Now you see it, now you don't: Estrogen exposure and obesity effects on HCA development and regression

Abstract

Hepatocellular adenomas (HCAs) are rare benign hepatic tumors commonly associated with exogenous estrogen exposure, particularly in women using combined hormonal contraception (CHC). [1] Complications of HCAs include risk of hemorrhage and malignant transformation. The genotype-phenotype classification system of HCAs has defined several subtypes of HCAs with distinct patient, imaging, and pathophysiological characteristics. [2] Clinical management of HCAs, including resection/embolization versus watchful waiting, is dependent on size of tumor, sex, β-catenin activation mutation, and complications. CHC use confers a 30-40fold increase in the incidence of HCAs; thus, cessation of these agents is the first step for HCA management. [3,4] However, HCA disease course is variable after CHC cessation, suggesting that other factors may contribute to their progression. [4,5] In this multicenter study, Demory et al. retrospectively analyzed 183 patients with a total of 267 histologically confirmed HCA lesions. Of these, 96 (52%) underwent treatment, most of which were treated by resection. [6] The median age of patients was 38 years old; 88% were women, 22% obese, 45% had

How I Approach Hepatocellular Adenomas in Hormonally Distinct Populations: Time to Think Outside the (Contraceptive Pill) Box

“…Such options include progestin-only pills, the hormonal intrauterine device, subcutaneous implant, and depo-medroxyprogesterone injection (8). Beyond CHC cessation, weight loss of at least 5% has recently been shown to induce HCA regression (9,10). This likely relates to a decrease in levels of adipose-derived estrogens, increase in sex hormone-binding globulin leading to reduced bioavailable levels of endogenous sex hormones, and reduced levels of circulating insulins.…”