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Influence of Estrogen on Skeletal Muscle Damage, Inflammation, and Repair
Abstract
Estrogen may influence the disruption and diminish or delay leukocyte infiltration that occurs after muscle damage. This paper examines a mechanism by which estrogen may diminish the early postdamage migration of neutrophils into muscle and discusses the potential implications of these effects on muscle repair.
... Most research has been conducted with males, despite several reports of sex differences in EIMD (Kerksick et al. 2008;Sewright et al. 2008;Fernandez-Gonzalo et al. 2014;Minahan et al. 2015). Females can experience attenuated EIMD relative to males, potentially driven by an oestrogenmediated stabilization of myofibre membranes (Tiidus 2003). Maintaining membrane stability aids calcium homeostasis and reduces the loss of intramuscular enzymes into the circulation (Duncan and Jackson 1987) and to this end, females have demonstrated lower post-exercise elevations in [CK] compared with males (Sewright et al. 2008;Minahan et al. 2015). ...
... Despite disagreement (Sayers and Clarkson 2001;Hubal and Clarkson 2009;Dannecker et al. 2012;Morawetz et al. 2020), EIMD can be attenuated in females (Kerksick et al. 2008;Sewright et al. 2008;Fernandez-Gonzalo et al. 2014;Minahan et al. 2015), which is attributed to protective effects of oestrogen on myofibre integrity (Tiidus 2003). The present study conducted measurements in females during the latefollicular phase of the menstrual cycle when plasma oestrogen concentration is elevated, albeit not peaked (Owen 1975). ...
... The present study conducted measurements in females during the latefollicular phase of the menstrual cycle when plasma oestrogen concentration is elevated, albeit not peaked (Owen 1975). Oestrogen maintains myofibre membrane permeability following tissue injury (Bär et al. 1988;Tiidus 2003) and hence might explain why peak elevations in post-exercise [CK] were attenuated in females compared with males, akin to previous observations (Fernandez-Gonzalo et al. 2014;Minahan et al. 2015;Hicks et al. 2016). However, this association is speculative here, as neither oestrogen concentration nor ultrastructural myofibre damage was measured. ...
Milk-based proteins are a common choice of post-exercise nutrition to enhance exercise recovery and adaptation. Peri-exercise milk protein ingestion may attenuate exercise-induced muscle damage (EIMD), which is a particular risk to untrained individuals. However, most research has been conducted with males, and due to potential sex differences in EIMD, research with both sexes is required. This parallel-group randomized controlled trial examined the impact of milk protein ingestion on recovery from EIMD. Untrained males and females performed a single bout of leg-based resistance exercise and consumed a milk protein (MILK-PRO: n = 4 males, n = 8 females) or isoenergetic control (CON: n = 4 males, n = 8 females) supplement over 4 days post-exercise (17 doses total). Maximum strength was assessed ≥3 wk pre- and 72 and 168 h post-exercise, and measures of leg circumference, range of motion, muscle soreness, pressure-pain threshold (PPT), and serum creatine kinase concentration ([CK]) were conducted pre-, immediately post-, and 24, 48, 72, and 168 h post-exercise. Resistance exercise induced mild muscle damage that was not attenuated with MILK-PRO relative to CON. Peak increases in [CK] and reductions in PPT were greater in males compared with females. Changes in other markers were comparable between sexes. We conclude that moderate resistance exercise in naïve individuals induces muscle damage without compromising muscle strength. We support sex differences in EIMD and emphasize the need for further research with both sexes. Milk protein ingestion was not beneficial for recovery from EIMD, thus alternative management strategies should be investigated. This trial was prospectively registered at ClinicalTrials.gov PRS (protocol ID: 290580A).
... skeletal muscle inflammation and damage. To this end, the post exercise leakage of muscle proteins, such as creatine kinase (CK), into circulation is largely explained by compromised sarcolemma function because of exercise-associated oxidative damage and membrane instability (Tiidus 2003;Enns and Tiidus 2010). For this reason, the change in serum CK activity following exercise is a marker of sarcolemma stability. ...
... For this reason, the change in serum CK activity following exercise is a marker of sarcolemma stability. In a series of early studies, Tiidus and colleagues found that E2 treatment versus placebo in ovariectomized (OVX) rodents attenuated the increase in serum CK activity after exercise and this protection increased markedly with the duration of estrogen therapy (reviewed by Tiidus 2003;Enns and Tiidus 2010). Similarly, estrogen treatment reduced the influx of neutrophils into muscle and the activity of the protease, calpain in muscle following exercise. ...
... Similarly, estrogen treatment reduced the influx of neutrophils into muscle and the activity of the protease, calpain in muscle following exercise. Tiidus (2003) described the sequence for estrogen's protection as follows: the sarcolemma is stabilized by estrogen, which results in less calcium leaking into the cytosol and thus less calpain activation. Reduced calpain activity results in less expression of chemoattractant peptides that explains the decrease in neutrophil infiltration and overall reduced muscle damage; encompassing the primary pro-inflammatory phase of the muscle damage/repair process (Peake et al. 2017). ...
Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-β-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes.
... Despite elevated CK for men and prolonged muscle soreness for women, women seemed to experience a greater strength loss than men immediately after EIMD (2). Growing evidence suggests that these differential responses to EIMD between men and women may be attributed, at least in part, to estrogen, which increases membrane stability and has anti-inflammatory properties (3). Thus, greater estrogen concentrations in women could limit the extent of muscle damage and thus reduce inflammatory cell infiltration, altering the initial inflammatory response to EIMD and the postexercise recovery time course (3). ...
... Growing evidence suggests that these differential responses to EIMD between men and women may be attributed, at least in part, to estrogen, which increases membrane stability and has anti-inflammatory properties (3). Thus, greater estrogen concentrations in women could limit the extent of muscle damage and thus reduce inflammatory cell infiltration, altering the initial inflammatory response to EIMD and the postexercise recovery time course (3). ...
... Furthermore, in a rodent model, estrogen has been shown to delay inflammatory cell infiltration (7). However, results in humans are conflicting (3). To date, results on EIMD-induced strength loss and muscle soreness for men and women have been inconsistent (1,27); thus, it is difficult to conclude the direct role of TNF-α on physical performance. ...
Introduction:
The purpose of this study was to determine the effect of resistance exercise (RE)-induced hormonal changes on intramuscular cytokine gene expression after muscle damage in untrained men and women.
Methods:
Men (n = 8, 22 ± 3 yr) and women (n = 8, 19 ± 1 yr) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either an upper body RE bout (EX) or a time-matched period (CON). Muscle samples (vastus laterals) were analyzed for mRNA expression of interleukin (IL) 6, IL-10, IL-15, TNFA, TGFB, CCL2, and CD68 at PRE, 12 h, and 24 h after the session.
Results:
A significant time-sex-condition interaction was found for TGFB with an increase for EX in men at 12 h from PRE. For EX, TGFB was also greater in men than in women at 12 and 24 h. Significant time-sex and condition-sex interactions were found for IL-10 with an increase for men that was greater than for women at 12 and 24 h. IL-10 was lower in EX than CON for men. A significant time-sex interaction was found for TNFA with an increase for men that was greater than for women at 24 h. A significant time-condition interaction was found for CD68 with an increase at 12 h and decrease at 24 h for EX and CON. CD68 was lower in EX than CON at 12 h. A significant time effect was found for IL6 and CCL2 with an increase at 12 and 24 h.
Conclusions:
Results suggest that women seem to have a muted intramuscular cytokine (i.e., IL-10, TNF-α, and TGF-β) response to muscle damage compared with men.
... differ based on sex, age, etc. (Kraemer et al., 1999;Luk et al., 2022;Pierce et al., 2020). Evidence from rodent studies has demonstrated that estrogens are protective against the effects of muscle damage and reduce the subsequent inflammatory response (Tiidus, 2003); however, results from studies comparing men and women are less conclusive (Jomard & Gondin, 2023;Stupka et al., 2000). This could be due to different confounding factors such as inherited muscle fiber type differences, plasma volume shift, training status, etc. (Pizza, 2009). ...
... Conversely, in women, the absence of differences in the immune functional pathways between conditions is aligned with our prior results, where no changes were detected in intramuscular cytokine transcripts . This lack of responses could be partly explained by estrogen's protective role in maintaining muscle cell membrane integrity; therefore, the extent of muscle damage induced by the damaging protocol and subsequent inflammatory response (Tiidus, 2003) may have been limited regardless of condition. Additionally, the lack of differences noted between men and women might have been influenced by rigorous statistical approaches that made differences too small to detect and the protective effects of both testosterone and estrogen. ...
Muscle recovery after damage is mediated by circulating factors and intracellular signaling pathways. Our previous studies have demonstrated that resistance exercise (RE)‐induced circulating factors elicited sex‐differential responses in damaged muscle. However, the global effects of these circulating factors on damaged muscle are largely understudied. We examined the differential effects of RE‐induced circulating factors and sex on the damaged muscle proteome. Damaged vastus lateralis muscle from 3 men and 3 women from a parent study were analyzed. Participants completed 2 identical bouts of unilateral eccentric knee extensions immediately followed by either upper body RE to induce circulating factors (EXE) or 20‐min seated rest (CON). Muscle biopsies collected from the damaged leg at 24 h were used. 900 proteins were identified by LC–MS/MS analysis. Ingenuity Pathway Analysis was used to detect activation prediction using z‐scores for functional and pathway analyses. In men, 79 proteins were downregulated and 15 were upregulated in EXE versus CON. These differentially expressed proteins were associated with immunological and inflammatory signaling pathways. Biological functions of the differentially expressed proteins in EXE vs. CON in men include inactivating acute inflammatory signaling, neutrophil extracellular trap signaling, ROS production, and activating IL‐12 signaling. These results underline that RE‐induced circulating factors have a sex‐specific effect on the damaged muscle proteome, where immune signaling is altered in men but not women. Given that the immune response is critical for recovery from muscle damage, these results highlight the potential role of RE‐induced circulating factors that could be essential in mediating muscle recovery.
... Furthermore, estrogen may act to diminish skeletal muscle damage and inflammatory responses after exercise by exerting a protective effect on muscle membranes via direct receptor-mediated mechanisms, and is a bioactive in stabilizing plasma membranes and limiting free radicals [9,96]. This reduction in muscle membrane disruption may also be important for muscle repair and regeneration. ...
... This reduction in muscle membrane disruption may also be important for muscle repair and regeneration. Estrogen and progesterone have also demonstrated antioxidant-like characteristics through promoting the expression of antioxidant enzymes, which inhibits inflammatory responses post-exercise and attenuates exerciseinduced muscle damage in the late FP and mid-LP, thereby accelerating recovery [9,96]. A recent review of the menstrual cycle effects on exercise-induced fatigability found fifteen studies with a statistical difference between the FP and LP in EUM menstrual cycles. ...
The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the use of hormonal contraception (oral contraceptives and hormonal intrauterine devices) on metabolism, muscular strength, and recovery in active females. Ovarian hormones are known to influence metabolism because estrogen is a master regulator of bioenergetics. Importantly, the menstrual cycle may impact protein synthesis, impacting skeletal muscle quality and strength. Studies investigating muscular strength in eumenorrheic women report equivocal findings between the follicular phase and luteal phase with no differences compared to oral contraceptive users. Studies examining recovery measures (using biomarkers, blood lactate, and blood flow) do not report clear or consistent effects of the impact of the menstrual cycle or hormonal contraception use on recovery. Overall, the current literature may be limited by the evaluation of only one menstrual cycle and the use of group means for statistical significance. Hence, to optimize training and performance in females, regardless of hormonal contraception use, there is a need for future research to quantify the intra-individual impact of the menstrual cycle phases and hormonal contraceptive use in active females.
