Testicular Function and Bone in Young Men with Severe Childhood-Onset Obesity

Abstract

Background: Previous studies suggest increased risk for hypoandrogenism and fractures in men with obesity. We aimed to describe the effects of severe childhood-onset obesity on the cross talk between metabolic state, testes, and skeleton at late puberty. Methods: A cohort of adolescent and young adult males with severe childhood-onset obesity (n = 21, mean age 18.5 years) and an age-matched control group were assessed for testicular hormones and X-ray absorptiometry-derived bone mass. Results: Current median body mass indexes for the obese and control subjects were 37.4 and 22.9. Severe early-onset obesity manifested with lower free testosterone (median [interquartile range] 244 [194–332] vs. 403 [293–463] pmol/L, p = 0.002). Lower insulin-like 3 (1.02 [0.82–1.23] vs. 1.22 [1.01–1.46] ng/mL, p = 0.045) and lower ratio of testosterone to luteinizing hormone (2.81 [1.96–3.98] vs. 4.10 [3.03–5.83] nmol/IU, p = 0.008) suggested disrupted Leydig cell function. The degree of current obesity inversely correlated with free testosterone (τ = –0.516, p = 0.003), which in turn correlated positively with bone area at all measurement sites in males with childhood-onset obesity. Conclusions: Severe childhood-onset obesity is associated with impaired Leydig cell function in young men and lower free testosterone may contribute to impaired skeletal characteristics.

Male seminal parameters are not associated with Leydig cell functional capacity in men

“…The findings from the two studies presented here imply that poor sperm parameters and Leydig cell functional capacity in young adulthood are likely to have a separate postnatal aetiology from that caused by a common association in early life, and that lifestyle and/or exposures in childhood and adolescence are likely to be playing a significant role. In particular, the Swedish study highlights the marked negative influence of BMI on chronic Leydig cell functional capacity, reinforcing preliminary findings from a recent study looking at late adolescent boys, 46 as well as other more diverse cohorts 19,40 . How BMI affects circulating INSL3 levels is not known, but unlike for testosterone where the increased levels of aromatase in fat tissue will have a directly modifying effect on the circulating androgen, it appears more likely that adipose tissue factors may be influencing Leydig cell function.…”

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men

“…Using this assay, INSL3 concentrations were lower in both untreated boys with Klinefelter syndrome ( n =83) or hypogonadotrophic hypogonadism ( n =103). Unlike serum testosterone, INSL3 was not affected by BMI, body fat percentage or alcohol consumption ( 41 ) and was not affected by diurnal variation.…”

Evaluating and implementing block jackknife resampling Mendelian randomization to mitigate bias induced by overlapping samples

“…Therefore, identifying any modifiable risk factors contributing to changes in testosterone levels would be valuable for preventing this condition. Childhood-onset adiposity, previously identified as an early life risk factor for multiple cardiovascular diseases and cancer ( 31 , 32 ), was reported to associate with lower testosterone levels in adulthood in an observational study ( 33 ). This association could be owing to confounding and thus should be further studied using MR to determine whether childhood adiposity has a causal effect on lower levels of testosterone.…”