Insulin-like growth factor-1 is a mediator of age-related decline of bone health status in men

Abstract

Objective: The role of insulin-like growth factor-1 (IGF-1) in bone health in men is debatable. This study aimed to determine whether IGF-1 is a mediator in age-related decline of bone health status measured by calcaneal speed of sound (SOS) in Malaysian men.

Methods: The study recruited 279 Chinese and Malay men. Their demographic data, weight, height, calcaneal SOS were taken and fasting blood was collected for total testosterone, sex-hormone binding globulin and IGF-1 assays. The associations between the studied variables were assessed using multiple linear regression (MLR) analysis. Mediator analysis was performed using Sobel test.

Results: There was a significant and parallel decrease of IGF-1 and SOS with age (p?<?0.05). Serum IGF-1 was significantly and positively associated with SOS (p < 0.05) but after further adjustment for age, the significance was lost (p?>?0.05). The strength of the association between age and SOS decreased after adjusting for IGF-1 level but it remained significant (p?<?0.05). Sobel test revealed that IGF-1 was a significant partial mediator in the relationship between age and SOS (z?=??4.3).

Conclusion: Serum IGF-1 is a partial mediator in the age-related decline of bone health in men as determined by calcaneal ultrasound. A prospective study should be performed to validate this relationship.     

Associations of physical exercise as a lifestyle habit with lean and fat body mass and handgrip strength and age in Asian men

Abstract

Background: We evaluated how the intensity of physical exercise as a lifestyle habit is associated with age, body composition and handgrip strength.

Methods: Total body composition was analyzed using DEXA. Exercise scores were derived from an administered questionnaire and the scoring was calculated using the Metabolic Equivalent of Task (MET). Handgrip strength was measured using a dynamometer.

Results: Age, independent of exercise intensity, was associated with declining lean mass, and handgrip strength and with increasing total body fat. A regular physical exercise regime of intensity greater than 1230 MET-min/week was associated with higher total lean mass and lean mass in the limbs, and handgrip strength and lower fat mass in the limbs.

Discussion: We have shown that age was associated with lower lean mass especially in the limbs and handgrip strength and higher total fat mass. Regular physical exercise as a lifestyle habit of any type and of sufficient intensity could help improve muscle strength in the limbs.     

Serum levels of inhibin B in men of different age groups

The decline of testosterone levels in aging men is well documented. However, it is unclear to what extent the Sertoli cell marker inhibin B changes during aging. Herein we report on the determination of serum levels of inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in 906 patients from 16 to 89 years of age, presenting to our department for different complaints. There was a weak but significant correlation of the levels of inhibin B with age (r = 0.064, p < 0.05). A significant negative correlation of FSH and inhibin B was documented in all age groups (r = -0.423, p < 0.01). Also, the LH levels increased significantly with low inhibin B levels (r = -0.289, p < 0.01). Testosterone levels showed no significant correlation with inhibin B. We conclude from our study that Sertoli cell function as documented by serum levels of inhibin B is stable throughout life. In addition, the ongoing correlation of FSH and inhibin levels also indicates no significant decline of Sertoli cell function in the aging male.     

Relationship between testosterone serum levels and lifestyle in aging men

Objective.?The aim of this study was to evaluate the association between serum levels of testosterone and free testosterone to lifestyle in aging males.

Methods.?Men between 45 and 85 years were assessed regarding body mass index (BMI), nicotine and alcohol consumption, stress level, physical and social activity, and sleeping quality by a self-administered questionnaire. In parallel, serum levels of testosterone (T), free testosterone (fT), LH, FSH, DHEA-S, E2 and SHBG were obtained.

Results.?In total, 375 men with a mean age of 59.9 years (9.2 ± SD) entered this study; 25.4% and 27.4% had hypogonadal testosterone or free testosterone serum levels, respectively. Nicotine consumption (smokers had higher levels of T and fT; p < 0.01), BMI (negative correlation to T; p < 0.01) and age (negative correlation to fT; p < 0.001) correlated with serum levels of testosterone or free testosterone. Physical and social activity, nicotine and alcohol consumption, stress level and sleep quality did not show a significant association with serum androgen levels.

Conclusion.?This prospective study of 375 men aged 45 to 85 years confirms the correlation between age, BMI and smoking with serum levels of testosterone and free testosterone, whereas the investigated variety of lifestyle factors did not show a significant association to serum androgen levels.     

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men.

Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (?+?) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods.