... However, the increase in CK activity was not significantly different between the M-LP and E-FP groups. In animal studies, estrogen supplementation in rats suppressed the increase in CK activity after exercise [27,28]. In other studies, the significant increase in CK activity was smaller in females than in males after exercise [29][30][31], suggesting that differences in sex hormone concentrations may have an effect on muscle damage. ...
... Estrogen primarily suppresses neutrophil infiltration by inhibiting muscle damage through membrane stabilization, antioxidant effects, and inhibition of increased calpain [27]. Nevertheless, although we found no difference in the degree of muscle damage, leukocyte changes were more significant in E-FP than in M-LP. ...
... However, the increase in CK activity was not significantly different between the M-LP and E-FP groups. In animal studies, estrogen supplementation in rats suppressed the increase in CK activity after exercise [27,28]. In other studies, the significant increase in CK activity was smaller in females than in males after exercise [29][30][31], suggesting that differences in sex hormone concentrations may have an effect on muscle damage. ...
... Estrogen primarily suppresses neutrophil infiltration by inhibiting muscle damage through membrane stabilization, antioxidant effects, and inhibition of increased calpain [27]. Nevertheless, although we found no difference in the degree of muscle damage, leukocyte changes were more significant in E-FP than in M-LP. ...
We investigated the influence of the menstrual cycle (MC) on leukocyte response after exercise-induced muscle damage (EIMD). During the early follicular (E-FP, n = 12) or mid-luteal phase (M-LP, n = 12), 24 untrained females with eumenorrhea performed 60 eccentric exercises using nondominant arms. Blood samples were collected at pre- and 4, 48, and 96 h postexercise to analyze estradiol and progesterone concentrations, leukocyte count and fractionation, and creatine kinase (CK) activity. We also assessed the maximal voluntary isometric contraction torque of elbow flexion, range of motion in the elbow joint, upper-arm circumference, and muscle soreness as indirect muscle damage markers at pre-; immediately post-; and 4, 48, and 96 h postexercise. The percent change in neutrophil counts from pre- to 4 h postexercise was lower in M-LP than in E-FP (E-FP, 30.7% [15.9–65.7%] vs. M-LP, 10.3% [−2.3–30.0%]; median [interquartile range: 25–75%]; p = 0.068). Progesterone concentration at pre-exercise was significantly negatively correlated with the percent change in neutrophil counts from pre- to 4 h postexercise in M-LP (r = −0.650, p = 0.022). MC did not affect CK activity or other muscle damage markers. Thus, progesterone concentration rather than MC may be related to neutrophil response following EIMD.
... Effects of estrogens on SkM mass are not clear (Enns and Tiidus, 2010;Hansen and Kjaer, 2014), although some evidence points toward muscle mass retention in post-menopausal females receiving hormone replacement therapy (Tiidus, 2003). In premenopausal females, estrogens and progesterone are produced by the ovaries in a cyclical fashion over a 15-50 day period, with an average of a 29.3 day cycle (Bull et al., 2019). ...
... One potential mechanism identified in a rat model, is the inhibition of the inflammatory response via estrogen through reductions in neutrophil infiltration post-exercise (Tiidus et al., 2001). In human studies, decreased focal damage, bcl2-and LCA-positive inflammatory cell infiltration post-exercise has also been observed in muscle from females when compared to males (Stupka et al., 2000;Tiidus, 2003). In addition, a clinical study utilizing hormonal therapy in post-menopausal females also observed attenuated SkM damage, further demonstrating the immune modulating and protective role of estrogen (Dieli-Conwright et al., 2009). ...
As the fields of kinesiology, exercise science, and human movement developed, the majority of the research focused on male physiology and extrapolated findings to females. In the medical sphere, basing practice on data developed in only males resulted in the removal of drugs from the market in the late 1990s due to severe side effects (some life-threatening) in females that were not observed in males. In response to substantial evidence demonstrating exercise-induced health benefits, exercise is often promoted as a key modality in disease prevention, management, and rehabilitation. However, much like the early days of drug development, a historical literature knowledge base of predominantly male studies may leave the exercise field vulnerable to overlooking potentially key biological differences in males and females that may be important to consider in prescribing exercise (e.g., how exercise responses may differ between sexes and whether there are optimal approaches to consider for females that differ from conventional approaches that are based on male physiology). Thus, this review will discuss anatomical, physiological, and skeletal muscle molecular differences that may contribute to sex differences in exercise responses, as well as clinical considerations based on this knowledge in athletic and general populations over the continuum of age. Finally, this review summarizes the current gaps in knowledge, highlights the areas ripe for future research, and considerations for sex-cognizant research in exercise fields.
... In 2005, Tiidus et al. demonstrated for the first time that estrogen supplementation to male rats significantly increased SC numbers in both type I and type II skeletal muscle fibers following three days of downhill running [61]. ese findings were reported following a number of studies observing lower myofibrillar damage, reduced release of markers for muscle damage (creatine kinase), and reduced inflammatory response after eccentric exercise in female rats compared to male rats and estrogen-deficient ovariectomized (OVX) rats [62,63]. Since then, a number of papers have been published elucidating the mechanisms by which estrogen influences SC regulation. ...
... However, a notable observation by the authors was that 17β-estradiolinduced attenuation of muscle damage and leucocyte infiltration was unaffected by the ER antagonist. e latter may relate to estrogen having a stabilizing effect on the muscle membrane [63] and thereby reduces the damage and subsequent need for leucocyte infiltration independently of the ERs. e role of the ERs in SC regulation was further examined in a follow-up study by omas et al., specifically investigating the role of ER-α in SC activation. ...
Recent years have seen growing scholarly interest in female physiology in general. Moreover, particular attention has been devoted to how concentrations of female sex hormones vary during the menstrual cycle and menopausal transition and how hormonal contraception and hormonal therapy influence skeletal muscle tissue. While much effort has been paid to macro outcomes, such as muscle function or mass, rather less attention has been paid to mechanistic work that may help explain the underlying mechanism through which sex hormones regulate skeletal muscle tissue. Evidence from animal studies shows a strong relationship between the female sex hormone estrogen and satellite cells (SCs), a population of muscle stem cells involved in skeletal muscle regulation. A few human studies investigating this relationship have been published only recently. Thus, the purpose of this study was to bring an updated review on female sex hormones and their role in SC regulation. First, we describe how SCs regulate skeletal muscle maintenance and repair and introduce sex hormone signaling within the muscle. Second, we present evidence from animal studies elucidating how estrogen deficiency and supplementation influence SCs. Third, we present results from investigations from human trials including women whose concentrations of female hormones differ due to menopause, hormone therapy, hormonal contraceptives, and the menstrual cycle. Finally, we discuss research and methodological recommendations for future studies aiming at elucidating the link between female sex hormones and SCs with respect to aging and training.
... Estrogen has antioxidant and anti-inflammatory effects, which are suggested to contribute to the protective effects of estrogen against exercise-induced muscle damage (19)(20)(21). It has also been suggested that estrogen prevents the leakage of CK from skeletal muscle by enhancing cell membrane stability (22,23). These studies imply that estrogen plays an important role in preventing exercise-induced muscle damage. ...
... Moreover, though the detailed mechanisms are not clarified, estrogen may enhance cell membrane stability and protect against skeletal muscle membrane disruption. Estrogen can be directly incorporated into cell membranes and interact with membrane components, which may enhance cell membrane stability and reduce CK leakage from the skeletal muscles (22,23). In the present study, male subjects with the CYP19A1 TT genotype showed higher serum estradiol levels than those with CC þ CT genotype, which would contribute lower serum CK activity in male runners with the CYP19A1 TT genotype than those with CC þ CT genotype. ...
This study aimed to clarify 1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and 2) whether estrogen-related genetic polymorphisms, such as the CYP19A1 rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced muscle damage. Serum estradiol levels were examined in young men (n = 167). In a different cohort, serum creatine kinase (CK) activity, an index of skeletal muscle membrane disruption, was analyzed in a 2-days ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms in CYP19A1 rs936306 C/T and ESR1 rs2234693 T/C were analyzed using the TaqMan SNP genotyping assay. Male subjects with the TT genotype of the CYP19A1 polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher post-race serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with the CYP19A1 TT genotype than in those with the CC+CT genotypes, and was correlated with the number of C alleles in ESR1 rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r = ‒0.279, P = 0.003). The results of this study suggest that genetic polymorphisms in CYP19A1 rs936306 influence serum estradiol levels in men, and genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity in men.
... Instead, it appears that these changes arise following long-term endurance training, which supports the hypothesis that endurance gene expression in women is activated to a lesser extent than in men. This hypothesis could be supported by the attenuated inflammatory response that has been described in the skeletal muscle of recreationally active female subjects compared with men (Stupka et al., 2000;Tiidus, 2003). This has been hypothesized to be related to the intrinsically elevated estrogen levels in women, although the topic is unsettled in the literature (Hubal and Clarkson, 2009;Tiidus and Enns, 2009). ...
... Furthermore, MEs have a significantly enhanced expression in pathways relating to the activation of the immune response compared with FEs ( Figure 3D). It is tempting to speculate that these differences in the inflammatory pathways could result in an attenuated adaptation to long-term training, but it is not entirely clear that these sex differences explain the differences between female and male athletes (Tiidus, 2003). Additionally, given the cross-sectional nature of this study, it must be noted that these differences could arise from disparate training intensities/frequencies and/or genotypic differences. ...
To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases. This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important “exercise-responsive” genes that could attenuate metabolic disease.
... The loss of skeletal muscle with age shows a strong correlation with morbidity and mortality (Rantanen et al. 2003), thus maintaining skeletal muscle mass is important for healthy aging (Carter et al. 2015). The steroid hormone, estrogen, has been shown to have a protective effect on skeletal muscle (Tiidus 2003;Tiidus et al. 2013) and thus the reduced estrogen content observed in postmenopausal females may influence muscle damage potentially contributing to sarcopenia. The protective effects of exercise on skeletal muscle are numerous and perhaps not surprisingly, exercise has been shown to elevate muscle content of the cyto-protective proteins known as "stress" or "heat shock proteins" (HSPs). ...
... Compared with SCs, LCs are known to result in greater levels of fibre swelling, membrane disruption, protein leakage, fibre necrosis, and loss of force (Fridén et al. 1983;McCully and Faulkner 1985;Stupka et al. 2000;Fridén and Lieber 2001). Given the purported role of estrogen in muscle protection (Tiidus 2003;Tiidus et al. 2013) and its role in regulating HSP expression (Bombardier et al. 2009), it follows that reduced estrogen levels may render muscles more susceptible to certain types of contraction induced damage. In view of this, the purpose of this work was to characterize HSP expression and muscle damage in tibialis anterior (TA) muscles from ovariectomized (OVX) and ovary-intact (OVI) rats following maximally stimulated LC. ...
