This purpose of this review was to determine if significant sex differences in ultramarathon runners exist, which could justify the development of separate guidelines for males and females. While the overall quality of evidence from the included studies is low, by pooling the results, coherence in some areas has emerged. Evidence of sex differences in ultramarathon runners was identified in the predictors of performance, the physiological responses to racing, and the risk of acute and chronic illness and injury. Areas where no sex differences were found included cognitive performance, central fatigue, and overall injury rates. However, given the predominance of low-quality evidence, confidence in this evidence is also low, and these results should be interpreted with caution. Presently, a personalised approach based on the individual’s responses to training, racing, nutrition, and recovery interventions is recommended.
Areas Where Evidence of Sex Differences Exists
See Fig. 2.
Predictors of Performance
There is reasonable evidence that ultramarathon performance is differently predicted in males and females [15, 16, 26–29]. This is important as it could translate into different training priorities for each sex. For example, a strong correlation between ankle rebound performance and female ultramarathon performance was demonstrated by Martinez-Navarro et al. [28] Conversely, mean inspiratory pressure was correlated to performance in males only [28]. Indeed, there is evidence that females have superior fatigue resistance of the respiratory muscles, indicating that this may be less of a performance limiting factor than in males [69]. While these findings may imply that males and females would benefit from targeting different variables in training, this is a single study with a small sample size. Furthermore, the method employed for measuring inspiratory pressure is largely dependent on the effort imparted by the subject and these results may therefore represent differences in motivation, rather than respiratory muscle strength and fatiguability. Therefore, larger studies utilising respiratory muscle nerve stimulation techniques are required before conclusions can be drawn.
Significant sex differences were also found when anthropomorphic variables were examined [15, 26, 27, 29]. Several studies found that BMI and body composition correlated with ultramarathon performance in males, but not in females [15, 26, 29]. Furthermore, while Martinez-Navarro et al. found that body composition correlated to performance in both sexes, this relationship did not persist after multiple regression analysis [16]. Conversely, much larger studies of runners engaging in races of half marathon distance and below have found that body composition is predictive of performance in males and females [70, 71]. Thus, it is possible that the association between body composition and performance becomes less important for female runners as race length increases. However, given the small sample sizes and the high probability that females participating in studies of extreme endurance events are not representative of the wider female ultrarunning community, it is not possible to draw conclusions at this time.
The classic physiological measures of fitness that predict performance also differ between males and females. In one study of runners completing a 107 km race, performance was independently predicted by MFO and Vpeak in males, but only by V̇O2max in females [16]. This implies that high-intensity training targeting V̇O2max improvements could optimise female performance, whereas males may benefit from more sustained efforts to improve fatigue resistance and fat oxidation rates. However, as these studies only provide evidence of correlation of these physiological measures and performance, this hypothesis needs to be tested. Studies investigating the sex differences in response to varying ultramarathon training stimuli would provide useful and practical insights for ultramarathon coaches and their athletes.
In summary, there is currently low-level evidence that male and female ultramarathon performance is predicted by different variables, but this area of research needs significant development before these findings can be used to guide training priorities.
Fatigue
During demanding physical pursuits such as ultramarathons, fatigue affects many body systems and can strongly influence performance [72]. This review found evidence that females experience less peripheral and cardiac fatigue than males in ultramarathons, which could confer an advantage in longer races, and influence training plan design [36, 37, 39, 40]. Indeed, the performance gap between males and females does appear to decrease with increasing race length [73]. This review included two small cohort studies which examined muscle fatigue in relative performance-matched, female and male ultramarathon runners. The female runners demonstrated less peripheral fatigue of the plantar flexors and smaller decrements in knee extensor maximal voluntary contraction (MVC) following ultramarathon races [36, 37]. This is in agreement with studies in non-athlete populations, and could be due to several factors including differences in muscle fibre type, and less accumulation of anaerobic metabolites involved in inhibitory feedback loops [2, 17, 74, 75].
