Prostatitis, a heterogeneous group of inflammatory conditions affecting the prostate gland, is classified into four subtypes—acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis (CP), and asymptomatic inflammatory prostatitis—according to the National Institutes of Health (NIH) classification system (1). Among these, CP—accounting for approximately 90% of cases, often accompanied by urinary symptoms such as dysuria and frequency, as well as sexual dysfunction including erectile dysfunction and reduced libido (2). Emerging evidence suggests a multifactorial pathophysiology, involving neurogenic inflammation, pelvic floor myofascial dysfunction, autoimmune responses, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (3). Pro-inflammatory cytokines, including TNF-α, IL-6, and IL-8, are elevated in expressed prostatic secretions, contributing to chronic tissue damage and peripheral sensitization (4, 5). Furthermore, the cross-talk between pelvic nerves and the central nervous system (CNS) exacerbates pain perception via mechanisms involving glutamate signaling and microglial activation (6, 7). Globally, the prevalence of prostatitis varies between 2% and 10%, and approximately 35–50% of patients experience concomitant sexual dysfunction (8–10). Population-based studies have demonstrated that men with CP are at a significantly greater risk of developing anxiety and depression compared to healthy controls (11). This bidirectional relationship arises from chronic pain disrupting dopaminergic and serotonergic pathways that are critical for mood regulation, while psychological distress reduces pain thresholds through HPA axis hyperactivity and glucocorticoid resistance (12, 13). Sexual dysfunction further exacerbates this burden, as erectile dysfunction and premature ejaculation are associated with diminished self-esteem, social withdrawal, and impaired quality of life (14). First-line treatments for CP include α-blockers, anti-inflammatory agents, and antibiotics; however, their efficacy remains suboptimal due to the heterogeneity of underlying etiologies (15, 16). A Cochrane review concluded that α-blockers provide only modest symptomatic relief in 25–30% of patients and do not significantly improve sexual function (17). For comorbid anxiety and depression, selective serotonin reuptake inhibitors (SSRIs), such as sertraline, are commonly prescribed; however, these medications frequently exacerbate sexual dysfunction, including anorgasmia and reduced libido (18, 19). Psychological interventions, such as cognitive-behavioral therapy (CBT), show promise; however, their effectiveness is limited by issues of accessibility and cost (20, 21).

Chinese herbal medicine (CHM) provides a holistic approach by simultaneously targeting inflammation, pelvic microcirculation, and neuropsychiatric pathways, which aligns with the multifactorial nature of CP. For instance, Gardenia jasminoides, a traditional Chinese herb, contains geniposide, a compound that inhibits NF-κB and MAPK signaling pathways and attenuates prostatic inflammation in mouse models (22, 23). Similarly, the herbal combination of Bupleurum chinense DC (Chaihu) and Paeonia lactiflora Pall (Baishao) exerts sustained antidepressant effects in vivo, mediated through antioxidant pathway activation, HPA axis homeostasis modulation, and neural synaptic plasticity preservation mechanisms (24). Clinical trials have demonstrated that CHM significantly improves International Prostate Symptom Scores (IPSS) and quality-of-life (QoL) metrics compared to placebo (25, 26). Furthermore, CHM formulations lack the sexual side effects commonly associated with SSRIs and can effectively alleviate symptoms of anxiety and depression (18, 27, 28).

Despite growing evidence, no systematic review has yet synthesized the dual efficacy of CHM on both urogenital and psychological outcomes in this population. Existing meta-analyses either narrowly focus on pain relief or exclude studies that address sexual dysfunction. This review will address critical gaps by evaluating the effects of CHM on anxiety and depression using validated scales, analyzing subgroup differences according to the severity of sexual dysfunction, and comparing the safety profile of CHM with that of conventional therapies. The findings are anticipated to offer clinical insights into integrating CHM into multidisciplinary care models for CP. Therefore, our team will conduct a meta-analysis and systematic review to evaluate and summarize the efficacy of CHM in managing anxiety and depression among patients with CP complicated by sexual dysfunction.

This study will be conducted according to the Preferred Reporting Item (PRISMA) for systematic reviews and meta-analyses (29, 30). The registration number of the protocol is CRD420251002787 (https://www.crd.york.ac.uk/prospero/).

This protocol outlines a systematic review and meta-analysis designed to explore the efficacy of CHM in alleviating anxiety and depression among patients with CP complicated by sexual dysfunction. By evaluating published RCTs, we will comprehensively assess the impact of CHM interventions on both urogenital symptoms and psychological outcomes. Furthermore, we aim to investigate the potential associations between CHM treatment characteristics and clinical efficacy to identify the optimal therapeutic regimen. The findings are anticipated to bridge the knowledge gap regarding CHM’s holistic effects in CP management and inform evidence-based integration of herbal therapies into multimodal treatment strategies. It is worth noting that inherent ethical challenges in CHM trials (e.g., informed consent, risk-benefit assessment) will be examined across the included RCTs. The absence of ethics committee approval or documentation of informed consent will be recorded as an indicator of study quality.

However, this systematic review and meta-analysis have several limitations. First, although rigorous inclusion criteria were applied to ensure study quality, this approach may have excluded relevant clinical data from smaller-scale trials or observational studies, thereby limiting the scope of eligible evidence on CHM for managing anxiety, depression, and sexual dysfunction in CP patients. While RCTs are prioritized for efficacy assessment due to minimized confounding, we recognize that real-world evidence (e.g., observational studies) may provide complementary insights on CHM safety and long-term outcomes. Given our focus on quantifying causal effects, RCTs remain the gold standard. Future updates could expand to observational designs once methodological standards for CHM real-world data mature. Second, restricting the analysis to English- and Chinese-language publications introduces potential language-based publication bias, as negative results or regional herbal formulations reported in other languages were not considered. Nevertheless, empirical evidence confirms that excluding non-indexed languages with limited CHM literature (e.g., Korean, Japanese) does not significantly alter conclusions, and rigorous screening of reference lists will mitigate publication bias. Third, our analysis primarily focused on commonly prescribed CHM interventions but did not systematically evaluate rare herbal combinations or traditional decoction methods, which may affect the generalizability of efficacy and safety conclusions across diverse CHM practices.

Despite these limitations, this study synthesizes the current evidence on CHM’s dual role in alleviating both psychological distress and urogenital symptoms in CP populations and underscores the need for standardized outcome reporting in future trials. These findings could inform the design of pragmatic, culturally adapted CHM regimens for complex CP cases.