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. 2025 Jul 2;23(1):92.
doi: 10.1186/s12958-025-01425-9.

Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study

Sandro La Vignera  1 , Rossella Cannarella  2   3 , Vincenzo Garofalo  1 , Andrea Crafa  1 , Federica Barbagallo  1 , Rosita A Condorelli  1 , Aldo E Calogero  1
Affiliations

Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study

Sandro La Vignera et al. Reprod Biol Endocrinol. .

Abstract

Background: Tirzepatide (TZP), a dual agonist of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has recently been introduced in Italy for the treatment of obesity. Obesity is frequently associated with metabolic hypogonadism, which is characterized by low testosterone levels and normal low levels of gonadotropin. This condition exacerbates metabolic dysfunction and increases the risk of type 2 diabetes mellitus (DM). This study aims to evaluate the effects of TZP on metabolic hypogonadism in patients with obesity.

Methods: Male patients with obesity and metabolic hypogonadism were enrolled. Exclusion criteria included recent use of medications for hypertension, dyslipidemia, DM, anti-androgens, or hyperprolactinemia. All participants followed a hypocaloric diet and engaged in 20 min of daily brisk walking. Patients were allocated to one of the following treatment groups: Group A received 2.5 mg of TZP weekly for the first month, with the dose increased to 5 mg from the second month; Group B received no pharmacological treatment: Group C received transdermal testosterone. Clinical evaluations were conducted at 2 months including assessment of body composition, the Binge Eating Scale (BES), 5-item International Index of Erectile Function (IIEF-5) questionnaire to evaluate erectile dysfunction (ED), and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total testosterone (TT), and 17β-estradiol (E2). Free (fT) and bioavailable testosterone (bioT) were calculated using the Vermeulen formula.

Results: A total of 83 patients with obesity (mean age 55.3 ± 5.5 years) were included in the study, divided into three groups: Group A (28 patients, mean age 56.3 ± 4.7 years), Group B (30 patients, mean age 55.1 ± 5.2 years), and Group C (25 patients, mean age 54.0 ± 6.5 years). At baseline, significant differences were observed in waist circumference (WC), which was higher in Group B, as well as in the BES score, lean mass (LM), and serum LH levels, all of which were higher in Group A. After 2 months, Group A showed significantly greater reductions in body weight, WC, BES score, and fat mass, along with a notable increase in LM and IIEF-5 score compared to Groups B and C. Additionally, Group A exhibited significantly higher serum levels of LH, FSH, SHBG, TT, fT, and bioT, while E2 levels were significantly lower than both Groups B and C.

Conclusion: The results of this study suggest that TZP is effective in improving both metabolic parameters, ED, and gonadal hormone levels in patients with obesity and metabolic hypogonadism. These findings position TZP as a promising treatment for obese patients with functional hypogonadism arising from metabolic-related alterations.

Keywords: Body composition; Fat mass; Gonadotropins; Metabolic hypogonadism; Testosterone; Tirzepatide.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol was carried out in accordance with the ethical principles of the Declaration of Helsinki and its subsequent amendments. Ethical approval was waived as the procedures that patients underwent are standard components of routine clinical practice, and no participants were subjected to any experimental interventions. All participants provided informed consent for the use of their personal and clinical data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Intergroup comparison: Delta chance in Anthropometric parameters, Binge Eating Scale (BES) score and body composition. Group A showed a greater reduction in body weight, body mass index (BMI), waist circumference, BES score, and fat mass percentage compared to Groups B and C. The increase in lean mass was higher in Group A than in Group B, but not significantly different from Group C. The one-way analysis of variance or the Kruskal-Wallis test followed by Dunn’s post hoc analysis were used to evaluate intergroup differences, depending on whether the data were normally or non-normally distributed, respectively. A p-value of <0.05 was considered statistically significant
Fig. 2
Fig. 2
Intergroup comparison: Delta chance in 5-item International Index of Erectile Function (IIEF-5) questionnaire score. The increase in the score was higher in Group A than in Group B, but not significantly different from Group C. The one-way analysis of variance or the Kruskal-Wallis test followed by Dunn’s post hoc analysis were used to evaluate intergroup differences, depending on whether the data were normally or non-normally distributed, respectively. A p-value of <0.05 was considered statistically significant
Fig. 3
Fig. 3
Intergroup comparison: Delta chance in serum hormone levels. Group A showed a greater increase in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), sexual hormone-binding globulin (SHBG), total testosterone (TT), free testosterone (fT) and bioavailable testosterone (bioT), along with significantly lower E2 levels compared to both Groups B and C. The one-way analysis of variance or the Kruskal-Wallis test followed by Dunn’s post hoc analysis were used to evaluate intergroup differences, depending on whether the data were normally or non-normally distributed, respectively. A p-value of <0.05 was considered statistically significant
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