Lynn Ogoniak, Sarah Sandmann, Julian Varghese, Michael J Ziller, Nina Neuhaus, Alexander Siegfried Busch
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引用次数: 0
Abstract
Objective: Age-related decline in circulating testosterone levels in men varies significantly and is often linked to comorbidities such as type 2 diabetes, and cardiovascular disease (CVD). While the genetic basis of testosterone levels is well-studied, the role of genetics in age-related testosterone decline remains unclear. This study aims to investigate the genetic contribution to age-related testosterone decline in men and its association with comorbidities.
Design: A longitudinal, population-based study in 6,354 men including consecutive testosterone (T), bioavailable testosterone (BAT), and sex hormone-binding globulin (SHBG) measurements.
Methods: We assessed the association of longitudinal serum biomarker changes with changes in disease prevalences and a polygenic score (PGS) for BAT developed in 183,909 UK Biobank participants.
Results: In the follow-up cohort (mean age: 58.2 years; mean follow-up: 4.3 years), baseline levels of BAT, T, and SHBG were each negatively associated with their respective relative changes at follow-up (all p<0.001). A PGS for BAT, strongly associated with baseline levels (p=2.2x10-16, R²=0.16), was not associated with BAT decline over time. Genome-wide analysis of BAT change identified no significant genetic loci. Instead, the BAT decline was associated with prevalence of several comorbidities including cancers and CVD (p=0.007 and 0.012, respectively).
Conclusions: Non-genetic factors are strongly associated with age-related BAT decline, whereas genetic predisposition may have a limited role. However, this does not rule out a potential genetic contribution. Our findings offer insight into the relationship between comorbidities and hormonal changes, supporting further research into their roles in testosterone decline and related health risks in aging men.
期刊介绍：
European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica.
The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology.
Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials.
Equal consideration is given to all manuscripts in English from any country.
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