Sex- and gender-specific differences in treatment efficacy and safety of traditional Chinese medicine: a scoping review.

Background: While Western medicine is increasingly investigating sex- and gender-specific differences in health and disease, and despite TCM theory and practice placing particular emphasis on individual differences-including sex- and gender-related characteristics, research on sex- and gender- sensitive medicine in TCM remains underexplored. Objective: We conducted a scoping review to map and synthesize the existing evidence on sex- and gender-specific differences in the efficacy and safety of TCM interventions and to analyze possible underlying mechanisms. Methods: The scoping review followed the JBI guidance. Six Chinese and English databases (CNKI, WF, VIP, SinoMed, PubMed, and Web of Science) were searched from inception to July 2025 for preclinical and clinical studies. Key information was extracted from the included studies, and data were synthesized using descriptive statistics and systematic narrative synthesis. GraphPad Prism 10.0 was used to generate figures. Results: Database searches identified 6,720 records; after removing 250 duplicates, 6,470 records were screened by title and abstract, and 2,417 proceeded to full-text eligibility assessment. Ultimately, 16 studies were included, comprising randomized controlled trials, animal experiments, non-randomized controlled trials, and single-arm trials. Conclusions drawn from the original studies indicated that changes in all relevant outcome measures were associated with sex. Sex-specific differences in TCM efficacy were observed across herbal, acupuncture, and combined interventions. Female animals demonstrated predominant benefits in bone metabolism, whereas female human participants showed greater benefits in pain perception, emotional regulation, neurological recovery, and pulmonary functional outcomes. Male animals exhibited more pronounced gut microbiota responses to metabolic interventions, while male human participants showed stronger effects in obesity-related outcomes and sensorimotor responses. These divergent patterns likely reflect sex-related differences in pharmacokinetics, gut-brain axis interactions, and neuroendocrine mechanisms. None of the included studies examined gender-related sociocultural factors. Conclusion: This review highlights a persistent theoretical and methodological gap in TCM research, which has yet to fully integrate sex- and gender-sensitive medicine principles. The limited high-quality clinical evidence underscores the need for rigorous sex-informed trials to evaluate efficacy across sexes. These findings support the integration of sex as a key determinant in TCM clinical decision-making, alongside syndrome differentiation, to advance precision medicine and improve personalized therapeutic outcomes. Systematic Review Registration: DOI: 10.17605/OSF.IO/QABTY.