtraining and detraining (39). High levels of circulating hormones
increase the likelihood of interaction with receptors (15), which may have particular
hypertrophic importance in the post-workout period when muscles are primed for anabolism.
Moreover, hormonal spikes may enhance intracellular signaling so that post-exercise protein
breakdown is rapidly attenuated and anabolic processes are heightened, thereby leading to a
greater supercompensatory response.
Although the hormone hypothesis has received considerable support in the literature,
several researchers have questioned its veracity (45, 61), with some speculating that the purpose
of post-exercise hormonal elevations is to mobilize fuel stores rather than promote tissue
anabolism (94). Therefore, the purpose of this paper will be to critically and objectively review
the current literature, and then draw relevant conclusions as to the potential role of acute
systemic factors on muscle protein accretion. To carry out this review, English-language
literature searches of the PubMed, EBSCO, and Google Scholar databases were conducted for all
time periods up to April 2012. Combinations of the following keywords were used as search
terms: "skeletal muscle"; hypertrophy"; “muscle growth”; "cross sectional area"; "IGF-1";
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"acute"; "transient"; "growth hormone"; "testosterone"; "anabolic hormone"; "metabolic stress";
"metabolite buildup"; metabolite accumulation"; "resistance training"; "resistance exercise";
"weight lifting"; and "bodybuilding". The reference lists of articles retrieved in the search were
then screened for any additional articles that had relevance to the topic. Given the broad scope of
the topic, a narrative approach was chosen as the best way to convey pertinent information and
inclusion criteria was based on applicability to the particular area of discussion.
Hormones and Muscle Growth
Studies have demonstrated that increases in muscle hypertrophy can occur in the relative
absence of post-exercise hormonal increases (93, 96). What remains equivocal is whether such
hormonal elevations can potentiate the hypertrophic response, thereby maximizing muscle
growth. A number of hormones have been shown to mediate anabolic signaling, with the
majority of studies focusing on IGF-1, testosterone and GH. What follows is an overview of each
of these hormones and their presumed roles in the growth process.
IGF-1
IGF-1 is a homologous peptide with structural similarities to insulin. Intracellular IGF-1
signaling is carried out through multiple pathways including PI3K-Akt-mTOR, MAPK-ERK,
and possibly Ca2+ -dependent calcineurin (24, 65, 70). These cascades exert both anabolic and
anti-catabolic effects, mediating hypertrophic adaptations (67). Cell culture studies have
repeatedly shown that IGF-1 acts to stimulate protein synthesis, suppress proteolysis, and
increase mean myotube diameter and the number of nuclei per myotube (31). Despite these
diverse anabolic actions, however, research indicates that a functional IGF-1 receptor is not
obligatory for compensatory muscle growth (75).
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Three distinct IGF-1 isoforms have been identified in humans: IGF-1Ea, IGF-1Eb, and
IGF-1Ec. Both IGF-1Ea and IGF-1EB are systemic isoforms whose production is primarily
derived from the liver. Other tissues also express these isoforms, however, with the extent of
non-hepatic production increasing in response to exercise. In fact, exercised muscles are the
primary producers of systemic IGF-1 during intense physical training, and the majority of
circulating IGF-1 is ultimately taken up by the working musculature (12, 19). Alternatively, IGF-
1Ec is a splice variant of the IGF-1 gene exclusively expressed by muscle tissue in response to
mechanical loading and then exerting its influence in an autocrine/paracrine fashion (19). The
local actions of IGF-1Ec dictate that it is more accurately classified as a myokine rather than a
hormone. Because this isoform is activated mechanically and has a different carboxy peptide
sequence to systemic IGF-1, it has been termed mechano growth factor (MGF).
Current theory suggests that MGF is more relevant to compensatory muscle growth than
the systemic IGF-1 isoforms (31). It has been proposed that MGF helps to “kick-start” the post-
exercise adaptive process, resulting in enhanced muscle protein accretion and the local repair of
damaged tissue (19). A recent cluster analysis provides compelling support for this view.
