effect of a gnrh analog on hepatic steatosis

Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease; Nonalcoholic Fatty Liver; Endometriosis

Summary: menopause increases the risk of metabolic dysfunction-associated steatotic liver disease (masld), possibly owing to the abrupt lack of estrogen. gonadotropin-releasing hormone (gnrh) treatment in endometriosis is regarded as a model of pharmaceutical menopause. thus, the effect of goserelin acetate, a gnrh analog that results in transient menopause, on hepatic steatosis and fibrosis will be evaluated in this study.

the prevalence of metabolic dysfunction-associated steatotic liver disease (masld), which until recently was known as nonalcoholic fatty liver disease (nafld), has risen to 30% of the global adult general population, whereas the pharmaceutical interventions against it remain limited. owing to the epidemiologic and pathophysiologic association of masld with obesity, type 2 diabetes mellitus, dyslipidemia and arterial hypertension, the diagnostic criteria for masld are similar to those of the metabolic syndrome. menopause has been associated with higher masld prevalence, with the lack of estrogen being a very plausible pathogenetic contributor to this liver disease. other pathogenetic contributors of masld, including abdominal obesity, increase in insulin resistance (ir) and dysmetabolism of carbohydrates and lipids, are aggravated after menopause, thus adversely contributing to the pathogenesis of masld. regarding the effect of the lack of estrogen on the liver, most to date data are derived from experimental studies, largely showing a favoring effect on masld. epidemiological studies have also shown menopause as an associate of masld. however, existing clinical studies are mostly observational, thereby not being able to show a causative association between menopause and masld. gonadotropin-releasing hormone (gnrh) treatment in disorders such as endometriosis can be regarded as a model of pharmaceutical menopause. more specifically, gnrh analogs, like goserelin acetate, lead to pharmaceutical menopause by suppressing the axis hypothalamus-pituitary-ovaries, thus, causing an iatrogenic, reversible ovarian cessation, which lasts as long as the use of gnrh. the adverse effects of gnrh are generally mild and reversible after their discontinuation. this is a prospective, interventional non-randomized study, which aims to evaluate the effect of goserelin acetate on hepatic steatosis in women with histologically confirmed endometriosis compared with women with endometriosis that will not receive pharmacological treatment post-surgically.

Eligibility criteria:
inclusion criteria: * women of reproductive age * diagnosis of endometriosis. the disease is suspected by patient's individual history (chronic pelvic pain, dyspareunia or/and dysmenorrhea) and the ultrasonographic imaging (chocolate cysts). the diagnosis is confirmed histologically, after laparoscopic surgical treatment and biopsy sampling, which will be interpreted by an independent blinded pathologist. * use of contraceptives, which is the first line treatment, is contraindicated or the patient does not consent to receive contraceptives, due to personal preferences. * written informed consent to participate to the study exclusion criteria: * mean ethanol consumption \>10 g/day * history of other chronic liver disease (e.g., viral hepatitis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and overlap syndromes, drug-induced liver injury, hemochromatosis, wilson's disease, α1-antitrypsin deficiency) * liver cirrhosis * any malignancy * chronic kidney disease * uncontrolled hypothyroidism or hyperthyroidism * severe sexual hormone disorders (congenital adrenaline hyperplasia, down syndrome, turner syndrome). * use of the following medications within a 12-month period before baseline, which are associated with drug-induced liver injury (dili): interferon, tamoxifen, amiodarone, aloperidin, glucocorticoids, hormone replacement therapy, contraceptives, anabolic steroids, any medication against tuberculosis, epilepsy or viruses, methotrexate, parenteral nutrition * use of the following medications within a 12-month period before baseline, which are probably associated with improvement in hepatic steatosis: vitamin e, pioglitazone, insulin, glucagon-like peptide-1 receptor agonists (glp-1ras), sodium- glucose co-transporter-2 inhibitors (sglt-2i), orlistat, ursodeoxycholic acid * use of any gnrh agonist or antagonist within a 12-month period before baseline

Keywords: endometriosis goserelin acetate hepatic fibrosis masld mash metabolic dysfunction-associated steatotic liver disease metabolic dysfunction-associated steatohepatitis nafld nash nonalcoholic fatty liver disease nonalcoholic steatohepatitis treatment menopause