Peripheral biomarkers in compulsive sexual behavior disorder: a systematic review.

Compulsive sexual behavior disorder (CSBD) is defined by a persistent inability to regulate sexual impulses, leading to significant distress and impairment. Although it is recognized as a disorder in the International Classification of Diseases-11, the underlying neurobiological mechanisms are not yet fully understood. The aim of this systematic review is to summarize recent findings on peripheral biomarkers in individuals with CSBD and to provide a comprehensive overview of the current state of the field. We searched articles published in the last 10 years in PubMed, Scopus, and Web of Science following The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Eligible studies included adult participants formally diagnosed with CSBD, hypersexual disorder, or sexual addiction, and that assessed peripheral biomarkers. Exclusion criteria comprised studies focused on neurological comorbidities, neuroimaging alone, or animal models. A total of 10 articles met the inclusion criteria. The primary outcomes were associations between peripheral biomarkers and clinical or psychological variables in CSBD, including hormone levels, epigenetic patterns, and immune markers. The reviewed studies investigated neuroendocrine, epigenetic, and immunological biomarkers in individuals with CSBD. Altered DNA methylation was identified in stress-related genes (e.g., CRH, CRHR1, FKBP5, NR3C1), often associated with HPA axis dysregulation and non-suppression in the dexamethasone suppression test (DST). Specific microRNAs (e.g., MIR4456, MIR708) showed differential methylation and expression patterns. Neuroendocrine findings included elevated post-DST cortisol and ACTH levels, increased plasma oxytocin and LH levels, and associations between salivary testosterone and CSBD symptoms in men. Immunological alterations included increased TNF-α and decreased IL-6. These preliminary findings suggest biological alterations related to stress, hormonal regulation, and inflammation in CSBD, but clinical application remains limited. This is the first systematic review focused on peripheral biomarkers in CSBD. However, limited sample diversity, cohort overlap, and lack of replication restrict generalizability. Evidence supports a multifactorial biological profile in CSBD. Future longitudinal, multimodal studies in diverse populations are essential to clarify the diagnostic and clinical relevance of these biomarkers.