Bamman et al. (7) categorized 66 subjects into extreme responders (mean myofiber hypertrophy
of 58%), moderate responders (mean myofiber hypertrophy of 28%) and non-responders (no
increase in myofiber hypertrophy) based on their hypertrophic response to a 16 week resistance
training protocol for the knee extensors. Assessment by muscle biopsy found that MGF was
differentially expressed across clusters: whereas extreme responders upregulated MGF by 126%,
levels remained relatively unchanged in non-responders. These results strongly suggest that
transient exercise-induced elevations in MGF gene expression are important hypertrophic cues.
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MGF is believed to regulate muscle hypertrophy in several ways. For one, it acts directly
on muscle fibers to influence protein synthesis, presumably by exerting downstream effects via
PI3K-Akt-mTOR on p70 S6 kinase (2, 3, 55). MGF also may heighten protein synthesis by
downregulating catabolic signaling processes involved in protein degradation. Specifically, there
is evidence that local IGF-1 production suppresses FoxO nuclear localization and transcriptional
activities, blocking downstream proteolytic actions (21). These combined actions can help to
trigger greater post-exercise muscle protein accretion.
MGF also mediates compensatory hypertrophy by regulating satellite cell activity.
Satellite cells are muscle stem cells that reside between the basal lamina and sarcolemma. In the
resting state, these precursor cells remain in a dormant state. When muscle is subjected to
mechanical overload, however, satellite cells enter the cell cycle and initiate muscular repair by
first undergoing proliferation and then differentiating into myoblast-like cells (59). Differentiated
myoblasts can then fuse to traumatized myofibers and donate their nuclei to increase the
muscle’s ability to synthesize new contractile proteins. Myoblasts also can fuse to each other to
form new functional myofibers (59), although it remains questionable whether such hyperplasia
occurs during traditional resistance training in humans (1). In addition, satellite cells co-express
myogenic regulatory factors such as c-met myogenin, MyoD, Myf5 and MRF4 that mediate
muscle growth (20). There is some controversy as to whether satellite cells are obligatory for
muscle hypertrophy (52), but recent evidence suggests they may be vital for maximizing
muscular development in humans (58). A complete discussion of the topic is beyond the scope of
this paper, and interested readers are referred to the point/counterpoint articles by O'Connor and
Pavlath (56) and McCarthy and Esser (51).
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Locally expressed MGF has been shown to be involved primarily in the initial phase of
satellite cell activity. This is consistent with studies showing that MGF mediates ERK1/2
signaling while systemic isoforms do not, as well as the fact that it is expressed earlier than
hepatic-type IGF-1 in response to exercise (8, 20). Accordingly, there is evidence that MGF is
critical for inducing satellite cell activation and proliferation (32, 98). In this way, MGF helps
increase the number of myoblasts available for post-exercise repair as well as facilitating
replenishment of the satellite cell pool.
The hypertrophic role of systemic IGF-1 is less clear and considerable debate exists as to
whether it is in fact involved in exercise-induced skeletal muscle growth. An age-related decline
of circulating IGF-1 levels has been found to correlate with losses of muscle mass and strength
(29). This may indicate that there is a threshold for systemically produced IGF-1 below which
muscle development is compromised. On the other hand, blood levels of IGF-1 do not always
correlate with post-exercise increases in muscle protein synthesis (102). Moreover,
compensatory hypertrophy is not blunted in liver IGF-1-deficient mice that display an ~80%
reduction in circulating levels of IGF-1 (48). These conflicting data have yet to be reconciled and
require further study.
There is speculation that IGF-1Ea may act in concert with MGF to mediate satellite cell
activity. As noted, MGF is rapidly upregulated following mechanical loading while systemic
IGF-1 production is delayed and lasts considerably longer (57). Thus, the primary hypertrophic
role of systemic IGF-1 may be in later stage satellite cell regulation, stimulating differentiation
and fusion following myotrauma and thereby facilitating the donation of myonuclei to muscle
fibers so that optimal DNA-to-protein ratios are maintained (82, 86). Whether the systemic
isoforms have additional hypertrophic actions following resistance training remains to be
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elucidated. A complete discussion of the roles of the various IGF-1 isoforms is beyond the scope
of this paper. Those interested in further exploration of the topic are referred to recent reviews by
Velloso and Harridge (87) and Philippou et al. (60).
