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Do Sex Differences in Physiology Confer a Female Advantage in Ultra-Endurance Sport?

Authors:
  • Lundquist Institute at Harbor-UCLA Medical Center

Abstract and Figures

Ultra-endurance has been defined as any exercise bout that exceeds 6 h. A number of exceptional, record-breaking performances by female athletes in ultra-endurance sport has roused speculation that they might be predisposed to success in such events. Indeed, while the male-to-female performance gap in traditional endurance sport (e.g., marathon) remains at ~10%, the disparity in ultra-endurance competition has been reported as low as 4% despite the markedly lower number of female participants. Moreover, females generally outperform males in extreme-endurance swimming. The issue is complex, however, with many sports-specific considerations and caveats. This review summarizes the sex-based differences in physiological functions and draws attention to those which likely determine success in extreme exercise endeavors. The aim is to provide a balanced discussion of the female versus male predisposition to ultra-endurance sport. Herein, we discuss sex-based differences in muscle morphology and fatigability, respiratory-neuromechanical function, substrate utilization, oxygen utilization, gastrointestinal structure and function, and hormonal control. The literature indicates that while females exhibit numerous phenotypes that would be expected to confer an advantage in ultra-endurance competition (e.g., greater fatigue-resistance, greater substrate efficiency, and lower energetic requirements), they also exhibit several characteristics that unequivocally impinge on performance (e.g., lower O2-carrying capacity, increased prevalence of GI distress, and sex-hormone effects on cellular function/ injury risk). Crucially, the advantageous traits may only manifest as ergogenic in the extreme endurance events which, paradoxically, are the races that females less often contest. The title question should be revisited in the coming years when/if the number of female participants increases.
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Females in ultra-endurance sport
Do sex-differences in physiology confer a female advantage in ultra-
endurance sport?
Nicholas B. Tiller1, Kirsty J. Elliott-Sale2, Beat Knechtle3,4, Patrick B. Wilson5, Justin D.
Roberts6, Guillaume Y. Millet7,8
1Institute of Respiratory Medicine and Exercise Physiology, The Lundquist Institute for
Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
2Musculoskeletal Physiology Research Group, Sport, Health, and Performance Enhancement
Research Centre, School of Science and Technology, Nottingham Trent University,
Nottingham, United Kingdom.
3Medbase St. Gallen Am Vadianplatz, 9001 St. Gallen, Switzerland.
4Institute of Primary Care, University of Zurich, 8091 Zurich, Switzerland.
5Department of Human Movement Sciences, Old Dominion University, Norfolk, VA 23529,
USA
6Cambridge Centre for Sport and Exercise Sciences, School of Psychology and Sports
Science, Anglia Ruskin University, Cambridge, UK.
7Univ Lyon, UJM-Saint-Etienne, Inter-university Laboratory of Human Movement Biology, EA
7424, F-40023, Saint-Etienne, France.
8Institut Universitaire de France (IUF).
Correspondence:
Nicholas B. Tiller, Ph.D. | 1124 W. Carson Street, CDCRC Building, Torrance, CA 90502 |
Email: nicholas.tiller@lundquist.org | Tel: (+1) 310-980-8163 | Orchid: https://orcid.org/0000-
0001-8429-658X
Funding Disclosures/conflicts of interest: The authors declare no conflicts of interest and
do not have any financial disclosures.
Females in ultra-endurance sport
ABSTRACT
1
Ultra-endurance has been defined as any exercise bout that exceeds 6 h. A number of
2
exceptional, record-breaking performances by female athletes in ultra-endurance sport has
3
roused speculation that they might be predisposed to success in such events. Indeed, while
4
the male-to-female performance gap in traditional endurance sport (e.g., marathon) remains
5
at ~10%, the disparity in ultra-endurance competition has been reported as low as 4% despite
6
the markedly lower number of female participants. Moreover, females generally outperform
7
males in extreme-endurance swimming. The issue is complex, however, with many sports-
8
specific considerations and caveats. This review summarizes the sex-based differences in
9
physiological functions and draws attention to those which likely determine success in extreme
10
exercise endeavors. The aim is to provide a balanced discussion of the female versus male
11
predisposition to ultra-endurance sport. Herein, we discuss sex-based differences in muscle
12
morphology and fatigability, respiratory-neuromechanical function, substrate utilization,
13
oxygen utilization, gastrointestinal structure and function, and hormonal control. The literature
14
indicates that while females exhibit numerous phenotypes that would be expected to confer
15
an advantage in ultra-endurance competition (e.g., greater fatigue-resistance, greater
16
substrate efficiency, and lower energetic requirements), they also exhibit several
17
characteristics that unequivocally impinge on performance (e.g., lower O2-carrying capacity,
18
increased prevalence of GI distress, and sex-hormone effects on cellular function/ injury risk).
19
Crucially, the advantageous traits may only manifest as ergogenic in the extreme endurance
20
events which, paradoxically, are the races that females less often contest. The title question
21
should be revisited in the coming years when/if the number of female participants increases.
22
23
KEY POINTS
24
Females exhibit numerous physiological characteristics that would be expected to confer
25
an advantage in ultra-endurance competition. However, these traits may only manifest in
26
the extreme distance events that females less often contest
27
Several aspects of female physiology unequivocally inhibit performance making it unlikely
28
that the fastest females will surpass the fastest males in this sport
29
More direct physiological comparisons between male and female ultra-endurance
30
athletes are needed, particularly when/if female participation numbers increase
31
3
1.0 INTRODUCTION
32
A 1992 correspondence published in the journal Nature posed the question ‘Will women soon
33
outrun men? The analysis of distance-running records throughout the 1900s revealed an
34
essentially linear chronological increase in mean running velocity (𝑉
̅-slope), which was
35
considerably steeper in the women’s marathon relative to the men’s (~37.8 vs. 9.2 m[insert
36
raised dot]min1[insert raised dot]decade1) [1]. From this historical trend, Whipp and Ward
37
calculated that the intersection for the men’s and women’s marathon would occur in the late
38
1990s [1]. Although linear models have accurately described performance trends in ultra-
39
distance swimming [2], their utility predicting the gender gap in other sports has been
40
criticized on the basis that athletic adaptation and performance rarely, if ever, follow a linear
41
progression [3]. In 1989, using a non-linear (hyperbolic) model, Peronnet et al. calculated a
42
~10% disparity between male and female running performances, owing primarily to greater
43
maximal aerobic capacities (V
̇O2max) in the former. The model also predicted that males
44
would retain a biological distance-running advantage well into the future [4]. In point of fact, a
45
contemporary analysis of ~92,000 marathon finishes revealed a ~10% discrepancy between
46
non-elite male and female finish times (males = 4 h 28 min ± 53 min; females = 4 h 54 min ±
47
52 min; [5]). Thus, if females are to further diminish the endurance performance gap, it is most
48
likely in those contests which depend less on maximal aerobic capacities.
49
Participation in ultra-endurance sport (which has been defined as an exercise bout that
50
exceeds 6 h; [6]) has steadily increased over the last 30 years [7,8]. Success in these events
51
is determined by a complex interplay among various factors, including: oxidative capacity, the
52
energy cost of locomotion, substrate efficiency, fatigue-resistance and musculoskeletal
53
conditioning, race nutrition, gastrointestinal (GI) function, age/experience, pain management,
54
decision-making, and motivation and psychological disposition [915]. Furthermore, extreme
55
endurance exercise evokes considerable perturbations in respiratory, neuromuscular,
56
cardiovascular, digestive, and immune functions [12,13,16,17]. Accordingly, the most
57
successful competitors are those who not only exhibit the most diverse range of ergogenic
58
attributes, but who also best endure the high training volumes and extreme physiological strain
59
of participation.
60
Males and females compete side-by-side in ultra-endurance sport. Males are generally
61
faster than females over any given distance [2,18,19], but the data may be confounded by the
62
considerably lower number of female participants, particularly in the very long-distance races.
63
For instance, while modern marathons comprise fairly equal numbers of males and females
64
(54% and 46%, respectively; [20]), only 20% of ultra-marathon finishes since the 1970s have
65
been accomplished by females [7,18]. In ultra-distance cycling (Race Across America;
66
RAAM), females comprised only ~11% of finishers between 1982 - 2011 [19]. Notwithstanding,
67
some have calculated the performance gap to be as low as 4% in ultra-marathon [21], 6% in
68
4
ultra-distance open-water swimming [2], and negligible in cycling events of >200 miles [22]. In
69
rare instances (yet, more often in ultra-endurance events than in shorter races) females may
70
surpass their male counterparts [23]. Pertinently, the performance disparity between males
71
and females is generally smallest in those events of greatest duration [19,21,24], and in those
72
races with the highest number of female contestants [18,25]. At present, it is unclear what
73
physical/physiological attributes underpin female ultra-endurance performance, and whether
74
females might surpass males in this sport should their participation numbers equalize.
