No sex differences in oxygen uptake or extraction kinetics in the moderate or heavy exercise intensity domains

The integrative response to exercise differs between sexes, with oxidative energy contribution purported as a potential mechanism. The present study investigated whether this difference was evident in the kinetics of oxygen uptake (V□O2) and extraction (HHb+Mb) during exercise. Sixteen adults (8 males, 8 females, age: 27±5 years) completed three experimental visits. Incremental exercise testing was performed to obtain lactate threshold and V□O2peak. Subsequent visits involved three six-minute cycling bouts at 80% of lactate threshold and one 30-minute bout at a work rate 30% between the lactate threshold and power at V□O2peak. Pulmonary gas exchange and near-infrared spectroscopy of the vastus lateralis were used to continuously sample V□O2 and HHb+Mb, respectively. The phase II V□O2 kinetics were quantified using mono-exponential curves during moderate and heavy exercise. Slow component amplitudes were also quantified for the heavy intensity domain. Relative V□O2peak values were not different between sexes (p=0.111). Males achieved ∼30% greater power outputs (p=0.002). In the moderate and heavy intensity domains, the relative amplitude of the phase II transition was not different between sexes for V□O2 (∼24 and ∼40% V□O2peak, p≥0.179) and HHb+Mb (∼20 and ∼32% ischemia, p≥0.193). Similarly, there were no sex differences in the time constants for V□O2 (∼28 s, p≥0.385) or HHb+Mb (∼10s, p≥0.274). In the heavy intensity domain, neither V□O2 (p≥0.686) or HHb+Mb (p≥0.432) slow component amplitudes were different between sexes. The oxidative response to moderate and heavy intensity exercise did not differ between males and females, suggesting similar dynamic responses of oxidative metabolism during intensity-matched exercise. New and Noteworthy This study demonstrated no sex differences in the oxidative response to moderate and heavy intensity cycling exercise. The change in oxygen uptake and deoxyhaemoglobin were modelled with mono-exponential curve fitting, which revealed no differences in the rate of oxidative energy provision between sexes. This provides insight into previously reported sex differences in the integrative response to exercise.