Growth Hormone
GH is a superfamily of polypeptide hormones secreted by the anterior pituitary gland and
released in a pulsatile fashion, with the greatest non-exercise secretions occurring during sleep.
GH has been shown to mediate both anabolic and catabolic processes (86). Specifically, it acts as
a repartitioning agent to induce fat metabolism toward mobilization of triglycerides, as well as
stimulating cellular uptake and incorporation of amino acids into various proteins, including
those in skeletal muscle (88). GH also plays a role in a wide array of other bodily actions
involving multiple organs and physiological systems. A total of more than 100 molecular
isoforms of GH are produced endogenously (54), and the precise functions of each have yet to be
determined.
With respect to muscle tissue, it is believed that GH primarily mediates hypertrophic
adaptations through the actions of IGF-1 (86). Murine studies indicate that the effects of GH on
muscle function and mass are dependent on an intact IGF-1 receptor (35). These findings are
supported by a wealth of research showing that circulating IGF-1 levels are increased following
GH administration (6, 28, 64). In addition to exerting effects on systemic IGF-1 isoforms,
evidence suggests that GH also can directly act on muscle-derived IGF-1. Klover and
Henninghausen (36) displayed that deletion of the genes for signal transducers and activators of
transcription (STAT), which are critical mediators of GH-induced transcription of the IGF-I
gene, resulted in a selective loss of STAT5 protein in skeletal muscle while liver expression
remained unaffected (36). This is consistent with in vitro research showing that murine myoblast
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C1C12 cells exposed to recombinant GH displayed a direct and preferential increase in MGF
expression prior to that of IGF-1Ea (34). Furthermore, exogenous GH administration in dwarf
lit/lit mice significantly increased MGF, providing evidence that MGF mRNA is expressed in
parallel with GH action (33). On the other hand, GH-independent expression of IGF-I Ea and
MGF has been noted in hypophysectomized rats after compensatory overload (97), indicating
that the effects of GH potentiate rather than control IGF-1 function. Interestingly, in vivo human
studies show that while recombinant GH administration markedly enhances mRNA levels of
MGF when combined with resistance exercise in elderly men (28), such effects are not observed
in young adult men (6). The reasons for these inconsistent findings remain to be elucidated.
Some researchers dispute the claim that GH is solely reliant on IGF-1 to mediate skeletal
muscle growth, and propose the hypertrophic effects of the 2 agents are in fact additive (74, 86).
The IGF-1-independent action of GH is implied by the fact that IGF-I knockout mice display less
growth retardation than in those lacking both an IGF-I and GH receptor (46). Moreover, a
decrease in myofiber size has been noted in skeletal muscle lacking functional GH receptors
(74). It is believed that these effects are carried out, at least in part, by later-stage GH-mediated
cell fusion, thereby increasing the number of nuclei per myotube (74). GH also appears to have a
permissive, or perhaps even a synergistic, effect on testosterone-mediated protein synthesis (89).
Whether these autonomous effects are associated with transient endogenous post-exercise GH
spikes is not clear at this time and requires further study. The actions of the GH superfamily are
highly diverse and complex, and a complete discussion of the topic is beyond the scope of this
paper. Those interested in further reading are referred to recent reviews by Ehrnborg and Rosen
(17) and Kraemer et al. (40).
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Several researchers have dismissed the anabolic role of GH primarily based on research
showing that administration of recombinant GH has minimal effects on muscle growth in
humans in vivo (61, 63, 94). Indeed, studies on both young and older men have failed to show
significant increases in skeletal muscle mass when GH was administered exogenously in
combination with resistance training compared to placebo (43, 99, 100). Moreover, while whole
body protein synthesis was found to be increased in those taking supplemental GH, no increases
in skeletal muscle protein synthesis were noted (99). These studies have led to the supposition
that GH does not mediate hypertrophic adaptations and that its anabolic effects are limited to
synthesis of non-contractile tissue (i.e. collagen) (63).
