Adhesive Capsulitis (AC), also known as “frozen shoulder,” is an idiopathic glenohumeral joint disorder characterized pathologically by capsular thickening and contracture, with clinical manifestations including peri-shoulder pain and progressive limitation of range of motion (1). The prevalence of AC in the general population is approximately 2–5%, and it is more common in women over 40 years of age (2). AC is typically self-limiting, with most patients experiencing spontaneous symptom resolution within 1–2 years without intervention (3). However, emerging evidence suggests that without standardized treatment, some patients may suffer from persistent shoulder dysfunction and pain, significantly impairing daily activities (4).

The current treatment goals for AC primarily include pain relief, improvement in joint range of motion, and reduction of functional impairment, thereby enhancing patients’ quality of life. Intra-articular shoulder injection serves as an important conservative treatment modality between physical therapy and surgical intervention, and is widely used in clinical practice. Among these interventions, CS injection is often considered a first-line treatment option due to its potent anti-inflammatory and analgesic effects (5). Multiple studies have confirmed that CS can significantly alleviate pain and restore joint function in the short term (6, 7). However, the therapeutic effect is often difficult to sustain over the long term, with a potential decline in efficacy or recurrence of symptoms over time (8, 9). Furthermore, repeated CS injections carry potential risks, such as cartilage damage and reduced tendon structural strength (10, 11). In recent years, PRP has garnered considerable attention as a regenerative medicine therapy in the treatment of musculoskeletal disorders (12). By releasing high concentrations of growth factors, PRP modulates local inflammatory responses and promotes tissue healing and regeneration (13). This suggests that PRP may intervene at a more fundamental level in the pathological process of AC and has the potential to provide more sustained clinical benefits.

Although several RCTs have compared the efficacy of PRP with CS in the treatment of AC, the results remain inconsistent. Therefore, this study aims to conduct a meta-analysis based on relevant RCTs to comprehensively evaluate whether there is a difference in efficacy between the two treatments from three dimensions: pain level, shoulder joint function, and range of motion improvement. The findings are expected to provide high-quality evidence-based medical evidence for clinical decision-making.

This study adhered to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (14). The review protocol has been registered in the PROSPERO database (Registration No. CRD420251156731).

This meta-analysis pooled data from 13 RCTs to comprehensively compare the efficacy of PRP versus CS injections for the treatment of AC. The main results indicated that although PRP and CS demonstrated comparable effects in terms of pain relief at 1 and 3 months, functional improvement at 1 month, and flexion, PRP exhibited significant advantages at the 6-month follow-up. Specifically, PRP was significantly superior to CS in pain control at 6 months, functional recovery from 3 to 6 months, and improvements in shoulder abduction, external rotation, and internal rotation range of motion.

Regarding the VAS score, the study by Yadav et al. (19) also found that PRP and CS exhibited comparable analgesic effects at the 1-month and 3-month follow-ups. However, the findings of Gupta et al. (20) and Kamra et al. (21) demonstrated that CS exhibited a significant advantage over PRP in terms of short-term pain relief. Early-stage pain in AC is primarily dominated by intense inflammatory pain, resulting from persistent stimulation of nociceptors by various inflammatory cytokines within the joint capsule, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-1 (COX-1) (22). CS rapidly interrupt the inflammatory cascade by potently inhibiting COX and the production of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α (23). This targeted mechanism allows CS to provide rapid pain relief in the early stages of AC. It is noteworthy, however, that PRP itself contains cytokines that antagonize inflammation (e.g., IL-1Ra) and promotes a microenvironment conducive to repair by modulating macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype (24). This provides a basis for the early analgesic effect of PRP, explaining the similarity in short-term efficacy between the two treatments. Regarding the superior analgesic effect of PRP at the 6-month follow-up, this conclusion is supported by multiple studies (25–27). As AC progresses to the chronic phase, pain initially generated solely by inflammatory stimuli evolves into mixed pain: firstly, mechanical pain resulting from traction at the end range of motion due to fibrotic contracture of the joint capsule; and secondly, neuropathic pain caused by sensitization of local nerve fibers due to persistent chronic inflammation (28). At this stage, the limitations of CS injections become evident, as they cannot reverse established fibrosis and their efficacy diminishes over time. In contrast, the core advantage of PRP lies in its disease-modifying effects. Through the release of growth factors that promote fibroblast proliferation and organized collagen deposition (29), PRP aids in repairing the thickened and contracted joint capsule, restoring its extensibility and gliding function. As tissue structure improves, nociceptive pain triggered by end-range stretching and abnormal stimulation of mechanoreceptors will be fundamentally alleviated (30). Therefore, the analgesic superiority of PRP is essentially a natural outcome of its successful promotion of tissue regeneration and elimination of the root cause of pain. This characteristic of PRP is not an isolated phenomenon but aligns with evidence from its application in other chronic musculoskeletal disorders. A meta-analysis comparing PRP with CS for knee osteoarthritis (KOA) similarly indicated that while CS demonstrated superior analgesic effects in the short term (4–12 weeks), PRP exhibited significant and sustained advantages in long-term (6–12 months) pain relief and functional improvement (31). Although KOA and AC differ in pathology—the former primarily involves cartilage degeneration (32), while the latter is characterized by capsular fibrosis—both conditions share core processes of chronic inflammation and progressive structural deterioration. The “delayed yet sustained” efficacy pattern demonstrated by PRP in both disorders strongly suggests that its mechanism extends beyond mere anti-inflammatory effects and is more likely attributable to its disease-modifying potential. This provides a plausible biological explanation for its ability to maintain significant therapeutic effects even at the 6-month follow-up.