75
In recent years, these unknowns have been deliberated ad nauseam in the mainstream
76
media [2632], but while each publication has argued that females may outperform males in
77
ultra-endurance sport, most have only speculated on the mechanisms, or provided cursory
78
overviews of the empirical/published data. Thus, to address the title question, this paper will
79
review the sex-mediated differences in human physiological function, and draw attention to
80
those attributes which facilitate or impinge on female success in extreme duration exercise.
81
The aim is to provide a balanced discussion of the female versus male physiological
82
propensity for ultra-endurance sport.
83
84
1.1 Performance Trends
85
It has been argued that the disproportionate improvement in women’s endurance performance
86
in recent decades is attributable largely to sociocultural reform [33]. Women were prohibited
87
from competing at the first modern Olympic Games in 1896, whereas women comprised ~36%
88
of athletes at the Olympic Games a century later [34]. Thus, while it is unequivocal that
89
success in ultra-endurance competition has a strong biological component, the performance
90
trends may partially reflect factors such as greater participation and training opportunities. The
91
published competition data are complex and difficult to interpret owing to the variety of sports
92
examined, the considerable range in distances/durations, age-group categories, and varying
93
participation numbers. Nevertheless, to contextualize the forthcoming discussions on
94
physiological differences, what follows is a summary of the trends in male versus female ultra-
95
endurance performance.
96
When viewed in its entirety, the data show that males generally outperform females in
97
most sports, irrespective of distance, although the range in the performance disparity is large
98
(0 17%) and there are several notable exceptions. In an analysis of world-record running
99
performances ranging from 100 m to 200 km, males were on average 12.4% faster than
100
females [35]. Moreover, in 24-h ultra-marathon, a gap of ~17% was reported between the
101
annual fastest male and female finishers, ~11% for the annual 10 fastest, and ~14% for the
102
annual 100 fastest [24]. These data are likely confounded by the lower numbers of female
103
contestants. Studies that account for the participation disparity show a slightly diminished
104
performance gap. For example, in a multiple linear regression analysis of >93,000 ultra-
105
5
marathon finishes between 1975 and 2013 (across the range of distances), the sex difference
106
in performance was generally <10%, and the discrepancy in finish time was lowest in events
107
where females participated in greater numbers [18].
108
The data also indicate that the magnitude of the male-to-female performance
109
discrepancy is influenced by sport, distance, and age category. For instance, females have
110
reduced the performance gap to less than 10% in ultra-endurance (Ironman) triathlon, and to
111
just ~7% in the marathon stage of the event [36]. In terms of race distance, the sex difference
112
in running speed for the fastest ever women and men was higher in 50 km (~15%) relative to
113
100 km (5.0%) [37]. Moreover, in a study of ~13,000 cycling races, males were generally faster
114
than females in events of 100 and 200 miles, but no difference was found in the 400- and 500-
115
mile races [22]. Others make similar observations of a diminished performance disparity over
116
longer distances in endurance running [38]. From 1977 to 2012, the sex-difference in 24-hour
117
ultra-marathon was as low as 4.6 ± 0.5% for all women and men [24], with other reports of a
118
similar difference (~4% over 100 miles) in footraces up to 2017 [21]. Interestingly, although
119
the difference in running speed between the fastest males and females over 100 miles has
120
been reported as ~17% [39], the decrease in the sex difference observed for 50 and 100-mile
121
footraces suggests that females are reducing the performance gap [39]. With respect to age
122
categories, the difference in average cycling speed between men and women, across all race
123
distances, decreased with increasing age [22], and a recent ultra-marathon analysis similarly
124
showed that sex differences in performance were attenuated with increasing distance and age
125
[21].
126
To account for absolute differences in athlete ability, several studies have compared
127
ultra-marathon performances between males and females whose race times had been
128
matched over a given distance. One study concluded that equivalent performances were
129
retained in longer races, and two studies showed the opposite. Specifically, Hoffman
130
examined race results over three distances (50, 80, and 161-km) between 1990 and 2007,
131
finding that females and males who were time-matched for 50-km performed similarly in
132
running races of 80- and 161-km [40]. By contrast, a study by Bam et al. [23] compared the
133
fastest male and female running speeds over distances ranging from 5 90 km, and showed
134
that men were quicker over 5 42.2 km but not over 90 km (mean velocity = 2.8 vs. 2.9
135
m[insert raised dot]s1). Additionally, females with marathon times equivalent to males have
136
been shown to produce significantly quicker times in a 90-km ultra-marathon [41]. The notion
137
that female endurance runners may be closing the gap to males in longer distance/duration
138
races is supported by a recent unpublished analysis of trends in ultra-marathon running over
139
the last 23 y, which showed that females were 0.6% faster than males in races >195 miles
140
[42].
141
6
Finally, performances in ultra-distance swimming appear paradoxical to the trend,
142
showing a general female dominance. Indeed, while in 10-km open-water swimming the
143
annual fastest males were ~6% quicker than the fastest females [2], the top 20 females in
144
extreme-endurance competition (46 km) were ~12 14% faster than their male counterparts
145
[43]. This observation does not appear anomalous. A recent review assessing male and
146
female performances in several extreme-endurance, open-water swimming events, showed
147
that females were on average 0.06 km·h-1 faster than males [44]. Female dominance in ultra-
148
distance swimming, and the possible explanations, are discussed later.
149
When taken collectively, the data suggest that males generally outperform females in
150
most ultra-endurance events and over most distances, with the exception of extreme-distance
151
swimming. However, when scrutinizing the performance trends, the disparity is generally
152
smallest in very long-distance races, and when there is a relatively greater number of female
153
participants.
154
155
2.0 PHYSIOLOGICAL CONSIDERATIONS
156
The following discussion summarizes the sex-based differences in physiological functions,
157
specifically those which are mostly relevant to ultra-endurance performance. Much of the
158
literature has erroneously employed the terms “sex” and “gender” interchangeably. For clarity,
159
a brief description of these terms, and how they will be used henceforth, is warranted.
160
According to the National Institute of Health (NIH) [45] and the Canadian Institute of Health
161
Research (CIHR) [46], sex is a biological constituent which comprises the genetic
162
complement of chromosomes, including cellular and molecular differences [47]. By contrast,
163
gender has been described as a social (rather than a biological) construct which varies with
164
the roles, norms and values of a given society or era [48]. It has been suggested that because
165
sex is reflected physiologically, the terms male and female should be employed when
166
describing the sex of human subjects or when referring to other sex-related
167
biological/physiological factors [49]. Accordingly, the term sex-based differences and the
168
nouns male and female will be employed throughout this manuscript, except when referring
169
to pre-defined race categories (e.g., the women’s marathon).
170
171
2.1 Muscle Morphology and Fatigability
172
Fatigue can be defined as a disabling symptom in which physical and cognitive function is
173
limited by interactions between perceived fatigability and performance fatigability [50]. The
174
latter of these, also known as neuromuscular fatigue (NMF), results from diminished voluntary
175
activation (central component) and/or contractile function (peripheral component) [51]. We
176
presently focus on the sex-differences in acute NMF, and how it might mediate performance
177
in ultra-endurance competition. In controlled studies, females generally exhibit greater fatigue
178
7
resistance than males [52,53]. Furthermore, in a detailed review of sex differences in
179
fatigability, Hunter et al. made two specific observations: (i) females typically outperform males
180
during exercise performed at submaximal intensities; and (ii) the magnitude of the difference
181
is attenuated as contraction intensity increases [52].
182
As aforementioned, the sex-based differences in fatigue have been assessed in ultra-
183
marathons of up to 90 km, showing equivocal results [23,40,41]. However, a more
184
comprehensive exploration requires the objective assessment of fatigue using electrical
185
and/or magnetic nerve stimulation to artificially stimulate the locomotor muscles. Several
186
studies have made such assessments following 24-h treadmill running [54], field-based ultra-
187
marathon [55], and ultra-distance road cycling [56]. Nevertheless, a paucity of data in females
188
- owing to the low number of female ultra-endurance athletes - makes a direct male/female
189
comparison problematic. To the best of our knowledge, only one study has examined sex
190
differences in NMF following a bout of ultra-endurance exercise. Temesi et al. used
191
superimposed transcranial magnetic stimulation and peripheral nerve stimulation to assess
192
contractile fatigue in males and females matched by relative performance level [57]. After a
193
110-km ultra-marathon with a large cumulative ascent (Ultra-Trail du Mont-Blanc®, Alps) the
194
authors showed that: (i) males exhibited greater peripheral fatigue in the plantar flexors; (ii)
195
the magnitude of central fatigue in the plantar flexors and knee extensors was similar between
196
sexes; and (iii) there were no between-sex differences in changes in corticospinal excitability
197
or inhibition. Thus, while there were no overt differences in central fatigue between males and
198
females, the latter exhibited less peripheral fatigue following the race. There are several
199
mechanisms that may underpin the potential disparity in male/female muscle fatigability,
200
including sex-differences in muscle fiber type, muscle mass, and neuromuscular control [52]
201
(see Fig. 1).