While these studies justifiably cast doubt on the hypertrophic benefits of supplemental
GH, several mitigating factors must be taken into account when extrapolating conclusions to
acute post-exercise hormonal elevations. For one, recombinant GH is almost exclusively
comprised of the 22-kDa isoform (17). As previously noted, a wide spectrum of GH isoforms are
produced endogenously (54) and these isoforms may possess greater anabolic properties than the
22-kDa isoform or perhaps even work in combination with one another to potentiate
hypertrophic effects on skeletal muscle. This may have particular relevance to resistance training
protocols given that supraphysiological doses of GH have been found to suppress exercise-
induced stimulation of endogenous circulating isoforms of GH for up to 4 days in trained men
(91). Furthermore, exogenous GH administration does not mimic the in vivo response to
exercise-induced GH secretions either temporally or in magnitude. Considering that the anabolic
milieu is primed during the post-workout period, it is conceivable that the large GH spikes seen
following resistance exercise may facilitate muscular repair and remodeling. The implications of
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these factors are not clear at this time and additional research is needed to further our
understanding of the topic.
Testosterone
Testosterone is a steroid hormone synthesized from cholesterol in the Leydig cells of the
testes via the hypothalamic-pituitary-gonadal axis, with small amounts derived from the ovaries
and adrenals (13). Circulating testosterone levels are approximately tenfold higher in men
compared to women, and this is believed to be a primary reason why men display substantially
greater post-pubescent muscle bulk (31). The vast majority of circulating testosterone is bound to
either albumin (38%) or steroid hormone binding globulin (60%), with the remaining 2%
circulating in an unbound state. While only the unbound form is biologically active and available
for use by tissues, weakly bound testosterone can become active by its rapid disassociation from
albumin (44). Unbound testosterone binds to androgen receptors (AR) of target tissues located in
the cell’s cytoplasm. This results in a conformational change that transports the testosterone/AR
complex to the cell nucleus where it mediates gene transcription (89).
Evidence supporting the anabolic functions of testosterone is inconvertible. Numerous
studies have shown that exogenous testosterone administration can promote marked increases in
skeletal muscle hypertrophy (9, 11, 71), and these effects are magnified when combined with
resistance exercise (10). Older women with low basal testosterone levels display blunted
increases in maximal strength and hypertrophy compared to those with higher testosterone
concentrations (26, 27). Kvorning et al. (41) demonstrated that suppressing testosterone
production via administration of a gonadotropin-releasing hormone analogue (goserelin)
significantly blunted hypertrophic adaptations in young men following an 8 week resistance
training program. Follow-up work by this group showed that blunting of muscular adaptations
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resultant to acute testosterone suppression were seen despite no changes in acute mRNA
expression of myoD, myogenin, myostatin, IGF-IEa, IGF-IEb, IGF-IEc and AR, implying that
that the testosterone response may regulate intracellular signaling downstream from these factors
(42). In this study, total and free testosterone levels in the placebo group increased by ∼15%
immediately after resistance training while those in the goserelin group showed a decrease in
testosterone and free testosterone 15 minutes post-exercise. These results suggest a potential
hypertrophic effect from acute testosterone elevations.
The growth-related effects of testosterone on muscle are believed to be carried out in part
by increasing myofibrillar protein synthesis and attenuating protein breakdown (84, 101).
Testosterone may also contribute indirectly to muscle protein accretion by potentiating the
release of other anabolic factors such such as GH (85) and IGF-1/MGF (69), while reducing
mRNA concentrations of the IGF-1 inhibitor IGFBP-4 (84). Moreover, the combination of
increased testosterone and GH has been shown to confer a synergistic effect on muscle IGF-1
production (89). In addition, ARs have been identified in myoblasts and there is emerging
evidence that testosterone production has a dose-dependent effect on satellite cell proliferation
and differentiation, with higher levels increasing the number of myogenically committed cells
(31, 71).
The role of ARs in post-exercise adaptations is purported to be of particular importance
to post-exercise hypertrophic adaptations (5). There is evidence that AR concentration is reduced
in the immediate post-workout period but then becomes upregulated several hours after
resistance exercise (89). Interestingly, this upregulation has been shown to be present only when
the training bout results in a substantial post-exercise elevation in testosterone levels (76). Thus,
acutely increasing testosterone levels may have the dual effect of mediating adaptations to
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resistance training both directly as well as through its effects on ARs. A complete discussion of
this topic is beyond the scope of the present paper and interested readers are referred to the
recent review article by Vingren et al. (89).
