Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations.

Fibroblast growth factor receptor 1 ( FGFR1 ) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l -1 , follicle-stimulating hormone (FSH) levels were 1.0 IU l -1 , and testosterone levels were 1.3 nmol l -1 . In contrast, the de novo group had LH levels of 0.2 IU l -1 , FSH levels of 0.5 IU l -1 , and testosterone levels of 0.9 nmol l -1 , indicating milder hypothalamus-pituitary-gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

Percent body fat was negatively correlated with Testosterone levels in male.

BACKGROUND: Lower testosterone levels in men have been consistently associated with metabolic abnormalities, particularly obesity. This study aims to investigate the relationship between testosterone and obesity by analyzing the correlation between testosterone levels and body fat percentage using data from the NHANES (National Health and Nutrition Examination Survey) database. METHODS: The study included a total of 5959 participants from the NHANES 2011-2016. Multivariable linear regression models were used to assess the association between testosterone levels and body composition parameters, including total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android to gynoid ratio (A/G), and lean mass percent (LMP). Subgroup analyses stratified by sex were conducted using multivariable linear regression. To account for potential non-linear relationships, fitted smoothing curves and generalized additive models were utilized. A separate analysis of participants with a BMI ≥ 30 kg/m2 was conducted to validate the conclusions. RESULT: Among males, testosterone levels showed a significant negative correlation with TPF (ß = -11.97, P <0.0001), APF (ß = -9.36, P<0.0001), GPF (ß = -10.29, P <0.0001), and A/G (ß = -320.93, P<0.0001), while a positive correlation was observed between LMP and testosterone levels (ß = 12.62, P<0.0001). In females, a contrasting pattern emerged in the relationship between testosterone and body fat, but no significant correlation was found between testosterone and body composition in obese women. CONCLUSIONS: The findings of this study support a negative association between body fat and testosterone levels in males.