Introduction
The transition from rest to exercise involves an integrated response from the pulmonary, cardiovascular, and muscular systems to rapidly increase the supply and utilisation of oxygen for oxidative adenosine triphosphate (ATP) provision (Poole & Jones, 2012).The speed at which this process can occur can be quantified using pulmonary oxygen uptake (V ̇O2) kinetics, and is thought to be an influencing factor in high-intensity exercise performance (Burnley & Jones, 2007).The V ̇O2 response can be broken down into three phases, beginning with the initial cardio-dynamic phase (phase I, 10-20 s) which represents an increased venous return via the muscle pump effect, as well as increased pulmonary blood flow (Grassi et al., 1996).
Thereafter, increases in pulmonary V ̇O2 are considered to reflect increased muscle oxygen uptake in response to exercise (phase II), until the energy demand of exercise is met by oxidative phosphorylation and V ̇O2 reaches a steady state (Hughson et al., 2001).A steady state response is attainable within the moderate intensity domain, whereas in either heavy or severe intensity domains, a further rise in V ̇O2 is observed, termed the slow component.This three-phase response is ubiquitous in exercising humans; however, the biological characteristics of the individual can influence the rates at which they occur.
The time constant of phase II kinetics are considered to be a crucial determinant of the decrease in contractile function experienced by the exercising individual (Goulding et al., 2021).As oxidative phosphorylation does not immediately meet the demand for ATP, substrate-level phosphorylation is required (Burnley & Jones, 2007).Intuitively, the rate at which oxidative metabolism can be upregulated at the onset of exercise is inversely linked with the accumulation of deleterious metabolites such as hydrogen ions [H + ] and inorganic phosphate [Pi], as well as the depletion of phosphocreatine [PCr] stores, which all interfere with excitation-contraction coupling (Allen et al., 2008).Accordingly, Temesi et al. (2017) demonstrated a positive correlation between the time constant (τV ̇O2) of the phase II response and the decrease in quadriceps potentiated twitch force.Similarly, elite endurance athletes demonstrate faster τV ̇O2 (Koppo et al., 2004) and lesser declines in contractile function (Ducrocq et al., 2021) compared to untrained individuals when exercising at similar relative intensities.Collectively, this evidence suggests that those individuals able to meet the ATP demand with oxidative metabolism quicker, experience less contractile impairment during exercise.
A consistent finding in studies comparing males and females exercising at the same metabolic intensity is that females experience a lesser degree of contractile impairment of the kneeextensors (Ansdell et al., 2019;Ansdell et al., 2020a;Azevedo et al., 2021).Previously, this has been suggested to be a result of sex differences in skeletal muscle composition, whereby females consistently demonstrate a greater proportional area of type I fibres (Staron et al., 2000;Roepstorff et al., 2006).The consequences of this fibre type difference are multifactorial; for-instance, it is well established that type I fibres are more fatigue-resistant (Schiaffino & Reggiani, 2011).Additionally, female vastus lateralis capillary density is ~23% greater in females compared to males (Roepstorff et al., 2006), while females also demonstrate greater mitochondrial oxidative function and intrinsic respiratory rates than males of equivalent training status (Cardinale et al., 2018).One factor that remains unexplored is whether these physiological sex differences result in differences in the metabolic response to exercise.Conceivably, the superior aerobic phenotype of female skeletal muscle could imply that females might be able to meet the ATP demand of exercise through oxidative means faster than males, however this is a hypothesis that remains untested.
When the slow component is considered, the increase in V ̇O2 during constant-load exercise implies an impairment of efficiency and is likely an amalgamation of several concurrent physiological changes.Within skeletal muscle, the accumulation of metabolites and associated contractile dysfunction is linked with the loss of efficiency (Grassi et al., 2015).This dysfunction then leads to a compensatory recruitment of larger motor units that express predominantly type II muscle fibres (Krustrup et al., 2004).Of relevance here, is that female skeletal muscle has consistently been demonstrated to be more fatigue-resistant (Ansdell et al., 2019;Ansdell et al., 2020a), and require less additional motor unit recruitment in states of fatigue (Ansdell et al., 2017;Ansdell et al., 2019).This could represent a lesser requirement for additional oxygen uptake during constant load exercise in females, however, this remains unexplored.
Despite more aerobically-suited skeletal muscle, females have lower levels of haemoglobin (Murphy, 2014), which is thought to impair O2 carrying capacity during exercise (Harms et al., 1998).During exercise where O2 delivery and utilisation are both limiting factors (e.g., cycling), these factors are thought to counteract each other to enable comparable relative metabolic thresholds between the sexes (Ansdell et al., 2020b).To date, the only investigation to systematically investigate the oxidative adjustment at the onset of exercise between sexes did so during low intensity treadmill walking (Beltrame et al., 2017).Data from this study suggested faster O2 extraction in females, fitting with the notion that phase II V ̇O2 kinetics are influenced by intramuscular factors in healthy humans (Poole & Jones, 2012).Despite this, treadmill walking is not considered to be limited by O2 delivery, therefore the findings do not necessarily translate to high-intensity locomotor exercise, during which all levels of the O2 cascade are considered to be influential in determining metabolic responses to exercise (Goulding & Marwood, 2023).
Accordingly, the present study aimed to compare the kinetics of pulmonary V ̇O2 as well as muscle oxygen extraction, inferred from deoxyhaemoglobin and myoglobin (HHb+Mb) kinetics, in both sexes during moderate and heavy intensity exercise.It was hypothesised that females would demonstrate a smaller value for the phase II time constant (i.e., faster kinetics) for V ̇O2 and HHb+Mb at the onset of exercise, and a smaller slow component amplitude in the heavy intensity domain.