Estrogen appears to play a role in minimizing skeletal muscle damage as well as regulating the expression of the protective heat shock proteins (HSPs). To clarify the relationship between estrogen, muscle HSP content, and muscle damage, tibialis anterior (TA) muscles from ovary-intact (OVI; n = 12) and ovariectomized (OVX; 3 weeks, n = 12) female Sprague–Dawley rats were subjected to either 20 or 40 lengthening contractions (LCs). Twenty-four hours after stimulation, TA muscles were removed, processed, and assessed for HSP25 and HSP72 content as well as muscle (damage) morphology. No differences in muscle contractile properties were observed in TA muscles between OVI and OVX animals for peak torque during the LCs. In unstressed TA muscles, the basal expression of HSP72 expression was decreased in OVX animals (P < 0.05) while HSP25 content remained unchanged. Following 20 LCs, HSP25 content was elevated (P < 0.05) in TA muscles from OVX animals but unchanged in muscles from OVI animals. Following 40 LCs, HSP25 content was elevated (P < 0.01) in TA muscles from both OVI and OVX animals while HSP72 content was elevated only in TA muscles from OVI animals (P < 0.05). Taken together, these data suggest the loss of ovarian hormones, such as estrogen, may impair the skeletal muscle cellular stress response thereby rendering muscles more susceptible to certain types of contraction induced damage.
NoveltyOvariectomy alters muscle HSP72 content.
Muscle contractile measures are maintained following ovariectomy.
... Estrogens exert various beneficial effects on athletic performance via their effects on exercise-induced inflammation and muscle damage, as well as muscular recovery and repair rates [64]. More specifically, estradiol exerts a significant effect on muscle membrane stability while at the same time ameliorating exercise-induced muscle damage [65]. ...
... In general, endurance exercise training seems to have significant effects on the major male reproductive hormone, testosterone. A growing body of evidence suggests that basal testosterone levels are lowered in endurance-trained males [64,65]. The mechanism of this effect is currently speculative, but it may be related to HPG axis dysfunction. ...
A constant topic reported in the lay press is the effect of sex hormones on athletic performance and their abuse by athletes in their effort to enhance their performance or to either boost or sidestep their hard, protracted, and demanding training regimens. However, an issue that it is almost never mentioned is that the athletic training itself affects the endogenous production of androgens and estrogens, while also being affected by them. Among sports, soccer is a particularly demanding activity, soccer players needing to possess high levels of endurance, strength, and both aerobic and anaerobic capacity, with the very great physiological, metabolic, physical, and psychological exertion required of the players being both influenced by sex steroids and, reciprocally, affecting sex steroid levels. This review focuses on the currently available knowledge regarding the complex relationship between athletic training and competition and sex steroid hormone adaptation to the demands of the exercise effort. In the first part of the review, we will examine the effects of endogenous testosterone, estrogen, and adrenal androgens on athletic performance both during training and in competition. In the second part, we will explore the reciprocal effects of exercise on the endogenous sex hormones while briefly discussing the recent data on anabolic androgenic steroid abuse.
... The RBE has been extensively researched in males; however data concerning females is limited. This is particularly important because oestrogen is widely considered to be responsible, in part, for attenuating symptoms of muscle damage in females and could influence a number of factors including effects on muscle membrane integrity (32). ...
... Additionally the secondary inflammatory response may be sex dependent, with reports of sex differences in leukocyte and cytokine infiltration into skeletal muscle post exercise (25,32). ...
The repeated bout effect (RBE) refers to the prophylactic effect from damaging exercise following a single prior bout of exercise. There is a paucity of data examining the RBE in females, and investigations employing exercise paradigms beyond isolated eccentric contractions are scarce. In light of the limited literature, this investigation aimed to determine whether two different sport-specific exercise bouts would elicit a RBE in females. Twenty-one female dancers (19 ± 1 years) completed either a dance-specific protocol (n=10) or sport-specific repeated sprint protocol (n=11). Muscle soreness (DOMS), limb girths, creatine kinase (CK), countermovement jump height, reactive strength index, maximal voluntary contraction and 30 m sprint time were recorded pre, 0, 24, 48, and 72 h post-exercise. An identical exercise bout was conducted approximately four weeks following the initial bout, during which time the subjects maintained habitual training and dietary behaviours. DOMS and 30 m sprint time decreased following a second bout of both activities (P = 0.003; ηp = 0.38 and P = 0.008; ηp = 0.31 respectively). Circulating CK was also lower at 24, 48 and 72 h following the second bout, independent of group (P = 0.010; ηp = 0.23). Compared to the repeated sprint protocol, the magnitude of change in DOMS was greater following a subsequent bout of the dance protocol (P = 0.010; ηp = 0.19). These data are the first to demonstrate that dance and repeated sprint activity resulting in muscle damage in females confers a protective effect against muscle damage following a subsequent bout.
... Also, skeletal muscle tissue has estrogen receptors. These receptors modify the expression of myosin heavy chain (MHC) isoform and reduce muscle damage [2]. Estrogen deficiency induces decrease phosphorylation of muscle protein kinase Akt, which decline muscle mass, strength and physical activity [3]. ...
... Lastly, female estrogen level may possibly be a contributing factor to increased fatigue resilience. Estrogen may provide a protective effect on skeletal muscle, according to previous studies, and therefore, mediating resistance to fatigue and inflammation during and after exercise (5,15,19,35). These positive protective effects should, however, again be interpreted cautiously based on conclusion of Hunter (15) -the influence of estrogen on younger females appears negligible compared to older females. ...
The purpose of the study was to examine the difference between the current norm repetition-intensity recommendations and the performed repetitions of females at concurrent intensities. Females (n = 17) with six-months of consistent resistance training experience completed five testing sessions. Session-one consists of one-repetition maximum (1RM) testing for the squat (SQ), bench press (BP), and deadlift (DL). Sessions 2-5 involved repetition-maximum testing at 65, 75, 85, and 95% 1RM, in the order of SQ, BP, then DL, with 10-15 minutes of rest between exercises. A 3 (exercise) x 4 (percentage-intensity) Mixed Factorial ANOVA determined significant differences in repetitions performed between exercises at each intensity level. A series of one-sample t-tests were performed to indicate female differences between established target repetitions for each exercise across all intensities (65% = 15, 75% = 10, 85% = 6, 95% = 2). Significance level was set at p < .05. There was no significant main effect (p=0.14) between repetitions completed during SQ, BP, or DL at 65% (26.1±6.8, 21.3±6.8, 23.4±6.3, respectively), 75% (18.0±6.2, 14.4±4.2, 15.7±4.7, respectively), 85% (10.3±3.7, 9.0±4.6, 9.6±4.1, respectively), nor 95% 1RM (4.1±2.4, 2.5±2.0, 3.4±2.0, respectively). No significant difference was recognized (p = 0.09) between current norms and female BP repetitions at 95%. Significantly higher repetitions were completed by females at all other percentages during SQ, BP, and DL. These results suggest different resistance training intensity-repetition ratios should be prescribed for females in comparison to current norms; meriting future research aimed at establishing a sex-specific intensity-repetition ratio.
... Last, we did not include women in our study to minimize variation arising from fluctuations in oestrogen as part of the menstrual cycle. Oestrogen is known to influence inflammatory responses in muscle after exercise (Tiidus, 2003). We acknowledge that our results may not be applicable to women. ...
Cold water immersion is often used to recover from exercise in the belief that it reduces muscle soreness and inflammation. However, no data currently exist to support this notion—at least in humans. We compared the effects of cold water immersion versus active recovery on neutrophil and macrophages, pro‐inflammatory cytokines, neurotrophic and growth factors, heat shock proteins and transcription factors in muscle after resistance exercise. In a randomized cross‐over design, 10 active men performed resistance exercise using one leg on separate days. On one day, they immersed their lower body in cold water (10°C) for 10 min after exercise. On the other day they cycled at a low‐intensity for 10 min after exercise. Muscle biopsies were collected from each leg before, 2, 24 and 48 h after exercise. Exercise induced a strong inflammatory response, as indicated by increases in neutrophil and macrophage counts and IL‐1β, TNF‐α, IL‐6 and MCP‐1 mRNA (P<0.05). Growth arrest and DNA damage‐inducible 45 protein (Gadd 45) mRNA also increased markedly (P<0.05). As evidence of hyperalgesia, nerve growth factor (NGF) and glial cell‐line derived neurotrophic factor (GDNF) mRNA increased after exercise (P<0.05). The protein abundance of Forkhead box class O (FOXO) and αB‐crystallin in the cytosolic fraction of muscle homogenates decreased after exercise (P<0.05), indicating nuclear translocation. Despite these robust responses, there were no significant differences in any of these factors between the two trials. Therefore, contrary to popular belief, cold water immersion did not attenuate inflammation or markers of soreness in muscle after intense resistance exercise.
... This suggests that the higher AUC of CK and IL-6 in men may be due to estrogen function, which is specific to women. Indeed, it has previously been reported that the increases in Ca 2 þ levels and the inflammatory response that occur after eccentric exercise are suppressed by estrogen (24,25). In addition, CK and IL-6 may be associated with muscle recovery; Paulsen et al. (26) reported that elevated Ca 2 þ levels and inflammatory responses delay muscle recovery. ...
Individual differences in muscle strength recovery after eccentric exercise may be influenced by sex and genotype. A candidate genetic polymorphism associated with response during muscle recovery is the MMP3 gene rs522616 polymorphism, encoding matrix metalloproteinase (MMP-3). Here, we investigated the effect of the MMP3 gene rs522616 polymorphism and sex on muscle strength recovery after eccentric exercise. A total of 95 healthy subjects (50 men and 45 women) performed 5 sets of 6 maximal eccentric elbow flexion exercises. Maximal voluntary contraction torque (MVC), range of motion (ROM), and muscle soreness, as well as blood parameters (creatine kinase [CK] and interleukin-6 [IL-6]), were assessed immediately before and after and 1, 2, 3, and 5 days after eccentric exercise. No significant time × group interaction in MVC torque after exercise was observed between groups in both sexes. Furthermore, the study revealed sex differences in the area under the curves (AUC) of CK and IL-6, where the AUC values for both CK and IL-6 were higher in men compared to women. A significant genotype-sex interaction was identified in the recovery of MVC, calculated by subtracting the MVC immediately after exercise from the MVC on day 5 after eccentric exercise. The G allele showed a significantly lower recovery of MVC than the AA genotype in men. However, no significant differences were observed in women. This study demonstrated the interaction between the MMP3 rs522616 polymorphism and sex in muscle strength recovery after eccentric exercise.
... Lastly, true LGMDR9-related gender differences can still be influenced by sex hormones and life style. Although it has been suggested that estrogen has a protective role of the skeletal muscle membrane [60] , there may be other relevant effects of sex hormones in LGMDR9. The fact that the skeletal and cardiac muscle involvement showed opposite relation to gender may indicate that these tissues are influenced by different factors. ...
We aimed to investigate the epidemiology and natural history of FKRP-related limb-girdle muscular dystrophy R9 (LGMDR9) in Norway. We identified 153 genetically confirmed subjects making the overall prevalence 2.84/100,000, the highest reported figure worldwide. Of the 153 subjects, 134 (88 %) were homozygous for FKRP c.826C>A giving a carrier frequency for this variant of 1/101 in Norway. Clinical questionnaires and patient notes from 101 subjects, including 88 c.826C>A homozygotes, were reviewed, and 43/101 subjects examined clinically. Age of onset in c.826C>A homozygotes demonstrated a bimodal distribution. Female subjects showed an increased cumulative probability of wheelchair dependency and need for ventilatory support. Across the cohort, the need for ventilatory support preceded wheelchair dependency in one third of the cases, usually due to sleep apnea. In c.826C>A homozygotes, occurrence of cardiomyopathy correlated positively with male gender but not with age or disease stage. This study highlights novel gender differences in both loss of ambulation, need for ventilatory support and the development of cardiomyopathy. Our results confirm the need for vigilance in order to detect respiratory insufficiency and cardiac involvement, but indicate that these events affect males and females differently.
