S2417 The Skinny on Estrogen and Liver Fat

Abstract

INTRODUCTION: Hepatic steatosis is a common condition defined as fat comprising >5% of liver sample without evidence of inflammation. We present a case of a 23 year old transgender female who presented with an abrupt rise in liver enzymes after 18 months of hormone therapy found to have significant steatosis on biopsy. CASE DESCRIPTION/METHODS: There was evidence of mildly elevated liver enzymes prior to starting estrogen therapy for transition with low normal BMI and enzymes were monitored closely while on estrogen. A complete serologic evaluation was done without evidence of alternate cause for rise in enzymes and biopsy revealed 40% steatosis without hepatocyte ballooning, necroinflammation or fibrosis. The patient had no medical history and denied medications or supplement use aside from those used for gender affirmation. There was no history of obesity, rapid weight gain or metabolic conditions. Her BMI was 23 and she had been on a stable dose of estrogen (with sub-therapeutic estrogen levels) for 18 months. DISCUSSION: This case represents a unique presentation of hepatic steatosis in the transgender population. The majority of what is known regarding liver toxicity of estrogen is derived from the study of hormone replacement therapy and oral contraceptive use and these are not identical to the regimens used for transition. Oral contraceptives usually include estrogen and progesterone and hormone replacement regimens use lower doses than in gender affirmation. Liver disease related to estrogen use varies widely depending on dose and formulation, but has not been studied in the transgender population using estrogen for gender affirmation. Tamoxifen, a selective estrogen receptor modulator, widely used in breast cancer therapy has been shown to have estrogenic effects on the liver, bone, and brain. Up to a third of tamoxifen patients develop steatosis independent of weight gain. It generally develops in the first 2 years of therapy and may progress to cirrhosis in as few as 3 years. The use of high dose estrogen therapy in gender affirmation may more closely mimic the mechanism of effect on liver tissue of tamoxifen rather than the direct correlate of hormone replacement as the doses are significantly lower and not adjusted based on serum levels in post-menopausal women. This case highlights the need for further study into estrogenic effects on the liver tissue and optimal screening and evaluation for transgender women who require high dose estrogen supplementation lifelong.