MON-195 - Multiple Focal Nodular Hyperplasia in A Transgender Man

Sex hormones may influence the genesis and growth of hepatic lesions, raising important considerations for the maintenance of hormone therapy in transgender individuals. Testosterone, depending on its formulation and route of administration, may exert distinct effects on hepatic metabolism and cellular architecture.

Case Report: We present a 39-yo transgender man, menarche at 15 yrs, who initiated cross-sex hormone therapy with IM testosterone cypionate at age 28. At 32, mild elevation of liver enzymes prompted imaging, revealing hepatic nodules. MRI findings suggested focal nodular hyperplasia (FNH) versus adenoma. After discontinuation of therapy, testosterone undecanoate was reintroduced at age 34. At 39, CT demonstrated stability of the nodules. Given diagnostic uncertainty, videolaparoscopic nodulectomy was performed, confirming FNH. Hormone therapy was subsequently modified to transdermal testosterone.

Discussion: Oral testosterone formulations, particularly 17α-alkylated derivatives, are well known for their hepatotoxic potential, including risks of cholestasis, adenoma, and hepatocellular carcinoma. This toxicity is linked to intense hepatic first-pass metabolism. In contrast, injectable formulations (e.g., cypionate, undecanoate) bypass first-pass metabolism but deliver supraphysiologic peaks, which may stress hepatocellular function and contribute to nodular hyperplasia. Transdermal testosterone provides more stable serum levels, minimizing hepatic impact. Histopathological findings in this case (hepatocellular proliferation with fibrous septa, inflammatory infiltrate) illustrate cellular modifications that may be potentiated by androgenic stimulation.

Conclusion: This case highlights the relevance of testosterone’s pharmacokinetics and tissue-level effects in the evaluation of hepatic lesions in transgender individuals. The choice of formulation and route of administration is critical for minimizing hepatic risk and guiding long-term therapy.

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