Ethical Approval
This study received institutional ethical approval from the Northumbria University Health and Life Sciences Research Ethics Committee (submission reference: 49189) and was conducted according to all aspects of the Declaration of Helsinki, apart from pre-registration in a database.Participants volunteered for the study and provided written informed consent.
Hormonal status was not an exclusion criterion or controlled for in this study.Female participants were tested in any phase of their menstrual cycle and there were no restrictions on hormonal contraceptive usage.This decision was based on evidence from (Mattu et al., 2020) who demonstrated no hormonal effects on V ̇O2 kinetics during cycling exercise.All participants were free from cardiovascular, respiratory, and neurological disease as well as musculoskeletal injury.

Experimental Design
All participants visited the laboratory on three occasions.During the first visit, participants were familiarised with the experimental procedures and completed two incremental exercise tests to quantify lactate threshold and peak oxygen uptake (V ̇O2peak).The second and third visits were identical and involved three six-minute bouts of moderate intensity exercise (80% of lactate threshold, LT), separated by six minutes of unloaded pedalling.Thereafter, a single bout of heavy intensity exercise (30% ∆LT -V ̇O2peak) was performed for 30 minutes.

Visit 1: Familiarisation & Incremental Testing
The first visit began with participants completing a screening questionnaire to ensure inclusion criteria were met.Thereafter, participants moved onto the cycle ergometer (Velotron, SRAM, Chicago, IL, USA) which was set up with the seat height aligned with the hip, and handlebar height set according to the participants' comfort, these measurements were recorded and replicated for subsequent trials.The breath-by-breath gas exchange mask was then placed over the participant's mouth and nose, and an air-tight seal was ensured before resting data was recorded.Following resting measures, participants completed five minutes of warm-up cycling at a light intensity (60 W) at a self-selected cadence between 70-100 rpm, before commencing an incremental exercise test.The first incremental exercise test began at 75 W and increased by 25 W every five minutes.At the end of each stage, a capillary blood sample was drawn from the participants' fingertip and immediately analysed to determine whole blood lactate concentration (mmol.L -1 , Biosen C-Line, EKF Diagnostics, Germany).The test was terminated once LT was identified as the first work rate at which a non-linear increase in blood lactate concentration was observed, after which, participants were provided 20 minutes of passive rest.
Next, participants began the second incremental test with five minutes of warm-up cycling at a light intensity (60 W) at the same self-selected cadence as before.Thereafter, a ramp test beginning at 75 W commenced, with power output increasing 1 W every 2.4 seconds.This test was terminated at volitional exhaustion, defined as cadence falling >10 rpm for five seconds.Strong verbal encouragement was provided to participants throughout.A final blood lactate sample was drawn immediately after volitional exertion.The greatest 30 second average V ̇O2 value was used to quantify V ̇O2peak, whilst the final power output was used to quantify maximal ramp test power (Pmax).

Visits 2 & 3: Square-Wave Exercise Bouts
Visits two and three were identical, and performed with a minimum of 24 h between visits.The visits involved continuous sampling of pulmonary gas exchange and near infrared spectroscopy (NIRS) of the vastus lateralis.Trials commenced with participants performing three minutes of unloaded pedalling on the cycle ergometer.Thereafter, participants performed three repetitions of six-minute cycling bouts at 80% of LT (moderate intensity exercise), interspersed with six minutes of unloaded pedalling.Following this, participants cycled for 30 minutes at a work rate 30% between the LT and V ̇O2peak (30%∆, heavy intensity exercise).Exercise intensity was altered abruptly in a 'square-wave' fashion for each repetition.
Immediately following all exercise, participants were laid supine on a physiotherapy table, and an automatic personalised tourniquet system for blood flow restriction (Delfi Medical Innovations Inc., Vancouver BC, Canada) was placed around the thigh, proximal to the NIRS optode, and inflated for five minutes at 120% of limb occlusion pressure, in order to occlude blood flow.This system automatically measures limb occlusion pressure, defined as the minimum pressure required for complete restriction of arterial blood flow in a limb, and maintains the pressure during inflation to ensure consistent occlusion.Following this, pressure in the cuff was released and the hyperaemic response measured (see Near Infrared Spectroscopy).This protocol is termed 'physiological calibration' (Barstow, 2019), and allows all NIRS data to be expressed as a % of an individual's physiological minimum and maximum values.Physiological calibration negates any potential influence of adipose tissue thickness on NIRS data (Ryan et al., 2012).

