Discontinuation of hormone replacement therapy in young GH-treated hypopituitary women increases liver enzymes

ObjectiveHypopituitarism, often characterized by hypogonadism, is associated with central obesity, increased cardiovascular and endocrine morbidity and mortality. In Turner syndrome, which is also characterized by hypogonadism liver enzymes are often elevated, but readily suppressed by a short course of hormone replacement therapy (HRT). We investigated the effect of HRT on liver enzymes, lipid levels and measures of insulin sensitivity 26 in hypopituitary women.DesignWe studied 26 hypopituitary women (age 38.8 ± 11.0 (mean ± SD years), BMI 27.4 ± 5.1 kg/m2) during HRT and 28 days off therapy.MethodsWe measured liver enzymes, fasting levels of lipids, insulin and glucose as well as adiponectin and leptin levels. Body composition was assessed by means of anthropometry and bioimpedance.ResultsAlanine transaminase (ALT) and aspartate transaminase (AST) increased after discontinuation of HRT (ALT; treated: 22.3 ± 11.5 vs. untreated: 27.1 ± 11.1 (U/L) (P < 0.02); AST; treated: 20.4 ± 6.1 vs. untreated: 24.6 ± 8.9 (U/L) (P < 0.002)), whereas other liver function tests remained unchanged. Measures of insulin sensitivity and fasting lipids were also unaffected by HRT, whereas leptin levels decreased with cessation of HRT (leptin; treated: 23 (8–71) vs. untreated: 20 (8–64) (μg/L) (P < 0.0005)).ConclusionShort time discontinuation of HRT in young hypopituitary women increased liver enzymes, whereas measures of insulin sensitivity and lipid levels remained unchanged. We speculate that the estrogen component of HRT has beneficial effects on hepatic metabolism through various pathways. Further studies including liver imaging and with a time-dependent design are needed to clarify the role of HRT on liver enzyme levels, metabolic variables and liver fat content.