Females also demonstrated reduced exercise-induced cardiac fatigue (EICF) in races under 100 km [39, 40]. EICF is characterised by a reduction in left ventricular systolic and diastolic function following prolonged, strenuous activity [41]. A propensity for less EICF could not only imply a female advantage in ultramarathon racing, but could also have implications for the long-term cardiac effects of ultramarathon training [76]. The reason for this relative fatigue resistance in females is not known; however, given the protective effects of oestrogen on the myocardium, it is likely that sex hormones play a role [76]. This could be investigated by comparing EICF in post-menopausal and premenopausal females in future studies.
It should be noted that an alternative explanation for the apparent superior “fatigue resistance” of female athletes exists. It has been suggested that male and female athletes approach ultramarathon races with different competition intentions which could explain the greater fatigue often reported in males [17]. For example, in Besson et al.’s study, females reported greater motivation to enjoy races < 60 km, whereas males were more competitively oriented, although no sex differences were found for races > 100 km [17]. This competitive orientation could result in males tapping into their “security reserves” more than females, resulting in greater decrements in force production capacities.[17]. Indeed, a survey of 344 female recreational ultramarathon runners found that females rated personal achievement and physical health as greater motivators than competition [77]. However, it is likely that motivational factors also vary significantly between recreational “weekend warriors” and top ultramarathon athletes competing for prize money [78]. Regardless of whether physiological or motivational factors underlie the findings, the examined literature suggests that males experience more peripheral and cardiac fatigue than females which could impact the design of training plans with regard to planning recovery.
Pacing
It is possible that interactions exist between the aforementioned relative fatigue resistance in females, and pacing strategies utilised during races [2]. This could provide useful information for coaches and athletes planning racing strategies. Tiller et al. postulate that females may be better able to maintain running pace as a consequence of less peripheral muscular fatigue [2]. However, the findings of this review were mixed. While three studies looking at 24 h time-limited marathons failed to find sex differences in pacing strategies, females demonstrated more even pacing over the 100 km World Masters Championship race and a relatively flat 100 mile race [64,65,66,67,68]. Conversely, females had greater pace variation during the Ultra-Trail du Mont-Blanc, a mountain ultramarathon involving 10,000 m vertical gain [9]. Given that males have greater muscle mass relative to fat mass, it has been suggested that they may be better able to maintain pace going uphill and hence have less pace variation on mountainous terrain [9]. However, the link between body composition and pacing remains speculative at this stage, and the relationship between race format and terrain and sex differences in pacing requires further examination.
Health
As with the wider population, the health concerns most commonly affecting athletes can differ according to sex [79]. This review found this to be true in ultramarathon runners. For example, female ultramarathon runners were found to report higher rates of sleep disorders, have greater rates of bone stress injuries, and be more at risk of eating disorders [49,50,51]. These findings should be considered when designing training and recovery programmes for females.
Sleep plays an important role in performance, injury rates, inflammation, and recovery [49]. While only one study in this review examined sleep disorder prevalence, it had a reasonably sized female cohort (n = 95) and the findings are supported by larger studies in both ultramarathon runners and general populations [49, 80,81,82]. A meta-analysis of 29 studies found that females were 40% more likely to suffer from insomnia than males [82]. However, these studies largely relied on self-reported measures of sleep. A recent paper on sleep in junior endurance athletes found that females had worse subjective sleep quality, but objectively achieved higher total sleep time and greater sleep efficiency [83]. Thus, it is unclear if the preponderance of self-reported sleep disorders in female ultrarunners represents an objectively worse quality of sleep which could impact training and recovery. Interestingly, in the aforementioned study, objective sleep quality was influenced by different stages of the menstrual cycle, which could indicate variable recovery requirements for female athletes across the cycle [83]. This premise needs further development, and studies on the effect of the menstrual cycle and sleep in ultramarathon runners do not yet exist. However, given the widely acknowledged important role sleep plays in athletic recovery, it is reasonable to conclude that all ultramarathon runners, irrespective of sex, would benefit from interventions to improve sleep [84].
