Physiological changes of cortisol and oxytocin following manual therapy: a scoping review

Introduction: Neuroendocrine responses to manual therapy (MT), including changes in cortisol and oxytocin, have long been proposed as potential physiological mechanisms of MT-related effects. Over the past three decades, a growing body of literature has examined hormonal/neuropeptide responses following MT; however, findings remain heterogeneous and unevenly distributed across outcomes and MT intervention types. The objective of this scoping review was to map and characterize the existing evidence for changes in cortisol (CORT) and/or oxytocin (OXT) levels in response to three commonly used MT interventions and to identify patterns and gaps within the literature. Methods: Five databases [Cumulated Index to Nursing and Allied Health Literature (CINAHL), Embase, PubMed, Scopus, and Web of Science] were searched from inception to July 2025. Eligible studies included those which were (a) in English, (b) in humans, (c) original data studies, (d) included a form of MT (massage, osteopathic manipulative treatment, spinal manipulation, etc.), and (e) at least one physiological measure (e.g., saliva, urine, plasma) of CORT and/or OXT. Two reviewers independently screened studies and extracted data using a structured approach consistent with scoping review methodology. Results: The literature search identified 2,374 studies, with 72 articles meeting the eligibility criteria. Studies varied widely in MT intervention type, population characteristics, sample size, rigor, biological sampling methods, and timing of outcome assessment. Most of the included studies measured cortisol outcomes, whereas fewer investigated oxytocin. Both reported hormonal/neuropeptide responses as mixed across MT intervention approaches. Conclusions: CORT and OXT responses to MT were variable across studies, reflecting heterogeneity in intervention delivery, sample size, timing of hormone/neuropeptide collection, and analytical methods. This review underscores the need to standardize how MT-related neuroendocrine outcomes are collected, address the many gaps in the evidence particularly as it relates to OXT, and to clarify the potential mechanistic role of CORT and OXT in MT-related clinical outcomes. Systematic Review Registration: doi: 10.17605/OSF.IO/A78TU, Open Science Framework.