MON-278 - A Patch Too Far: Severe Hypertriglyceridemia-Induced Pancreatitis Triggered by Transdermal Estrogen

Introduction
Estrogen therapy is widely used for contraception and hormone replacement and is generally well tolerated. It can, however, alter lipid metabolism by increasing hepatic very low-density lipoprotein (VLDL) production and reducing lipoprotein lipase activity, leading to impaired triglyceride clearance. While estrogen-associated hypertriglyceridemia is well described, it is most commonly reported with oral formulations. Transdermal estrogen is typically considered to have a lower metabolic risk due to avoidance of first-pass hepatic metabolism.

Case Presentation
A 33-year-old female with a history of polycystic ovarian syndrome (PCOS) presented with two days of progressive epigastric pain, nausea, and diarrhea. She denied alcohol use or recent illness. She had initiated a transdermal norelgestromin–ethinyl estradiol patch approximately two months prior to presentation.
Laboratory evaluation revealed severe hypertriglyceridemia with triglycerides of 7,132 mg/dL ( < 150 mg/dL), lipase of 117 U/L (13-60 U/L), and an anion gap of 25. Computed tomography of the abdomen demonstrated acute pancreatitis without evidence of gallstones or biliary obstruction.
She was managed with aggressive intravenous fluids and an insulin infusion with dextrose, resulting in rapid reduction in triglycerides to 432 mg/dL within 48 hours. She was transitioned to fenofibrate therapy, insulin infusion was discontinued, and estrogen therapy was stopped. Her symptoms improved, and she was discharged on fenofibrate and atorvastatin.

Discussion
Hypertriglyceridemia-induced pancreatitis typically occurs at triglyceride levels >1,000 mg/dL and is often seen in the setting of secondary triggers superimposed on underlying metabolic susceptibility. Estrogen is a recognized but uncommon contributor, primarily via increased VLDL production. Although transdermal preparations are thought to have less hepatic impact, this case highlights that clinically significant hypertriglyceridemia can still occur.
Patients with insulin resistance, including those with PCOS, may be particularly vulnerable. Insulin infusion remains an effective strategy in the acute setting by enhancing lipoprotein lipase activity and accelerating triglyceride clearance.

Conclusion
Transdermal estrogen is not entirely metabolically neutral and can precipitate severe hypertriglyceridemia and pancreatitis in susceptible individuals. Consideration should be given to baseline lipid assessment and clinical risk stratification prior to initiation in high-risk patients.

References:
Seo D, Suh H, Lee JK, et al. Estrogen-induced acute pancreatitis: A case report and literature review. Obstet Gynecol Sci. 2017;60(5):485-489. doi:10.5468/ogs.2017.60.5.485

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