202
2.1.1 Muscle fiber type. Human skeletal muscle fibers are classified as oxidative type-
203
I (slow-twitch), oxidative type-II and glycolytic type-II (fast-twitch) [58]. Type-I fibers are more
204
fatigue-resistant, partially owing to a greater myoglobin/mitochondrial content [59]. In an
205
analysis of mRNA in male and female lower-limbs, type-I fibers accounted for 44% of the total
206
biopsy area in females but only 36% in males [60]. Moreover, of the four myosin-heavy chains
207
(MyHC) which dominate gene expression in adult mammalian skeletal muscle, females
208
express ~35% more type-I MYH mRNA (those that are smaller and of a more oxidative
209
phenotype) when compared to males who express more type-II MYH mRNA (those that are
210
larger and richer in glycolytic enzymes) [61]. The greater proportion of type-I fibers in females
211
is associated with greater vasodilatory capacity [62] and capillarization [63]. Pertinent to the
212
present discussion, individual fibers are ‘typed’ by a particular isoform which determines
213
characteristics like contractile velocity and enzymatic makeup [59] (Table 1). Thus, the greater
214
relative distribution of slow-twitch fibers in females may partially explain their greater
215
8
contractile fatigue-resistance compared to males; although speculative, this offers a
216
compelling argument for a sex-based physiological predisposition for ultra-endurance
217
performance.
218
219
*Insert Table 1*
220
221
2.1.2 Muscle mass and strength. As is the case for age-related discrepancies in
222
muscle fatigue, muscle mass and strength may partially explain the sex-related differences.
223
Over 3,000 genes are differentially expressed in male versus female skeletal muscles (e.g.
224
GRB10 and ACVR2B) [61] and largely mediate sexual dimorphism in muscularity and
225
strength, in addition to interactions among sex-specific hormones (see 2.4 Endocrine
226
Function). It is the greater fiber diameter in males, rather than fiber number, that results in
227
muscle mass differences [64]. Pertinently, stronger muscles exert higher intramuscular
228
pressures onto the feed arteries, thereby restricting blood flow and rendering them more
229
fatigable during submaximal isometric exercise [52,65]. Subsequently, the attributes that
230
confer males an advantage in strength- and power-based sports, may be a potential
231
disadvantage in events of extreme endurance in which peripheral NMF is an important
232
determinant.
233
2.1.3 Central command. The greater relative fatigability observed in males has been
234
associated with greater central deficits in motor output [66,67], although it should be noted
235
that these findings were made largely during maximal efforts and may not extend to
236
submaximal tasks or sustained dynamic contractions. One explanation for the smaller deficits
237
in female central motor output is a lesser accumulation of anaerobic metabolites during
238
sustained, submaximal exercise (owing to more oxidative fibers), resulting in attenuated type-
239
III and IV muscle afferent feedback; i.e., less inhibitory inputs to the motoneuronal pool.
240
Although this may evoke less subsequent impairment of voluntary activation, this is considered
241
an unlikely mechanism to explain central fatigue in ultra-marathon [68]. Given that ultra-
242
marathons, particularly those contested on trail or mountainous terrain, encompass long
243
downhill sections and exacerbated eccentric contractions in lower-limb extensors, it is worth
244
examining sex differences in maximal force reduction after repeated lengthening contractions.
245
The literature on this topic is somewhat equivocal: animal studies suggest that females are
246
more resistant to muscle damage, while human studies suggest that females exhibit greater
247
force decline when compared to males following eccentric contractions [52]. Thus, no firm
248
conclusions can be made at this stage.
249
When interpreting the data on NMF, an important consideration is that the magnitude
250
and prevalence of fatigue is task-dependent; i.e., different neuromuscular sites will be stressed
251
when the requirements of the task are altered, and the stress on these sites can differ for
252
9
males and females [52]. As such, while females may exhibit less muscle fatigue than males
253
during maximal voluntary (isometric) contractions [69], such localized responses may be of
254
little relevance to dynamic, whole-body activities [70] including ultra-endurance exercise. The
255
greater muscle mass involved in such activities evokes greater demands on cardiorespiratory
256
and central nervous systems (e.g., greater afferent feedback and central drive), resulting in
257
lower end-exercise impairments in contractile function [71] and, more generally, different NMF
258
etiology compared to isolated exercises. In studies evaluating fatigue responses during
259
dynamic, submaximal exercise, sex differences in fatigability are less consistent [7274].
260
Accordingly, while females exhibit various characteristics that associate with better
261
fatigue resistance, supported by data from nerve stimulation studies [57], more research is
262
needed to compare the phenomenon directly between males and females during and following
263
ultra-endurance exercise. It is also likely that psychological/sociological factors (e.g.,
264
competitiveness and risk-taking) may be masking a true understanding of the sex-based
265
differences in performance and fatigability.
266
2.1.4 Respiratory muscle fatigue. Extending the fatigue data from the locomotor
267
muscles, numerous studies support the notion of better fatigue resistance in the female
268
respiratory muscles. The primary muscles of inspiration and expiration are the diaphragm and
269
major abdominals, respectively, which have concurrent roles in ventilating the lungs and
270
postural control. Respiratory muscle fatigue is a phenomenon whereby muscles attached to
271
the thoracic cage exhibit a reduced force-generating capacity relative to baseline, usually
272
following exhaustive exercise [7578]. In male versus female comparisons, resistive breathing
273
evoked a slower rate of inspiratory muscle fatigue in the latter, a finding that was independent
274
of muscle strength [79], although both groups exhibited a similar relative decline in maximal
275
inspiratory pressure (15%). In another study using cervical magnetic stimulation to artificially
276
activate the diaphragm before and after constant work-rate cycling, diaphragm fatigue
277
occurred in 11 out of 19 males (58%) and 8 out of 19 females (42%) [80]; however, contractile
278
function diminished to a greater extent in the males (31 vs. 21%). Collectively, these data point
279
to a female diaphragm that may be more fatigue-resistant, and this phenomenon might be
280
partially attributed to a greater reliance on accessory inspiratory muscles for ventilation during
281
dynamic exercise [81]. During high-intensity exercise, respiratory muscle fatigue may
282
compromise ventilatory capacity and endurance, exacerbate dyspnea (sensations of
283
breathlessness), and compromise limb-locomotor blood flow through “respiratory steal” [75].
284
However, its effects on ultra-endurance performance have not been adequately studied. Due
285
to the expiratory muscles’ important role in postural control [82], it has been speculated that
286
fatigue of the abdominals during ultra-marathon could place the runner at an increased risk of
287
injury due to a relative inability to sustain the rigors of competition, particularly on challenging
288
10
terrain [16]. A fatigue resistance in the respiratory muscles may, therefore, be advantageous
289
to ultra-marathon performance.
290
These observations should be balanced against the fact that, when compared to
291
males, females exhibit a greater resistive work of breathing at a given level ventilation during
292
exercise, attributed to innate sex-based differences in lung size and the diameter of conducting
293
airways [83]. As a result, females are more likely to exhibit expiratory flow limitation and
294
exerciseinduced arterial hypoxaemia [84]. The respiratory muscles of females also utilize a
295
greater relative percentage of V
̇O2 during exercise [85] which may, at least in part, diminish
296
oxygen economy (see 2.3 Oxygen Utilization).
297
2.1.5 Pacing strategies. A relative fatigue-resistance in female muscles has been
298
postulated to influence pacing strategies during racing. A comprehensive analysis of marathon
299
finish times in the United States revealed that females were 1.46-times more likely to maintain
300
their running pace (defined as a decrease in velocity of <10%) and 0.36-times as likely to
301
exhibit marked slowing (defined as a decrease of >30%) compared to males [5]; the mean
302
change in pace was 15.6% and 11.7% for male and females, respectively (p<0.001). Similar
303
observations of more even pacing strategies in female marathon runners - have been
304
reported elsewhere [86,87]. To our knowledge, only one study has assessed sex-differences
305
in pacing during ultra-endurance sport. In a 100-km ultra-marathon, Renfree et al. [88]
306
assessed the difference between male and female velocities at 10-km splits, finding that
307
females exhibited a slower relative starting speed but a higher finishing speed than males.
308
These findings suggest that females may pace better than their male counterparts during both
309
marathon and ultra-marathon running, certainly in the non-elite category.
310
The mechanisms underpinning the differences in pacing may extend beyond
311
differences in fatigue resistance. Males have been observed to slow significantly more than
312
females in short-distance running races (5 km), even when accounting for differences in
313
absolute finish times [89]. Although peripheral neuromuscular fatigue may still manifest over
314
such short distances, other aspects of localized fatigue such as glycogen depletion and
315
dehydration can be discounted in the population at large. The authors supposed, therefore,
316
that sex-differences in pacing may reflect disparities in decision making, such as over-
317
confidence, risk perception, or willingness to tolerate discomfort [89]. Compared to females,
318
males consistently overestimate their abilities in endurance sport, congruent with a greater
319
degree of slowing in the latter stages of racing [90]. Individuals with a greater proclivity for risk
320
appear to slow more considerably in distance running, even in regression models which
321
account for other psychological constructs, training, and experience [91]. Testosterone
322
concentrations have been associated with risk-taking behavior [92], and we speculate this as
323
an additional explanation. Accordingly, the sex differences in pacing may be attributable to
324
11
differences in physiology, decision making, or both [5], but likely play a crucial role in ultra-
325
endurance performance.