Binding of testosterone to membrane receptors can cause rapid (within seconds)
activation of second messengers associated with downstream protein kinase signaling (16),
suggesting that transient post-exercise elevations may enhance protein synthesis. However, while
the majority of research shows substantial increases in IGF-1 and GH immediately after
resistance exercise, studies on acute testosterone release have been somewhat inconsistent. Some
trials have reported that testosterone was elevated to a greater extent following hypertrophy-
oriented resistance training compared with strength-type routines (13, 23, 25, 53, 72), but others
have failed to find significant differences (37, 62, 77). It should be noted that factors such as
gender, age, and training status profoundly influence testosterone release (39), and these factors
may account for discrepancies between studies. Further investigation into the topic is needed to
clarify discrepancies.
Indirect Research Investigating the Hormonal Hypothesis
Several researchers have sought to quantify the strength of the relationship, if any,
between the post-exercise endocrine response and muscle morphology (see Table 1). McCall et
al. (50) studied the hypertrophic response of 11 college-aged men with recreational resistance
training experience to 12 weeks of high-volume resistance training. Strong correlations were
noted between acute elevations of GH and the degree of both type I (r = 0.74) and type II (r =
0.71) fiber hypertrophy. Similarly, Ahtiainen et al. (4) studied the effects of post-exercise
hormonal fluctuations on muscle growth in 16 young men (8 strength athletes and 8 physically
active individuals) over the course of a 21 week heavy resistance training program. Results
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showed that acute elevations in testosterone production were strongly correlated with increases
in quadriceps femoris muscle CSA (r = 0.76). Both of these studies had small sample sizes,
however, thereby limiting conclusions. Recently, West and Phillips (95) conducted a larger trial
(n = 56) where young untrained men performed intense resistance exercise for 12 weeks.
Analysis revealed a weak positive correlation between acute elevations of GH and increases in
type II fiber area (r = 0.28). These elevations were determined to explain approximately 8% of
the variance in hypertrophic adaptations. No correlations were found between the acute response
testosterone response and muscle hypertrophy. An interesting adjunct to the study was an
evaluation of hormonal differences between hypertrophic "responders" and "non-responders"
(those in the top and bottom ~16%), with results showing a strong trend for an association
between increased IGF-1 levels and gains in lean body mass (p = 0.053). While the results of the
aforementioned studies are intriguing, caution must be taken in drawing definitive conclusions as
correlation is not necessarily indicative of causation.
In an effort to better determine a causal relationship between acute hormonal
concentrations and hypertrophy, West et al. (92) investigated the anabolic response to exercise
with high post-exercise hormonal levels versus low hormonal levels. Subjects were 8 young men
with no previous resistance training experience. A within-subject design was employed where
participants completed 2 separate trials of unilateral elbow flexion. In one trial, only the elbow
flexors were trained (LH) while in the other trial high-volume lower body training was added to
elicit an increased hormonal response (HH). The trials were randomized and counterbalanced to
account for arm-dominance and trial order. Results showed that despite a marked increase in
acute hormonal concentrations in HH, both trials elevated myofibrillar protein synthesis to a
similar extent. Furthermore, JAK2, STAT3, and p70S6k phosphorylation were similar between
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groups, indicating that anabolic signaling was also unaffected by post-exercise hormonal
elevations. It is important to note that protein synthesis measured following an acute bout of
exercise does not always occur in parallel with chronic upregulation of causative myogenic
signals (14) and is not necessarily predictive of long-term hypertrophic responses to regular
resistance training (81). The implications of these findings are therefore limited in scope.
Direct Research Investigating the Hormonal Hypothesis
Several studies have attempted to directly investigate the hormone hypothesis (see Table
2). Hansen et al. (30) was the first to do so. Sixteen young, untrained men were divided into 1 of
2 groups: an arm-only training group (A) and an arm plus leg training group (LA) designed to
induce greater acute hormonal secretions. Both groups performed unilateral resistance exercise
of the elbow flexors twice a week (8 sets of standing and seated biceps curls for 8-12 repetitions
per set with 90 second rest intervals), but LA performed an additional 8 sets of the leg press.