... Estrogen deficiency can also lead to bone loss, articular cartilage degeneration, and increased risk of fracture, possibly causing pain, loss of mobility, and the development of osteoporosis (117). In muscle, estrogen has a significant effect on the stability of muscle membranes and can reduce or delay leukocyte infiltration after muscle injury (118). In the central nervous system, decreased estrogen levels influence cognition, sleep and mood and affect many neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression (119,120). ...
Progressive loss of physiological integrity and accumulation of degenerative changes leading to functional impairment and increased susceptibility to diseases are the main features of aging. The ovary, the key organ that maintains female reproductive and endocrine function, enters aging earlier and faster than other organs and has attracted extensive attention from society. Ovarian aging is mainly characterized by the progressive decline in the number and quality of oocytes, the regulatory mechanisms of which have yet to be systematically elucidated. This review discusses the hallmarks of aging to further highlight the main characteristics of ovarian aging and attempt to explore its clinical symptoms and underlying mechanisms. Finally, the intervention strategies related to aging are elaborated, especially the potential role of stem cells and cryopreservation of embryos, oocytes, or ovarian tissue in the delay of ovarian aging.
... Were adopted as exclusion criteria the use of any vitamin supplements or anti-inlammatory medications, the used of creatine in the previous 6 months prior to study enrollment, and if the participant could no longer attend to the testing sessions. As the level of estrogen has a protective function in the muscle cell membrane to EIMD [16], only male participants were selected to avoid possible confounding efects related to sex. All participants provided written informed consent to participate in the study, which was approved by the Human Research Ethics Committee of the Universidade Federal do Rio Grande do Sul (number 180680). ...
Purpose
Strength training is performed using multi-joint (MJ) or single-joint (SJ) exercises; however, it is not clear whether different time of recovery is necessary between the two types of exercise. The aim of the present study was to compare the time course of recovery of indirect markers of exercise-induced muscle damage (EIMD) in the elbow flexors after performing MJ and SJ exercises.
Methods
Twenty-four (n = 24) untrained men were randomized in to the MJ (n = 12) or SJ group (n = 12). Exercise protocol to induce muscle damage consisted of four sets of ten repetitions at 80% of one repetition maximum (1RM) in front pull-down (MJ exercise) or biceps curl (SJ exercise). Maximal voluntary isometric contraction, muscle soreness during elbow extension, ultrasound imaging (muscle thickness and echo intensity) and creatine kinase (CK) were measured before and up to 96 h after exercise.
Results
Significant effect of time (p < 0.05) at all times after exercise was observed for isometric strength, muscle soreness, muscle thickness and at 48, 72 and 96 h for echo intensity, with no time × group interaction. However, significant time × group interaction (p = 0.03) was observed only for CK activity at 96 h (MJ = 3348 ± 2911 IU/l vs. SJ = 890 ± 1426 IU/l; p < 0.05). In addition, there was a significant increase in CK after MJ at 48 h, 72 h and 96 h after exercise (p < 0.05), while SJ increased only at 48 h after exercise.
Conclusion
Despite a dissimilar time course of CK response, MJ and SJ exercises induced a similar recovery pattern for muscle strength, thickness, echo intensity and soreness.
... Accordingly, some investigations suggest that there are differences between female and male muscles, such as energy metabolism, fiber type composition, and contractile speed, greatly dependent on estrogen levels present in females [120]. Interestingly, estrogens may play an important protective role against muscle damage, by attenuating the inflammatory and oxidative process [121][122][123] and/or influencing muscle regeneration [124,125], thus affecting all the parameters modulated by exercise. ...
Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive lethal disorder caused by the lack of dystrophin, which determines myofibers mechanical instability, oxidative stress, inflammation, and susceptibility to contraction-induced injuries. Unfortunately, at present, there is no efficient therapy for DMD. Beyond several promising gene- and stem cells-based strategies under investigation, physical activity may represent a valid noninvasive therapeutic approach to slow down the progression of the pathology. However, ethical issues, the limited number of studies in humans and the lack of consistency of the investigated training interventions generate loss of consensus regarding their efficacy, leaving exercise prescription still questionable. By an accurate analysis of data about the effects of different protocol of exercise on muscles of mdx mice, the most widely-used pre-clinical model for DMD research, we found that low intensity exercise, especially in the form of low speed treadmill running, likely represents the most suitable exercise modality associated to beneficial effects on mdx muscle. This protocol of training reduces muscle oxidative stress, inflammation, and fibrosis process, and enhances muscle functionality, muscle regeneration, and hypertrophy. These conclusions can guide the design of appropriate studies on human, thereby providing new insights to translational therapeutic application of exercise to DMD patients.
... Progesterone and estrogen are major pregnancy hormones released during pregnancy and estrogen plays a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. [62][63][64] To determine whether progesterone and estrogen are contributing to the superior muscle healing capacity of pregnant mice, we administrated mifepristone and tamoxifen in the pregnant serum to block progesterone and estrogen, respectively, and to assess the in vitro myogenic differentiation capacity of non-pregnant MPCs. This experiment could not be performed in vivo since female hormones are essential during pregnancy. ...
The decline of muscle regenerative potential with age has been attributed to a diminished responsiveness of muscle progenitor cells (MPCs). Heterochronic parabiosis has been used as a model to study the effects of aging on stem cells and their niches. These studies have demonstrated that, by exposing old mice to a young systemic environment, aged progenitor cells can be rejuvenated. One interesting idea is that pregnancy represents a unique biological model of a naturally shared circulatory system between developing and mature organisms. To test this hypothesis, we evaluated the muscle regeneration potential of pregnant mice using a cardiotoxin (CTX) injury mouse model. Our results indicate that the pregnant mice demonstrate accelerated muscle healing compared to nonpregnant control mice following muscle injury based on improved muscle histology, superior muscle regeneration, and a reduction in inflammation and necrosis. Additionally, we found that MPCs isolated from pregnant mice display a significant improvement of myogenic differentiation capacity in vitro and muscle regeneration in vivo when compared to the MPCs from nonpregnant mice. Furthermore, MPCs from nonpregnant mice display enhanced myogenic capacity when cultured in the presence of serum obtained from pregnant mice. Our proteomics data from these studies provides potential therapeutic targets to enhance the myogenic potential of progenitor cells and muscle repair.
... Third, we reported sex-related differences in isometric strength and muscle soreness, but we did not control for the menstrual cycle of the female subjects. Estrogen has been found to impact the immune system and the effects of EIMD in both humans and animals (13,29). Finally, the sample size that was retained for analysis was dissimilar for the male and female groups, leaving some of the results at risk of type 2 error. ...
West, JT, Miller, WM, Jeon, S, and Ye, X. The effects of a preconditioning rolling session on subsequent eccentric exercise-induced muscle damage. J Strength Cond Res 34(8): 2112-2119, 2020-The aim of this study was to examine the effects of a preexercise unilateral quadriceps muscle rolling intervention on subsequent ipsilateral (IPSI) or contralateral (CTRA) knee extension eccentric exercise-induced muscle damage. Twenty-seven healthy volunteers (14 men) underwent an eccentric exercise protocol (6 sets of 10 repetitions with 75% of the maximal isometric strength) with a single-leg knee extension machine. Before the eccentric exercise, the subjects were randomly assigned to either (a) IPSI group: rolling the ipsilateral knee extensor muscles, (b) CTRA: rolling the contralateral muscles, or (c) Control: sitting for 6 minutes (same duration as the rolling intervention protocol) relaxed. The muscle soreness, passive knee extension range of motion, and knee extension isometric strength were measured before, immediately, 24 hours, and 48 hours after exercise. The magnitudes of the range of motion decrement were attenuated in both the IPSI (p = 0.031) and CTRA (p = 0.014) groups 24 hours after the eccentric exercise, when compared with the control. Isometric strength (p = 0.783) and muscle soreness (p = 0.586) responses were not significantly different among the 3 groups (time points and sexes merged). Additionally, women displayed an overall faster recovery than men in isometric strength (p = 0.001) and muscle soreness (p = 0.024), evidenced by the measurements at 48 hours after exercise. Our study suggests that unilateral quadriceps rolling intervention before high-intensity muscle-damaging exercise has a beneficial effect on maintaining range of motion in both the ipsilateral and contralateral muscles.
... Therefore, making conclusions about the impact of CF on markers of muscle damage is difficult, indicating that more research is warranted. Furthermore, none of the previous studies involved female participants, likely due to the purported protective effects of estrogen against muscle damage (Tiidus, 2003) and physiological variations across the menstrual cycle . Therefore, investigating the effect of CF supplementation on muscle recovery in females is required. ...
Polyphenol consumption has become a popular method of trying to temper muscle damage. Cocoa flavanols (CF) have attracted attention due to their high polyphenol content and palatability. As such, this study will investigate whether an acute dose of CF can aid recovery following exercise-induced muscle damage. The study was a laboratory-based, randomized, single-blind, nutrient-controlled trial involving 23 participants (13 females and 10 males). Participants were randomized into either control ∼0 mg CF (n = 8, four females); high dose of 830 mg CF (CF 830 , n = 8, five females); or supra dose of 1,245 mg CF (CF 1245 , n = 7, four females). The exercise-induced muscle damage protocol consisted of five sets of 10 maximal concentric/eccentric hamstring curls and immediately consumed their assigned drink following completion. To measure muscle recovery, maximal voluntary isometric contraction (MVIC) of the knee flexors at 60°and 30°, a visual analog scale (VAS), and lower-extremity function scale were taken at baseline, immediately, 24-, 48-, and 72-hr postexercise-induced muscle damage. There was a main effect for time for all variables (p < .05). However, no significant differences were observed between groups for all measures (p ≥ .17). At 48 hr, there were large effect sizes between control and CF 1245 for MVIC60 (p = .17, d = 0.8); MVIC30 (p = .26, d = 0.8); MVIC30 percentage change (p = .24 d = 0.9); and visual analog scale (p = .25, d = 0.9). As no significant differences were observed following the consumption of CF, there is reason to believe that CF offer no benefit for muscle recovery when ingested acutely.
... Other anabolic hormones relevant to the female athlete such as, insulin-like growth factor-1 (IGF-1) and growth hormone (GH), have been shown to promote muscle growth and development of muscle tissue (Frystyk, 2010;Lee et al., 2017) and may provide additional insights in regards to muscular adaptations to training. Estradiol (E 2 ) is a form of the hormone estrogen, which is responsible for female sex characteristics and has been shown to have various beneficial effects on athletic performance through anti-inflammatory properties and improved muscle recovery and repair rates (Tiidus, 2003;Koundourakis and Margioris, 2019). Estrogen may exert a protective effect on muscle tissue during exercise by acting as an antioxidant, membrane stabilizer, and through receptor substrate characteristics (Cano Sokoloff et al., 2016;Koundourakis and Margioris, 2019). ...
