The influence of body composition on the response to dynamic stimulation of the endocrine pituitary-testis axis

BACKGROUND: Testosterone treatment is generally not recommended in men with obesity induced low serum testosterone. However, distinguishing this condition from overt testosterone deficiency in men with obesity where treatment should be initiated is a diagnostic challenge and tools to differentiate these conditions are scarce but could be of important clinical relevance. OBJECTIVES: To investigate the association between body composition and dynamic responses of the pituitary-testis axis in men. METHODS: Single-center cross-sectional study including 112 healthy men. Participants went through a full biochemical assessment of the pituitary-testis axis, and dynamic stimulatory tests of luteinizing hormone (LH) secretion (gonadotropin-releasing hormone (GnRH)-test) and testosterone secretion (choriogonadotropin (hCG)-test). A subset (N = 78) further had a DXA-scan performed. RESULTS: A higher body mass index (BMI) was associated with lower basal serum LH (βu = −0.44, 95% CI: −0.88 to −0.01, p = 0.04). The GnRH-stimulated LH increase was not significantly associated with BMI (βu = −0.10, 95% CI: −0.72 to 0.51, p = 0.74). Furthermore, a high BMI was associated with low basal testosterone (βu = −0.02, 95% CI: −0.03 to −0.02, p < 0.001), and free testosterone (βu = −15.0, 95% CI: −19.9 to −10.0, p < 0.001) and men with overweight and obesity had significantly lower testosterone (9%, p = 0.003 and 24%, p < 0.001) and free testosterone (25%, p = 0.006 and 50%, p < 0.001) concentrations compared to men with normal weight. The HCG-stimulated testosterone increase was significantly less dependent on BMI compared to the influence of BMI on basal testosterone concentrations (p = 0.04 for the interaction). CONCLUSIONS: Dynamic sex hormone responses following pituitary-testis axis stimulation were less dependent on BMI, compared to the influence of BMI on basal hormone concentrations and could potentially assist clinical decision making in patients with obesity suspected of testosterone deficiency.