Study on Analgesic-Induced Endocrine Gland Damage and its potential mechanisms

Analgesics are widely used for pain management, yet their association with endocrine dysfunction remains understudied. This pharmacovigilance study analyzes endocrine-related adverse events (AEs) linked to analgesics, identifies high-risk populations, and explores mechanistic pathways. FAERS data (Q1 2004 to Q3 2023) were analyzed via OpenVigil 2.1 disproportionality analysis to assess analgesic-endocrine AE associations. Risk variations were evaluated through age/gender stratification, and molecular pathways were investigated via enrichment analysis. Opioids exhibited the strongest endocrine associations, particularly codeine with parathyroid injury (Reporting Odds Ratio [ROR]: 14.867, 95% Confidence interval [95% CI]: 12.336-17.918) and hypothalamic-pituitary injury (ROR: 3.197, 95% CI: 1.52-6.722), and methadone with testicular injury (ROR: 2.126, 95% CI: 1.446-3.126). Flurbiprofen (NSAIDs) exhibited pancreatic injury risk (ROR: 8.416, 95% CI: 5.187-13.656). Gabapentin/pregabalin showed no significant associations. Stratified analyses revealed elevated risks in females (e.g. codeine-parathyroid injury: ROR = 19.028 vs. non-significance in males) and in patients aged ≥60 years. Enrichment analysis implicated dysregulated hormone-metabolic pathways underlying tissue-specific injuries and pointed to disruption of several key signaling pathways. Specific analgesics (not all) are associated with endocrine risks, particularly in females and older adults, necessitating personalized monitoring despite limited dose-response data.