Beyond steroid monotherapy: a systematic review and meta-analysis of combination therapy for severe to profound...

To systematically evaluate the comparative efficacy of initial combination therapy with systemic and intratympanic corticosteroids versus systemic corticosteroid monotherapy for hearing recovery in patients with severe or profound Sudden Sensorineural Hearing Loss (SSNHL).

A systematic review was conducted in PubMed, EMBASE, and LILACS through August 2025. Eligible studies included adults with severe or profound idiopathic SSNHL comparing systemic corticosteroid monotherapy with systemic plus intratympanic corticosteroid therapy. The primary outcome was hearing recovery measured by Pure-Tone Average (PTA) or standardized audiometric scales. Secondary outcomes included recovery rates, speech discrimination, tinnitus, and adverse events. The risk of bias was assessed using the RoB2 tool for randomized controlled trials and the Newcastle-Ottawa Scale (NOS) for observational studies.

Thirteen studies (3 randomized controlled trials, 2 case-control, 4 cohort, and 4 observational series) were included. Combination therapy consistently demonstrated superior hearing outcomes compared to systemic monotherapy. Qin et al. (2025) reported greater PTA improvement (31.0 ± 10.0 Db vs. 45.0 ± 9.8 dB) and higher complete recovery rates (46.5% vs. 29.4%, p = 0.005). Jung et al. (2016) found improved speech discrimination (72.3% vs. 57.4%, p = 0.042), and Gundogan et al. (2013) observed higher overall recovery (89% vs. 61.1%, p = 0.049). Observational cohorts supported these trends, especially with early treatment initiation. However, protocol heterogeneity and moderate-to-high risk of bias limited the strength of the evidence.

Combined systemic and intratympanic corticosteroid therapy generally yields better hearing recovery and speech discrimination outcomes than systemic monotherapy in patients with severe or profound SSNHL. The therapeutic benefit appears greatest when treatment is initiated early. Despite promising evidence, further large-scale, standardized randomized trials are required to confirm the optimal treatment protocol.