Metabolic Dysfunction-Associated Steatotic Liver DiseasePhase 4EndomMASLDNCT06523530
Effect of a GnRH Analog on Hepatic Steatosis
A Phase 4 study testing Goserelin Acetate 3.6 mg inj, implant in people with Metabolic Dysfunction-Associated Steatotic Liver Disease and Nonalcoholic Fatty Liver, run by Aristotle University Of Thessaloniki at 2 sites in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Nonalcoholic Fatty Liver, Endometriosis
- What is being tested?
- Goserelin Acetate 3.6 mg inj, implant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 2 sitesGreece
- Study dates
- 26 Nov 2024to Oct 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
Greece2 sites
424 General Military Hospital
Thessaloniki, Thessaloniki, 56429
1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki
Thessaloniki, 56403
About this study
Official title: Effect of the Pharmacological Cessation of Menstruation With a GnRH Analog on Hepatic Steatosis in Women With Endometriosis
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.
Read the detailed description
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.
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Nonalcoholic Fatty Liver, Endometriosis
- Being tested
- Goserelin Acetate 3.6 mg inj, implant
- 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
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Endometriosis, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Goserelin Acetate 3.6 mg inj, implantDrug
Also called Zoladex
3.6 mg (1ml) administered subcutaneously once every month for 6 months (totally 6 injections)
| Study group | Role | What they receive |
|---|---|---|
| Goserelin | Experimental | 31 women with histologically confirmed endometriosis will receive goserelin acetate post-surgically. Receives: Drug: Goserelin Acetate 3.6 mg inj, implant |
| Control | No intervention | 31 women with histologically confirmed endometriosis will not receive pharmacological treatment post-surgically. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 6 months
Secondary outcomes (22)
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
Measured: 6 months
Liver function tests II - γGT
Between-within group interactions will be performed for:
γ-glutamyltransferase (GGT; IU/l)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months
Adiponectin
Adiponectin is measured in μg/mL.
Between-within group interactions will be performed.
Measured: 6 months
Leptin
Leptin is measured in ng/mL.
Between-within group interactions will be performed.
Measured: 6 months
Tumor Necrosis Factor-α (TNF-α)
TNF-a is measured in pg/mL.
Between-within group interactions will be performed.
Measured: 6 months
Sex hormones I - Estradiol
Estradiol is measured in pg/mL.
Between-within group interactions will be performed.
Measured: 6 months
Sex hormones II - Testosterone
Testosterone is measured in ng/mL.
Between-within group interactions will be performed.
Measured: 6 months
Sex hormones III - Sex Hormone Binding Globulin (SHBG)
SHBG is measured in nmol/L.
Between-within group interactions will be performed.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2024
- Study start26 Nov 2024
- Primary completionApr 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Metabolic Dysfunction-Associated Steatotic Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, interventional, open label, non-randomized, parallel group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Collaborators
- 424 General Military Hospital
- Responsible party
- Principal investigator, Stergios A Polyzos, Aristotle University Of Thessaloniki
- Investigators
- Dimitrios A Anastasilakis, MD, PhDc, Study director, School of Medicine, Aristotle University of ThessalonikiAthina I Gkiomisi, MD, PhD, Study director, 424 General Military Hospital, Thessaloniki, GreeceDimitrios G Goulis, MD, PhD, Study director, School of Medicine, Aristotle University of ThessalonikiAngelos Daniilidis, MD, PhD, Study director, School of Medicine, Aristotle University of ThessalonikiAthanasios A Anastasilakis, MD, PhD, Study director, 424 General Military Hospital, Thessaloniki, GreeceChrysi Nalmpantidou, MD, Study director, "G. Gennimatas" General Hospital, Thessaloniki, GreeceStergios A Polyzos, MD, PhD, Principal investigator, School of Medicine, Aristotle University of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06523530
- Sponsor's protocol ID
- 5221
- Acronym
- EndomMASLD
- Status last verified
- Jul 2026
- First submitted
- 10 Jul 2024
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be available to other researchers upon reasonable request
Publications
Henry L, Paik J, Younossi ZM. Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment Pharmacol Ther. 2022 Sep;56(6):942-956. doi: 10.1111/apt.17158. Epub 2022 Jul 26.
PubMed 35880713Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Dec 1;78(6):1966-1986. doi: 10.1097/HEP.0000000000000520. Epub 2023 Jun 24.
PubMed 37363821Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006 May;23(5):469-80. doi: 10.1111/j.1464-5491.2006.01858.x.
PubMed 16681555Polyzos SA, Lambrinoudaki I, Goulis DG. Menopausal hormone therapy in women with dyslipidemia and nonalcoholic fatty liver disease. Hormones (Athens). 2022 Sep;21(3):375-381. doi: 10.1007/s42000-022-00369-8. Epub 2022 May 9.
PubMed 35532850Polyzos SA, Goulis DG. Menopause and metabolic dysfunction-associated steatotic liver disease. Maturitas. 2024 Aug;186:108024. doi: 10.1016/j.maturitas.2024.108024. Epub 2024 May 14.
PubMed 38760254Palmisano BT, Zhu L, Stafford JM. Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. doi: 10.1007/978-3-319-70178-3_12.
PubMed 29224098Venetsanaki V, Polyzos SA. Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives. Curr Vasc Pharmacol. 2019;17(6):546-555. doi: 10.2174/1570161116666180711121949.
PubMed 29992886Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, Isaka K. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res. 2016 Sep;42(9):1152-8. doi: 10.1111/jog.13023. Epub 2016 May 26.
PubMed 27225336Ferrero S, Evangelisti G, Barra F. Current and emerging treatment options for endometriosis. Expert Opin Pharmacother. 2018 Jul;19(10):1109-1125. doi: 10.1080/14656566.2018.1494154. Epub 2018 Jul 5.
PubMed 29975553DiVasta AD, Laufer MR. The use of gonadotropin releasing hormone analogues in adolescent and young patients with endometriosis. Curr Opin Obstet Gynecol. 2013 Aug;25(4):287-92. doi: 10.1097/GCO.0b013e32836343eb.
PubMed 23770813Polyzos SA, Kang ES, Boutari C, Rhee EJ, Mantzoros CS. Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. Metabolism. 2020 Oct;111S:154203. doi: 10.1016/j.metabol.2020.154203. Epub 2020 Mar 6.
PubMed 32151660Polyzos SA, Kountouras J, Tsatsoulis A, Zafeiriadou E, Katsiki E, Patsiaoura K, Zavos C, Anastasiadou VV, Slavakis A. Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones (Athens). 2013 Jul-Sep;12(3):405-16. doi: 10.1007/BF03401306.
PubMed 24121382Pafili K, Paschou SA, Armeni E, Polyzos SA, Goulis DG, Lambrinoudaki I. Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones. J Endocrinol Invest. 2022 Sep;45(9):1609-1623. doi: 10.1007/s40618-022-01766-x. Epub 2022 Mar 18.
PubMed 35303270