Pulmonary Gas Exchange
During all visits, expired gas was analysed breath-by-breath using an online system (Vyntus CPX, Jaeger, CareFusion, Germany).Oxygen (O2) and carbon dioxide (CO2) concentrations were quantified via a paramagnetic chemical fuel cell and non-dispersive infrared cell respectively.Before each test, the analysers were calibrated using ambient air and a gas of known O2 (14.00%) and CO2 (4.97%) concentrations.Ventilatory volumes were inferred from measurement of gas flow using a digital turbine transducer (volume 0 to 10 L, resolution 3 mL, flow 0 to 15 L•s -1 ) and calibrated prior to each test (Hans Rudolph Inc. Kansas City, USA).

Near Infrared Spectroscopy
A multi-distance, continuous-wave, single channel NIRS (NIRO-200NX, Hamamatsu) was used to evaluate changes in vastus lateralis muscle deoxyhaemoglobin and myoglobin (HHb+Mb) concentrations, sampled at a rate of 5 Hz.The light-emitting probe comprises of light emitting diodes operating at three wavelengths (735, 810, and 850 nm).The probe was placed on the vastus lateralis, 20 cm above the fibular head.Optodes were held in place by an elasticised bandage and covered by an opaque, dark material to avoid motion and ambient light influences.

Data Analysis V ̇O2 Kinetics
The breath by breath data was manually filtered to remove outlying breaths, defined as breaths deviating more than 500 ml.min -1 from the mean value from the preceding five breaths.
Thereafter, breath by breath data was linearly interpolated to provide second-by-second values.The multiple repetitions of the square-wave exercise bouts were then averaged, and V ̇O2 responses were time aligned to the onset of exercise.Data from the onset of the transition to 20 s was removed, then the resultant data was modelled with a monoexponential curve, including data from -60 to 360 seconds (moderate) or -60 to 120 seconds (heavy), with the following equation: Where V ̇O2(t) is the V ̇O2 at time t; V ̇O2(b) is the baseline V ̇O2 measured in the 60 s preceding the transition in work rate; and Ap, TDp, and τp are the amplitude, time delay, and the time constant of the phase II response, respectively (Rossiter et al., 2001).For exercise in the heavy intensity domain, the amplitude of the V ̇O2 slow component was determined by subtracting the phase II amplitude from the highest 30 s average of V ̇O2 during the 30 min bout.To facilitate comparisons between sexes, amplitudes were also normalised to each individual's V ̇O2peak as well as being presented in L.min -1 .

Deoxyhaemoglobin Kinetics
Prior to curve fitting, data from NIRS were normalised to the minimum values during, and the maximum values following the five minute arterial occlusion (Ryan et al., 2012), then averaged into 1 s and 5 s bins.The multiple repetitions of the square-wave exercise bouts were then averaged, and HHb+Mb responses were time aligned to the onset of exercise.The TD for the HHb+Mb response was determined using the 1 s averaged data as the time between exercise onset and the first point at which HHb+Mb signal started to systematically increase.This was performed for each transition individually, with all TDs averaged to provide a single value.The 5 s averaged data was then modelled with a monoexponential curve in the same manner as V ̇O2 data, including data up to 90 s after the transition (Murias et al., 2010).

Statistical Analysis
Data are presented as mean ± SD within the text and figures.Normal distribution of data was confirmed with the Shapiro-Wilk test.As all variables had normally distributed data, males and females were compared with independent samples t tests.The significance level for all statistical tests was set at p < 0.05.

