Osteocalcin Levels in Male Idiopathic Hypogonadotropic Hypogonadism: Relationship With the Testosterone Secretion and Metabolic Profiles

Yu-Ying Yang,Hong-Yan Zhao,Wei-Qing Wang,Yu-Wen Zhang,Yu-Hong Chen,Shou-Yue Sun,Wen-Cui Wang,Jian-Min Liu,Zu-Wei Yang,Si-Chang Zheng,Chang Shan,Yan Qi,Wei-Qiong Gu

doi:10.3389/fendo.2019.00687

Abstract

Idiopathic hypogonadotropic hypogonadism (IHH) patients are characterized by the absence of puberty and varying degrees of deteriorated metabolic conditions. Osteocalcin (OC) could regulate testosterone secretion and energy metabolism, but it remains unknown whether such an effect exists in IHH patients. Our study is aimed to examine the relationship between serum OC levels with testosterone and its responsiveness to gonadotropin stimulation and metabolic profiles in male IHH patients. A total of 99 male patients aged 18–37 years and diagnosed with IHH were enrolled in the current study, and the relationships between OC and testicular volume, baseline total testosterone (TT), free testosterone (FT), and peak TT (Tmax) levels after human chorionic gonadotropin (hCG) stimulation, gonadotropin responsiveness index (GRI), which is calculated by dividing Tmax by testicular volume, as well as metabolic profiles, such as 2-h post-challenge glucose (2hPG) and fat percentage (fat%), were analyzed. The results showed that OC had an independent negative relationship with testicular volume (r = −0.253, P = 0.012) and a positive association with Tmax (r = 0.262, P = 0.014) after adjusting for confounders. In addition, OC was a major determinant of GRI (adjusted R2 for the model = 0.164, P = 0.012), fat% (adjusted R2 for the model = 0.100, P = 0.004), and 2hPG (adjusted R2 for the model = 0.054, P = 0.013) in IHH patients. In conclusion, OC is associated with testosterone secretion upon gonadotropin stimulation, glucose metabolism, and fat mass variations in IHH. This study was registered at clinicaltrials.gov (NCT02310074).

Highlights

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disease characterized by the absence of puberty with low gonadotropin and sex steroid levels, with a prevalence of 1–10/100000 [1]
In addition to the defect in sex development, IHH patients have varying degrees of deteriorated metabolic profiles, including higher body mass index (BMI), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and fat percentage, as well as lower high-density lipoprotein cholesterol (HDL-C) and fat-free mass compared with healthy controls [6,7,8], which might be attributed to the low levels of testosterone [9,10,11,12,13] and gonadotropins [8]
In contrast to the expectation that OC might be positively associated with testicular volume in IHH patients, we found a negative association between these two markers

Summary

Introduction

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disease characterized by the absence of puberty with low gonadotropin and sex steroid levels, with a prevalence of 1–10/100000 [1]. This condition is pathophysiologically caused by the congenitally deficient secretion of gonadotropinreleasing hormone (GnRH), which stimulates the release of gonadotropins and regulates the Osteocalcin in Male IHH development of gonads. Determination of the association between OC and metabolic parameters in this group of patients is of interest

Methods

Results

Conclusion