臨床研究等提出・公開システム

Testosterone Replacement Trial in Patients with Late-Onset Hypogonadism Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease

Testosterone Replacement Trial in Patients with Late-Onset Hypogonadism Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease

Matsuda Takaaki

Institute of Medicine, University of Tsukuba

1-1-1 Tennodai, Tsukuba, Ibaraki

matsuda.takaaki.dd@ms.hosp.tsukuba.ac.jp

Takaaki Matsuda

Institute of Medicine, University of Tsukuba

1-1-1 Tennodai, Tsukuba, Ibaraki

+81-29-853-3053

matsuda.takaaki.dd@ms.hosp.tsukuba.ac.jp

Recruiting

April. 23, 2026

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

All of the following conditions (1-6) must have been met within 26 weeks prior to obtaining informed consent.
1. Male participants aged 40 years or older.
2. An Aging Males' Symptoms (AMS) score of 27 points or higher.
3. Serum total testosterone levels < 346 ng/dL (12 nmol/L) and/or free testosterone levels < 7.5 pg/mL.
4. Presence of steatotic liver on abdominal ultrasonography.
5. Meeting at least one of the cardiometabolic risk factor criteria for metabolic dysfunction-associated steatotic liver disease (MASLD).
6. Individuals from whom written informed consent was obtained voluntarily after they had received a full explanation of the study and demonstrated sufficient understanding.

1. Alcohol consumption of 210 g or more of ethanol per week.
2. Diagnosis of active viral hepatitis (including carriers), autoimmune hepatitis, primary biliary cholangitis, hemochromatosis, Wilson's disease, or other chronic liver diseases.
3. Current use of medications known to induce hepatic steatosis, including valproic acid, amiodarone, tamoxifen, methotrexate, or systemic corticosteroids.
4. Testosterone replacement therapy administered within 26 weeks prior to the eligibility assessment date.
5. Ongoing anti-androgen therapy or anti-estrogen therapy at the time of eligibility assessment.
6. A prostate-specific antigen (PSA) level of 2.0 ng/mL or greater at the time point closest to the eligibility assessment date within 26 weeks prior to eligibility assessment.
7. Diagnosis of prostate cancer or breast cancer, or presence of untreated benign prostatic hyperplasia.
8. History of treatment for malignant tumors within five years prior to the eligibility assessment date.
9. A hematocrit level of 50% or greater at the time point closest to the eligibility assessment date within 26 weeks prior to eligibility assessment.
10. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels three times or greater than the upper limit of normal at the time point closest to the eligibility assessment date within 26 weeks prior to eligibility assessment.
11. An estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at the time point closest to the eligibility assessment date within 26 weeks prior to eligibility assessment.
12. Untreated obstructive sleep apnea at the time of eligibility assessment.
13. Uncontrolled hypertension (systolic blood pressure of 180 mmHg or higher and/or diastolic blood pressure of 110 mmHg or higher), excluding patients adequately controlled with antihypertensive therapy.
14. Ongoing acute-phase treatment for thromboembolic disease.
15. Heart failure classified as New York Heart Association (NYHA) class 3 or higher.
16. Inability to undergo magnetic resonance imaging (MRI).
17. Desire for fertility or plans for childbearing.
18. Determination by the investigator that study participation is inappropriate.

Male

Late-onset hypogonadism complicated by metabolic dysfunction-associated steatotic liver disease

The following two testosterone replacement agents will be administered concomitantly for a period of 24 weeks.
1. Enarmon Depot (testosterone enanthate) will be administered at a dose of 250 mg by intramuscular injection once every four weeks.
2. Glowmin (testosterone) will be administered transdermally at a dose of 3 mg of testosterone (2 cm per application) twice daily (morning and evening) for 14 consecutive days from Day 14 to Day 27, with the day of intramuscular injection defined as Day 0. If the interval between visits is within the acceptable range, apply the medication until the day before the next visit.

Change from baseline in hepatic fat content as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) at Week 24.

1. Liver function parameters (AST, ALT, LDH, ALP, GGT, total bilirubin, cholinesterase, etc.).
2. Indices based on liver function tests, including the Fatty Liver Index (FLI), Fibrosis-4 (FIB-4) index, Hepatic Steatosis Index (HSI), and Albumin-Bilirubin (ALBI) score.
3. Parameters of glucose metabolism, including HbA1c, fasting plasma glucose, insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR).
4. Parameters of lipid metabolism, including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and free fatty acids.
5. Endocrine function parameters, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total testosterone, free testosterone, dihydrotestosterone (DHT), estradiol, dehydroepiandrosterone sulfate (DHEA-S), and cortisol.
6. Body composition parameters, including waist circumference, body weight, skeletal muscle mass, and fat mass.
7. Handgrip strength.
8. Mental health status assessed by the Patient Health Questionnaire-9 (PHQ-9).
9. Aging Males' Symptoms (AMS) score.
10. Physical activity assessed by the International Physical Activity Questionnaire (IPAQ).

+81-29-853-3749

Mar. 18, 2026

No

none