However, this meta-analysis identified significant heterogeneity among the studies included for the 1-month, 3-month, and 6-month VAS scores. Although sensitivity analysis did not identify the source of heterogeneity, subgroup analysis based on gender composition revealed distinctly different patterns of antinociceptive effects: in studies with a predominantly female population, CS demonstrated significantly superior antinociceptive efficacy compared to PRP at the 1-month follow-up; conversely, in studies with a predominantly male population, PRP showed a significant advantage as early as the 3-month follow-up. This finding is unlikely to be coincidental and strongly suggests the inherent sexual dimorphism in pain perception and analgesic mechanisms. Diffuse noxious inhibitory control (DNIC) is an endogenous “pain inhibits pain” analgesic mechanism. As females generally exhibit less efficient DNIC function than males, they tend to experience heightened pain sensitivity (33). Consequently, the potent and rapid-onset anti-inflammatory effects of CS may better address the urgent need for fast and powerful analgesia in female patients, thereby yielding superior therapeutic outcomes within the first month. In contrast, males, possessing a more robust endogenous analgesic baseline, may derive greater benefit from the reparative effects of PRP over time. Furthermore, subgroup analysis of the VAS at 3 months indicated that PRP demonstrated superior analgesic efficacy when the CS dosage was 1 mL, while the therapeutic effects of the two treatments were comparable when a 2 mL CS dosage was used. Although neither the sensitivity analysis nor the subgroup analysis definitively identified the source of heterogeneity in the 6-month VAS, both confirmed the reliability of the primary conclusion: PRP was significantly superior to CS in pain relief at 6 months post-intervention. In summary, we speculate that the high heterogeneity may stem from patient gender differences and the dosage of CS. Additionally, variations in injection techniques (such as injection depth and the use of ultrasound guidance) could also be potential sources of heterogeneity. Regarding the assessment of publication bias, the results of Egger’s test and Begg’s test for the 6-month VAS were inconsistent: Egger’s test suggested the possible presence of publication bias (p = 0.006), whereas Begg’s test showed no statistical significance (p = 0.462). This discrepancy may be attributed to the greater sensitivity of Egger’s test to heterogeneity in effect sizes and to studies with small sample sizes, while Begg’s test might have had insufficient statistical power under the present data distribution. Nevertheless, given the positive signal indicated by Egger’s test, caution is warranted when interpreting the pooled results for the 6-month VAS.

Regarding functional recovery and range of motion improvement, this meta-analysis indicates that PRP treatment offers significant advantages over CS, particularly evident at the 3-month and 6-month follow-ups. The findings of multiple randomized controlled trials are consistent with the conclusions of this study (20, 21, 34). No significant difference in functional improvement was observed between the two treatments at the 1-month mark, which may be attributed to the rapid analgesic effect achieved by CS through its anti-inflammatory action, thereby contributing to a certain degree of functional recovery in the short term. In contrast, the growth factors contained within PRP support the entire process of wound healing and repair (13). Although this biological process develops relatively slowly, it establishes a structural foundation for functional recovery at 3 and 6 months, which is also consistent with the significant improvements observed in the DASH scores at these time points. In terms of the ROM, the marked superiority of PRP in abduction, external rotation, and internal rotation further corroborates its role in modulating pathological processes such as capsular fibrosis and contracture. Abduction and rotational movements of the shoulder are highly dependent on the extensibility of the glenohumeral joint capsule and the smooth gliding of the humeral head within the glenoid fossa. Specific capsuloligamentous structures, such as the middle glenohumeral ligament and the inferior glenohumeral ligament complex, play key roles in restricting excessive translation of the humeral head, thereby directly influencing the terminal angles of abduction and rotation (35, 36). PRP directly improved mechanical kinematic performance in these directions by promoting tissue healing and collagen reorganization. Notably, no significant difference in flexion range of motion was observed between the two groups. This may be attributed to the greater reliance of shoulder flexion on compensatory mechanisms of the scapulothoracic joint, rather than solely on the extent of capsular release in the glenohumeral joint. Using three-dimensional motion analysis, McClure et al. (37) quantified the scapular contribution to shoulder flexion in healthy individuals, demonstrating that the scapulothoracic joint accounts for approximately one-third of the total range of motion during arm elevation. Furthermore, Lin et al. (38) investigated the impact of shoulder stiffness on kinematics and observed that subjects with stiff shoulders exhibited altered scapular movement patterns and rhythm in an effort to maintain functional upper limb mobility. These findings directly support the notion that shoulder flexion relies more heavily on compensatory mechanisms compared with other planes of motion.

