The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross-over. The median study length was 3 months (range 1-36 months). Our meta-analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut-off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta-regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta-analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low-normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long-term safety data are not available. The present meta-analysis highlights the need, and pitfalls, for large-scale, long-term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle-aged and elderly men with reduced T levels and ED.

Musculoskeletal aging is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Bone and muscle tissues were increasingly recognized, as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. During growth, bone mineral content closely correlates with muscle mass, and several evidences suggest that osteoporosis and sarcopenia present common pathophysiological factors and show the correlation between low bone mineral density and sarcopenia in both men and women. Then, sarcopenia and osteoporosis, typical features of aging, are often associated with each other and with the frailty syndrome. In particular, sarcopenia and osteoporosis are major contributors to disability and frailty and the common denominators are age-related chronic inflammation, changes in body composition and hormonal imbalance. Frailty syndrome is characterized by a reduced response to stress, triggering the decline of the physiological functioning of the various systems. Frailty syndrome, typical of the older people, is frequently associated with a reduction in the quality of life and mobility. Falls often are the basis of reduced mobility and ability to perform the common functions of daily life and the increase in the number of institutionalizations. Moreover, the reduction of muscle mass, associated with altered muscle composition, fat and fibrous infiltration and alterations in innervations, and the increase in fat mass, have a synergistic effect on the increase in cardiovascular risk. The aim of this review is to analyze the pathophysiological mechanisms underlying the frailty syndrome and its association with sarcopenia and osteoporosis, and investigate possible intervention measures.

Our results indicate that a subpopulation of obese patients has a significant low lumbar BMD than expected for age. Thus, a careful characterisation of skeletal metabolism might be useful in all obese individuals to avoid fragility fractures later in life.