326
327
*Insert Fig. 1*
328
329
2.2 Substrate Utilization. Carbohydrate and fat provide the majority of energy to fuel muscle
330
metabolism during prolonged, submaximal exercise. Ultra-endurance exercise depends
331
heavily on oxidative metabolism for the efficient use of glucose and lipids, and there is a
332
substantial increase in the use of free fatty acids (FFA) with increasing race distance [93]. Fat
333
is also more energy dense than carbohydrate (containing 9 versus 4 kcal[insert raised
334
dot]g1), and improved substrate efficiency towards better lipid use exerts a glycogen-sparing
335
effect to prevent early-onset fatigue [94]. Thus, the ability to better mobilize and oxidize lipids
336
during ultra-endurance exercise would be considered advantageous and should be a focus of
337
the periodized ultra-endurance training program [12].
338
During exercise, muscle contractions signal the translocation of clusters of
339
differentiation-36 (CD36)/fatty acid binding protein to plasma and mitochondrial membranes,
340
thereby facilitating FFA transport and metabolism [95]. The overexpression of CD36 is
341
associated with a fourfold greater fatty acid oxidation by contracting muscle in mice [96]. In
342
humans, females exhibit greater mRNA expression of genes associated with fatty acid
343
metabolism, including CD36 [97,98]. Females are generally known to exhibit larger estrogen-
344
mediated reserves of intramyocellular lipids (IMCL) to support fuel demands for endurance
345
exercise, as well as a greater percentage of IMCL in contact with mitochondria following a
346
bout of endurance exercise when compared to males (indicative of greater capacity) [99].
347
These genotypes may be primarily responsible for the sex-based differences in lipid oxidation
348
rates.
349
A whole-room calorimeter study over a 24-h period showed that, irrespective of
350
physical activity levels, females exhibited 24 - 56% greater fat oxidation normalized to fat-fee
351
mass (FFM) when compared to males, and that the former had an enzymatic profile which
352
favored cellular β-oxidation [100]. Such differences are also apparent during submaximal
353
exercise. When exercising at a constant work-rate of ~65% V
̇O2max, Tarnopolsky et al. [101]
354
showed that males utilized 25% more muscle glycogen and exhibited significantly higher
355
respiratory exchange ratios than females, even when accounting for differences in diet,
356
training status, and hormonal status relating to female menstrual phase. Others have made
357
similar observations throughout the range of submaximal exercise intensities up to 85%
358
V
̇O2max [102], and that the exercise intensity eliciting the highest rate of fat oxidation occurs
359
at a higher percentage of V
̇O2max in females relative to males (58 versus 50% V
̇O2max) [102].
360
12
As a result, at any submaximal relative exercise intensity, the female fat oxidation curve is
361
rightward- and upward of the male curve [103]. This is a similar pattern one would expect to
362
see in a more highly-endurance-trained individual. Females may also exhibit greater metabolic
363
flexibility [104]. These collective differences may confer a metabolic advantage for females
364
during exercise of extreme duration.
365
There are important caveats to the interpretation of these data. Firstly, the metabolic
366
advantage of greater lipid oxidation in females may be partially negated by the obligatory
367
feeding that occurs during ultra-endurance races. In ultra-marathon, for example, runners may
368
need to consume between 200 400 kcal[insert raised dot]h1 from various food sources [12].
369
Relatively greater proportions of carbohydrate are recommended for ultra-distance triathlon
370
[105] which, in turn, may decrease the expression of genes involved in lipid metabolism for at
371
least 4 h [106]. Males oxidize more fat than females post-exercise when fasted, but the
372
difference is nullified when food is consumed to facilitate recovery [107]. Secondly, when
373
expressed in absolute terms, males generally exhibit greater lipid oxidation rates owing to
374
greater active muscle mass, lower fat mass, and greater overall energy expenditure during
375
exercise; thus, the female metabolic advantage may be limited to weight-dependent sports
376
(e.g., running, cycling, triathlon, etc.) in which lipid oxidation relative to FFM is pertinent.
377
Finally, the magnitude of the sexual dimorphism in lipid oxidation is small, and any potential
378
benefit should be framed in the context of ultra-endurance performance. For instance, while a
379
greater reliance on lipid metabolism by females may spare muscle glycogen during prolonged
380
exercise (e.g., marathon), this may not confer a considerable advantage during ultra-
381
endurance exercise which is characterized by lower relative work rates and slower rates of
382
glycogen depletion. Accordingly, we propose that the better substrate efficiency in females
383
may instead confer an advantage by attenuating caloric requirements (which may be
384
considerable during a 24 48 h event), and by reducing the need to consume exogenous
385
carbohydrate which has been shown to be a primary nutrition-related cause of GI distress (see
386
2.5 Gastrointestinal Distress).
387
388
2.3 Oxygen Utilization.
389
2.3.1 Maximal oxygen uptake (V
̇O2max). Maximal oxygen uptake sets the upper-limit
390
for aerobic metabolism and predicts most of the variance in middle-to-long distance endurance
391
events including running [108] and cycling [109]. A study in female marathon runners found
392
that V
̇O2max was the strongest predictor of performance (r = 0.74, p<0.01) explaining 56%
393
of the variance in finish time [110]. The superior performances of males compared to females
394
in standard endurance events may be largely explained by their higher V
̇O2max values, in
395
both trained [111] and untrained states [112].
396
13
It is generally accepted that a lower V
̇O2max in females is the result of sex-differences
397
in fat mass, and hemoglobin and hematocrit levels [113,114]. When V
̇O2max in males and
398
females was adjusted to FFM, some showed the sex differences to disappear [115] while
399
others found that males retained higher values [116]. Equalizing hemoglobin concentrations
400
between sexes via blood withdrawal also failed to completely equalize absolute VO2max [115],
401
thus suggesting that the sex-differences in aerobic capacity are likely attributable to a
402
combination of the aforementioned factors. The sex-mediated disparity in oxygen utilization
403
may also be determined at a cellular level (see 2.1.1 Muscle fiber type). For example, the rate
404
of oxidative phosphorylation is influenced by mitochondrial density, and while respiration in
405
isolated mitochondria is higher in female muscles compared to male [117], the latter tend to
406
have a higher expression of genes encoding mitochondrial proteins [61]. Importantly,
407
mitochondrial function, as well as membrane microviscosity, may depend to a large extent on
408
estrogen concentrations, with lowered levels associated with diminished mitochondrial
409
function [118] (See 2.4 Endocrine Function).
410
Pertinent to the present discussion is that although V
̇O2max is important in ultra-
411
marathon - correlating positively with the distance run in a timed laboratory simulation [9] - its
412
predictive power on performance diminishes with increasing race distance [119]. Indeed, when
413
females outperformed males in 90-km ultra-marathon, their performances were not attributed
414
to greater maximal aerobic capacity or running economy, but rather a greater fraction of
415
V
̇O2max sustained during racing [41]. In cycling, the peak power-to-weight ratio did not
416
correlate with bike finish time in an ultra-endurance triathlon [120] and, in Ironman triathlon
417
more broadly, factors such as hydration and energy homeostasis are considered the most
418
prominent predictors of performance [121]. Consequently, while maximal aerobic capacities
419
and work rates are generally lower in females, this may not represent the distinct disadvantage
420
in ultra-endurance competition that it does in the ‘standard’ endurance events like marathon
421
and Olympic-distance triathlon.
422
2.3.2 Oxygen economy and energy efficiency. Aside from V
̇O2max, several other
423
factors underpin middle-to-long distance endurance performance including velocity at V
̇O2max
424
(vV
̇O2max), lactate threshold, and oxygen economy/work efficiency [108,122124]. Although
425
the greater relative adiposity in females would be expected to diminish their oxygen economy
426
and work efficiency in weight-dependent sports, the data pertaining to sex-differences in these
427
characteristics are inconsistent. Some suggest that females tend to have poorer oxygen
428
economy at a given submaximal work rate [125,126] despite generally exhibiting a lower body
429
mass. By contrast, at various relative intensities of lactate threshold, Fletcher et al. found no
430
sex-mediated differences in running economy [127], and there are several reports of lower
431
(better) values for running economy in trained adult females versus trained adult males
432
[128,129]. In terms of gross energy efficiency - defined as the ratio of work accomplished to
433
14
total energy expended Yasuda et al. observed no sex-differences during cycling or arm-
434
cranking across a range of submaximal relative exercise intensities, even in males and
435
females who were matched for V
̇O2 at the gas exchange threshold [130]. Similar observations
436
of no sex-differences in energy efficiency have been made in cross-country skiing [131,132]
437
and in distance running when comparing elite male and female athletes [133,134].