After 9 weeks, strength increased ~9% in A versus ~37% in LA. These findings correlated with
post-exercise levels of testosterone and GH, which were significantly elevated in LA compared
to A. The study was flawed, however, in that initial strength levels were ~20 to 25% lower in the
LA group thereby indicating results were likely confounded by selection bias. Moreover,
researchers did not evaluate changes in muscle mass. Thus, if any actual strength differences did
indeed exist between groups post-testing, it remains speculative as to whether they were related
to muscular or neural mechanisms.
Subsequently, Madarame et al. (47) expanded on the Hansen et al. (30) model by using
lower extremity restricted blood flow training (Kaatsu) to examine the impact of post-exercise
hormonal elevations on muscle morphology. Fifteen untrained young men were randomly
divided into either a normal training group (NOR) or an occlusion group (OCC). Both groups
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performed 3 sets of 10 repetitions of unilateral dumbbell curls at 50% 1RM with 3 minutes rest
between sets. After performance of the arm exercise, OCC performed restricted blood flow
exercise for the legs (1 set of 30 repetitions followed by 2 sets of 15 repetitions of knee
extensions and knee curls at 30% 1RM with 30 second rest intervals); NOR performed the same
lower body protocol without blood flow restriction. Training was carried out twice a week for 10
weeks. Results showed a significantly greater increase in muscle cross sectional area for the
upper arm in OCC compared to NOR. However, although OCC training showed a trend toward
greater GH increases versus NOR, the extent of these differences did not rise to statistical
significance. The authors attributed this null finding to a lack of statistical power (small sample
size and large inter-individual variation) and theorized that systemic factors may have in fact
played a role in muscular adaptations. No significant elevations were noted in post-exercise
testosterone levels.
Employing a within-subject repeated measures design, West et al. (93) conducted an
experimental study on the topic. Twelve untrained young men performed unilateral elbow
flexion exercise on separate days under 2 different hormonal environments: a low hormone (LH)
condition where one arm performed arm curl exercise only (3 to 4 sets of 8 to 12 repetitions) and
a high hormone (HH) condition where the contralateral arm performed the same arm curl
exercise followed immediately by a bout of leg resistance exercises (5 sets of 10 repetitions of
leg press and 3 sets of 12 repetitions of leg extension/leg curl supersets). Training was carried
out over the course of 15 weeks. During the first 6 weeks, subjects trained 3 times every 2 weeks
with 72 hours between sessions; for the final 9 weeks, subjects trained twice a week with the
timing of between-trial sessions reduced to 48 hours. As expected, significant post-exercise
increases in anabolic hormones (GH, IGF-1, and total and free testosterone) were seen in the HH
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group whereas hormonal levels were mostly unchanged in LA. Muscle girth of the upper arms
increased similarly in LH and HH, with no significant differences noted between groups. These
findings indicate that acute hormonal elevations are not involved in hypertrophic adaptations. It
should be noted that the extra session in the final 9 weeks reduced recovery between arms to ~24
hours, which may have positively impacted protein synthesis in the untrained arm during the
recuperative period.
Most recently, Ronnestad et al. (66) employed a similar within-subject protocol to that of
West et al. (93), except that leg exercise was performed before the arm curl in the HH group.
Subjects were 11 young men without resistance training experience. Exercise consisted of four
weekly training sessions; 2 each for LH and HH with at least 48 hours recovery afforded
between trials for the same arm. Study length spanned 11 weeks. In contrast to the findings of
West et al. (93), greater increases in muscle CSA of the elbow flexors were seen in the HH
group, implying that elevated hormones were responsible for hypertrophic gains. Differences
were specific to distinct regions of elbow flexors, with increases in CSA seen only at the 2
middle sections where muscle girth was largest. While this may seem counterintuitive, it has
been well-demonstrated that muscles often develop in non-uniform manner (4, 27, 49),
seemingly caused by the regional-specific muscle activation associated with a given exercise
(90). The reasons for the discrepancies between results in this study compared to West et al. (93)
are not clear. The authors postulated that spiking hormonal levels prior to arm training may have
played a role in morphological adaptations. Another possibility is that differences may be related
to the volume of training for the arms. Subjects in the study by West et al. (93) performed 3 to 4
sets of arm curl exercise while those in Ronnestad et al. (66) performed a total of 6 sets (2 sets
each of biceps curl, hammer curl, and reverse curl). It is conceivable that the effects of post-
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exercise hormonal elevations are magnified by an increased myotrauma from a higher training
volume. Further study is needed to reconcile these hypotheses. It also should be noted that the
overall magnitude of differences in CSA were relatively small, raising question as to the
practical application of results.
