Body Composition, Adipocytokine, and Metabolic Parameters in Men With Congenital Hypogonadotropic Hypogonadism

Objective: This study aimed to evaluate the long-term effects of hormone therapies on the body composition, adipokines and metabolic parameters of adult men with congenital hypogonadotropic hypogonadism (CHH).

Methods: Sixty-six patients with CHH and 21 healthy controls were recruited. Patients were divided into untreated (n = 33) and treated (n = 33) groups based on hormone therapy history. Body composition was assessed using dual-energy X-ray absorptiometry (DXA), and adipokines and metabolic parameters were measured in all participants.

Results: Compared to the healthy control group, patients in the treated group had lower serum testosterone levels (p < 0.001), increased body fat percentage (BFP) and visceral adipose tissue (VAT) volume, decreased lean soft tissue (LST) and bone mineral content (BMC) (p < 0.05), increased serum leptin levels accompanied by decreased adiponectin (ADP) (p < 0.05), higher HOMA-IR with lower QUICKI (p < 0.05). Compared to the untreated group, patients in the treated group (therapy duration 4.8 ± 2.3 years) had higher serum testosterone levels (p < 0.001), decreased BFP and VAT volume, increased LST and BMC (p < 0.05), decreased serum leptin levels (p < 0.001), and decreased HOMA-IR accompanied by increased QUICKI (p < 0.05). Among them, VAT volume, LST, BMC, HOMA-IR and QUICKI reached healthy control levels (p > 0.05). Multiple stepwise linear regression analysis showed serum testosterone levels were negatively correlated with BFP (β = -0.564, p < 0.001) and VAT volume (β = -0.260, p = 0.045), positively correlated with LST (β = 0.305, p = 0.018) and BMC (β = 0.423, p = 0.001). Serum testosterone levels were independently negatively correlated with leptin levels (β = -0.277, p = 0.004).

Conclusions: Patients with untreated CHH had impaired body composition, adipokines and metabolic parameters. While hormone therapies can improve body composition and glucolipid metabolism in patients with CHH, this imperfect treatment does not fully rescue body composition abnormalities when compared to healthy individuals. Abnormal metabolic parameters in patients with CHH are associated with increased fat mass and abnormal serum leptin level. Serum testosterone levels were independently negatively correlated with leptin levels.