Background: Concentrations of endogenous sex hormones fluctuate across the menstrual cycle (MC), which could have implications for exercise performance in women. At present, data are conflicting, with no consensus on whether exercise performance is affected by MC phase. Objective: To determine the effects of the MC on exercise performance and provide evidence-based, practical, performance recommendations to eumenorrheic women. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched for published experimental studies that investigated the effects of the MC on exercise performance, which included at least one outcome measure taken in two or more defined MC phases. All data were meta-analysed using multilevel models grounded in Bayesian principles. The initial meta-analysis pooled pairwise effect sizes comparing exercise performance during the early follicular phase with all other phases (late follicular, ovulation, early luteal, mid-luteal and late luteal) amalgamated. A more comprehensive analysis was then conducted, comparing exercise performance between all phases with direct and indirect pairwise effect sizes through a network meta-analysis. Results from the network meta-analysis were summarised by calculating the Surface Under the Cumulative Ranking curve (SUCRA). Study quality was assessed using a modified Downs and Black checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group. Results: Of the 78 included studies, data from 51 studies were eligible for inclusion in the initial pairwise meta-analysis. The three-level hierarchical model indicated a trivial effect for both endurance- and strength-based outcomes, with reduced exercise performance observed in the early follicular phase of the MC, based on the median pooled effect size (ES_0.5 = − 0.06 [95% credible interval (CrI): − 0.16 to 0.04]). Seventy-three studies had enough data to be included in the network meta-analysis. The largest effect was identified between the early follicular and the late follicular phases of the MC (ES_0.5 = − 0.14 [95% CrI: − 0.26 to − 0.03]). The lowest SUCRA value, which represents the likelihood that exercise performance is poor, or among the poorest, relative to other MC phases, was obtained for the early follicular phase (30%), with values for all other phases ranging between 53 and 55%. The quality of evidence for this review was classified as “low” (42%). Conclusion: The results from this systematic review and meta-analysis indicate that exercise performance might be trivially reduced during the early follicular phase of the MC, compared to all other phases. Due to the trivial effect size, the large between-study variation and the number of poor-quality studies included in this review, general guidelines on exercise performance across the MC cannot be formed; rather, it is recommended that a personalised approach should be taken based on each individual's response to exercise performance across the MC.

New Findings: What is the topic of this review?We review sex differences within physiological systems implicated in exercise performance; specifically, how they integrate to determine metabolic thresholds and fatigability. Thereafter, we discuss the implications that these sex differences might have for long‐term adaptation to exercise. What advances does it highlight?The review collates evidence from recent physiological studies that have investigated sex as a biological variable, demonstrating that the physiological response to equivalent ‘dosages’ of exercise is not the same in males and females; thus, highlighting the need to research diversity in physiological responses to interventions. The anatomical and physiological differences between males and females are thought to determine differences in the limits of human performance. The notion of studying sex as a biological variable has recently been emphasized in the biosciences as a vital step in enhancing human health. In this review, we contend that the effects of biological sex on acute and chronic responses must be studied and accounted for when prescribing aerobic exercise, much like any intervention targeting the optimization of physiological function. Emerging evidence suggests that the response of physiological systems to exercise differs between males and females, potentially mediating the beneficial effects in healthy and clinical populations. We highlight evidence that integrative metabolic thresholds during exercise are influenced by phenotypical sex differences throughout many physiological systems. Furthermore, we discuss evidence that female skeletal muscle is more resistant to fatigue elicited by equivalent dosages of high‐intensity exercise. How the different acute responses affect the long‐term trainability of males and females is considered, with discussion about tailoring exercise to the characteristics of the individual presented within the context of biological sex. Finally, we highlight the influence of endogenous and exogenous sex hormones on physiological responses to exercise in females. Sex is one of many mediating influences on the outcomes of exercise, and with careful experimental designs, physiologists can advance the collective understanding of diversity in physiology and optimize outcomes for both sexes.