The purpose of this study was to evaluate the effects of a competitive soccer season on biomarkers and performance metrics in order to determine the correlation between changes in biomarkers, body composition, and performance outcomes. Twenty-one Division 1 female collegiate soccer players were monitored throughout the 16-week season. Player workload was measured using heart rate and Global Position Satellite systems at all practices and games. Performance testing, including vertical jump, VO2max, and 3-repetition maximum testing for bench press, squat and deadlift, occurred prior to pre-season and immediately post-season. Blood draws occurred prior to preseason and every 4-weeks thereafter, following a game. Body composition was assessed prior to the start of season (week 0) and weeks 6, 10, 14, and 17 (post-season). Delta area under the curve was calculated for biomarkers and body composition variables to account for seasonal changes adjusted for baseline. Pearson-product moment correlations were used to assess relationships with significance set at p < 0.05. Trends were considered p ≤ 0.10. No significant time main effects were seen for anabolic biomarkers (p > 0.05). Significant time effects were seen for catabolic biomarkers throughout the season (p = 0.001). No changes in body weight, VO2max, vertical jump, and deadlift occurred. Squat and bench press improved (p = 0.01 and p = 0.02, respectively) with a decline in percent body fat (p = 0.03) and a trend for increased fat free mass (p = 0.09). Additionally, total cortisol (TCORT) negatively correlated with fat free mass (r = −0.48; p = 0.03) and positively correlated with VO2max (r = 0.47; p = 0.04). A trend was shown for a positive correlation between both TCORT and free cortisol (FCORT) and percent body fat (r = 0.39; r = 0.40; p = 0.08, respectively). IGF-1 and growth hormone positively correlated to deadlift (r = 0.57; P = 0.02 and r = 0.59; p = 0.03), whereas creatine kinase showed a trend for a positive correlation with deadlift (r = 0.49; p = 0.06). IL-6 negatively correlated with bench press (r = −0.53; p = 0.03). These findings support a relationship between biomarkers, performance outcomes, and body composition. Biomarker monitoring may be useful to detect individual player's physiological response to an athletic season and may help provide insights in efforts to optimize performance outcomes.
... [3,6,29,30] Studies done on mice speculate the molecular mechanism of estrogen on skeletal muscle, by improving the reductionoxidation state in muscle fibers and thus keeping muscle proteins myosin free from post-translational oxidative modifications, could contribute to the maintenance of protein structure-function and ultimately maintain strength. [5,31] Limitation of the study was very less sample size of the subjects as follow-up of the subjects for recording of the onset of muscle fatigue for 3 consecutive months for 4 recordings per month was difficult. ...
... Although previous work in the same participants as the current study displayed a loss of muscle mass and strength across 14 d of immobilization (28), unlike previous reports in men (10), our data indicate an unaltered propensity for H 2 O 2 emission and 4HNE adducts in skeletal muscle. Although sex differences remain to be investigated, it is possible that the antioxidant influence of 17-b estradiol (33,34) could play a role in preserving the propensity for ROS emission despite a reduction in mitochondrial content; alternatively, this discrepancy may reflect methodological differences between studies (isolated mitochondria vs. permeabilized muscle fibers). Although previous work has demonstrated an increased propensity for H 2 O 2 emission following v-3 supplementation (19) and that greater v-3 incorporation into phospholipid membranes could alter substrate transport and are substrate for lipid peroxidation (35)(36)(37)(38)(39), our data suggest this did not predispose women to greater ROS emission in the presence of immobilization. ...
Omega‐3 (ω‐3) supplementation attenuates immobilization‐induced atrophy; however, the underlying mechanisms remain unclear. Since mitochondrial dysfunction and oxidative stress have been implicated in muscle atrophy, we examined whether ω‐3 supplementation could mitigate disuse‐mediated mitochondrial dysfunction. Healthy young women (age = 22 ± 3 yr) randomly received control (n = 9) or ω‐3 supplementation (n = 11; 3 g eicosapentaenoic acid, 2 g docosahexaenoic acid) for 4 wk prior to and throughout 2 wk of single‐limb immobilization. Biopsies were performed before and after 3 and 14 d of immobilization for the assessment of mitochondrial respiration, H2O2 emission, and markers of ADP transport/lipid metabolism. In controls, immobilization rapidly (3 d) reduced (∼20%) ADP‐stimulated mitochondrial respiration without altering ADP sensitivity or the abundance of mitochondrial proteins. Extending immobilization to 14 d did not further reduce mitochondrial coupled respiration; however, unlike following 3 d, mitochondrial proteins were reduced ∼20%. In contrast, ω‐3 supplementation prevented immobilization‐induced reductions in mitochondrial content and respiration throughout the immobilization period. Regardless of dietary supplement, immobilization did not alter mitochondrial H2O2 emission in the presence or absence of ADP, markers of cellular redox state, mitochondrial lipid–supported respiration, or lipid‐related metabolic proteins. These data highlight the rapidity of mitochondrial adaptations in response to muscle disuse, challenge the necessity for increased oxidative stress during inactivity, and establish that ω‐3 supplementation preserves oxidative phosphorylation function and content during immobilization.—Miotto, P. M., McGlory, C., Bahniwal, R., Kamal, M., Phillips, S. M., Holloway, G. P. Supplementation with dietary ω‐3 mitigates immobilization‐induced reductions in skeletal muscle mitochondrial respiration in young women. FASEB J. 33, 8232–8240 (2019). www.fasebj.org
... Studies by Amelink et al. [4] showed a primary effect of estrogen may be to protect muscle membranes from muscle damage induced by exercise. The reduction of muscle membrane disruption may also be important in the inflammatory and muscle repair [5]. It has been reported that the loss of estrogen after menopause may result in more power loss associated with aging and a reduced rate of gain of strength in older women. ...
... Although, the male and female muscles are affected by muscular dystrophy, some studies suggest that there are differences between them, mainly considering the energy metabolism, fiber type composition, and contractile speed, and also these differences are greatly attributed to estrogen levels present in females (Grounds et al., 2008). It is also established that estrogen has an effect on muscle damage, attenuating the inflammatory and oxidative process (Tiidus, 2000(Tiidus, , 2001(Tiidus, , 2003 and/or influencing muscle regeneration (Enns et al., 2008;Velders et al., 2012). This influence occurs from the interaction of the hormone with its specific receptors, alpha (ER-a) and beta (ER-b), which act as transcription factors through a specific DNA sequence called the estrogen responsive element (ERE) (Klinge, 2001;Klinge et al., 2004). ...
... In conclusion, a moderate level of oestradiol supplementation enhances neutrophil infiltration in injured muscle and this is associated with a beneficial effect on strength recovery. As compared to males, females have been associated with decreased muscle injury susceptibility and/or a faster recovery therefrom (Kendall & Eston, 2002;Tiidus, 2003;Enns & Tiidus, 2010); however, there are dissenting reports (Clarkson & Hubal, 2001). This sex difference has been attributed primarily to the hormone oestrogen. ...
Key points:
The female hormone oestrogen may protect muscle from injury by reducing inflammation but this is debatable. In this study, the inflammatory response of injured muscle from oestrogen-replete mice was comprehensively compared to that from oestrogen-deficient mice. We show that oestrogen markedly promotes movement of neutrophils, an inflammatory white blood cell type, into muscle over the first few days after injury but has only a minor effect on the movement of macrophages, another inflammatory cell type. Despite the enhancement of inflammation by oestrogen in injured muscle, we found strength in oestrogen-replete mice to recover faster and to a greater extent than it does in oestrogen-deficient mice. Our study and others indicate that lower doses of oestrogen, such as that used in our study, may affect muscle inflammation and injury differently from higher doses.
Abstract:
Oestrogen has been shown to protect against skeletal muscle injury and a reduced inflammatory response has been suggested as a possible protective mechanism. There are, however, dissenting reports. Our objective was to conduct an unbiased, comprehensive study of the effect of oestradiol on the inflammatory response following muscle injury. Female C57BL6/J mice were ovariectomized and supplemented with and without oestradiol. Tibialis anterior muscles were freeze injured and studied primarily at 1-4 days post-injury. Oestradiol supplementation increased injured muscle gene expression of neutrophil chemoattractants (Cxcl1 and Cxcl5) and to a lesser extent that of monocyte/macrophage chemoattractants (Ccl2 and Spp1). Oestradiol markedly increased gene expression of the neutrophil cell surface marker (Ly6g) but had less consistent effects on the monocyte/macrophage cell surface markers (Cd68, Cd163 and Cd206). These results were confirmed at the protein level by immunoblot with oestradiol increasing LY6G/C content and having no significant effect on CD163 content. These findings were confirmed with fluorescence-activated cell sorting counts of neutrophils and macrophages in injured muscles; oestradiol increased the proportion of CD45+ cells that were neutrophils (LY6G+ ) but not the proportion that were macrophages (CD68+ or CD206+ ). Physiological impact of the oestradiol-enhanced neutrophil response was assessed by strength measurements. There was no significant difference in strength between oestradiol-supplemented and -unsupplemented mice until 2 weeks post-injury; strength was 13-24% greater in supplemented mice at 2-6 weeks post-injury. In conclusion, a moderate level of oestradiol supplementation enhances neutrophil infiltration in injured muscle and this is associated with a beneficial effect on strength recovery.
... This may be due to the difference in the exercise protocol (i.e., submaximal vs. maximal), but it is also possible that sex difference in muscle damage already exists during the pre-pubertal period. Previous studies (Tiidus, 2003;Sipaviciene et al., 2013) reported that the sex difference in muscle damage was due to estrogen concentration that could protect plasma membrane damage. However, it does not appear that high estrogen concentration protects muscle damage, since muscle damage was greater for post-pubescent and pubescent groups than pre-pubescent group (Figures 1, 2). ...
This study compared changes in indirect muscle damage markers, proprioception and arterial stiffness after elbow flexor eccentric exercise between pre-pubescent (9–10 y), pubescent (14–15 y), and post-pubescent (20–24 y) healthy, untrained females (n = 13/group). The maturation of the participants was confirmed by the hand bone age. All participants performed two bouts of 30 sub-maximal eccentric contractions (EC1, EC2) using a dumbbell set at 60% of pre-exercise maximal voluntary isometric elbow flexion strength at 90°. Changes in maximal voluntary concentric contraction (MVC) torque, muscle soreness (SOR), plasma creatine kinase activity, proprioception (position sense, joint reaction angle) and arterial stiffness (carotid-femoral pulse-wave velocity: cfPWV) before to 5 days after EC1 and EC2 were compared among groups by a mixed-design two-way ANOVA. Pre-exercise MVC torque and cfPWV were smaller (P < 0.05) for the pre-pubescent (MVC: 10.0 ± 0.9 Nm, cfPWV: 903 ± 60 cm/s) and the pubescent (14.3 ± 1.1 Nm, 967 ± 61 cm/s) than the post-pubescent (19.1 ± 1.4 Nm, 1,103 ± 73 cm/s). Changes in all variables after EC1 were smaller (P < 0.05) for the pre-pubescent (e.g., MVC at 1 d post-exercise: −10 ± 6%, peak SOR: 5 ± 2 mm) than the pubescent (−15 ± 9%, 12 ± 6 mm) and the post-pubescent (−25 ± 7%, 19 ± 13 mm). After EC2, changes in all variables were smaller (P < 0.05) than those after EC1 for all groups (e.g., MVC at 1 d post-exercise, pre-pubescent: −4 ± 6%, pubescent: −9 ± 4%, post-pubescent: −14 ± 5%; peak SOR: 3 ± 2, 7 ± 3, 11 ± 6 mm), but the magnitude of the repeated bout effect was not different (P > 0.05) among the groups. These results show that the extents of muscle damage, and proprioception and arterial stiffness changes after eccentric exercise are greater at later stages of maturation, but the repeated bout effect is not affected by maturation.
... This lower level of oxidative stress may be because of smaller muscle mass, leading to lower levels of mitochondrial flux and lower ROS production (Ide 2012). Additionally, Tiidus (1995Tiidus ( , 2003 proposed that estrogen may act as an antioxidant against lipid peroxidation of the cell membrane during exercise. Estrogens possess a hydroxyl group on their A (phenolic) ring in a similar structure to tocopherol (vitamin E), which is a known antioxidant (Ayres et al. 1998;Persky et al. 2000). ...
