Effect of the Pharmacological Cessation of Menstruation With a GnRH Analog on Hepatic Steatosis in Women With Endometriosis
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- Hepatic fibrosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Control
31 women with histologically confirmed endometriosis will not receive pharmacological treatment post-surgically.
Goserelin
31 women with histologically confirmed endometriosis will receive goserelin acetate post-surgically.
干预措施: Goserelin Acetate 3.6 mg inj, implant (Drug)
结局指标
主要结局
Hepatic fibrosis
时间窗: 6 months
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.
Hepatic steatosis
时间窗: 6 months
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
次要结局
- Lipid profile(6 months)
- Non-invasive hepatic steatosis index I - Fatty Liver Index (FLI)(6 months)
- Non-invasive hepatic steatosis index II - Hepatic Steatosis Index (HSI)(6 months)
- Liver function tests I - ALT and AST(6 months)
- Insulin resistance(6 months)
- Non-invasive hepatic fibrosis index IV - Metabolic dysfunction-Associated Fibrosis Score (MAF-5)(6 months)
- Sex hormones III - Sex Hormone Binding Globulin (SHBG)(6 months)
- Non-invasive hepatic fibrosis index II - Fibrosis-4 index (FIB-4)(6 months)
- Non-invasive hepatic steatosis indices V - NAFLD test(6 months)
- Non-invasive hepatic steatosis index VI - Metabolic Score for Insulin Resistance (MetS-IR)(6 months)
- Non-invasive hepatic steatosis index VIII - Liver Fat Score (LFS)(6 months)
- Non-invasive hepatic fibrosis index III - AST-to-Platelet Ratio Index (APRI)(6 months)
- Liver function tests II - γGT(6 months)
- Non-invasive hepatic steatosis index IV - Tyg-BMI(6 months)
- Non-invasive hepatic steatosis index III - Triglyceride/Glucose Index (TyG)(6 months)
- Adiponectin(6 months)
- Tumor Necrosis Factor-α (TNF-α)(6 months)
- Non-invasive hepatic steatosis index VII - Lipid Accumulation Product index (LAP)(6 months)
- Non-invasive hepatic fibrosis index I - NAFLD fibrosis score (NFS)(6 months)
- Leptin(6 months)
- Sex hormones I - Estradiol(6 months)
- Sex hormones II - Testosterone(6 months)
研究者
Stergios A Polyzos
Associate Professor of Pharmacology
Aristotle University Of Thessaloniki