Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle‐aged men: a meta‐analysis

Isidori, Andrea M.; Giannetta, Elisa; Greco, Emanuela A.; Gianfrilli, Daniele; Bonifacio, Vincenzo; Isidori, Aldo; Lenzi, Andrea; Fabbri, Andrea

doi:10.1111/j.1365-2265.2005.02339.x

Cited by 611 publications

(539 citation statements)

References 72 publications

(230 reference statements)

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“…The reduction in HDL levels may be explained by a reported testosteroneinduced decrease in lipoprotein lipase activity in humans (Rebuffe-Scrive et al 1991), but the mechanism underlying testosterone-induced decrease in HDL levels has not been clarified. Our data were consistent with a meta-analysis (Whitsel et al 2001) and a recent systematic review (Fernandez-Balsells et al 2010) that reported a significant small decrease in HDL cholesterol levels in men treated with testosterone; however, a meta-analysis found no change in HDL cholesterol levels in response to testosterone treatment (Isidori et al 2005). A low HDL is linked to an increased morbidity and mortality of cardiovascular disease, and in a recent study on old men with limitations in mobility, cardiovascular and respiratory events were significantly increased during testosterone therapy compared to placebo (Basaria et al 2010).…”

Section: Discussionsupporting

confidence: 92%

“…The increase in LBM was not associated with the testosterone level at inclusion. The changes in body composition were in accordance with the results previously described during testosterone therapy (Isidori et al 2005) also in aging males (EmmelotVonk et al 2008). Skeletal muscle accounts for approximately 80% of the glucose uptake in the insulin-stimulated state (Shulman et al 1990).…”

Section: Discussionsupporting

confidence: 91%

“…In both studies, no significant increase in LBM was found. These findings suggested that the testosterone dose applied in these studies was insufficient to obtain the expected increase in LBM during testosterone treatment (Isidori et al 2005). In one of these studies, an oral formulation of testosterone may be the explanation for the lack of increase in testosterone (Marin et al 1992).…”

Section: Discussionmentioning

confidence: 92%

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Testosterone therapy increased muscle mass and lipid oxidation in aging men

Frederiksen

Højlund

Hougaard

et al. 2011

AGE

115

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The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebocontrolled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b=1.9 kg, p=0.003) increased while HDL-cholesterol (b=−0.12 mmol/l, p=0.043) and TFM decreased (b=−1.2 kg, p=0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b=5.65 mg/min/m 2 , p=0.045) increased and basal glucose oxidation (b=−9.71 mg/min/m 2 , p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b=−0.01mg/min/m 2 , p=0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 92%

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Testosterone therapy increased muscle mass and lipid oxidation in aging men

Frederiksen

Højlund

Hougaard

et al. 2011

AGE

115

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“…Isidori et al (2005)) in another metaanalysis study reported beneficial effects enough to justify the demand for other interventional studies on this issue. On the other hand, there is the existent, but small risk of side effects, showed in another metaanalysis (Calof et al 2005).…”

Section: Discussionmentioning

confidence: 97%

Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies

Neto

Gama

Rocha

et al. 2015

AGE

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The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the metaanalysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, AGE (2015) ) kg, although it was heterogeneous (I 2 =98 %). Effect estimate was 3.59 [2.38-4.81]. Androgen therapy decreased fat mass; effect estimate was −1.78 [−2.57, −0.99] that analysis had also a high level of heterogeneity (I 2 =81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.

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“…63 Overviews of randomized controlled trials of testosterone therapy in men without or with underlying chronic illness using a variety of testosterone formulations report improvements in body composition with increased lean body mass and reduced fat mass, but limited benefit in physical capabilities and equivocal improvements in quality of life measures, including general well-being and fatigue. [64][65][66] However, the studies reported tend to be of limited size and duration, with a lack of large-scale trials with extended long-term follow-up. Thus, additional studies have been recommended incorporating vitality, well-being and/or quality of life as end points.…”

Section: Testosterone General Health and Quality Of Life In Aging Menmentioning

confidence: 99%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle‐aged men: a meta‐analysis

Cited by 611 publications

References 72 publications

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies

Are declining testosterone levels a major risk factor for ill-health in aging men?

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