The consumption of milk following eccentric exercise attenuates the effects of muscle damage in team-sport athletes. However, participation in team sport involves both concentric–eccentric loading and metabolic stress. Therefore, the aim of this study was to investigate the effects of postexercise milk consumption on recovery from a cycling protocol designed to simulate the metabolic demands of team sport. Ten female team-sport athletes participated in a randomised crossover investigation. Upon completion of the protocol participants consumed 500 mL of milk (MILK) or 500 mL of an energy-matched carbohydrate (CHO) drink. Muscle function (peak torque, rate of force development, countermovement jump, 20-m sprint), muscle soreness and tiredness, serum creatine kinase, high-sensitivity C-reactive protein, and measures of oxidative stress (protein carbonyls and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio) were determined at pre-exercise and 24 h, 48 h, and 72 h postexercise. MILK had a possible beneficial effect in attenuating losses in peak torque (180°/s) from baseline to 24 h (3.2% ± 7.8% vs. –6.2% ± 7.5%, MILK vs. CHO) and a possible beneficial effect in minimising soreness (baseline-48 h; baseline-72 h) and tiredness (baseline-24 h; baseline-72 h). There was no change in oxidative stress following the exercise protocol, though a likely benefit of milk was observed for GSH/GSSG ratio at baseline-24 h (0.369 ×/÷ 1.89, 1.103 ×/÷ 3.96, MILK vs. CHO). MILK had an unclear effect on all other variables. Consumption of 500 mL of milk after repeat sprint cycling had little to no benefit in minimising losses in peak torque or minimising increases in soreness and tiredness and had no effect on serum markers of muscle damage and inflammation.
... Recently, antifibrotic agents that inhibit the expression of TGF-β1 such as suramin (Fukuchima et al. 2001;Chan et al. 2003) and losartan (Bedair et al. 2008;Burks et al. 2011;Kobayashi et al. 2013) have been shown to enhance muscle regeneration after injury or disuse atrophy. The protective role of estrogen on muscle damage and inflammation after strenuous exercise is well documented (Tiidus 2003). Estrogen activates satellite cells via estrogen receptors to proliferate in skeletal muscle of female rats following downhill running . ...
Diarylheptanoids exhibit numerous biological activities and have been used as traditional medicine in Asian countries. However, their effects on myogenesis are still unknown. This study determined the effects of eight different diarylheptanoid compounds including 1,7-diphenyl-(6E)-6-hepten-3-one (compound 1) and its analogs (compounds 2–8) isolated and purified from Curcuma comosa Roxb. on mouse myoblasts (C2C12 cells) proliferation and differentiation. All compounds (10⁻⁹–10−5 M) were non-toxic to C2C12 cells, and had no anti-oxidant activity except (3S)-1-(3,4–dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (compound 8), which showed higher activity compared to that of ascorbic acid. Additionally, this compound (10−8 M) effectively prevented the toxic effect of H2O2 on C2C12 cells. Proliferation of C2C12 cells was significantly increased by all compounds except compound 1 and (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (compound 4), whereas differentiation of myoblasts was enhanced by all compounds. The effect on proliferation was not blocked by ICI 182,780, but this blocker completely inhibited the effects of diarylheptanoids on differentiation. In addition, silencing the transcription of oestrogen receptor α (ERα), but not estrogen receptor β (ERβ), completely abolished the enhancement of differentiation. Together, the results indicate that diarylheptanoids enhance proliferation of C2C12 cells by a non-estrogenic mechanism, but induce differentiation selectively via ERα. These compounds may have potential for further development as therapeutic agents for treatment of muscle injury and/or diseases.
... Last, we did not include women in our study to minimize variation arising from fluctuations in oestrogen as part of the menstrual cycle. Oestrogen is known to influence inflammatory responses in muscle after exercise (Tiidus, 2003). We acknowledge that our results may not be applicable to women. ...
Key points:
Cold water immersion and active recovery are common post-exercise recovery treatments. A key assumption about the benefits of cold water immersion is that it reduces inflammation in skeletal muscle. However, no data are available from humans to support this notion. We compared the effects of cold water immersion and active recovery on inflammatory and cellular stress responses in skeletal muscle from exercise-trained men 2, 24 and 48 h during recovery after acute resistance exercise. Exercise led to the infiltration of inflammatory cells, with increased mRNA expression of pro-inflammatory cytokines and neurotrophins, and the subcellular translocation of heat shock proteins in muscle. These responses did not differ significantly between cold water immersion and active recovery. Our results suggest that cold water immersion is no more effective than active recovery for minimizing the inflammatory and stress responses in muscle after resistance exercise.
Abstract:
Cold water immersion and active recovery are common post-exercise recovery treatments. However, little is known about whether these treatments influence inflammation and cellular stress in human skeletal muscle after exercise. We compared the effects of cold water immersion versus active recovery on inflammatory cells, pro-inflammatory cytokines, neurotrophins and heat shock proteins (HSPs) in skeletal muscle after intense resistance exercise. Nine active men performed unilateral lower-body resistance exercise on separate days, at least 1 week apart. On one day, they immersed their lower body in cold water (10°C) for 10 min after exercise. On the other day, they cycled at a low intensity for 10 min after exercise. Muscle biopsies were collected from the exercised leg before, 2, 24 and 48 h after exercise in both trials. Exercise increased intramuscular neutrophil and macrophage counts, MAC1 and CD163 mRNA expression (P < 0.05). Exercise also increased IL1β, TNF, IL6, CCL2, CCL4, CXCL2, IL8 and LIF mRNA expression (P < 0.05). As evidence of hyperalgesia, the expression of NGF and GDNF mRNA increased after exercise (P < 0.05). The cytosolic protein content of αB-crystallin and HSP70 decreased after exercise (P < 0.05). This response was accompanied by increases in the cytoskeletal protein content of αB-crystallin and the percentage of type II fibres stained for αB-crystallin. Changes in inflammatory cells, cytokines, neurotrophins and HSPs did not differ significantly between the recovery treatments. These findings indicate that cold water immersion is no more effective than active recovery for reducing inflammation or cellular stress in muscle after a bout of resistance exercise.
... This may be due to the difference in the exercise protocol (i.e., submaximal vs. maximal), but it is also possible that sex difference in muscle damage already exists during the pre-pubertal period. Previous studies (Tiidus, 2003;Sipaviciene et al., 2013) reported that the sex difference in muscle damage was due to estrogen concentration that could protect plasma membrane damage. However, it does not appear that high estrogen concentration protects muscle damage, since muscle damage was greater for post-pubescent and pubescent groups than pre-pubescent group (Figures 1, 2). ...
... Tiidus 124 and Tiidus et al., 121 have demonstrated that estrogen may protect skeletal muscle from muscle damage and inflammation, specifically neutrophil infiltration, following exercise through inhibition and stabilization of calcium-activated calpains. Since it is believed that estrogen can act as a membrane stabilizer, it may act to minimize the disruption of the membrane during injury, which prevents the influx of calcium down its concentration gradient. ...
... 472 A limitation of the study is that the menstrual cy-473 cle was not controlled. Although some studies did not 474 observed a protective effect to the damage induced 475 by exercise [13,14], other studies have found that es-476 trogen had a protective function vis-à-vis the muscle 477 cell membrane [9,36], thus different stages at men-478 strual cycle may have affected the current results of 479 the women. Therefore, studies investigating the MD in 480 men and women following a traditional resistance ex-481 ercise should employ control over the women's men-482 strual cycle. ...
BACKGROUND: Contradictory results exist regarding sex-related differences following exercise-induced muscle damage and little is known concerning the follow-up of a traditional resistance exercise protocol.
OBJECTIVE: To investigate sex differences-related time course of recovery following a traditional strength training protocol (4 sets at 80% of 1-RM).
METHODS: Ten women and ten men participated in the study. Peak torque (PT), arm circumference (CIR), delayed onset muscle soreness (DOMS), muscle thickness (MT) and echo intensity (EI) were measured before (Pre), immediately post (0 hours), 24, 48, and 72 hours after.
RESULTS: Men demonstrated significantly greater relative strength loss than women at 0 h (−26.8 ± 5.0% vs. −15.5 ± 12.4%; P < 0.05), with no significant difference at other time points. Men also experienced a larger increase of CIR (p < 0.05) and MT (p < 0.05) at 0 h compared to women, with no significant difference at other time points. At 72 h, men showed a significantly greater development of DOMS (p < 0.05). EI revealed no sex differences.
CONCLUSION: Following a traditional strength training protocol the recovery appears to be similar in untrained young women and men. Furthermore the next training session should not take place before a rest period of at least 72 h.
Background:
The aim of this study was to examine the effects of long-term (10 months) volleyball training on biochemical responses in adolescent female athletes since the cumulative effects of chronic training on this population are not yet clear.
Methods:
Twenty-one adolescent female volleyball players competing at the national level served as the participants. All athletes carried out volleyball training, which consisted of ball handling, specialized drills, and practical game-style exercises, including physical training in the school gymnasium. The average training cycle consisted of 6 days per week, with a total of about 2 to 2.5 hours of volleyball training per day. In order to determine the cumulative effects on autonomic, immune, renal function and bone resorption, salivary and urinary samples were collected before volleyball training on 3 consecutive days (days 1, 3 and 5) at months 0 and 10, respectively.
Results:
No significant changes in body mass, salivary secretion rate, urinary albumin, L-type fatty acid binding protein and type I collagen cross-linked N-telopeptide concentration were found. In contrast, significant decreases were noted in salivary α-amylase activity (% change: -22.9), total protein (%change: -21.4), and immunoglobulin A concentration (% change: -20.1).
Conclusions:
The results of this study imply that the autonomic function after chronic volleyball training in adolescent female athletes may be enhanced due to training adaptation, although the immune function may be attenuated as a result of cumulative overtraining. Moreover, long-term volleyball training in adolescent female athletes appears to suppress bone resorption and not to induce cumulative damage to renal function.
Sexual dimorphism, driven by the sex hormones testosterone and estrogen, influences body composition, muscle fiber type, and inflammation. Research related to muscle stem cell (MuSC) responses to exercise has mainly focused on males. We propose a novel hypothesis that there are sex-based differences in MuSC regulation following exercise, such that males have more MuSCs while females demonstrate a greater capacity for regeneration.
Menopause is accompanied by a sharp decline in estrogen levels. Estrogen has many positive effects on skeletal muscle including protection against exercise-induced damage, attenuation of post-damage inflammation, enhancement of post-damage muscle repair, enhancement of post-atrophy recovery of muscle mass, improved maintenance, enhancement of postmenopausal muscle mass and strength, and improved muscle hypertrophic response to exercise. These along with enhancement of other well-known metabolic and bone mass maintenance effects of estrogen the former of which is also noted in this review can have a profound influence on the health and functional abilities of postmenopausal females. Experimental evidence for these effects derived from animal and human models is discussed. In addition, the physiological and cellular signaling mechanisms of how estrogen may influence muscle damage, inflammation, repair, and mass as gleaned from both animal and human-based experiments are also noted. Finally, evidence for the safety of estrogen replacement in postmenopausal women is discussed based on epidemiological and health data as well as experimental animal models, and the case is made for the benefits of hormone replacement in menopause for the maintenance of optimal muscle functioning in older women.KeywordsEstrogenMuscle massInflammationMuscle damageMuscle strengthMenopause
Background:
Females are typically less fatigable than males during sustained isometric contractions at lower isometric contraction intensities. This sex difference in fatigability becomes more variable during higher intensity isometric and dynamic contractions. While less fatiguing than isometric or concentric contractions, eccentric contractions induce greater and longer lasting impairments in force production. However, it is not clear how muscle weakness influences fatigability in males and females during sustained isometric contractions.