Incremental Exercise Testing
Anthropometric data and outcome variables from the two incremental exercise tests performed in the first visit are presented in Table 1.As expected, males had a greater stature and body mass than females (p ≤ 0.006) as well as a greater absolute V ̇O2peak (mean difference: 39%, p = 0.002).However, when V ̇O2peak was expressed relative to body mass, no sex difference was observed (mean difference: 14%, p = 0.111).Males also exercised at greater power outputs than females, with Pmax and LT being ~30% greater in males (p ≤ 0.023), however when LT was expressed as a % of Pmax, no sex difference was observed (p = 0.373).This resulted in the power outputs for the moderate and heavy intensity bouts being greater in males compared to females (p ≤ 0.023).

V ̇O2 Kinetics
The transition from unloaded pedalling to moderate and heavy intensity cycling elicited an increase in V ̇O2 (see Figure 2), and the monoexponential curve used to describe the increase in V ̇O2 in males and females demonstrated excellent r 2 values (see Table 2).In absolute units (L.min -1 ) males experienced greater rises in V ̇O2 during the phase II kinetics (p ≤ 0.024), however when this was made relative to the individual (% V ̇O2peak) no sex differences were observed (p ≥ 0.179).Similarly, the V ̇O2 slow component amplitude was similar between sexes in relative units (p = 0.686).As visualised in Figure 1, there were no sex differences in τV ̇O2 in either the moderate (p = 0.385) or heavy (p = 0.633) intensity domains.

Deoxyhaemoglobin Kinetics
The transition from unloaded pedalling to moderate and heavy intensity cycling elicited an increase in HHb+Mb concentration (Figure 3), and the monoexponential curve used to describe the increase in HHb+Mb in males and females demonstrated excellent r 2 values (Table 3).One female's data had to be removed due to issues with the NIRS signal, resulting in n = 7 females being used for NIRS analyses.