438
Notwithstanding, the importance of oxygen economy/work efficiency in ultra-
439
endurance footraces has been contested. In a race with considerable cumulative ascent (that
440
prolonged exercise time), performance was not correlated with the energy cost of running, nor
441
with any post-race changes in running economy [135]. It has also been suggested that ultra-
442
marathon runners make tactical decisions (e.g., developing lower-body musculature, changing
443
stride frequencies, using robust footwear, using poles, etc.) that sacrifice running economy in
444
favor of mitigating the musculoskeletal damage and fatigue that more prominently impinge on
445
performance [10]. These strategies may be crucial for very long races, especially those
446
contested on mountainous and/or technical terrain that are associated with the greatest
447
muscle damage and peripheral fatigue.
448
Consequently, in weight-bearing endurance events of standard distance, the
449
male/female performance disparity may in large part be associated with differences in maximal
450
aerobic capacities and work rates. However, these attributes may be less important in ultra-
451
endurance sport, with performance therein underpinned by a complex interplay among
452
physiological, neuromuscular, biomechanical, and psychological factors. Fatigue-resistance,
453
substrate efficiency, mitigating muscle damage, and avoiding GI distress may be just as
454
relevant as aerobic capacities in the ultra-endurance model [10] (Fig. 2). Although speculative,
455
it may be that in this context female athletes exhibit a more complete complement of ergogenic
456
attributes.
457
Finally, given that females generally outperform males in swimming events of extreme
458
duration, the various factors that underpin ultra-distance swimming performance warrant
459
independent consideration. It is unlikely that female success in this sport is due to a superior
460
maximal oxygen uptake. Indeed, male open-water swimmers have been shown to exhibit
461
considerably higher V
̇O2max values than females (5.51 vs. 5.06 L.min-1, respectively) [136].
462
Moreover, despite the lactate thresholds occurring at speeds equivalent to 89 and 95%
463
V
̇O2max for males and females, respectively, the absolute V
̇O2 at lactate threshold was still
464
higher in males (4.90 vs. 4.81 L.min-1). Thus, female dominance in this sport is likely due to
465
factors other than oxygen utilization, and may instead relate to differences in the energy cost
466
of swimming, second to lower hydrodynamic resistance [137]. Indeed, although increases in
467
body mass have been shown to diminish oxygen economy during running [138], a higher fat
468
mass may be ergogenic in swimming. Fat has a lower density than muscle, and the greater
469
relative female adiposity - as well as important differences in adipose tissue distribution - likely
470
15
increases buoyancy and reduces drag [139]. The generally smaller body size of females
471
confers a further decrease in hydrodynamic drag, as do shorter lower limbs that result in a
472
more horizontal and streamlined position in the water [140,141]. Others speculate that female
473
success in ultra-distance swimming may also be associated with better pacing strategies [44].
474
Evidently, the extent to which a biological trait (e.g., lower body fat) can be considered
475
ergogenic, is determined by the specific demands and characteristics of the event in question.
476
477
*Insert Fig. 2*
478
479
2.4 Endocrine Function. Estrogens, progestogens, and androgens regulate human
480
reproductive function, but also act on non-reproductive tissues (e.g., muscle and bone) in
481
numerous ways that affect both health and exercise performance, and which are specific to
482
the respective male and female physiological environments [142]. However, the data are
483
extremely complex and often equivocal; as such, what follows is an abridged summary of the
484
intricate and interrelated functions of the sex hormones, and the extent to which they might
485
impact on the organism’s capacity for ultra-endurance exercise.
486
Testosterone is the primary male sex hormone which facilitates increases in muscle
487
strength and power [143] and decreases in body fat in a dose- and concentration-dependent
488
fashion [144]. It also appears to act on substrates in the brain to increase aggression and
489
competitiveness [145]. While not studied directly, higher testosterone concentrations may be
490
ergogenic in ultra-endurance competition: directly, due to its association with hemoglobin
491
concentrations [144], mitochondrial function [146], and lipid metabolism [147]; and indirectly,
492
by augmenting muscle protein synthesis and thereby facilitating recovery [148]. Importantly,
493
males exhibit a 30-fold increase in circulating testosterone from puberty, resulting in levels
494
that are 15 20 times higher in adult males than females [149]. This sexual dimorphism is
495
thought to largely account for the sex-based differences in athletic performance. Interestingly,
496
Storer et al. failed to observe a dose-dependent relationship between testosterone and muscle
497
fatigability; as such, the higher testosterone concentrations exhibited by male athletes may
498
not strictly regulate this aspect of exercise performance [143].
499
In females, estrogen and progesterone exhibit large fluctuations throughout the
500
monthly menstrual cycle [150] (Fig. 3). Estrogen augments muscle size, strength, and collagen
501
content, all of which are conducive to sporting performance [151] (for a review of the effects
502
of female sex hormones on the nervous system and muscle strength, see [152]).
503
Paradoxically, elevated estrogen concentrations reduce tendon and ligament stiffness [151],
504
which may impinge on ultra-endurance performance in two ways. First, there is a significant
505
positive correlation between tendon stiffness and running economy in females [127], such that
506
an estrogen-mediated decrease in stiffness might also deteriorate running economy. Second,
507
16
there are cyclical changes in anterior knee laxity throughout the menstrual cycle [153], and
508
while there is no consensus that female injury rates are necessarily hormone-mediated, it is
509
possible that fluctuating sex-hormone concentrations may partially explain the higher
510
prevalence of anterior cruciate ligament (ACL) ruptures in eumenorrheic females compared to
511
males [154]. Worthy of note, the knee is one of the most frequently injured body parts in ultra-
512
endurance athletes [155], and the risk may be greater when traversing technical/challenging
513
terrain that increases impact and shear forces through the lower limbs. A greater propensity
514
for injury would certainly attenuate the ability to both train and compete.
515
2.4.1 Estrogen and substrate metabolism. There are data to suggest that the lower
516
female dependence on carbohydrate during exercise (and, therefore, their superior relative
517
rates of lipid oxidation) may be estrogen-mediated. For instance, a study by Hamadeh et al.
518
showed that males who were supplemented with estrogen, exhibited an enhanced lipid
519
oxidation both at rest and during submaximal exercise [156]. Moreover, postprandial lipid
520
oxidation is lower in postmenopausal females (i.e., those with diminished estrogen
521
concentrations) [157], thereby supporting the notion that hypogonadism/estrogen deficiency
522
negatively impacts on fat oxidation. There are methodological difficulties in quantifying such
523
effects (e.g., differences in exercise modality, sex-hormone concentrations, and training status
524
of participants), but the paradoxical effects of estrogen and progesterone on exercise
525
metabolism further obfuscates the matter: estrogen appears to impede glucose kinetics in
526
females while progesterone appears to potentiate it [158]. It has also been suggested that
527
estrogen-progesterone interactions may influence substrate metabolism to a greater extent
528
than either hormone independently, and that the estrogen-to-progesterone ratio must be
529
sufficiently elevated to evoke metabolic changes (for review, see [159]).
530
The flux in lipid oxidation with estrogen concentrations may be partly due to changes
531
in mitochondrial function and membrane microviscosity, both of which associate with the
532
estrogen steroid hormone 17β-estradiol [118]. As a result, female ultra-endurance
533
performance would be expected to fluctuate congruent with monthly perturbations in estrogen,
534
even if only trivially. Some have reported that the sex-based discrepancy in ultra-marathon
535
performance begins to widen at around 45 y, after which female performances diminish [18];
536
this coincides with the increased body fat percentage, decreased lipid oxidation, and
537
decreased mitochondrial function occurring with the menopause and the associated reduction
538
in estrogen levels. As an aside, a secondary consequence of an estrogen-mediated
539
mitochondrial dysfunction is an increased hydrogen peroxide production [160], and decreased
540
levels of antioxidant genes [160,161]. This may be of particular relevance for ultra-endurance
541
events which exacerbate oxidative stress and reactive oxygen species in a linear fashion with
542
exercise duration [162], although it is yet to be decisively determined if alternations in redox
543
homeostasis affect performance in ultra-endurance sport.
544
17
2.4.2 Energy availability. An important consideration for the female ultra-endurance
545
athlete is the effect of energy availability on sex hormone concentrations, and the combined
546
manifestations. The foremost nutritional challenge facing ultra-endurance athletes is the ability
547
to meet their daily caloric demands [12]. Low energy availability resulting from high training
548
volumes and/or unintentional or deliberate restriction of dietary energy intake - can affect both
549
male [163] and female endurance athletes [164]. There is, however, less evidence to support
550
the magnitude of its effects on male health and performance. The consequences of low energy
551
availability likely affect females more profoundly and rapidly owing to its synergism with
552
menstrual dysfunction (i.e., amenorrhea) that, in turn, reduces bone health (as described in
553
the Female Athlete Triad [165]). Given that estrogen associates positively with bone mineral
554
density via osteoblast activity [166], females with diminished estrogen levels (e.g.,
555
amenorrheic athletes) are at an increased risk of stress fracture [167], and this may have
556
implications for the high-mileage running that characterizes ultra-marathon, ultra-distance
557
triathlon, and adventure racing. Even eumenorrheic females appear to be more susceptible
558
than males to adverse changes in bone health following short-term low energy availability
559
[168]. For a detailed summary of endocrine changes in the hypothalamic pituitary gonadal
560
axis, using markers of low energy availability in males and females, see Elliott-Sale et al. [169].