Methods:
We investigated the effects of eccentric exercise-induced muscle weakness on time to task failure (TTF) during a sustained submaximal isometric contraction in young (18-30 years) healthy males (n = 9) and females (n = 10). Participants performed a sustained isometric contraction of the dorsiflexors at 35° plantar flexion by matching a 30% maximal voluntary contraction (MVC) torque target until task failure (i.e., falling below 5% of their target torque for ≥2s). The same sustained isometric contraction was repeated 30 min after 150 maximal eccentric contractions. Agonist and antagonist activation were assessed using surface electromyography over the tibialis anterior and soleus muscles, respectively.
Results:
Males were ∼41% stronger than females. Following eccentric exercise both males and females experienced an ∼20% decline in MVC torque. TTF was ∼34% longer in females than males prior to eccentric exercise-induced muscle weakness. However, following eccentric exercise-induced muscle weakness, this sex-related difference was abolished, with both groups having an ∼45% shorter TTF. Notably, there was ∼100% greater antagonist activation in the female group during the sustained isometric contraction following exercise-induced weakness as compared to the males.
Conclusion:
This increase in antagonist activation disadvantaged females by decreasing their TTF, resulting in a blunting of their typical fatigability advantage over males.
Introduction: Nowadays more women are trying to shape their figure properly. Changes in the menstrual cycle can affect the dynamic muscle parameters of women. Aim: The aim of the study was to assess muscle strength in various phases of the menstrual cycle in young women Material and methods: The study involved 23 women aged 20–22. All the women had menstrual periods (27 ± 3.16 days). The strength measurement was made by means of Microfet2 (Hoggan Health Industries, USA), which was fixed permanently to the floor. The test was performed on the knee flexors at the angle of 10° and 90° and hip flexors in the neutral position and the glenohumeral joint (shoulder) extensors at the flexion of 90°. The lever arm was marked with the use of anthropometric points. The test was performed three times in each phase of the menstrual cycle; in the early follicular phase (2nd–5th day), the ovular (12th–15th day) and in the luteal phase (16th–28th day). Results and discussion: No statistically significant differences in the muscle torque values during the menstrual cycle were confirmed in the test. The P value of the arm extensors is 0.33, for hip flexors is 0.79 and hamstring muscle with a bent knee joint in 90° and 10° is 0.311, 0.567, respectively. No statistically significant differences between the particular cycles phases were confirmed either. Conclusions: In the menstrual cycle in young women, there are no significant differences in muscle strength during the individual phases.
This study investigate the effects of high-intensity interval training (HIIT) on systemic levels of inflammatory and hormonal markers in postmenopausal women with metabolic syndrome (MS). Fifteen postmenopausal women with MS completed the training on treadmills. Functional, body composition parameters, maximal oxygen uptake (VO2max), and lipid profile were assessed before and after HIIT. Serum or plasma levels of cytokines and hormonal markers were measured along the intervention. The analysis of messenger RNA (mRNA) expression of these cytokines was performed in peripheral blood mononuclear cells (PBMC). VO2max and some anthropometric parameters were improved after HIIT, while decreased levels of proinflammatory markers and increased levels of interleukin-10 (IL-10) were also found. Adipokines were also modulated after 12 weeks or training. The mRNA expression of the studied genes was unchanged after HIIT. In conclusion, HIIT benefits inflammatory and hormonal axis on serum or plasma samples, without changes on PBMC of postmenopausal MS patients.
Cachexia is a debilitating condition that occurs with chronic disease including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex. The Apc(Min/+) mouse is genetically predisposed to develop intestinal tumors; interleukin-6 (IL-6) signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and the progression of cancer cachexia in the female Apc(Min/+) mouse. Ovarian reproductive function was monitored in female Apc(Min/+) mice. Disease-related cessation of estrous cycling (acyclicity) was seen in 38% of mice. Acyclicity was associated with severe cachexia including morphological and functional losses and enhanced muscle inflammatory gene expression. Interestingly, ovariectomy rescued body weight, muscle mass and function, but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproduction function and cachexia progression in female Apc(Min/+) mice.
Menopause is accompanied by a sharp decline in estrogen levels. Estrogen has many positive effects on skeletal muscle including, protection against exercise induced damage, attenuation of post-damage inflammation, enhancement of post-damage muscle repair, enhancement of post-atrophy recovery of muscle mass, improved maintenance and enhancement of postmenopausal muscle mass and strength and improved muscle hypertrophic response to exercise. These along with enhancement of other well-known metabolic and bone mass maintenance effects of estrogen can have profound influence on the health and functional abilities of postmenopausal females. Experimental evidence for these effects derived from animal and human models is discussed. In addition, the physiological and cellular signaling mechanisms of how estrogen may influence muscle damage, inflammation, repair and mass as gleaned from both animal and human based experiments are also noted. Finally evidence for the safety of estrogen replacement in postmenopausal women is discussed based on newer epidemiological and health data as well as experimental animal models and the case is made for the benefits of hormone replacement in menopause for maintenance of optimal muscle functioning in older women.
It is abundantly evident that both men and women lose muscle mass and strength with advancing age. Males tend to lose muscle and strength beginning in the late third or early fourth decade although this modest loss does not appear to be related to a decline in testosterone (T2). After the age of 40, there is a strong correlation between muscle mass loss and the decline in T2. Women lose approximately 10–15% of their muscle mass between the ages of 25 and the onset of menopause, but thereafter the decline accelerates to an average of 2% per year during the menopause and beyond. Aging-related declines in skeletal muscle mass and function result in reduced mobility and significantly affect quality of life for elderly women and men. This chapter summarizes the known effects of the sex hormones - estradiol and testosterone - on skeletal muscle aging and loss in women and men and discusses the benefits and adverse effects of using hormone replacement therapy in both sexes.
Safe and effective contraception is widely available to women with rheumatic diseases, although consistent contraception, even in patients on potentially teratogenic medications, continues to be underutilized. The most effective contraceptives are the long-acting forms, including intrauterine devices (IUDs), subdermal implants, and depot medroxyprogesterone acetate injections. Other effective methods include combined hormonal contraceptives. Barrier methods are the least effective, although they offer some protection against sexually transmitted diseases. The optimal choice of contraceptive for a particular patient depends on rheumatic disease diagnosis, level of disease activity, autoantibody profile, medications, physical limitations, and personal preference. Estrogen-containing contraceptives are a particular concern: they should be avoided in patients with antiphospholipid antibodies and active lupus erythematosus or other prothrombotic conditions. © 2014 Springer Science+Business Media New York. All rights are reserved.
Spectacular athleticism is a conspicuous feature of many animal courtship displays yet surprisingly
little is known about androgen dependence of skeletal muscles underlying these displays. Testosterone
(T) acts through androgen receptors (ARs) to stimulate muscular male Golden-collared
manakins of Panama to perform a remarkably athletic courtship display that includes loud wingsnaps
generated by the rapid and forceful lifting of the wings. We tested the hypothesis that
androgen sensitivity, reflected in the expression levels of AR mRNA, is a muscular adaptation
supporting these courtship displays. Quantitative PCR showed substantially greater AR mRNA
expression in all limb muscles of wild male and female manakins compared with two other avian
species that do not perform athletic displays, zebra finches and ochre-bellied flycatchers. AR expression
levels in the massive skeletal muscles were comparable with the minute oscine syringeal
muscle but greater than levels in nonmuscular androgen targets that did not differ across species.
Compared with zebra finches, male manakins also had greater activity of the T-activating enzyme
5�-reductase in a wing-lifting muscle. In addition,lowlevels of estrogen receptor� (ER)mRNAwere
detected in all muscles of control, T-treated, and estradiol-treated manakins. Treatment of manakins
with T, but not estradiol, significantly increased skeletal muscle ER expression, suggesting
that ER expression is AR-dependent. These results confirm manakin limb muscles as important
androgen targets where T may act to promote the speed, force, and/or endurance required for the
manakin display. Androgen-sensitive muscular phenotypes may adapt males of many species to
perform impressive athletic displays.
The purpose of this study was to evaluate the sex differences in delayed onset muscle soreness (DOMS), torque, and accumulation of technetium-99m (Tc-99m) neutrophils in eccentric-exercised muscle. A group of 10 female and 12 male subjects took part in this study. The subjects completed a pre-test using the descriptor differential scale (DDS) to describe DOMS, and tests of concentric and eccentric torque of the right quadriceps. A volume of 100 ml of blood was taken by venipuncture for neutrophil labelling in the early morning of the exercise day. The Tc-99m neutrophils were re-infused intravenously before the eccentric exercise. The exercise stimulus consisted of 300 eccentric repetitions of the right quadriceps muscles. Radionuclide images of both quadriceps muscles (lateral views) were taken at 2 and 4 h. The DDS, and concentric and eccentric torques of the quadriceps were subsequently evaluated at 0 h, 2, 4, 20 and 24 h post-exercise. The presence of Tc-99m neutrophils was greater in the exercised leg than the non-exercised leg at 2 and 4 h post-exercise (P </= 0.013) and greater in the exercised leg of the women compared to the men at 2 h (P = 0.03). The DOMS had increased post-exercise (P < 0.001) and torque had decreased post-exercise (P </= 0.002) but the patterns were different between the sexes. We concluded that the sex influences the presence of Tc-99m neutrophils in the exercised muscle following eccentric exercise. In addition, different patterns of DOMS and torque were observed between the sexes after eccentric exercise, and require further investigation.
Unaccustomed exercise is followed by delayed-onset muscle soreness and morphological changes in skeletal muscle. Animal studies have demonstrated that women have an attenuated response to muscle damage. We studied the effect of eccentric exercise in untrained male (n = 8) and female (n = 8) subjects using a unilateral exercise design [exercise (Ex) and control (Con) legs]. Plasma granulocyte counts [before (Pre) and 48 h after exercise (+48h)] and creatine kinase activity [Pre, 24 h after exercise (+24h), +48h, and 6 days after exercise (+6d)] were determined before (Pre) and after (+24h, +48h, +6d) exercise, with biopsies taken from the vastus lateralis of each leg at +48h for determination of muscle damage and/or inflammation. Plasma granulocyte counts increased for men and decreased for women at +48h (P < 0.05), and creatine kinase activity increased for both genders at +48h and +6d (P < 0.01). There were significantly greater areas of both focal (P < 0.001) and extensive (P < 0.01) damage in the Ex vs. Con leg for both genders, which was assessed by using toluidine blue staining. The number of leukocyte common antigen-positive cells/mm(2) tissue increased with exercise (P < 0.05), and men tended to show more in their Ex vs. Con leg compared with women (P = 0.052). Men had a greater total (Ex and Con legs) number of bcl-2-positive cells/mm(2) tissue vs. women (P < 0.05). Atrophic fibers with homogeneous bcl-2-positive staining were seen only in men (n = 3). We conclude that muscle damage is similar between genders, yet the inflammatory response is attenuated in women vs. men. Finally, exercise may stimulate the expression of proteins involved in apoptosis in skeletal muscle.
