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Despite sustained advances, our understanding of how inherent biological factors drive variations in exercise capacity and related pathologies is still developing. This review examines data primarily from human trials on hormonal and other physiological determinants of sex differences in exercise performance. Higher testosterone in men leads to greater muscle mass, haemoglobin, bone size and cardiac output, explaining much of the performance gap between sexes. Female physiology confers advantages during prolonged submaximal exercise, including greater fat oxidation, lower carbohydrate dependence and improved fatigue resistance, which may help explain narrower gaps in ultra\u2010endurance events. These differences translate into a persistent performance gap (around 10%\u201315%) in most sports, particularly those requiring strength and power, although the gap narrows as event duration increases. Sex differences also influence responses to training and risk of exercise\u2010related pathology, including differences in stress responses, reproductive dysfunction (e.g., hypothalamic amenorrhoea), musculoskeletal injury and thermoregulation. These insights inform specific approaches in sports medicine and clinical endocrinology, emphasising the importance of sex as a fundamental biological variable in exercise physiology, sports performance and in clinical management of athletes and those in physically demanding jobs.<\/jats:p>","DOI":"10.1111\/cen.70150","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:31:42Z","timestamp":1777523502000},"page":"151-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Physiological Basis of Sex Differences in Human Performance and Exercise\u2010Associated Pathology"],"prefix":"10.1111","volume":"105","author":[{"given":"David A.","family":"Holdsworth","sequence":"first","affiliation":[{"name":"Academic Department of Military Medicine, Research and Clinical Innovation Royal Centre of Defence Medicine Birmingham UK"},{"name":"Radcliffe Department of Medicine, Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Army Health and Performance Research Army Health Branch, Army Headquarters Andover UK"},{"name":"Division of Surgery and Interventional Science University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Doig","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Centre for Systems Health and Integrated Metabolic Research Nottingham Trent University Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Taylor","sequence":"additional","affiliation":[{"name":"Academic Department of Military Medicine, Research and Clinical Innovation Royal Centre of Defence Medicine Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasminder","family":"Dosanjh","sequence":"additional","affiliation":[{"name":"Academic Department of Military Medicine, Research and Clinical Innovation Royal Centre of Defence Medicine Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Woods","sequence":"additional","affiliation":[{"name":"Academic Department of Military Medicine, Research and Clinical Innovation Royal Centre of Defence Medicine Birmingham UK"},{"name":"Carnegie Institute of Sports Science Leeds Beckett University Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Stacey","sequence":"additional","affiliation":[{"name":"Academic Department of Military Medicine, Research and Clinical Innovation Royal Centre of Defence Medicine Birmingham UK"},{"name":"Department of Surgery of Cancer Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Gifford","sequence":"additional","affiliation":[{"name":"Academic Department of Military Medicine, Research and Clinical Innovation Royal Centre of Defence Medicine Birmingham UK"},{"name":"Institute for Neuroscience and Cardiovascular Research University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.r1698"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284198"},{"key":"e_1_2_9_4_1","unstructured":"\u201cWorld Athletics \u201d World Athletics accessed September 27 2025 www.worldathletics.org."},{"key":"e_1_2_9_5_1","unstructured":"\u201cChannel Swimming Records \u201d Channel Swimming Association accessed September 27 2025 www.channelswimmingassociation.com\/records."},{"key":"e_1_2_9_6_1","unstructured":"\u201cWorld Aquatics \u201d World Aquatics accessed September 27 2025 https:\/\/www.worldaquatics.com\/."},{"key":"e_1_2_9_7_1","unstructured":"\u201cIndividual Records \u201d Catalina Channel Swimming Federation accessed September 27 2025 www.swimcatalina.org\/individuals-records."},{"key":"e_1_2_9_8_1","unstructured":"\u201cDatabase. 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