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Counterpoint: Estrogen and Sex do not Significantly Influence Post-Exercise Indexes of Muscle Damage, Inflammation, and Repair

2009; American Physiological Society; Volume: 106; Issue: 3 Linguagem: Inglês

10.1152/japplphysiol.90848.2008a

8750-7587

Monica J. Hubal, Priscilla M. Clarkson,

Sports injuries and prevention

POINT-COUNTERPOINTCounterpoint: Estrogen and Sex do not Significantly Influence Post-Exercise Indexes of Muscle Damage, Inflammation, and RepairMonica J. Hubal and Priscilla M. ClarksonMonica J. Hubal and Priscilla M. ClarksonPublished Online:01 Mar 2009https://doi.org/10.1152/japplphysiol.90848.2008aMoreSectionsPDF (52 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Exercise-induced muscle damage (EIMD) occurs following strenuous, novel exercise and is assessed directly via tissue analysis and characterized indirectly by muscle dysfunction, inflammation, delayed onset muscle soreness, and increased levels of muscle proteins [e.g., creatine kinase (CK), myoglobin] in circulation. Repair typically takes place during the 7–14 days following the initial exercise bout.There has been much debate over the past 20 years concerning the existence of sex differences in EIMD and repair predicated on the assumption that estrogen levels affect skeletal muscle's response to damaging exercise (14, 28). Potential mechanisms by which estrogen levels could affect the EIMD response include estrogen's antioxidant properties and its potential to stabilize the membrane of the skeletal muscle cells during exercise. Either or both of these mechanisms would serve to protect females from EIMD and promote repair when compared with males.Indeed, animal studies have often demonstrated attenuated EIMD susceptibility in female or estradiol-supplemented animals, based largely on decreased levels of CK in the blood (1, 3). Animal studies (23) have also reported attenuations in the inflammatory process due to sex or estrogen status. However, other animal studies (17, 28) that used contractile deficits as the primary muscle damage marker have not found similar effects. In fact, Warren et al. (29) found that estradiol-supplemented ovariectomized mice demonstrated significantly greater contractile losses as compared to non-supplemented mice.In contrast to animal studies, the majority of human studies have reported similar responses for various EIMD markers when comparing men and women or groups with different estrogen levels (reviewed in Refs. 6–8).Direct muscle damage assessment.Two studies to date addressed the effect of sex on skeletal muscle ultrastructural properties following eccentric exercise in humans. Stupka et al. (24) found no differences between men (n = 8) and women (n = 8) in focal and extensive damage areas following unilateral eccentric leg exercise. A follow-up study (25) detected no effect of sex on the amount of Z-line streaming after a first bout of eccentric exercise. Although it may be beneficial to examine larger cohorts of men and women for direct markers of muscle damage in the future (given the variability associated with the biopsy method), these two studies indicate that ultrastructural changes in skeletal muscle following eccentric exercise are unaffected by sex.Muscle function.Several studies (4, 18, 20, 25) reported no sex differences in maximal isometric strength loss immediately following repetitive maximal eccentric contractions, while one study found that women demonstrate greater relative strength loss immediately after exercise (−57.8% in women vs. −50.4% loss in men) (21). In a recent study (13), we found that patterns of relative isometric and eccentric torque losses during 50 maximal eccentric actions of the arm were remarkably similar between men (n = 22) and women (n = 24). We also found similar decrements in other contractile properties (i.e., work, rate of force production, and half-relaxation time) throughout the exercise. Adding to this, several studies that examined women of different estrogenic status (e.g. pre- vs. postmenopausal or oral contraceptive users vs. nonusers) also demonstrated similar strength changes after both isometric (5) and eccentric (19, 26) exercise. Together, these data suggest that relative muscle fatigue during and immediately after exercise are unaffected by sex or estrogen levels.Studies that have examined recovery of strength following damaging exercise largely found no differences between men and women (20, 26). Some studies reported differences in contractile characteristics during recovery (4, 15), but these differences were based on statistical analysis of the change in absolute levels over time. Given the large baseline differences between men and women, it is important to account for these differences (or a surrogate such as lean body mass) in the analyses. For example, MacIntyre et al. (15) reported differences in concentric and eccentric torque recovery following 300 eccentric actions of the quadriceps. However, these differences were no longer significant when strength was normalized to body weight. Furthermore, although the recent Sewright et al. (21) paper demonstrated an acute difference in maximal isometric strength immediately postexercise, the overall strength loss/recovery pattern (to 10 days postexercise) was not significantly different between men and women. Studies examining strength recovery in relation to estrogenic status have demonstrated mixed results, with two reporting no group differences in strength recovery in the 5 days following exercise (5, 26) and one study suggesting a delay in recovery for oral