An accumulating body of evidence clearly establishes that estradiol is a potent neuroprotective and neurotrophic factor in the adult: it influences memory and cognition, decreases the risk and delays the onset of neurological diseases such as Alzheimer's disease, and attenuates the extent of cell death that results from brain injuries such as cerebrovascular stroke and neurotrauma. Thus, estradiol appears to act at two levels: 1) it decreases the risk of disease or injury; and/or 2) it decreases the extent of injury incurred by suppressing the neurotoxic stimulus itself or increasing the resilience of the brain to a given injury. During the past century, the average life span of women has increased dramatically, whereas the time of the menopause has remained essentially constant. Thus, more women will live a larger fraction of their lives in a postmenopausal, hypoestrogenic state than ever before. Clearly, it is critical for us understand the circumstances under which estradiol exerts protective actions and the cellular and molecular mechanisms that underlie these novel, nonreproductive actions.
Estrogens have a wide array of biological effects, targeting both genomic and nongenomic mechanisms. Classically, the estrogen receptors activating the transcription machinery in the nucleus were thought to be distinct from the extranuclear estrogen receptors. Recently, this conceptual wall has started to be dismantled as the result of the identification of novel routes of estrogen action.
Exercise-induced muscle damage is a well documented phenomenon that often follows unaccustomed and sustained metabolically demanding activities. This is a well researched, but poorly understood area, including the actual mechanisms involved in the muscle damage and repair cycle. An integrated model of muscle damage has been proposed by Armstrong and is generally accepted.
A more recent aspect of exercise-induced muscle damage to be investigated is the potential of estrogen to have a protective effect against skeletal muscle damage. Estrogen has been demonstrated to have a potent antioxidant capacity that plays a protective role in cardiac muscle, but whether this antioxidant capacity has the ability to protect skeletal muscle is not fully understood.
In both human and rat studies, females have been shown to have lower creatine kinase (CK) activity following both eccentric and sustained exercise compared with males. As CK is often used as an indirect marker of muscle damage, it has been suggested that female muscle may sustain less damage. However, these findings may be more indicative of the membrane stabilising effect of estrogen as some studies have shown no histological differences in male and female muscle following a damaging protocol.
More recently, investigations into the potential effect of estrogen on muscle damage have explored the possible role that estrogen may play in the inflammatory response following muscle damage. In light of these studies, it may be suggested that if estrogen inhibits the vital inflammatory response process associated with the muscle damage and repair cycle, it has a negative role in restoring normal muscle function after muscle damage has occurred.
This review is presented in two sections: firstly, the processes involved in the muscle damage and repair cycle are reviewed; and secondly, the possible effects that estrogen has upon these processes and muscle damage in general is discussed. The muscle damage and repair cycle is presented within a model, with particular emphasis on areas that are important to understanding the potential effect that estrogen has upon these processes.
This study investigated the effect of macrophages on in vitro satellite cell myogenesis in the turkey and mouse. Macrophages are considered to act as scavengers of tissue debris during the muscle degeneration-regeneration process. The number of dividing cells and of myoblasts expressing the myogenic regulatory factor MyoD indicated that macrophages enhanced satellite cell proliferation in both species. This was confirmed by observations with cultures treated for bromodeoxyuridine (BrdU) incorporation. In mouse and turkey macrophage–satellite cell cocultures, the number of differentiated myoblasts, the frequency of myogenin-positive cells, and the expression of developmental myosin isoforms were reduced as compared with control cultures, indicating that macrophages delayed satellite cell differentiation. The possibility that macrophages facilitate muscle fiber reconstitution by enhancing satellite cell proliferation should be taken into consideration in designing future strategies of satellite cell transplantation as a treatment for muscular dystrophies. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 724–732, 1999.
It is well established that periods of increased contractile activity result in significant changes in muscle structure and function. Such morphological changes as sarcomeric Z-line disruption and sarcoplasmic reticulum vacuolization are characteristic of exercise-induced muscle injury. While the precise mechanism(s) underlying the perturbations to muscle following exercise remains to be elucidated, it is clear that disturbances in Ca2+ homeostasis and changes in the rate of protein degradation occur. The resulting elevation in intracellular [Ca2+] activates the non-lysosomal cysteine protease, calpain. Because calpain cleaves a variety of protein substrates including cytoskeletal and myofibrillar proteins, calpain-mediated degradation is thought to contribute to the changes in muscle structure and function that occur immediately following exercise. In addition, calpain activation may trigger the adaptation response to muscle injury. The purpose of this paper is to: (i) review the chemistry of the calpain-calpastatin system; (ii) provide evidence for the involvement of the non-lysosomal, calcium-activated neutral protease (calpain) in the response of skeletal muscle protein breakdown to exercise (calpain hypothesis); and (iii) describe the possible involvement of calpain in the inflammatory and regeneration response to exercise.
We investigated whether oestrogens modulate the phenomenon of leukocyte accumulation during ischaemia and reperfusion of the myocardium. Anaesthetized rats were subjected to total occlusion (1 h) of the left main coronary artery followed by 1 h reperfusion. Sham myocardial ischaemia-reperfusion rats (Sham) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity, serum creatinine phosphokinase activity, serum and macrophages tumour necrosis factor (TNF-alpha) and the myocardial staining of intercellular adhesion molecule-1 (ICAM-1) were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum creatinine phosphokinase activity (348 +/- 38 U/ml) and cardiac myeloperoxidase activity, a marker of polymorphonuclear leukocyte accumulation, both in the area at risk and in the necrotic area (MPO 9 +/- 1.1 mU/g tissue and 8.2 +/- 1 mU/g tissue, respectively), and induced a marked increase in the macrophage (156 +/- 14 U/ml at the end of reperfusion) and serum (344 +/- 12 U/ml, at the end of reperfusion) levels of TNF-alpha. Finally, myocardial ischaemia-reperfusion injury increased ICAM-1 staining in the myocardium. Administration of 17beta-oestradiol (5, 10 and 20 microg/kg, i.m. 5 min after induction of myocardial ischaemia-reperfusion injury), lowered myocardial necrosis and myeloperoxidase activity in the area at risk and in the necrotic area, reduced serum and macrophages TNF-alpha (20 +/- 3 U/ml and 9 +/- 3 U/ml, respectively) and decreased serum creatinine phosphokinase activity (67 +/- 3 U/ml). Oestrogen treatment also blunted the increased staining of ICAM-1 in the injured myocardium. Finally, 17beta-oestradiol added in vitro to peritoneal macrophages collected from untreated rats subjected to myocardial ischaemia-reperfusion injury, significantly reduced TNF-alpha production. Our results suggest that 17beta-oestradiol, by inhibiting TNF-alpha production, limits the deleterious ICAM-1-mediated binding of leukocytes to injured myocardium and protects against myocardial ischaemia-reperfusion injury.
Specific antibodies against structural proteins of muscle fibres (actin, desmin, dystrophin) and extracellular matrix (fibronectin) were used to study the effect of eccentrically biased downhill running exercise (13,5 degrees, 17 m min(-1), 130 min) on the magnitude and properties of myofibre injury in the quadriceps femoris muscle of male and female rats. Muscle beta-glucuronidase activity, a quantitative indicator of muscle damage, showed clearly smaller increase in female than in male rats during the 4-day period following exercise. A similar course of histopathological changes was observed in both sexes, although females showed slower and less marked changes than males. In males, discontinuous or even lost submembrane protein dystrophin staining was observed in some swollen fibres immediately after exercise, before the loss of desmin and staining of disorganized actin, i.e. before the disruption of the cytoskeletal system and the contractile apparatus. The observation that no dramatic changes in the microarchitecture of the muscle fibres were detected immediately or even 6 h after the exercise in females compared with males may indicate that the sarcolemma of the females might be strengthened against membrane damage by a still unknown stabilizing compound.
The effects of 2 weeks of oestrogen (40 microg kg BW-1 beta-estradiol 3-benzoate) injection on 24 h post-exercise myeloperoxidase (MPO) activities were determined in plantaris and soleus muscles and liver of sexually mature male and female rats. The treadmill running protocol (45-60 min, at 28 m min-1, 15% grade) induced significant elevations in muscle MPO activities 24 h post-exercise in male rats, while prior oestrogen administration to male rats eliminated the post-exercise elevations in muscle MPO activities. Female rats experienced no significant post-exercise elevations in muscle MPO activities. Hence oestrogen administration to male rats attenuated post-exercise muscle MPO activities to levels found in female animals. Liver MPO activities were not significantly affected by exercise, gender or oestrogen administration. Oestrogen may be a factor in diminishing 24 h post-exercise skeletal muscle leukocyte infiltration and inflammatory response in both male and female muscle.
We hypothesized that estrogen administration would attenuate skeletal muscle neutrophil infiltration, indices of muscle membrane disruption, and muscle calpain activity shortly after the termination of exercise. Ovariectomized female rats were implanted with either an estogen pellet (25 mg beta-estradiol) or a placebo pellet. Two weeks postimplant, animals were killed either at rest or 1 h after running exercise (60 min at 21 m x min(-1), 12% grade). The 4 experimental groups (n = 12) used were: unexercised placebo (UP), unexercised estrogen (UE), exercised placebo (EP), and exercised estrogen (EE). Blood samples were analyzed for creatine kinase (CK) activity and estradiol content. Plantaris and gastrocnemius muscles were removed and histochemical determination of neutrophil content or biochemical determination of myeloperoxidase (MPO), glucose-6-phosphate dehydrogenase (G6PD), and calpain-like activity determined. Estrogen supplemented animals had 10-20-fold higher circulating estradiol levels than placebo animals. EP animals had significantly higher (P < 0.05) circulating CK activities than EE or unexercised animals. Muscle neutrophil concentrations were significantly (P < 0.01) elevated in EP and EE groups compared with unexercised controls, with EP muscle neutrophil levels also being over 60% greater (P < 0.05) than in EE animals. EP animals also had higher (P < 0.05) muscle MPO activities than unexercised or EE animals. Muscle G6PD activities were not significantly different between any groups. Muscle caplain-like activities were 80% higher (P < 0.01) in EP animals than EE animals with calpain-like activities in EE animals similar to unexercised groups. These results indicate that estrogen supplementation in ovariectomized rats attenuated 1-h post-exercise serum CK activities, muscle neutrophil infiltration, MPO activities, and calpain-like activities when compared with exercised, unsupplemented animals. This supports the possibility of a relationship between estrogen, calpain dependent production of neutrophil chemo-attractant peptides, and 1-h post-exercise skeletal muscle neutrophil infiltration.
The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17beta-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater (P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats (P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower (P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater (P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower (P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower (P < 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content (P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.
Exercise has been demonstrated as a physiological inducer of heat shock protein (HSP)70. Many of the proposed signals of this response exhibit sexual dimorphism. Thus the present objectives were to determine whether HSP70 induction after exercise exhibits gender specificity and to elucidate the mechanisms underlying such a phenomenon. Postexercise HSP70 induction in skeletal muscle was greater in male than female rats at the level of protein and mRNA (P = 0.005). Moreover, placebo-treated ovariectomized animals demonstrated a greater HSP70 response to exercise than those treated with estrogen (P = 0.015 and 0.019 for protein and mRNA, respectively). These findings indicate that the gender-specific HSP70 response to exercise is mediated by the female-specific hormone estrogen. Compounds structurally related to 17beta-estradiol, the major endogenous estrogen, but which do not activate the estrogen receptor, also attenuated HSP70 induction with exercise (P < 0.01), indicating a nongenomic hormonal mechanism. These findings highlight a specific example of the biological differences between males and females and reiterate the physiological effects of sex hormones extending beyond their roles in reproductive function.
- St Pierre-Schneider
- Tiidus