OR09-06 Tirzepatide as a Promising Treatment for Metabolic Hypogonadism in Obese Men: Effects on Metabolic and Hormonal Parameters

Abstract Disclosure: S. La Vignera: None. R. Cannarella: None. V. Garofalo: None. A. Crafa: None. R. Condorelli: None. A.E. Calogero: None. Background: Tirzepatide (TZP), a dual agonist of the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, was recently introduced in Italy for the pharmacological treatment of obesity. A significant percentage of obese patients experience metabolic hypogonadism, characterized by low testosterone levels that exacerbates metabolic dysfunction and increases the risk of developing type 2 diabetes mellitus (DM). This study aims to evaluate the effects of TZP in the treatment of metabolic hypogonadism in obese patients. Methods: Eighty-three obese patients (body mass index: 34.9±3.5 kg/m2; range: 30-42 kg/m2), aged 55.3±5.5 years (range: 44-63 years) with metabolic hypogonadism as previously defined (PMID: 36675601), were consecutively enrolled. Exclusion criteria included recent use of medications for hypertension, dyslipidemia, DM, anti-androgenic drugs, or hyperprolactinemia. Patients were prescribed a hypocaloric diet, reducing their daily caloric intake by 20%, and daily 20-min brisk walk. Group A (28 patients) received 2.5 mg of TZP weekly for the first month, increased to 5 mg in the second month; Group B (30 patients) received no treatment; Group C (25 patients) received transdermal testosterone. Clinical evaluations at 2 months (T1) included body composition, the Binge Eating Scale (BES), and measurement of serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), and 17β-estradiol (E2). Statistical analyses were conducted using t-test, Wilcoxon test, analysis of variance, or Kruskal-Wallis tests, as appropriate. Results: Before treatment (T0), Group A exhibited significantly lower LH levels and higher BES scores compared to Groups B and C, while no other differences were found at baseline at intergroup analysis. At T1, Group A showed significant reductions in body weight, waist circumference (WC), BES score, and fat mass percentage, along with a notable increase in lean mass percentage (p<0.001 for all). Furthermore, serum levels of LH, FSH, and TT (p<0.0001 for all) were significantly elevated in Group A, while E2 levels significantly decreased (p<0.0001) compared to T0 values. At intergroup analysis at T1, Group A showed significantly greater reductions in body weight, WC, BES score, and fat mass (p<0.000001 for all), as well as a greater increase in lean mass (p=0.03) compared to both Groups B and C. Furthermore, Group A had the highest serum levels of LH, FSH, and TT, and the lowest E2 levels (p<0.000001 for all) compared to both Groups B and C. Conclusion: These findings suggest that TZP effectively improves both metabolic parameters and gonadal hormone levels in obese patients with metabolic hypogonadism. This makes TZP a promising therapeutic option for this patient population. Presentation: Saturday, July 12, 2025