Results Men with coronary artery disease had lower total testosterone levels (17.01?±?6.42 vs. 19.37?±?6.58?nmol/l; p?<?0.05), testosterone/estradiol ratio (228.5?±?88.5 vs. 289.8?±?120.1; p?<?0.05) and free androgen index (FAI) (59.49?±?14.79 vs. 83.03?±?25.81; p?<?0.0001), and higher levels of estrone (49.5?±?27.7 vs. 36.6?±?12.7?pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p?<?0.05) between testosterone level and serum level of glucose (r?=??0.29), triglycerides (r?=??0.37), body mass index (r?=??0.55), waist (r?=??0.43), total body fat mass (r?=??0.3) and fasting insulin resistance index. A significant positive association (p?<?0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r?=?0.26).

Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.     

Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40–69 years (mean 55.9?±?7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r?=??0.38, p?=?0.0004), alcohol consumption (r?=??0.22, p?=?0.047) and serum testosterone (r?=??0.27, p?=?0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (β?=??0.17, p?=?0.0226), high density lipoprotein cholesterol (β?=?4.17, p?=?0.0312) and vessel diameter (β?=??4.37, p?<?0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.     

Association between testosterone levels and the metabolic syndrome in adult men

Abstract

Objective: To evaluate the relationship between testosterone levels and the metabolic syndrome (MS) in men older than 45 years.

Methods: Six hundred and sixty men (45–70 years) selected from 2906 participants of a population screening for prostate cancer were included in this study. Testosterone and the components of MS were assessed in all men. MS was diagnosed according to NCEP-ATP III criteria. Triglycerides (TG)/HDL-cholesterol (chol) index was calculated.

Results: The presence of MS was inversely associated with testosterone (χ², p?<?0.001), independently of age (OR 0.802, CI 95%: 0.724–0.887, p?<?0.0001). Hypertension was the most frequent abnormality observed followed by elevated TG and waist circumference (WC). Testosterone correlated positively with HDL-chol (r: 0.14, p?<?0.0001) and negatively with body mass index (BMI)(r: ?0.29, p?<?0.0001), WC (r: ?0.26, p?<?0.0001), TG (r: ?0.20, p?<?0.0001), TG/HDL-chol (r: ?0.20, p?<?0.0001), glucose (r: ?0.11, p?=?0.005) and MS score (r: ?0.23, p?<?0.0001).

Conclusions: Our results show that in men older than 45 years, as long as testosterone levels decline, the prevalence of MS increases, independently of age. The correlations found between testosterone and four of the five components of MS, as well as with BMI and TG/HDL-chol ratio, a surrogate marker of insulin resistance, suggest considering male hypogonadism as a determinant of developmental abnormalities typical of MS.     

The aging male in African ethnic cultures

Objective.?To test the relationship between gonadal status and objective measures and determinants of physical performance in older men and their determinants.

Methods.?The study included 455?≥?65 year older men of InCHIANTI study, Italy, with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance.

Results.?Three different groups of older men were created: (1) severely hypogonadal (N?=?23), total testosterone levels ≤230?ng /dl; (2) moderately hypogonadal (N?=?88), total testosterone >230 and?N?=?344), testosterone levels ≥350?ng/dl. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in haemoglobin levels, hand grip strength and SPPB score (p for trend?p for trend?=?0.004) and haemoglobin (p for trend?Conclusions.?In older men, gonadal status is independently associated with some determinants (haemoglobin and muscle strength) of physical performance.     

Effects of testosterone supplementation on prevention of age-related penile remodeling

Abstract

Erectile dysfunction develops among 46.2% of men between 40 and 70 years. Studies demonstrated substitution on detrusor muscle by collagen due testosterone deprivation. It is clear the correlation among aging and oxidative stress, accelerating apoptosis process in many tissues. This study aims to demonstrate the collagen substitution over the muscle fibers on muscle structure of rat’s penis and the effects of testosterone supplementation. Sixteen senescent Wistar rats were divided into two groups: treatment (receiving standard supplementation testosterone dose) and control (receiving equivalent saline solution). Testosterone was dosed on D0 and D56 of study. All penises were prepared with picrosirius colored histology; stereology was applied to determine the volumetric density of collagen fibers (Vv). Analysis of variance demonstrated testosterone group’s replacement therapy to be effective, while the androgenic decline continued by the time of experiment in control group (p?<?0.05). Testosterone group had Vv of 20.6%, lower than control group (47.8%); t-test (p?<?0.001). Pearson’s correlation demonstrated an inverse correlation between the Vv and testosterone’s levels (p?<?0.001). This is a pioneer study on demonstration of structural alterations over the cavernous corpora muscle caused by deprivation of testosterone on elderly rat. These finding implicate that the testosterone levels can influence, not only the libido, but also the erectile function.     

Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome

Abstract

Objective: We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months.

Methods: 50 males aged 50–65 years with TDS (Aging Males Symptoms Scale [AMS]?>?26 and calculated free testosterone [cFT] 250?pmol/l) were administered 50?mg testosterone gel daily for one year. During the second year, patients received 1000?mg of testosterone undecanoate every 2–3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry.

Results: There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p?<?0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months.

Conclusions: Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.     

A randomized,double-blind,placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up

Introduction: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. Aim: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). Methods: Randomized, double-blind, placebo-controlled study. Men, aged 50–80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males’ Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5–7.5?mg/day; n =183) or placebo gel (n =179), followed by 12 months open-label with T in all. Results: After 6 months, LBM increased in T- treated patients by 1.28?±?0.15?kg (mean ± SE) and FM decreased by 1.16?±?0.16?kg, with minor changes with placebo (LBM +0.02?±?0.10?kg and FM ?0.14?±?0.12?kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo (p < 0.05, T group vs. placebo). Conclusions: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months.     

Effects of oral testosterone undecanoate therapy on bone mineral density and body composition in 322 aging men with symptomatic testosterone deficiency: a 1-year,randomized, placebo-controlled,dose-ranging study

Abstract

Objective: We investigated the effects of oral testosterone undecanoate (TU) on bone mineral density (BMD), lean body mass (LBM) and body fat mass (BFM) in aging men with symptomatic testosterone deficiency (TD).

Methods: Three hundred twenty-two men ≥50 years with TD symptoms and calculated free testosterone <0.26?nmol/L participated in a multicenter, double-blind, placebo-controlled trial. Patients were randomized to placebo, oral TU 80?mg/d, oral TU 160?mg/d, or oral TU 240?mg/d, administered as divided doses with normal meals. BMD of the hip and lumbar spine were evaluated by dual energy X-ray absorptiometry (DEXA), and body composition (LBM and BFM) by whole body DEXA.

Results: Oral TU significantly increased BMD at Month 12 at the lumbar spine (240?mg/d), total hip (240?mg/d), and trochanter and intertrochanter (160 and 240?mg/d) compared with placebo. Oral TU significantly increased LBM at Months 6 and 12 for all oral TU groups compared with placebo. BFM significantly decreased at Month 6 (all oral TU groups) and Month 12 (160?mg/d) compared with placebo. The effects on BMD and body composition showed a clear dose response.

Conclusions: Treatment with oral TU led to improvement in BMD, LBM and BFM in aging men with symptomatic TD.     

Testosterone is not associated with mortality in older African-American males

Introduction.?Although testosterone and its association with disease progression and mortality is a widely studied topic, no studies have evaluated mortality risks related to testosterone levels in an older African-American population. The mechanisms for known racial differences in mortality risk for certain cancers and cardiovascular risk factors are largely unknown. Elucidating a mortality risk associated with testosterone levels may give insight into the elevated risk for certain diseases in African-Americans.

Methods and results.?Study data were derived from a cohort 622 African-Americans (age 80.05?±?6.4, range 68–102) from Saint Louis, Missouri that includes 190 males (age 79.38?±?6.2, range 70–102). The eligible sample for this report includes 56 of the 190 males (age 78.89?±?6.9, range 70–102) who donated blood at baseline in 1992–1994 and subsequently tested for total testosterone and bioavailable testosterone. Covariates for adjusted analyses were lower body functional limitations, physician visits and comorbidities, also collected at baseline. Males' mean bioavailable testosterone levels (ng/dl) were 33.33?±?24.4 (n above 70?ng/dl?=?5) and mean total testosterone levels (ng/dl) were 246.63?±?118.7 (n above 300?ng/dl?=?20). Vital status was determined through 2002; 41 males (73%) were deceased and 15 were alive. Mortality did not differ among males with testosterone levels?<300 versus 300+ (p?=?0.42) or with bioavailable testosterone levels?<70 versus > 70 (p?=?0.34). Total testosterone levels did not predict mortality when adjusted for age (Adjusted Hazard Ratio [AHR]?=?0.998; 95% confidence interval [CI] 0.995–1.001; p?=?0.28) or adjusted for age and other covariates (AHR?=?0.099; 95% CI 0.996, 1.002; p?=?0.35). Bioavailable testosterone levels did not predict mortality when adjusted for age (AHR?=?0.992; 95% CI .977–1.007; p?=?0.30) or when adjusted for age and other covariates (AHR 0.991; 95% CI .976–1.006; p?=?0.261).