561
On balance, there is a wealth of literature on the effects of estrogen and progesterone
562
on female musculoskeletal, metabolic, and cellular function, and all such effects directly or
563
indirectly influence ultra-endurance performance. However, the data are confounded by large
564
inter- and intraindividual variability in sex hormone concentrations. From puberty to
565
menopause, female sex-hormone concentrations are in a constant state of flux: (i) across any
566
given menstrual cycle; (ii) as a result of perturbations in the menstrual cycle (e.g., anovulation);
567
(iii) during pregnancy; (iv) due to clinical conditions (e.g., polycystic ovarian syndrome); (v) as
568
a consequence of low energy availability and subsequent amenorrhea; and (vi) in response to
569
external supplementation (e.g., hormonal contraceptives which are used by approximately half
570
of elite female athletes [170]). As such, while ultra-endurance performance may not be
571
inhibited by the female sex hormones, per se, it is the perturbations in estrogen concentrations
572
manifesting across the lifespan that likely contribute to the male/female performance disparity.
573
More high-quality, well-controlled studies are needed to explore the effects of
574
endogenous/exogenous estrogen and progesterone on ultra-endurance performance.
575
576
*Insert Fig. 3*
577
578
2.5 Gastrointestinal Distress. Ultra-endurance exercise is associated with widespread
579
reporting of gastrointestinal symptoms [171173]. The most well-documented, performance-
580
altering GI disturbances are nausea/vomiting [174] and abdominal cramping [175,176],
581
18
although other symptoms include reflux, bloating, loose stools, and flatulence [177]. GI
582
distress is often cited as a reason for non-completion and/or attenuated performance,
583
particularly in single stage running races [178]. The mechanisms that underpin GI distress
584
during ultra-endurance exercise are complex and multi-faceted, but likely include impairments
585
to gut perfusion and neuroendocrine alterations [179]. Gastrointestinal symptoms may also be
586
triggered or exacerbated by aggressive and/or unaccustomed nutritional intake [180].
587
Certainly, a biological propensity for less frequent/severe GI distress, and/or a greater ability
588
to tolerate/mitigate the symptoms, would be considered ergogenic in ultra-endurance
589
competition.
590
2.5.1 Gut anatomy and physiology. To contextualize the forthcoming overview of sex
591
differences in the character and prevalence of GI distress during exercise, a brief discussion
592
of the general differences in gut structure and function is warranted. On average, the female
593
stomach is ~10% smaller than the male stomach [181] and may, therefore, be less capable of
594
gastric accommodation after consuming a given food volume [182]. As a result, females are
595
likely to exhibit greater postprandial fullness following a standardized feeding [183]. Whole-
596
gut and colonic transit times are longer in females when compared to males [184,185], and
597
females exhibit attenuated rates of gastric emptying [186] for both solid foods and fluids [187].
598
These latter findings may have important implications for fueling during prolonged exercise.
599
While the precise mechanisms for sex-differences in gastric emptying are unclear, it has been
600
hypothesized to be related to female sex-hormone effects on the gastrointestinal tract [187],
601
speculation which has been supported empirically only in rodent models [188]. There are data
602
on sex-differences in the gut microbiome that is thought to influence gut function and GI
603
symptoms [189], but most of this research is also from animal models which may not closely
604
reflect human physiology and behavior. Finally, there may also be sex-differences in gut
605
barrier function which has been speculated to play a role in the development of endotoxemia
606
(bacterial translocation into the blood), congruent with systemic inflammation and GI
607
symptoms [190]. This may be particularly relevant to the present discussion owing to the
608
positive association of endotoxemia biomarkers with the frequency and/or severity of GI
609
symptoms (particularly nausea) during ultra-endurance competition [191,192], although this is
610
not a universal finding [193]. To the authorsknowledge, sex differences in the vulnerability to
611
GI permeability and endotoxemia has not been systematically studied in ultra-endurance
612
exercise. However, in studies assessing the phenomenon in various resting conditions - via
613
the postprandial measurement of urine or blood levels of non-metabolizable sugars - gut
614
permeability was shown to be higher in males versus females [194196].
615
2.5.2 Symptomology. In population-based research, females report a higher frequency
616
of GI symptoms [197199], most commonly nausea, bloating, abdominal pain, and
617
constipation. While a greater prevalence of bloating and constipation in females may be due
618
19
to slower whole-gut and colonic transit times [184,185] - thereby contributing to greater
619
fermentation of dietary fiber and reabsorption of colonic water - the greater frequency of
620
nausea and abdominal pain may be associated with the onset of monthly menses in
621
individuals with eumenorrhea [200]. The observations of population-based studies generally
622
extend to those made during exercise, although the most informative data stem from research
623
in standard- as opposed to ultra-endurance competition [172,201203]. For example, in a
624
1984 survey of >700 marathon runners (85% male), females more commonly reported
625
symptoms of lower-GI distress (e.g., abdominal cramping, urge to defecate, diarrhea, bloody
626
defecation) [203]. While interesting, these data may be confounded by external factors (e.g.,
627
training experience), particularly given that years of training associates negatively with GI
628
symptoms [201]. A multivariate analysis of >1,200 endurance runners contesting races from
629
10 - 42 km also observed female sex to independently associate with increased prevalence of
630
GI complaints [201].
631
Notwithstanding, reports on sex-differences in GI distress during ultra-endurance
632
exercise are sparse. This can be attributed to lower female participation numbers and/or the
633
failure of most studies to differentiate GI distress prevalence by sex (e.g., [204,205]). In reports
634
that do make such distinctions, the data are less equivocal than for marathon. For instance,
635
there was little difference in the frequency and/or severity of most GI symptoms between
636
males and females during a 161-km ultra-marathon, with the exception of stomach bloating
637
which was more common in females [173]. Furthermore, over a similar distance, Stuempfle et
638
al. [191] reported no sex-mediated differences in nausea. When interpreting these data it
639
should be noted that neither study was specifically designed to assess sex-differences in GI
640
distress. In addition, both had a relatively low number of female participants, congruent with
641
the trend in ultra-endurance participation numbers. Thus, more research is warranted to
642
establish if the greater female propensity for GI distress extends to ultra-endurance
643
competition. Such a predisposition would negatively impact on an athlete’s ability to perform:
644
directly, due to pain and discomfort associated with lower-GI issues; and/or indirectly owing to
645
the difficulty of adequately fueling and hydrating.
646
2.5.3 Gut training. There is a growing interest in the concept of “training the gut” to
647
enhance the digestion of, and tolerance to, exogenous carbohydrate and fluid intake during
648
prolonged exercise. Such gut-training strategies are premised on the notion that high intakes
649
of carbohydrate (at rest or during exercise) will increase the density and activity of intestinal
650
glucose transports, thereby facilitating greater carbohydrate absorption and oxidation during
651
exercise [206]. These adaptations would be expected to mitigate the magnitude and
652
prevalence of GI distress during exercise. Gut training may be particularly relevant for ultra-
653
endurance competition given the large energetic demands and nutritional intakes associated
654
with training and racing [12]. Although anecdotal accounts of speed eaters” show the GI tract
655
20
to be highly adaptable [207], studies focused on the physiological and ergogenic appraisal of
656
gut-training strategies are still relatively scarce. One such study on a group of trained cyclists
657
and triathletes showed that a 28-d period of aggressive in-task fueling facilitated metabolic
658
adaptations (including increased exogenous carbohydrate oxidation during exercise) [208].
659
Others report that gut-training evoked reductions in GI symptoms and carbohydrate
660
malabsorption [209]. Nevertheless, the ergogenic effects of these strategies are mixed. The
661
two studies that comprised mixed-sex cohorts showed that females were more likely to report
662
GI symptoms during exercise when challenged with high rates of carbohydrate intake (90 g.h-
663
1) [209,210]. Furthermore, following two weeks of gut training in a small group (5 male, 5
664
female), the magnitude of the reduction in GI symptoms associated with in-task fueling was
665
lower in females relative to males [209]. Clearly, more data from larger samples are needed
666
in order to make more robust direct comparisons.