Notably, although no significant heterogeneity was observed in the DASH scores at 1 month and 6 months, the 3-month DASH results exhibited substantial heterogeneity (I² = 90%). LOO analysis did not identify the source of heterogeneity but confirmed the robustness of this finding. Further subgroup analysis revealed that the heterogeneity primarily stemmed from the demographic characteristics of the included study populations, specifically the gender distribution of the patients. No heterogeneity was observed among studies with a higher proportion of male patients (I²=0%), and a significant difference was detected between PRP and CS treatment (p < 0.00001). A similar absence of heterogeneity (I² = 0%) and a significant intergroup difference (p = 0.0004) were also found in studies with a higher proportion of female patients. It is noteworthy that in studies with a higher proportion of male patients, the PRP group demonstrated superior functional recovery at the 3-month post-treatment follow-up. This finding may be related to the microenvironment of PRP-mediated tissue healing. Testosterone has been shown to stimulate the proliferation of human dermal fibroblasts and enhance their migratory capacity via an androgen receptor-dependent pathway (39). Furthermore, relevant molecular biology studies indicate that during tendon healing, the androgen receptor signaling pathway is activated in the early healing phase and regulates the expression of a series of genes associated with cell proliferation and matrix synthesis (such as type II myofibers genes encoding type II myosin heavy chain and parvalbumin) (40). The higher androgen levels in males may provide a more synergistic microenvironment for the growth factors in PRP, thereby amplifying its reparative efficacy. In contrast, estrogen exerts a complex bidirectional regulatory effect on the fibrotic process (41, 42). It may inhibit the excessive activation of fibroblasts at specific stages, which, while beneficial for reducing pathological scar formation, could also potentially slow the pace of PRP-mediated structural remodeling of the joint capsule to some extent. The above discussion on sex differences explains why PRP demonstrated superior outcomes in studies with a higher proportion of male participants. Regarding the clinical outcomes of ROM, significant heterogeneity was observed among studies for all movements except internal rotation (I² = 0%). Sensitivity analysis identified the study by Mirzaee et al. (43) as the source of heterogeneity. After its exclusion, heterogeneity was eliminated, and PRP still showed a significant advantage (p = 0.0001, I² = 0%). It was found that patient population characteristics could be a source of heterogeneity. Additionally, differences in rehabilitation protocols following treatment might also contribute to heterogeneity among studies. Sensitivity and subgroup analyses did not identify the source of heterogeneity for abduction and flexion.

Significant heterogeneity was observed in the analyses of VAS and some ROM measurements. To explore its sources, we systematically performed sensitivity analysis (LOO) and subgroup analyses (based on gender and corticosteroid dose). The results indicated that gender was a profound moderating factor: CS injections demonstrated superior short-term analgesic effects in studies with predominantly female participants, whereas PRP showed earlier advantages in studies with predominantly male participants. Although most of the heterogeneity could not be fully explained by a single factor (potentially due to insufficiently reported details such as PRP preparation protocols and injection techniques), all analyses confirmed the robustness of the core conclusion: PRP provided sustained superior outcomes compared to CS at the 6-month follow-up in terms of pain relief, functional improvement, and ROM. In accordance with the Cochrane Handbook, a random-effects model was employed to provide conservative estimates. We recommend that future studies standardize the reporting of intervention details to further elucidate the sources of heterogeneity.

This meta-analysis has several limitations: (1) Heterogeneity was observed in the source study data for some outcome measures. In accordance with the Cochrane Handbook, a random-effects model was applied to address this heterogeneity; however, heterogeneity introduced by factors such as variations in PRP preparation protocols, injection techniques, and post-treatment rehabilitation plans could not be disregarded. (2) The longest follow-up time point in this analysis was defined as 6 months, which may be insufficient to evaluate the true long-term efficacy for a chronic condition like AC. Future RCTs with longer follow-up durations are warranted. (3) Although outcomes from the included studies were reported independently, certain assessment variables (e.g., range of motion and functional scores) may be intrinsically correlated. By analyzing them separately, the results could have been skewed.

Based on the results of this meta-analysis, a novel “stage-adaptive” treatment strategy for AC is proposed: CS is recommended as a high-efficacy intervention in the acute phase, while PRP is suggested as the recommended treatment plan for the chronic/fibrotic stage. The core of this strategic shift lies in moving from merely controlling symptoms toward altering the natural course of the disease, representing an evolution in the AC treatment paradigm. Furthermore, an innovative finding of this study is the confirmation that sex is a significant moderator of treatment response. The pathological mechanisms of AC may exhibit sexual dimorphism, and understanding the role of sex factors opens new avenues for precision medicine in AC. Future research should further explore biomarkers such as sex hormones and genetic background to establish individualized treatment prediction models. Clinical decision-making should comprehensively evaluate the patient’s disease stage, primary symptoms, and expectations regarding long-term prognosis.