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Title: Late Onset Hypogonadism: Metabolic Impact.
Austin Authors: Grossmann, Mathis ;Ng Tang Fui, Mark ;Cheung, Ada S 
Affiliation: Medicine (University of Melbourne)
Issue Date: Nov-2020
Date: 2019-09-10
Publication information: Andrology 2020; 8(6): 1519-1529
Abstract: Obesity and dysglycemia (comprising insulin resistance, the metabolic syndrome and type 2 diabetes), i.e. diabesity, are associated with reduced circulating testosterone and, in some men, clinical features consistent with androgen deficiency. To review the metabolic impact of late onset hypogonadism (LOH). Comprehensive literature search with emphasis on recent publications. Obesity is one of the strongest modifiable risk factors for LOH, and coexisting diabetes leads to further hypothalamic-pituitary-testicular (HPT) axis suppression. The HPT axis suppression is functional and hence potentially reversible, and occurs predominantly at the level of the hypothalamus. While definitive mechanistic data are lacking, the evidence suggests that HPT axis suppression is mediated by dysregulation of pro-inflammatory cytokines leading to hypothalamic inflammation. Dysregulation of central leptin and insulin signalling may also contribute. In contrast, recent data challenge the paradigm that estradiol excess is a major contributor to HPT axis suppression. Instead relative estradiol signalling deficiency may contribute to metabolic dysregulation in men with diabesity. While weight loss and optimisation of comorbidities can reverse functional HPT axis suppression, testosterone treatment leads to metabolically favourable changes in body composition, and to improvements in insulin resistance. The relationship between diabesity and LOH is bi-directional. Preliminary evidence suggests that, in carefully selected men, lifestyle measures and testosterone treatment may have additive effects. While recent research has provided new insights into mechanistic and clinical aspects of diabesity-associated LOH, more evidence from well-designed large trials is needed to guide the optimal clinical approach to such men.
DOI: 10.1111/andr.12705
ORCID: 0000-0001-8261-3457
Journal: Andrology
PubMed URL: 31502758
Type: Journal Article
Subjects: Late onset hypogonadism
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