contraceptive users (19).Muscle enzyme activity in blood.Women have lower resting CK levels than men (2), but consistent differences in the CK response to exercise have not been reported. Following downhill running, Sorichter et al. (22) found no sex differences in several different muscle proteins in the blood, including CK, myoglobin, myosin heavy chain fragments, and troponin I. Eston et al. (12) also found no sex differences in CK following downhill running. After eccentric arm exercise, Sewright (21) found that women experienced a lower CK but not myoglobin elevations, while Stupka demonstrated lower CK values in women both before and after eccentric leg exercise (25).Studies of CK response to exercise in relation to estrogen levels in different groups of women have largely demonstrated no differences between groups (5, 16, 19, 26). Furthermore, while Arnett et al. (2) found an increased CK response in menarchal women vs. pre- or post-menarchal women following eccentric hamstring exercise, this effect was lost when the analysis was covaried for lean body mass.Pain/soreness and inflammation.Studies assessing pain or delayed onset muscle soreness measures typically have not found sex differences (10, 18, 21) or significant associations with estrogen (5, 19). One study that did report a difference in soreness patterns following eccentric exercise (15) looked only at soreness patterns over the first 24-h postexercise, while soreness levels typically peak several days following exercise.While overall inflammation (as assessed by swelling or circumference measures) has not typically demonstrated estrogenic effects (19, 26), alterations of certain components of the inflammatory process have been reported to be different between men and women, but these results have been inconsistent. MacIntyre et al. (15) reported higher numbers of neutrophils in women 2 h postexercise, while Stupka (24) demonstrated an exercise-induced rise in circulating granulocytes only in men. In a follow up study, Stupka (25) reported no sex difference in neutrophil and macrophage numbers following a single bout of exercise, while women demonstrated a rise in neutrophil concentration following a repeated bout of exercise.Variability.While studies suggested that the average EIMD response may be similar between men and women, some data suggest differences in the variability of responses. For example, Sayers et al. (20) found that women had a greater incidence of profound postexercise strength loss (>70%), while Sewright et al. (21) found that men had greater variability in CK levels. These findings may be in part due to interactions of sex or estrogen with genetic variability effects. Studies have reported associations between genetic mutations and variability in EIMD markers (9, 11), and a subset of these associations were sex dependent. Genetic variability interactions might also explain, in part, apparent species differences in EIMD studies.Conclusion.The majority of data from human studies have indicated that sex and estrogen levels do not significantly affect exercise-induced muscle damage, as measured directly (i.e., ultrastructural damage) or as indicated by functional losses, muscle protein levels in the blood, pain or soreness.REFERENCES1 Amelink GJ, Bar PR. Exercise-induced muscle protein leakage in the rat. Effects of hormonal manipulation. J Neurol Sci 76: 61–68, 1986.Crossref | PubMed | ISI | Google Scholar2 Arnett MG, Hyslop R, Dennehy CA, Schneider CM. Age-related variations of serum CK and CK MB response in females. Can J Appl Physiol 25: 419–429, 2000.Crossref | PubMed | Google Scholar3 Bar PR, Amelink GJ, Oldenburg B, Blankenstein MA. 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J Appl Physiol 80: 1660–1665, 1996.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited BySex differences in the impact of resistance exercise load on muscle damage: A protocol for a randomised parallel group trial29 September 2022 | PLOS ONE, Vol. 17, No. 9Evaluation of muscle thickness of the vastus lateralis by ultrasound imaging following blood flow restricted resistance exercise21 May 2021 | Clinical Physiology and Functional Imaging, Vol. 41, No. 4Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and WomenCell Reports, Vol. 31, No. 12Eccentric and concentric blood flow restriction resistance training on indices of delayed onset muscle soreness in untrained women31 August 2019 | European Journal of Applied Physiology, Vol. 119, No. 10The modulation of corticospinal excitability and inhibition following acute resistance exercise in males and females10 May 2018 | European Journal of Sport Science, Vol. 18, No. 7The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running23 February 2017 | Antioxidants, Vol. 6, No. 1Minimal Evidence for a Secondary Loss of Strength After an Acute Muscle Injury: A Systematic Review and Meta-Analysis21 April 2016 | Sports Medicine, Vol. 47, No. 1The Relevance of Sex Differences in Performance FatigabilityMedicine & Science in Sports & Exercise, Vol. 48, No. 11Sex differences in human fatigability: mechanisms and insight to physiological responses25 February 2014 | Acta Physiologica, Vol. 210, No. 4How Sex Hormones Promote Skeletal Muscle Regeneration26 July 2013 | Sports Medicine, Vol. 43, No. 11Sex Differences in Exercise-Induced Muscle Pain and Muscle DamageThe Journal of Pain, Vol. 13, No. 12Early inflammatory and myogenic responses to resistance exercise in the elderly20 August 2012 | Muscle & Nerve, Vol. 46, No. 3Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormonesMatthew J. 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