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Context Acute pancreatitis is related to drugs in 1.4-2% of cases. Estrogens are an uncommon but well-known risk factor of pancreatitis in women and men with preexisting hyperlipidemia. Case report We report the case of a 37-yearold man with covert hypertriglyceridemia who developed a severe life-threatening pancreatitis strongly associated with estrogen therapy preparatory to sex change surgery, characterized by a massive triglyceride level, pancreatic insufficiency and multiple organ failure at the time of the diagnosis. Other causes of the disease were ruled out. Conclusions To our knowledge, this is the first description of severe necrotizing estrogen-induced pancreatitis in a male. Baseline abnormal triglyceride levels should be checked by physicians before starting estrogen therapy in women and men..