Discussion
This study aimed to compare the kinetics of V ̇O2 and HHb+Mb during moderate and heavy intensity exercise in males and females.In contrast to the hypothesis, at the onset of exercise the phase II time constants (τ) for V ̇O2 and HHb+Mb were not different between the sexes, implying that both males and females were able to increase oxidative phosphorylation at comparable rates.In absolute units, males had larger amplitude increases than females, however when normalised to the individuals' maximum values, the rise in V ̇O2 and HHb+Mb were also equivalent between the sexes.Combined, these data demonstrate that the bioenergetic response to exercise is similar between sexes, which has implications for exercise prescription and provides mechanistic insight into previously observed sex differences in the integrative response to exercise.
Previous literature investigating sex differences in the onset kinetics of oxygen transport and utilisation conflicts with the present data, with Beltrame et al. (2017) demonstrating quicker τV ̇O2 and τHHb+Mb in females compared to males.One potential explanation for this discrepancy could be that Beltrame et al. utilised a treadmill walking task, compared to cycling.
In tasks where O2 delivery is not a limiting factor, females often outperform males.For instance, Ansdell et al. (2019) showed female knee-extensors had a greater relative critical torque than males during single-limb exercise.Whereas during cycling, where O2 delivery is a determinant of critical power (Goulding & Marwood, 2023), this metabolic threshold was not different between sexes (Ansdell et al., 2020a).Whilst consensus on whether O2 delivery does (Hughson et al., 2001) or does not (Grassi, 2001) limit τV ̇O2 has not been reached, it is conceivable that during tasks where O2 delivery and utilisation are both determinants in the metabolic response to exercise, the superior female skeletal muscle oxidative capacity (Cardinale et al., 2018) is counteracted by an inferior O2 carrying capacity (Murphy, 2014).
Within the present data, this balance manifests as a comparable τV ̇O2 in males and females, which agrees with data from do Nascimento Salvador et al. (2019), who demonstrated no sex difference in τV ̇O2 during a transition from unloaded pedalling to 'very heavy' (60% ∆) cycling exercise.
Data from incremental exercise suggests that the poorer O2 delivery in females results in a greater degree of O2 extraction to compensate (Murias et al., 2013).The present data contradicts this notion, as the amplitude of phase II HHb+Mb kinetics was similar between sexes (see Table 3).However, it is important to note that Murias et al. noted that this sex difference only occurred once incremental exercise exceeded the respiratory compensation point (i.e., the severe intensity domain), whereas the present study compared sexes in the moderate and heavy intensity domains.The lack of a sex difference in the phase II amplitude for HHb+Mb kinetics contradicts previously published NIRS data that demonstrated a smaller rise in HHb+Mb in females compared to males during constant-load exercise (Ansdell et al., 2020a).The crucial difference in methodologies employed between the previous study and the present study is the application of a 'physiological calibration' to negate the influence of adipose tissue thickness on NIRS signals (Ryan et al., 2012).Previously, the sex difference in the rise in HHb+Mb was suggested to reflect a lower oxygen cost of muscle contraction in female knee-extensors, however the present data, with more rigorous methodologies employed, refutes this.
The sex difference in muscle fibre type, whereby females demonstrate a greater proportional area of type I fibres, appears to have not influenced either V ̇O2 or HHb+Mb onset kinetics in the present study.This would concur with data from Barstow et al. (1996), who demonstrated no relationship between type I fibre percentage of the vastus lateralis and the time constant of phase II V ̇O2 kinetics.In contrast, Pringle et al. (2003) observed a negative correlation between type I fibre percentage and the phase II time constant in the heavy intensity domain only.Of note is that Pringle et al. included a wide range of participants with ~27 -85% type I fibres, and when groups were split into discrete groups of low and high fibre type percentages (mean difference: 25%), the high percentage group had faster phase II kinetics.The present study was not able to quantify the sex difference in muscle fibre typology, however, previous literature has observed a 5-13% difference in type I fibre percentage of the vastus lateralis (Simoneau & Bouchard, 1989;Staron et al., 2000;Roepstorff et al., 2006).Therefore, it could be the case that the sex difference in muscle fibre typology is not large enough to affect the phase II V ̇O2 or HHb+Mb kinetics.Muscle fibre typology has previously been demonstrated to affect the amplitude of the slow component within the heavy intensity domain, as individuals with a lower type I fibre percentage experience larger rises in V ̇O2 during constant-load exercise (Barstow et al., 1996;Pringle et al., 2003).It is suggested that the slow component is mechanistically underpinned by factors such as additional motor unit recruitment (Poole et al., 1994;Burnley et al., 2002) to compensate for fatigue-related changes in muscle metabolism.For instance, muscle PCr stores demonstrate a similar slow component in depletion during heavy intensity exercise (Rossiter et al., 2002).Given that female kneeextensors appears more fatigue-resistant and demonstrate lesser rises in the amplitude of surface electromyography during constant-load exercise (Ansdell et al., 2017;Ansdell et al., 2019;Ansdell et al., 2020a), we hypothesised that the relative amplitude of the slow component would be greater in males to reflect a greater rate of metabolic disturbance.
However, as is evident in Tables 2 and 3, no sex difference was observed in the relative slow component amplitude, implying that there was no difference in the metabolic response to constant-load exercise.
The lack of sex differences in either the phase II kinetics or slow component amplitude collectively suggest that the bioenergetic response to exercise was similar in males and females.Data on this topic is sparse, and due to the nature of methods such as magnetic resonance spectroscopy (MRS), limited to single-joint, isometric muscle contractions.
Previous literature using this technique to study muscle metabolic changes during a 60 s contraction of the dorsiflexors showed no sex difference in changes in PCr, Pi, or pH (Russ et al., 2005).Data from muscle biopsies of the vastus lateralis taken before and after repeated 30s cycling sprints suggested a greater preservation of ATP concentrations in females across a ~60 minute protocol (Esbjörnsson-Liljedahl et al., 2002); however the authors suggested that this was likely a result of sex differences in the 20 minute recovery periods, rather that metabolic differences during exercise.Accordingly, the same group observed no sex differences in the metabolic response to a single 30-second cycling sprint (Esbjörnsson-Liljedahl et al., 1999).Collectively, across multiple tasks and methodologies (MRS, biopsy and V ̇O2 kinetics), the data suggest that there is no sex difference in the bioenergetic response to high-intensity exercise.This information provides mechanistic insight into the sex differences in the integrative response to exercise.For instance, sex differences in fatigability have partly been attributed to a lesser accumulation of fatiguing metabolites (Hunter, 2014;Ansdell et al., 2020b).It is perhaps more accurate to suggest that previously observed sex differences in fatigue during intensity-matched exercise (Ansdell et al., 2020a;Azevedo et al., 2021) are more likely due to a greater fatigue-resistance of female muscle contractile apparatus, which experience similar degrees of metabolic stress as males.It is established that males and females differ in contractile properties such as calcium (Ca 2+ ) kinetics of the sarcoplasmic reticulum (Harmer et al., 2014), with lower Ca 2+ ATPase activity thought to permit a more fatigue-resistant skeletal muscle profile during equivalent exercise tasks (Hunter, 2014).
Therefore, the present study advances the contemporary understanding of sex differences in the integrative response to exercise and provides mechanistic insight into previously observed phenomena.
These data have applications across the spectrum of health and disease.For example, those prescribing steady state exercise to improve skeletal muscle performance in athletes or patients might not need to account for the sex of their participants (Gloeckl et al., 2022;Furrer et al., 2023).This statement should however, be caveated by the fact that evidence regarding the influence of sex on long-term adaptation to exercise is sparse (Ansdell et al., 2020b).
Indeed, one area for further exploration is the bioenergetic response to exercise within the severe intensity domain, where sex differences in fatigability have previously been observed (Ansdell et al., 2020a;Azevedo et al., 2021).The employment of complementary techniques to quantify O2 delivery and muscle fibre typology could also provide greater insight into the influence of sex on the O2 cascade in a variety of tasks.