667
Females report being less accustomed to feeding during exercise when compared to
668
males [209]; therefore, it may be that integrating gut-training into periodized race preparation
669
may still be beneficial for the female athlete, particularly if they intend on aggressively fueling
670
with carbohydrate when racing. Perhaps the more relevant consideration is whether high rates
671
of carbohydrate ingestion (>60 g·h-1) - after a period of gut training - are likely to enhance ultra-
672
endurance performance for the female athlete when compared to more modest intakes (30 -
673
60 g·h-1) that are less likely to provoke GI symptoms in the first instance. This may be
674
particularly relevant in light of a recent study showing the feasibility of very high rates of
675
carbohydrate intake (120 g·h-1) in elite ultra-marathon runners who had previously undergone
676
nutritional and gut-training [211]. Rather predictably, the study comprised an exclusively male
677
cohort, and so whether such nutritional strategies are viable, or even possible, in female ultra-
678
marathon runners remains unclear. Given the aforementioned sex-differences in the rates of
679
gastric emptying and gut transit time, not to mention the existing data in endurance events of
680
shorter duration, it is likely that females may be somewhat less tolerant to such high rates of
681
intake. Moreover, the appropriate gut-training strategy is almost certainly to differ between
682
sexes.
683
A final consideration is the extent to which sex-differences in substrate efficiency and
684
body mass impact on race nutrition and the propensity for nutrition-induced GI distress. Owing
685
to their greater dependence on lipid oxidation during exercise (see 2.2 Substrate Utilization),
686
female endurance athletes may be less susceptible to glycogen degradation [212] and its
687
debilitating effects. Better substrate efficiency may also explain, at least in part, the lower
688
carbohydrate and general caloric intakes of females during ultra-endurance competition
689
[213,214]. Lower caloric intakes in females is also a factor of a smaller average body size,
690
smaller stomach, and possibly deliberate strategies aimed at mitigating GI symptoms. A lesser
691
need to consume exogenous carbohydrate to sustain a given work rate may be pertinent given
692
21
that the primary nutritional cause of GI distress during endurance exercise is the high intake
693
of carbohydrate, particularly hyperosmolar solutions [171]. The lower average body mass of
694
the female athlete may also explain their lower sweat rates at both absolute and relative work
695
rates [215]. This may, in turn, attenuate their fluid requirements during exercise, and decrease
696
the need to ingest high volumes that provoke GI distress. Therefore, while it may be that
697
female athletes are more prone to GI distress during exercise, it remains unclear whether this
698
extends to the durations typical of ultra-endurance and whether this might be partially
699
mitigated by their reduced caloric, carbohydrate, and fluid requirements. More studies are
700
needed to further explore this complex issue in the context of ultra-endurance performance.
701
702
3.0 BEYOND PHYSIOLOGY
703
There are several considerations that should accompany the discussions presented in this
704
paper. Firstly, this review has not discussed sex differences in all aspects of human
705
physiology, just those that are prominent predicters of ultra-endurance performance. That
706
said, in the interest of concision, there were several omissions including sex-differences in
707
thermoregulation [215], the effects of sleep deprivation [216], and the responses to nutritional
708
and training regimens [99]. Furthermore, while physiology is certainly a crucial determinant of
709
performance in ultra-endurance sport, we did not explore sex-differences in psychological
710
attributes that are arguably the greatest predictors of success in such events. At the least, we
711
would expect there to be sex-based differences in sporting motivation, competitiveness, and
712
risk taking [217]; as such, these psychological characteristics and their impact on the
713
propensity for ultra-endurance performance warrant further consideration.
714
Second, we earlier reviewed the male and female performance trends in a number of
715
ultra-distance sports, finding that the sex-based disparity was generally smallest in the events
716
of longest distance/duration and when females were represented more numerously. It has
717
been postulated that females may have lesser interest in competitive sports, and that the lower
718
number of athletes may not simply be due to sociocultural factors and fewer opportunities
719
[217]. Thus, there may exist a degree of selection bias, in that those females competing in the
720
extreme endurance events may be self-selecting as the fittest, strongest, and most motivated
721
among their sex. This might, in turn, lead to a skewed interpretation of the performance trends.
722
Accordingly, direct comparisons remain problematic until participation numbers equalize.
723
Finally, this review discussed numerous physiological attributes that may facilitate or
724
impede ultra-endurance performance. However, ultra-endurance events are highly variable in
725
terms of the exercise mode (e.g., running, cycling, swimming, adventure racing, etc.),
726
distance/duration, cumulative ascent/descent, terrain, and environmental extremes. It stands
727
to reason, therefore, that the physical/physiological attributes of individuals will be differentially
728
suited to different events. For instance, those contested on relatively flat, non-technical terrain
729
22
may favor athletes with larger maximal aerobic capacities and higher ventilatory thresholds,
730
whereas individuals with smaller frames and greater peripheral conditioning/robustness may
731
excel on technical terrain with downhill running components. As such, the nuances of each
732
event should be considered before arbitrarily designating a physical/physiological trait as
733
advantageous. Certainly, optimal performances will stem from matching individual
734
physiological profiles with individual race types.
735
736
4.0 CONCLUSION
737
When compared to their male counterparts, females exhibit numerous phenotypes that would
738
be expected to confer an advantage in ultra- and/or extreme-endurance competition. These
739
include a greater relative distribution of type-I (oxidative) fibers, greater fatigue-resistance
740
owing to neuromuscular, contractile, and metabolic factors, better substrate efficiency (higher
741
rates of lipid oxidation), lower energetic requirements, and higher subcutaneous body fat
742
which is likely beneficial in ultra-distance swimming. The data also suggest that females may
743
be better at pacing. These factors may explain why the sex-mediated performance disparity
744
is lowest in ultra-endurance sport than in any other. However, there are two caveats. First,
745
these collective traits may only manifest as ergogenic in the extreme endurance events which,
746
paradoxically, are the races that females less-often contest. Second, several important
747
characteristics of female physiology - including mechanical-ventilatory function, O2-carrying
748
capacity, prevalence of GI distress, and sex-hormone effects on both cellular function and
749
injury risk unequivocally impinge on female ultra-endurance performance, making it unlikely
750
that the fastest females will ever outperform the fastest males (ultra-distance swimming a
751
notable exception). In light of these caveats and the numerous considerations proposed in our
752
discussion, we urge a skeptical approach to cursory or simplified answers to this complex
753
question. We encourage more research into the physiological determinants of ultra-endurance
754
sport, as well as more direct comparisons of male versus female ultra-endurance physiology,
755
particularly when/if the number of female participants increases.
756
757
Acknowledgements
758
The authors wish to thank Professor Sue Ward (University of Leeds, UK) for her guidance in
759
developing the manuscript.
760
761
Declarations
762
Funding. No funding was received in developing this manuscript. Nicholas B. Tiller is
763
funded by a postdoctoral fellowship from the Tobacco-Related Disease Research Program
764
(TRDRP; award no. T31FT1692).
765
23
Conflicts of interest. Nicholas B. Tiller, Kirsty J. Elliott-Sale, Beat Knechtle, Patrick B.
766
Wilson, Justin D. Roberts and Guillaume Y. Millet declare that they have no conflicts of interest
767
relevant to the content of this review.
768
Authors’ contributions. NBT, GYM, KJES, and PBW drafted the manuscript; JDR and
769
BK provided additional comments and contributions; all authors approved the final version
770
771
24
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TABLES AND FIGURES
1523
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Table 1. Comparison of contractile and metabolic properties of the various skeletal muscle
1525
fiber types. All values are expressed as a fold-change relative to ST oxidative fibers [59]. ST
1526
= slow-twitch; FT = fast-twitch.
1527
1528
Fig. 1. Proposed physiological mechanisms underpinning the sex difference in muscle fatigue,
1529
these include differences in: 1) motor neuron activation; 2) contractile function of the activated
1530
fibers; and 3) the magnitude of metabolites accumulating that interfere with contractile
1531
function. Mechanisms are stipulated with large arrows. Black boxes indicate processes within
1532
the muscle, white boxes are processes in the nervous system, and the grey are hormonal/
1533
sympathetic actions. Negative signs indicate physiological variables/processes that are
1534
exhibited less by females; positive signs indicate physiological variables/processes that are
1535
exhibited more by females Reproduced from Hunter [52], with permission.
1536
1537
Fig. 2. Determinants of performance in ultra-endurance events, and the compromise between
1538
energy cost and lower-limb tissue damage (dashed lines). The principal determinants are in
1539
bold. Reproduced from Millet et al [10], with permission. GI = gastrointestinal; NM =
1540
neuromuscular; V
̇O2max = maximal oxygen uptake.
1541
1542
Fig. 3. Schematic showing the hormonal fluctuations across an idealized 28-d menstrual cycle,
1543
with ovulation occurring at day 14 [150].
1544
... Female competitors started slower in the race and increased running speed towards the end than male competitors [17]. A potential explanation could be that women pace differently compared to men considering their strength and physiological differences [47]. ...
... The stringent selection criteria probably led to only the best women and men entering the race and finishing. A recent review assumed that women could have an advantage in ultra-endurance compared to men [47]. ...
... Firstly, the small sample size of women (13.2%) makes generalising the information difficult. However, women generally account for ~ 10% in ultra-marathon running [47]. A further limitation is the missing of split times for earlier years and additional race checkpoints, which were, however, not available from the race results. ...
