Search

Objective: Guidelines recommend using fasting samples to evaluate testosterone (T) levels in men, as free and total T levels decrease postprandially. However, it is not clear whether these dynamics are affected by age or obesity. This could be relevant given the obesity epidemic, ageing population and the barrier for screening which fasting could impose., Design/participants: A total of 43 men underwent a solid mixed meal tolerance test. Serum samples were taken fasting, and at 30, 60 and 120 minutes postprandially. A commercial immunoassay was used to determine sex hormone-binding globulin (SHBG) levels, liquid chromatography coupled to tandem mass spectroscopy for total T concentrations and free T levels were calculated., Results: Postprandially, both total and free T were lower at all-time points compared with fasting (all, P < .005). At 60 minutes, maximum mean decreases of 15 ± 15% and 17 ± 16% were seen for total and free T levels, respectively. Younger men had greater decreases in both total and free T levels compared with men older than 40 years (all, P < .05). A greater decrease at 30 and 60 minutes postprandially was observed for both total and free T levels in nonobese vs obese men (all, P < .05)., Conclusions: After a mixed meal, total and free T serum levels decreased whereas SHBG levels did not change. Interestingly, postprandial decreases were less pronounced in men older than 40 years and/or with obesity. Although this study indicates less pronounced decreases in certain men, fasting samples remain a prerequisite for establishing correct diagnosis of male hypogonadism., (© 2019 John Wiley & Sons Ltd.)

The natriuretic peptide signaling pathway has been implicated in many cellular processes, including endochondral ossification and bone growth. More precisely, different mutations in the NPR-B receptor and the CNP ligand have been identified in individuals with either short or tall stature. In this study we show that the NPR-C receptor (encoded by NPR3) is also important for the regulation of linear bone growth. We report four individuals, originating from three different families, with a phenotype characterized by tall stature, long digits, and extra epiphyses in the hands and feet. In addition, aortic dilatation was observed in two of these families. In each affected individual, we identified a bi-allelic loss-of-function mutation in NPR3. The missense mutations (c.442T>C [p.Ser148Pro] and c.1088A>T [p.Asp363Val]) resulted in intracellular retention of the NPR-C receptor and absent localization on the plasma membrane, whereas the nonsense mutation (c.1524delC [p.Tyr508 ∗ ]) resulted in nonsense-mediated mRNA decay. Biochemical analysis of plasma from two affected and unrelated individuals revealed a reduced NTproNP/NP ratio for all ligands and also high cGMP levels. These data strongly suggest a reduced clearance of natriuretic peptides by the defective NPR-C receptor and consequently increased activity of the NPR-A/B receptors. In conclusion, this study demonstrates that loss-of-function mutations in NPR3 result in increased NPR-A/B signaling activity and cause a phenotype marked by enhanced bone growth and cardiovascular abnormalities., (Copyright © 2018 American Society of Human Genetics. All rights reserved.)

Context: Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth., Objective: To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively., Design and Outcome Measurements: Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones., Results: Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development., Conclusion: Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

Background: Low levels of physical function have been associated with higher mortality hazard in older persons. However, few studies have investigated the association between functional changes and subsequent mortality. This study aimed to examine whether 3-year functional changes independently predict subsequent all-cause mortality., Methods: This population-based cohort study included 171 community-dwelling men aged ≥71years at wave 2 (baseline of the present analysis), living in the semi-rural community of Merelbeke (Belgium). Physical function assessments included the Short Form-36 (SF-36) Physical Function Index, Grip strength, Chair rising, and Timed Up and Go. Changes over a 3-year time were calculated using data obtained at four annual visits., Results: After a 15-year follow-up, 149 men (87%) died. Median survival time was 8.2 (4.2-12.4) years. Physical function assessed at a single time point (at wave 2 or wave 5) was significantly associated with subsequent mortality hazard, independently from future or preceding 3-year changes. Greater functional declines during the 3-year follow-up were associated with higher mortality hazards. These associations were 1) more pronounced within the first seven years, 2) independent from baseline age, polypharmacy, depression, disability, and physical function, and 3) no longer significant when closure physical function was taken into account., Conclusion: Physical function assessed at a single time point is a robust predictor of all-cause long-term mortality in community-dwelling older men. Yet, repeated assessments of physical function can provide prognostic information beyond that available from single initial assessment. However, with repeated assessments, most prognostic information can be found in the final assessment of physical function., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)