Effect of a GnRH Analog on Hepatic Steatosis
NCT Number: NCT06523530
Acronym: EndomMASLD
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease|Nonalcoholic Fatty Liver|Endometriosis
Interventions: DRUG: Goserelin Acetate 3.6 mg inj, implant
Sponsor: Aristotle University Of Thessaloniki
Collaborators: 424 General Military Hospital
Sex: FEMALE
Age: ADULT
Enrollment: 62
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10
Completion Date: 2027-04
Locations: 424 General Military Hospital, Thessaloniki, Greece|1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki, Thessaloníki, 56403, Greece

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.

Primary Outcome Measures: Hepatic steatosis, Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s.

Between-within group interactions in UGAP

UGAP is a non-invasive index based on the attenuation quantification of the ultrasound beam through the hepatic parenchyma, thus used for hepatic steatosis quantification. Cut-off values of ≥ 0.53 dB/cm/MHz, ≥ 0.60 dB/cm/MHz, and ≥ 0.65 dB/cm/MHz have been proposed for the diagnosis of steatosis grade S1, S2, and S3, respectively, 6 months|Hepatic fibrosis, Liver stiffness (LS) measured with 2D Shear Wave Elastography (2D SWE) on an ultrasound machine GE Logiq E10s.

Between-within group interactions in LS

2D SWE is a non-invasive tool measuring the hepatic parenchyma stiffness, thus indirectly suggesting fibrosis stage (F). Cut-offs values of \<8.27 kPa, 8.27-9.39 kPa, 9.40-11.88 kPa and ≥11.88 kPa have been proposed for F0-F1, F2, F3, and F4, respectively., 6 months
Secondary Outcome Measures: Liver function tests I - ALT and AST, Between-within group interactions will be performed for each of the following parameters:

Alanine aminotransferase (ALT; IU/l), aspartate aminotransferase (AST; IU/l);

ALT to AST ratio will be calculated, 6 months|Liver function tests II - γGT, Between-within group interactions will be performed for:

γ-glutamyltransferase (GGT; IU/l), 6 months|Insulin resistance, Between-within group interactions will be performed for Homeostasis Model Assessment - Insulin Resistance (HOMA-IR), which is calculated by the formula: fasting glucose (mg/dl) × insulin (mU/l)/405, and is an index of insulin resistance; higher score indicates greater insulin resistance., 6 months|Lipid profile, Between-within group interactions will be performed for each of the following parameters:

Total cholesterol (TC; mg/dL) Triglycerides (TG; mg/dL) High-density lipoprotein cholesterol (HDL-C; mg/dL) 4. Low-density lipoprotein cholesterol (LDL-C)

LDL-C (mg/dL) is calculated by the formula: TC (mg/dl) - HDL-C (mg/dl) - TG (mg/dl)/5., 6 months|Non-invasive hepatic steatosis index I - Fatty Liver Index (FLI), FLI is calculated by the formula \[(e0.953 × Loge (TG, mg/dL) + 0.139×BMI (kg/m2) + 0.718× Loge (GGT, U/L) + 0.053 × waist circumference (cm) -15.745) / (1 + e0.953 × Loge (TG, mg/dL) + 0.139×BMI (kg/m2) + 0.718×Loge (GGT, U/L) + 0.053 × waist circumference (cm) -15.745)\] × 100.

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis index II - Hepatic Steatosis Index (HSI), HSI is calculated by the formula: 8 \* ALT (U/L) / AST (U/L) + BMI (kg/m2) + 2 \[if type 2 diabetes melitus (T2DM)\] + 2 (if female).

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis index III - Triglyceride/Glucose Index (TyG), TyG is calculated by the formula: Ln\[TG (mg/dL) \* Glu (mg/dL) / 2\].

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis index IV - Tyg-BMI, Tyg-BMI is calculated by the formula: TyG \* BMI (kg/m2).

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis indices V - NAFLD test, NAFLD test is calculated by the formula: -0.695 + 0.031 \* BMI (kg/m2) + 0.003 \* TC (mg/dL) + 0.014 \* ALT (U/L) + 0.025 \* C-reactive protein (CRP) (mg/dL).

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis index VI - Metabolic Score for Insulin Resistance (MetS-IR), MetS-IR is calculated by the formula: Ln\[2 \* Glu (mg/dL) + TG (mg/dL)\] \* BMI (kg/m2) / Ln\[HDL-C (mg/dL)\].

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis index VII - Lipid Accumulation Product index (LAP), LAP is calculated by the formula: \[WC (cm) - 58\] \* \[TG (mg/dL) / 88.57\].

Between-within group interactions will be performed., 6 months|Non-invasive hepatic steatosis index VIII - Liver Fat Score (LFS), LFS is calculated by the formula: -2.89 + 1.18 (if metabolic syndrome) + 0.45 \* 2 (if T2DM) + 0.15 \* insulin (mU/L) + 0.04 \* AST (U/L) - 0.94 \* AST (U/L) / ALT (U/L).

Between-within group interactions will be performed., 6 months|Non-invasive hepatic fibrosis index I - NAFLD fibrosis score (NFS), NFS is calculated by the formula: -1.675 + 0.037 \* age (years) + 0.094 \* BMI (kg/m2) + 1.13 (if impaired fasting glucose or T2DM) + 0.99 \* AST (U/L) / ALT (U/L) - 0.013 \* platelet count \[\*10(9)/L\] - 0.66 \* albumin (g/dL).

Between-within group interactions will be performed., 6 months|Non-invasive hepatic fibrosis index II - Fibrosis-4 index (FIB-4), FIB-4 is calculated by the formula: age (years) \* AST (U/L) / {platelet count \[\*10(9)/L\] \* √ALT (U/L)}.

Between-within group interactions will be performed., 6 months|Non-invasive hepatic fibrosis index III - AST-to-Platelet Ratio Index (APRI), APRI is calculated by the formula: AST (U/L) / upper limit of normal \* 100 / platelet count \[\*10(9)/L\].

Between-within group interactions will be performed., 6 months|Non-invasive hepatic fibrosis index IV - Metabolic dysfunction-Associated Fibrosis Score (MAF-5), MAF-5 is calculated by the formula: -11.3674 + 0.0282 \* WC (cm) - 0.1761 \* BMI (kg/m2) + 0.0019 \* WC (cm) \* BMI (kg/m2) + 2.0762 (if T2DM) + 2.9207 \* Ln\[AST (U/L)\] - 0.0059 \* platelet count \[\*10(9)/L\].

Between-within group interactions will be performed., 6 months|Adiponectin, Adiponectin is measured in μg/mL.

Between-within group interactions will be performed., 6 months|Leptin, Leptin is measured in ng/mL.

Between-within group interactions will be performed., 6 months|Tumor Necrosis Factor-α (TNF-α), TNF-a is measured in pg/mL.

Between-within group interactions will be performed., 6 months|Sex hormones I - Estradiol, Estradiol is measured in pg/mL.

Between-within group interactions will be performed., 6 months|Sex hormones II - Testosterone, Testosterone is measured in ng/mL.

Between-within group interactions will be performed., 6 months|Sex hormones III - Sex Hormone Binding Globulin (SHBG), SHBG is measured in nmol/L.

Between-within group interactions will be performed., 6 months