Conclusions
Research is contradictory as to whether or not the post-exercise anabolic hormonal
response associated with metabolic stress plays a role in skeletal muscle hypertrophy. Given the
inconsistencies between studies, any attempts to draw definitive conclusions on the subject
would be premature at this time. Based on limited cellular signaling data, it is conceivable that
the primary effect of post-exercise hormonal elevations is to increase satellite cell activity as
opposed to mediating acute increases in muscle protein synthesis. If so, this could favor greater
long-term increases in muscle hypertrophy without significantly impacting short-term gains. This
hypothesis requires further study.
What seems relatively clear from the literature is that if a relationship does in fact exist
between acute systemic factors and muscle growth, the overall magnitude of the effect would be
fairly modest. The ~8% figure reported by West and Phillips (95) would seem to be a reasonable
upper estimate as to a potential contribution from transient hormonal elevations, but further
research is required to quantify any potential impact. Whether such modest effects are
meaningful is a separate issue and would be dependent on individual goals and needs. For the
recreational gym participant, slight increases in muscle mass might not have much practical
importance. However, for the athlete or bodybuilder, it could mean the difference between
winning and losing a competition. There also may be practical implications for the elderly, where
even small morphological improvements could lead to an enhanced functional capacity.
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20
Another possibility to consider is that genetic factors may influence a person’s response
to post-exercise hormonal elevations. It has been estimated that genetic differences can account
for approximately half of the variation in athletic performance (16). This is consistent with
studies showing that the hypertrophic response to resistance training displays tremendous
variance between individuals (7, 58). It is therefore conceivable that acute hormonal responses
may be more relevant to certain lifters as opposed to others. There is some evidence to support
this contention as a strong trend for a significant association has been shown between IGF-1 and
those who respond favorably to hypertrophy-type training (95).
Finally and importantly, studies in trained individuals on the topic are lacking and it
remains to be determined whether training status influences the morphological response to acute
exercise-induced hormonal elevations. Some researchers have proposed that post-exercise
hormonal fluctuations may be permissive for untrained individuals but follow a dose-response
relationship in those with considerable training experience. Indeed, hormonal levels following
resistance exercise were shown to be significantly more pronounced in strength athletes
compared to endurance athletes and sedentary individuals (83), suggesting that such elevations
may play a greater role in hypertrophic adaptations as one gains resistance training experience
(38). This hypothesis warrants further investigation.
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21
Table 1: Summary of Indirect Studies Investigating the Hormone Hypothesis
Study
Subjects
Study
Length
Results
McCall et al.
(50)
11 young recreationally
trained men
12 weeks
Strong correlation between acute
elevations of GH and fiber
hypertrophy
Ahtiainen et al.
(4)
16 young men (8
strength-trained
athletes and 8
physically active
individuals)
21 weeks
Strong correlation between acute
elevations of testosterone and fiber
hypertrophy
West and Phillips
(95)
56 young untrained
men
12 weeks
Weak correlation between acute
elevations of GH and the type II
fiber hypertrophy; no correlation
between acute testosterone
elevations and fiber hypertrophy
West et al. (92)
8 young untrained men
2 separate
trials
No additive effects from acute
hormonal elevations on
myofibrillar protein synthesis or
intracellular signaling
Table 2: Summary of Direct Studies Investigating the Hormone Hypothesis
Study
Subjects
Study
Length
Results
Hansen et al.
(30)
16 young untrained
men
9 weeks
Significant increases in muscle
strength as a result of acute
hormonal elevations
Madarame et al.
(47)
15 young untrained
men
10 weeks
Significant increases in fiber
hypertrophy as a result of acute
hormonal elevations
West et al. (93)
12 young untrained
men
15 weeks
No additive effects from acute
hormonal elevations on fiber
hypertrophy
Ronnestad et al.
(66)
11 young untrained
men
11 weeks
Significant increase in fiber
hypertrophy as a result of acute
hormonal elevations
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