Article
Full-text available
Background Pacing has been investigated in different kinds of ultra-marathon races, but not in one of the toughest ultra-marathons in the world, the ‘Spartathlon’. Objective The aim of the present study was to analyse the pacing of female and male finishers competing in the ‘Spartathlon’ in regards to their age and performance groups. Methods A total of 2598 runners (2255 men and 343 women) finishing ‘Spartathlon’ between 2011 and 2019 were analysed. We selected 10 checkpoints with split times corresponding to important race sections. Average running speed was calculated for each participant and the average checkpoint running speed for each of the 10 race checkpoints. Furthermore, to assess the pacing strategy of each runner, the percentage of change in checkpoint speed (CCS) in relation to the average race speed was calculated (for each of 10 checkpoints). Finally, the average change in checkpoint speed (ACCS) was calculated for each participant as a mean of the 10 CCSs. Results Both women and men slowed down through the first 7 checkpoints but increased running speed towards the end of the race (reverse J-shaped pacing). Men showed a significantly greater CCS in the first and second checkpoint ( p < 0.01 and p < 0.05, respectively), whereas women showed a more significant change in CCS in the last checkpoint ( p < 0.05). Furthermore, age and sex showed no effect on ACCS, whereas ACCS differed between the performance groups. In particular, the slowest and the fastest runners showed a more minor change in ACCS than the two medium groups of both men and women ( p < 0.01). Conclusions In summary, successful finishers in ‘Spartathlon’ showed a reverse J-shaped pacing curve with a decrease in running speed from the start to the 7th checkpoint and an increase in running speed thereafter. This strategy was most probably due to the profile of the race course. Men showed a more significant change in checkpoint speed in the first two checkpoints, whereas women showed a more substantial change in the last checkpoint. Age and sex did not affect average checkpoint speed, whereas this speed was different between the different performance groups. The slowest and the fastest runners showed fewer changes in average checkpoint speed than the two medium groups in men and women.
... com/ stateof-ultra-runni ng), whereas, based on unpublished data, the sex difference in performance appears constant with increasing distance when considering the first males and the first females. Second, the percentage of female participation in these events is much lower than reported for males, being as low as 10% in some events, which may confound the performance differences in the very long-distance races [19]. Third, many of the races above the marathon distance are trail running events. ...
... constant doses of oestrogen and progestogen for 21 days), Giacomoni and Falgairette [118] reported an improved RE at low intensities (7-9 km h −1 ) only during the late period of oral contraceptive use (i.e. days [19][20][21]. In this regard, Dokumacı and Hazır [119] recently reported an improved RE (i.e. in terms of energy or oxygen cost) in the luteal phase compared to the follicular phase in female competitive athletes with no oral contraceptives. ...
Article
Full-text available
In recent years, there has been a significant expansion in female participation in endurance (road and trail) running. The often reported sex differences in maximal oxygen uptake (VO2max) are not the only differences between sexes during prolonged running. The aim of this narrative review was thus to discuss sex differences in running biomechanics, economy (both in fatigue and non-fatigue conditions), substrate utilization, muscle tissue characteristics (including ultrastructural muscle damage), neuromuscular fatigue, thermoregulation and pacing strategies. Although males and females do not differ in terms of running economy or endurance (i.e. percentage VO2max sustained), sex-specificities exist in running biomechanics (e.g. females have greater non-sagittal hip and knee joint motion compared to males) that can be partly explained by anatomical (e.g. wider pelvis, larger femur-tibia angle, shorter lower limb length relative to total height in females) differences. Compared to males, females also show greater proportional area of type I fibres, are more able to use fatty acids and preserve carbohydrates during prolonged exercise, demonstrate a more even pacing strategy and less fatigue following endurance running exercise. These differences confer an advantage to females in ultra-endurance performance, but other factors (e.g. lower O2 carrying capacity, greater body fat percentage) counterbalance these potential advantages, making females outperforming males a rare exception. The present literature review also highlights the lack of sex comparison in studies investigating running biomechanics in fatigue conditions and during the recovery process.
... The importance of sex-related comparison in sports nutrition topics has been widely discussed over the past decade [1]. It is well-established that the nutritional requirements of athletes are potentially affected by physical and physiological differences between males and females [2,3]. These sex-based differences seem to be more predominant in ultra-endurance athletes who are recommended to pay superior attention to their specific nutritional needs due to the prolonged training/racing activities [4,5]. ...
Article
Full-text available
Sex has been recognized to be an important indicator of physiological, psychological, and nutritional characteristics among endurance athletes. However, there are limited data addressing sex-based differences in dietary behaviors of distance runners. The aim of the present study is to explore the sex-specific differences in dietary intake of female and male distance runners competing at >10-km distances. From the initial number of 317 participants, 211 endurance runners (121 females and 90 males) were selected as the final sample after a multi-level data clearance. Participants were classified to race distance (10-km, half-marathon, marathon/ultra-marathon) and type of diet (omnivorous, vegetarian, vegan) subgroups. An online survey was conducted to collect data on sociodemographic information and dietary intake (using a comprehensive food frequency questionnaire with 53 food groups categorized in 14 basic and three umbrella food clusters). Compared to male runners, female runners had a significantly greater intake in four food clusters, including “beans and seeds”, “fruit and vegetables”, “dairy alternatives”, and “water”. Males reported higher intakes of seven food clusters, including “meat”, “fish”, “eggs”, “oils”, “grains”, “alcohol”, and “processed foods”. Generally, it can be suggested that female runners have a tendency to consume healthier foods than males. The predominance of females with healthy dietary behavior can be potentially linked to the well-known differences between females and males in health attitudes and lifestyle patterns.
... Premenopausal females are thought to be better equipped than males to handle endurance sports due to their superior utilization of fatty acids [15][16][17]. During low-to moderate-intensity exercise, women typically derived a larger share of their exercise energy expenditure from fatty acids compared to their male counterparts [18]. ...
Article
Full-text available
Endurance training is associated with physiological changes in elite athletes, but little is known about female-specific effects of endurance training. Despite the significant rise in female sports participation, findings from studies performed on male athletes are largely extrapolated to females without taking into consideration sex-specific differences in metabolism. Subsequently, this study aimed to investigate the steroid hormone profiles of elite female endurance athletes in comparison with their non-athletic counterparts. Untargeted metabolomics-based mass spectroscopy combined with ultra-high-performance liquid chromatography was performed on serum samples from 51 elite female endurance athletes and 197 non-athletic females. The results showed that, compared to non-athletic females, certain androgenic, pregnenolone, and progestin steroids were reduced in elite female endurance athletes, while corticosteroids were elevated. The most significantly altered steroid hormones were 5alpha-androstan-3alpha,17alpha-diol monosulfate (FDR = 1.90 × 10⁻⁰⁵), androstenediol (3alpha, 17alpha) monosulfate (FDR = 2.93 × 10⁻⁰⁴), and cortisol (FDR = 2.93 × 10⁻⁰⁴). Conclusively, the present study suggests that elite female endurance athletes have a unique steroid hormone profile with implications on their general health and performance.
... However, we disagree with the simplistic assessment by Jouffroy et al. [1] that older athletes, "because they run slower have fewer overuse injuries" [1]. This is in contrast to the need to examine multiple variables as previously recommended (e.g., elite level, running speed, age, sex, terrain, running distance) [5,6], to be able to assess the risk of longterm health issues in UER. ...
Article
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Dear Editor, We really appreciate the Letter to the Editor by Jouffroy and colleagues [1], which added valuable information and discussion to our narrative review titled “Potential Long- Term Health Problems Associated with Ultra-Endurance Running” [2]. One of the primary aims of the paper was to “stimulate more open debate about the potential implications for long-term health” [2]. As such, the letter we received is evidence that this aim was fulfilled.
... This would suggest that this technology benefits female athletes more than males. As women, when compared with men, show greater fatigue resistance, greater substrate efficiency, and lower energetic demands during endurance events (Hunter, 2016;Tiller et al., 2021), the female lower body mass and/or a smaller shoes sizes could represent a possible explanation for this gender difference. It could be hypothesized that smaller shoe size is associated with a shorter but stiffer rigid plate in the AFT (Hoogkamer et al., 2017), and/or a higher midsole thickness/body mass ratio, facilitating a higher percentage of energy return in female runners . ...
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Running technique has been analyzed since antiquity, and yet the study of gait biomechanics is continually developing and unearthing new insights. This is undoubtedly linked to the great variety of skills required in the running and race walking events, despite their apparent simplicity: a fast but fair sprint start, safe and effective hurdle clearances, negotiation of the tight bends in indoor racing, and coping with changes in gradient in road and cross country running are just a few examples. Increasingly, coaches and governing bodies are looking to sports science to help improve their best athletes and raise participation rates in recreational sport, and need a comprehensive resource on technique, performance and training. Regardless of their standard, competitive athletes strive to improve performance and reduce the risk of injury, and biomechanists are ideally placed to support athletes and coaches in this universal sport.
... Thus, findings observed in men may not be translatable to women. Understanding biological similarities and differences between men and women is timely, as demonstrated by recent reviews summarizing sex-specific responses across a range of exercise-induced physiological, health and performance adaptations [12,[17][18][19][20][21][22][23][24]. ...