The greater rate of bone stress injuries (BSIs) in female ultrarunners is significant because injuries that relate to poor bone health are associated with osteoporosis and fragility fractures in older age [51, 52]. Moreover, female ultramarathon runners have an elevated risk of eating disorders and the athlete triad [51]. While low energy availability negatively affects all athletes, the consequences for females are more rapid, and even within-day deficits affect menstrual function and bone turnover [21, 85]. Interestingly, in the study by Høeg et al., male ultramarathon athletes were in fact more likely to have low bone mineral density than females, and further research is required to confirm this finding [51]. The same study found that over half of the female cohort, and none of the males, had below normal levels of serum 25-hydroxyvitamin D [51]. There is evidence that vitamin D supplementation may be protective against BSIs in athletic populations, and a recent review has suggested this approach in athletes with low serum levels [17]. Professionals working with female athletes should be aware of these findings, as a failure to address disordered eating practices, and/or the prescription of excessive training loads, could have severe short- and long-term effects on performance and health. Additionally, assessing serum 25-hydroxyvitamin D levels and supplementing those who are deficient appears to be especially important for female ultrarunners.
The studies included in this review found that, during multi-day ultramarathons, female runners were more likely to encounter a medical illness, and one study identified a four-fold increase in rates of acute kidney injury (AKI) [53, 54]. The reasons for these findings are not currently known, and further studies are needed to confirm this female propensity for illness and clarify the nature of illnesses encountered. Furthermore, while increases in serum creatinine (such as in AKI) are extremely common following an ultramarathon, renal function rapidly normalises in most individuals without clinical consequence [7, 86]. However, hospitalisations for renal failure, while rare, do occur among ultramarathon runners, and the long-term effects of repeated insults to renal function in this setting are not yet known [87]. It is therefore unclear what relevance this finding has for female ultramarathon runners.
Ultramarathons often take place in challenging environments, including extreme heat, and sex differences have been found in issues such as heat-related illness and muscle cramps [88]. Understanding an athlete’s ability to train and perform in the heat may be important for choosing goal races and planning training schedules and heat acclimatisation strategies. This review included two studies examining this issue. A study of 49 ultramarathon runners found no association between sex and the incidence of muscle cramping during a 56 km road race in Cape Town [56]. In contrast, a larger study of over 3000 athletes competing in a trail ultramarathon on Reunion Island found a higher incidence of heat-related symptoms and muscle cramps in males [55]. These disparate results could be due to the different climates in which the studied races took place, with Reunion Island having significantly higher average temperatures than Cape Town in the months that the races were held. It is also possible that the first study was underpowered to detect a difference given the smaller subject numbers. Females have demonstrated more efficient heat dissipation via sweat evaporation than males, and a greater ability to maintain their core temperature in hot and humid environments [88, 89, 91]. However, these data are not specific to ultraendurance exercise and research in ultramarathon runners is required to determine if these findings hold true under the conditions experienced by this population.
Ultrarunning is a significant source of oxidative stress, and there is robust evidence of increased reactive oxygen species (ROS) and free radicals following ultramarathon races [31, 35]. ROS are thought to regulate acute-phase inflammatory responses, and could therefore affect ultramarathon performance and recovery [35, 92]. This review found that the oxidative response to ultramarathons is influenced by sex, with females demonstrating significantly higher levels of protein peroxidation indicators and cellular DNA damage following an ultramarathon [35, 36]. Moreover, females showed a greater response to antioxidant supplementation on minimising DNA damage [35]. While this may seem beneficial, studies have shown that long-term AO supplementation can impair adaptation to endurance training [93,94,95]. Unfortunately, most of these studies have been carried out on male subjects. However, one study included only female runners and found that vitamin C supplementation was associated with a slowing of running speeds during training, although no effect on 5 km time trial performance was seen [96]. Thus, while AO supplementation may have a greater effect on reducing oxidative stress in females, the implications of this are unclear [97]. More studies examining the long-term effects of AO supplementation on health and performance are required before conclusions can be drawn.
Areas Where There Is No Evidence of Sex Differences
See Fig. 3.
Predictors of Performance
While most studies in this review found sex differences in the predictors of ultramarathon performance, there were several areas where male and female performance was similarly predicted. For example, while Martinez-Navarro et al. found that V̇O2max was predictive of female 107 km ultramarathon performance only, in a shorter 50 km race, V̇O2max and Vpeak were related to performance in both sexes [16, 29]. Given the significant difference in the lengths of these races, these conflicting findings are perhaps unsurprising and could be due to physiological demands changing as race length increases. For example, females may have a lesser propensity to experience fatigue of the myocardium, respiratory musculature, and skeletal muscles, and these factors could be less limiting to performance compared with males [36, 37, 39, 40, 69]. Consequently, maximal oxygen uptake may become less important for males as distance increases and other systems fatigue. Further studies looking at sex differences over a variety of race distances are needed to clarify how the physiological predictors of performance relate to race duration.
