English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Age-related decline of serum T and its clinical implications remain the subject of controversies. These are unlikely to be settled soon due to the lack of appropriate randomized trials. It nevertheless is important to keep adjusting clinical practice advice to current knowledge. Population means of serum T decline and SHBG increases with age, but there is considerable between-subject variation in prevalent (free) T in apparently healthy older men (1, 2). Genetic and lifestyle-related factors account for only part of T variation (1), which suggests that healthrelated factors contribute. Indeed, to define a “healthy state” for populations of elderly men with a high prevalence of (subclinical) comorbidities is not straightforward. Recently, serum T was reported as stable across age strata among men self-reporting very good health (3). Signs and symptoms of “normal aging” are reminiscent of those in young hypogonadal men (1, 4), which raised expectations that T substitution in (borderline) low T might help reverse or limit progression of some consequences of aging, if not improve general health and longevity. In apparent support of the concept of late-onset hypogonadism (LOH), observational studies have reported associations of serum (free) T below the reference for young men with symptoms that are part of the clinical picture of hypogonadism, ie, in particular sexual symptoms besides others such as fatigue, decreased muscle mass and physical vigor, or osteopenia (1, 2, 4–8). According to practice guidelines (4, 8), the diagnosis of androgen deficiency in the elderly or LOH, for which T treatment might be considered, should be based on the concurrent presence of consistent symptoms of hypogonadism and unequivocally low serum (free) T. However, symptoms and low T both become more prevalent and less specific with age, so that the likelihood of LOH diagnosis increases (5), whereas a causal link between clinical and hormonal findings becomes more evasive. A close look at the data shows that a majority of symptomatic men do not have low T, whereas a substantial part of those with low T are asymptomatic (5). Among men with LOH, clinicians thus have limited ability to distinguish those in whom low T is the cause of symptoms from those in whom low T is unrelated to their health problem or rather its consequence. As an epiphenomenon of comorbidity, low T can be irrelevant to the patient’s health state, or of clinical relevance by contributing to further deterioration of health, or a beneficial adaptive response to the present status (9). Beyond classical symptoms of hypogonadism, low T and LOH have been associated in observational studies with prevalent and/or incident obesity, metabolic syndrome, type 2 diabetes, dyslipidemia, and other cardiovascular risk factors (10, 11). The relation between serum T and metabolic disturbances is likely bidirectional, but a major component of reverse causality is apparent from effective restoration of serum T with lifestyle measures and weight loss (10). Systematic review and meta-analysis of community-based observational studies indicate a mostly modest association in elderly men of low endogenous T with incident cardiovascular disease and risk of cardiovascular and all-cause death. This might imply protective effects of T, but authors generally concur to consider residual confounding with low T a marker of poor health status as a plausible interpretation of the data (11– 13). Marked between-study heterogeneity, partly accounted for by characteristics of the subjects and study methods, tend to support the latter view (12). Yeap et al (14) reported a U-shaped association between T (and calculated free T) and all-cause mortality in older commu-

Mortality Associated to Late-Onset Hypogonadism: Reasons Not to Treat With Testosterone?