Longitudinal Changes in Testosterone Over Five Years in Community-Dwelling Men

Shi, Zumin; Araujo, Andre B.; Martin, Sean; O’Loughlin, Peter; Wittert, Gary

doi:10.1210/jc.2012-3842

Cited by 149 publications

(118 citation statements)

References 43 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with the findings that androgen status does not decline with aging among older men who remain in excellent (asymptomatic) health (45) although there is a decline associated with the co-morbidities of aging such as obesity, depression or cardiovascular disease. This is also consistent with the conclusions of other longitudinal studies (31,32). Nevertheless, our cross-sectional study cannot fully exclude that age itself, apart from co-morbidities, might also contribute to declines in age-related serum testosterone, DHT, and E 2 concentrations.…”

Section: Discussionsupporting

confidence: 92%

Age-specific population centiles for androgen status in men

Handelsman

Yeap

Flicker

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

Aim: The age-specific population profiles in men of circulating testosterone and its two bioactive metabolites dihydrotestosterone (DHT) and estradiol (E 2 ) across the adult lifespan and its determinants are not well described. Objective: Our objective was to deduce smoothed age-specific centiles of circulating testosterone, DHT, and E 2 in men using pooled data from population-based studies in three Australian cities from liquid chromatography-mass spectrometry steroid measurements in a single laboratory. Design, setting, and participants: We pooled data of 10 904 serum samples (serum testosterone, DHT, E 2 , age, height, and weight) from observational population-based studies in three major cities across Australia. Main outcome measures: Age-specific smoothed centiles for serum testosterone, DHT, and E 2 in men aged 35-100 years were deduced by large sample data analysis methods. Results: We found that serum testosterone, DHT, and E 2 decline gradually from ages 35 onwards with a more marked decline after 80 years of age. Higher weight, BMI, and body surface area as well as shorter stature are associated with reduced serum testosterone, DHT, and E 2 . Conclusions: Among Australian men, there is a gradual progressive population-wide decline in androgen status during male aging until the age of 80 years after which there is a more marked decline. Obesity and short stature are associated with reduced androgen status. Research into the age-related decline in androgen status should focus on the progressive accumulation of age-related comorbidities to better inform optimal clinical trial design.

show abstract

Section: Discussionsupporting

confidence: 92%

Age-specific population centiles for androgen status in men

Handelsman

Yeap

Flicker

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Previous studies demonstrated that testosterone plays an important role in metabolic activities, including the regulation of glucose and lipid metabolism (Aydilek and Aksakal 2005;Christoffersen et al 2010). Growing evidence has demonstrated that testosterone deficiency is associated with an increased incidence of obesity (Shi et al 2013;Stellato et al 2000). In addition, a positive correlation between obese-insulin resistance and testosterone deficiency has been reported (Grossmann et al 2008;Haffner et al 1994), but contradictory findings have been demonstrated in some animal models (Borst and Conover 2006;Erben et al 2000;Kakolewski et al 1968).…”

Section: Introductionmentioning

confidence: 99%

Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress

Pintana

Pongkan

Pratchayasakul

et al. 2015

AGE

View full text Add to dashboard Cite

Testosterone replacement improves metabolic parameters and cognitive function in hypogonadism. However, the effects of testosterone therapy on cognition in obese condition with testosterone deprivation have not been investigated. We hypothesized that testosterone replacement improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function, and hippocampal synaptic plasticity. Thirty male Wistar rats had either a bilateral orchiectomy (ORX: O, n = 24) or a sham operation (S, n = 6). ORX rats were further divided into two groups fed with either a normal diet (NDO) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n = 6/subgroup) and were given either castor oil or testosterone (2 mg/kg/day, s.c.) for 4 weeks. At the end of this protocol, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity, and brain mitochondrial function were determined. We found that testosterone replacement increased peripheral insulin sensitivity, decreased circulation and brain oxidative stress levels, and attenuated brain mitochondrial ROS production in HFO rats. However, testosterone failed to restore hippocampal synaptic plasticity and cognitive function in HFO rats. In contrast, in NDO rats, testosterone decreased circulation and brain oxidative stress levels, attenuated brain mitochondrial ROS production, and restored hippocampal synaptic plasticity as well as cognitive function. These findings suggest that testosterone replacement improved peripheral insulin sensitivity and decreased oxidative stress levels, but failed to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats. However, it provided beneficial effects in reversing cognitive impairment in testosterone-deprived non-obese rats.

show abstract

“…Several studies have shown that testosterone replacement exerted beneficial effects on brain function, including the prevention of neuronal cell death, the balancing of brain oxidative stress and antioxidant activity, improvement of synaptic plasticity and the involvement of cognitive formation in animal models (Janowsky 2006, Meydan et al 2010, Filova et al 2013. Interestingly, growing evidence demonstrated that testosterone deficiency is associated with obese insulinresistance in men (Haffner et al 1994, Stellato et al 2000, Grossmann et al 2008, Shi et al 2013). All of those findings indicate that testosterone-deprivation can lead to obesity and cognitive decline.…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl peptidase 4 inhibitor improves brain insulin sensitivity, but fails to prevent cognitive impairment in orchiectomy obese rats

Pintana¹,

Pongkan²,

Pratchayasakul³

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

It is unclear whether the dipeptidyl peptidase 4 (DPP4) inhibitor can counteract brain insulin resistance, brain mitochondrial dysfunction, impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived obese rats. We hypothesized that DPP4 inhibitor vildagliptin improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity. Thirty male Wistar rats received either a sham-operated (S, nZ6) or bilateral orchiectomy (ORX, nZ24). ORX rats were divided into two groups and fed with either a normal diet (ND (NDO)) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (nZ6/subgroup) to receive either a vehicle or vildagliptin (3 mg/kg per day, p.o.) for 4 weeks. After treatment, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity and brain mitochondrial function were determined in each rat. We found that HFO rats exhibited peripheral and brain insulin resistance, brain mitochondrial dysfunction, impaired hippocampal synaptic plasticity and cognitive decline. NDO rats did not develop peripheral and brain insulin resistance. However, impaired hippocampal synaptic plasticity and cognitive decline occurred. Vildagliptin significantly improved peripheral insulin sensitivity, restored brain insulin sensitivity and decreased brain mitochondrial reactive oxygen species production in HFO rats. However, vildagliptin did not restore hippocampal synaptic plasticity and cognitive function in both NDO and HFO rats. These findings suggest that vildagliptin could not counteract the impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived subjects, despite its effects on improved peripheral and brain insulin sensitivity as well as brain mitochondrial function.

show abstract

Longitudinal Changes in Testosterone Over Five Years in Community-Dwelling Men

Abstract: An age-related decline in T levels is not inevitable but is largely explained by smoking behavior and intercurrent changes in health status, particularly obesity and depression.

Cited by 149 publications

References 43 publications

Age-specific population centiles for androgen status in men

Age-specific population centiles for androgen status in men

Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress

Dipeptidyl peptidase 4 inhibitor improves brain insulin sensitivity, but fails to prevent cognitive impairment in orchiectomy obese rats

Contact Info

Product

Resources

About