Background: Oral contraceptive pills (OCPs) are double agents, which downregulate endogenous concentrations of oestradiol and progesterone whilst simultaneously providing daily supplementation of exogenous oestrogen and progestin during the OCP-taking days. This altered hormonal milieu differs significantly from that of eumenorrheic women and might impact exercise performance, due to changes in ovarian hormone-mediated physiological processes. Objective: To explore the effects of OCPs on exercise performance in women and to provide evidence-based performance recommendations to users. Methods: This review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A between-group analysis was performed, wherein performance of OCP users was compared with naturally menstruating women, and a within-group analysis was conducted, wherein performance during OCP consumption was compared with OCP withdrawal. For the between-group analysis, women were phase matched in two ways: (1) OCP withdrawal versus the early follicular phase of the menstrual cycle and (2) OCP consumption versus all phases of the menstrual cycle except for the early follicular phase. Study quality was assessed using a modified Downs and Black Checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation working group. All meta-analyses were conducted within a Bayesian framework to facilitate probabilistic interpretations. Results: 42 studies and 590 participants were included. Most studies (83%) were graded as moderate, low or very low quality, with 17% achieving high quality. For the between-group meta-analysis comparing OCP users with naturally menstruating women, posterior estimates of the pooled effect were used to calculate the probability of at least a small effect (d ≥ 0.2). Across the two between-group comparison methods, the probability of a small effect on performance favouring habitual OCP users was effectually zero (p < 0.001). In contrast, the probability of a small effect on performance favouring naturally menstruating women was moderate under comparison method (1) (d ≥ 0.2; p = 0.40) and small under comparison method (2) (d ≥ 0.2; p = 0.19). Relatively large between-study variance was identified for both between-group comparisons ( $$\tau$$τ _0.5 = 0.16 [95% credible interval (CrI) 0.01–0.44] and $$\tau$$τ _0.5 = 0.22 [95% CrI 0.06–0.45]). For the within-group analysis comparing OCP consumption with withdrawal, posterior estimates of the pooled effect size identified almost zero probability of a small effect on performance in either direction (d ≥ 0.2; p ≤ 0.001). Conclusions: OCP use might result in slightly inferior exercise performance on average when compared to naturally menstruating women, although any group-level effect is most likely to be trivial. Practically, as effects tended to be trivial and variable across studies, the current evidence does not warrant general guidance on OCP use compared with non-use. Therefore, when exercise performance is a priority, an individualised approach might be more appropriate. The analysis also indicated that exercise performance was consistent across the OCP cycle.

Sex hormone concentrations of eumenorrheic females typically fluctuate across the menstrual cycle and can affect neural function such that oestrogen has neuro-excitatory effects, and progesterone induces inhibition. However, the effects of these changes on corticospinal and intracortical circuitry, and the motor performance of the knee-extensors, are unknown. The present two-part investigation aimed to i) determine the measurement error of an exercise task, transcranial magnetic stimulation (TMS) and motor nerve stimulation (MNS) derived responses in females ingesting a monophasic oral contraceptive pill (hormonally-constant), and ii) investigate whether these measures were modulated by menstrual cycle phase (MCP), by examining them before and after an intermittent isometric fatiguing task (60% of maximal voluntary contraction, MVC) with the knee-extensors until task failure in eumenorrheic females on days 2, 14, and 21 of the menstrual cycle. The repeatability of neuromuscular measures at baseline and fatigability ranged between moderate-excellent in females taking the oral contraceptive pill. Maximal voluntary contraction was not affected by MCP (P=0.790). Voluntary activation (MNS and TMS) peaked on day 14 (P=0.007 and 0.008, respectively). Whilst corticospinal excitability was unchanged, short-interval intracortical inhibition was greatest on day 21 compared to days 14 and 2 (P=0.001). Additionally, time to task failure was longer on day 21 compared to both days 14 and 2 (24 and 36%, respectively; P=0.030). The observed changes were larger than the associated measurement errors. These data demonstrate that neuromuscular function and fatigability of the knee-extensors varies across the menstrual cycle, and may influence exercise performance involving locomotor muscles.

The initial increases in force production with resistance training are thought to be primarily underpinned by neural adaptations. This notion is firmly supported by evidence displaying motor unit adaptations following resistance training; however, the precise locus of neural adaptation remains elusive. The purpose of this review is to clarify and critically discuss the literature concerning the site(s) of putative neural adaptations to short-term resistance training. The proliferation of studies employing non-invasive stimulation techniques to investigate evoked responses have yielded variable results, but generally support the notion that resistance training alters intracortical inhibition. Nevertheless, methodological inconsistencies and the limitations of techniques, e.g. limited relation to behavioural outcomes and the inability to measure volitional muscle activity, preclude firm conclusions. Much of the literature has focused on the corticospinal tract; however, preliminary research in non-human primates suggests reticulospinal tract is a potential substrate for neural adaptations to resistance training, though human data is lacking due to methodological constraints. Recent advances in technology have provided substantial evidence of adaptations within a large motor unit population following resistance training. However, their activity represents the transformation of afferent and efferent inputs, making it challenging to establish the source of adaptation. Whilst much has been learned about the nature of neural adaptations to resistance training, the puzzle remains to be solved. Additional analyses of motoneuron firing during different training regimes or coupling with other methodologies (e.g., electroencephalography) may facilitate the estimation of the site(s) of neural adaptations to resistance training in the future.