Training volume is another predictor of performance which is potentially shared by the sexes, but the research on this is inconclusive [27]. While Citarella et al. found a strong association between training volume and record 100 km time in males and females, their sample consisted of only 10 elite athletes [27]. In contrast, O’Loughlin et al. studied recreational athletes running a 62 km ultramarathon and found that training volume was predictive of female performance only [15]. It is likely that the influence of training volume on performance varies according to race distance. Additionally, it is possible that different variables predict performance in elite runners, compared with recreational runners, and this is another area which warrants further investigation.
Fatigue
While females are considered more fatigue-resistant than males in general, this review found several areas where no sex difference was found. Firstly, there were no differences in measurements of central fatigue, brain cortical activity, mood states, and cognitive performance both during and after ultramarathon participation [36, 38]. Secondly, although males demonstrated greater peripheral fatigue of the plantar flexors, there were no sex differences in peripheral fatigue of the knee extensors [36, 37]. Temesi et al. postulate that this discrepancy may be explained by greater Achilles tendon compliance in females, which has been associated with superior maintenance of work output and greater mechanical efficiency of the soleus in rat models [36]. However, this association has not been replicated in human subjects and remains speculative at this stage. Additionally, despite evidence of greater decrements in contractile function in males relative to females, this did not translate into differences in the energy cost of running [37]. This may be because the sex differences in neuromuscular fatigue are not large enough to affect running economy [37]. It is therefore unclear what relevance these findings have for ultramarathon training and, as only one study looked at this relationship, these findings require confirmation.
Lastly, while sex differences in EICF were demonstrated in shorter ultramarathon races, none were found in races of 100 km and 160 km [39,40,41]. This could be related to the lower exercise intensity that is maintained in longer races. However, due to the small female cohorts studied, this research should be interpreted with caution. Larger studies including intensity-matched males and females are required to further investigate sex differences in EICF. Furthermore, research into the long-term consequences of repeated bouts of EICF is required before the relevance of these findings can be discussed further.
Health
Similar overall injury rates were found in males and females by all three studies examining the topic [52, 53, 57]. One study found that approximately 65% of ultramarathon runners had experienced a running-related injury in the preceding 12 months [52]. The other two studies examined injuries encountered during a race and found no association between sex and musculoskeletal, or skin-related problems [53, 57]. These findings are in agreement with research into runners in general. A recent meta-analysis found that while females are more likely to sustain BSIs, and males are more likely to be affected by Achilles tendinopathies, overall injury rates are the same [98].
Female sex has been reported as a risk factor for exercise-associated hyponatraemia (EAH), which most commonly results from overconsumption of hypotonic fluids [97]. However, where studies on ultramarathon runners are concerned, the majority failed to find a significant increase in the rates of EAH in females [58,59,60]. Two studies reported higher rates in females which failed to reach statistical significance, and one study actually demonstrated higher rates in males [59, 61, 62]. Thus, it seems unlikely that female ultramarathon runners are at a significantly greater risk of EAH. Nevertheless, there is a risk of over-drinking during races if females are not given individualised hydration guidelines based on body weight and sweat rates. Additionally, there are significant fluctuations in core temperature across the menstrual cycle, and elevations in oestradiol and progesterone are associated with fluid retention and greater sodium loss [13, 98]. These cyclical changes could confound the data, and further research on the effects of sex on sodium balance should account for hormonal fluctuations.
In terms of oxidative stress resulting from ultramarathon racing, AO supplementation effectively prevented rises in markers of lipid peroxidation in both sexes, and there were no differences found in antioxidant repair systems [31, 33]. Furthermore, when looking at markers of inflammation and muscle damage following ultramarathons, either with or without AO supplementation, no sex differences were found [33, 45]. Therefore, the significance of sex similarities and differences in oxidative stress is unclear at present.