Scoping review on androgen pathways and therapy in adult sepsis and septic shock

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Frontiers in Medicine Published May 10, 2026 Medically reviewed May 10, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that current evidence does not support routine androgen therapy for sepsis, with no proven survival benefit.

This is a systematic scoping review that maps the evidence on testosterone levels, androgen receptor activity, and androgen-based interventions in adult patients with sepsis or septic shock. The authors synthesized findings from diverse study designs, noting a lack of primary trial data and heterogeneity in interventions and outcomes.

The review reports an inverse association between testosterone levels and disease severity, with lower levels in patients with higher SOFA and APACHE II scores. It also finds lower testosterone levels in non-survivors compared with survivors. Experimental and translational studies demonstrate that the androgen receptor pathway can regulate cytokine production and immune cell metabolism.

A key synthesized finding is that testosterone supplementation showed no statistically significant improvement in survival. The authors acknowledge that the narrative synthesis of diverse studies limits causal inference and that the evidence is not sufficient to support routine use of androgen therapy in sepsis.

Practice relevance is restrained, as current evidence does not support routine use of androgen therapy in sepsis. The review highlights gaps in primary trial data and calls for more rigorous studies to clarify the role of androgen pathways in sepsis pathophysiology and treatment.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

IntroductionSepsis remains a major challenge in intensive care medicine, characterized by a dysregulated host response to infection and high mortality. Increasing evidence highlights complex interactions among the endocrine, immune, and metabolic systems, including a potential role of testosterone in modulating the immunometabolic response.AimTo systematically map and synthesize current evidence on the role of testosterone as a potential modulator of the immunometabolic response in sepsis.Materials and methodsA scoping review was conducted in accordance with the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed, Scopus, Web of Science, Cochrane Library, and EBSCO were searched for studies published between 2015 and 2025. Eligible studies included adult patients with sepsis or septic shock and investigated testosterone levels, androgen receptor activity, or androgen-based interventions. All study designs, including case reports, were considered.ResultsThirteen studies met the inclusion criteria. The majority of studies reported lower testosterone levels in patients with higher disease severity, reflected by higher SOFA and APACHE II scores, and in non-survivors compared with survivors. Experimental and translational studies have demonstrated that the androgen receptor (AR) pathway regulates cytokine production and immune cell metabolism. Clinical studies evaluating testosterone supplementation reported changes in selected metabolic and clinical parameters; however, no statistically significant improvement in survival was observed.ConclusionTestosterone and the androgen receptor pathway may contribute to immunometabolic dysregulation in sepsis. Testosterone deficiency is associated with greater disease severity and increased mortality; however, current evidence does not support the routine use of androgen therapy. Further well-designed translational and clinical studies, incorporating sex-specific analyses, baseline hormonal status, and multi-omics approaches, are required to enable personalized hormonal interventions in sepsis.