Conclusion
The present study aimed to compare the oxygen extraction and uptake kinetics during moderate and heavy intensity cycling exercise.Contrary to our hypotheses, no sex differences were observed in either the phase II or slow component kinetics for V ̇O2 or HHb+Mb.The lack of sex difference implies that males and females experience similar bioenergetic responses to exercise, which provides mechanistic insight into previously observed phenomena such as the sex difference in fatigability.Furthermore, based on these data and others demonstrating no hormonal influences (Mattu et al., 2020), we suggest that there is no rationale for the exclusion of female participants in research investigating cardiopulmonary responses to exercise.

Figure 1 :
Figure 1: Visualisation of the monoexponential curve fitting procedures for a representative participant's data in the moderate intensity domain.Panel A describes the V ̇O2 data (1 Hz) and Panel B describes the HHb+Mb data (0.2 Hz).

Figure 2 :
Figure 2: Group mean V ̇O2 data from males (blue) and females (red) during moderate (Panel A) and heavy (Panel B) intensity transitions.The bold lines represent group means and the thin lines represent standard deviation.
τ: time constant, TD: time delay consumption As shown in Figure 3, the phase II amplitude of HHb+Mb increase in both intensity domains was similar between sexes (p ≥ 0.193).Similarly, there was no sex difference in the amplitude of the slow component in the heavy intensity domain (p = 0.432).The time constant for phase II HHb+Mb kinetics (τHHb+Mb) was also similar in males and females in both intensity domains (p ≥ 0.274).

Figure 3 :
Figure 3: Group mean HHb+Mb data from males (blue) and females (red) during moderate (Panel A) and heavy (Panel B) intensity transitions.The bold lines represent group means and the thin lines represent standard deviation.

Table 1 :
Anthropometric data and outcome variables from incremental exercise testing.

Table 2 :
Data from the monoexponential modelling of V ̇O2 kinetics during moderate and heavy intensity transitions.
SC: slow component, τ: time constant, TD: time delay, V ̇O2: rate of oxygen consumption

Table 3 :
Data from the monoexponential modelling of deoxyhaemoglobin kinetics during moderate and heavy intensity transitions.