Conclusion.?In older African-American males, total and bioavailable testosterone levels, with and without adjustment for covariates, are not independently associated with mortality risk.     

Elevated high sensitivity C-reactive protein levels in aging men with low testosterone

Objective.?We examined baseline data from a lipid treatment study to assess the relationship between testosterone (T) and the cardiovascular inflammatory marker, high sensitivity C-reactive protein (hsCRP).

Methods.?The baseline T, hsCRP, lipid, glycemic, and anthropometric data were obtained from 467 men (mean age: 52 years). Inclusion criteria included low-density lipoprotein cholesterol ≥?3.4 to 4.9?mmol/l and triglycerides?≤?4.0?mmol/l. The baseline hsCRP levels were examined across the following T subgroups: <6.9?nmol/l (moderate to severe hypogonadism), 6.9 to <10.4?nmol/l (mild to moderate hypogonadism), 10.4 to <15?nmol/l (low-normal T), and?≥?15?nmol/l (normal T).

Results.?The median hsCRP levels were significantly (p?=?0.041) different across the four T subgroups; patients in the lower T subgroups had higher median hsCRP levels than patients in the higher T subgroups. The percentage of men with elevated hsCRP (>2?mg/l) was also significantly (p?=?0.038) different across the four T subgroups; 83% of men with T < 6.9?nmol/l had elevated hsCRP compared with 40% with T ≥ 15?nmol/l.

Conclusions.?This analysis demonstrated an inverse relationship between serum T and hsCRP in aging men. Urologists need to be aware that low T levels may not only adversely affect sexual function but also may worsen cardiovascular risk in aging, hypogonadal men.     

Effects of testosterone replacement therapy on hypogonadal men with osteopenia or osteoporosis: a subanalysis of a prospective randomized controlled study in Japan (EARTH study)

Objective: We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis.

Methods: From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n?=?35) and control (n?=?34) groups. The TRT group was administered 250?mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated.

Results: At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0?±?5.0 vs. 3.0?±?3.2; p?=?.0434) and in adiponectin value (?0.90?±?3.33 vs. 0.10?±?2.04; p?=?.0192). There were no significant changes in other parameters.

Conclusions: TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.     

The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer

Objective.?To evaluate body composition changes, specifically skeletal muscle mass, in men receiving androgen deprivation with luteinizing-hormone releasing hormone-agonist (LHRH-A) for prostate cancer (PCa) in comparison with healthy controls.

Design.?Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial.

Setting.?Clinical Research Center in Connecticut.

Participants.?Thirty men (> 60 years) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa.

Measurements.?Appendicular skeletal muscle/height² (ASM/ht²), lean and fat mass were assessed by dual energy x-ray absorptiometry. Total testosterone levels were assessed by enzyme immunoassay.

Results.?At baseline, 12/30 (40%) of the treatment group and 7/25 (28%) of the control group (p = 0.11) met criteria for sarcopenia. There were no differences between control groups in ASM/ht² or lean mass. The LHRH-A group had a higher percent body fat than the control group, 29.8 ± 6.3 versus 26.3 ± 4.6 (p = 0.02). ASM/ht² and lean mass decreased in the LHRH-A group from 7.5 ± 0.9 kg to 7.3 ± 0.9 kg (?2.3% ± 0.03; p ? 0.001) and 53.5 ± 5.4 kg to 52.3 ± 5.3 kg (?2.1% ± 0.03; p ? 0.001), respectively. There was no muscle loss in the control group. At 6 months, the LHRH-A group had increased percent body fat from 29.8 ± 6.4 to 32.2 ± 5.8 (9.5% ± 0.13; p ? 0.001), whereas the control group had decreased in percent body fat from 26.6 ± 4.6 to 25.3 ± 5.0 (?3.8% ± 0.08; p = 0.02).

Conclusions.?Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy. Lifestyle changes or medical interventions to minimize the effects of androgen deprivation therapy for PCa deserve investigation.     

Mild thyroid hormone excess is associated with a decreased physical function in elderly men

Introduction: In the adult, subclinical hyperthyroidism (Shyper) may alter skeletal muscle mass and strength. However, whether these effects are present in elderly subjects is not known. We explored the relationship between mild hyperthyroidism and physical function in a population-based sample of older persons. Methods: In a cross-sectional analysis, calf muscle cross-sectional area (CMA), handgrip strength, nerve conduction velocity (NCV), and Short Physical Performance Battery (SPPB) scores were compared between 364 euthyroid (Eut) and 28 Shyper men as well as between 502 Eut and 39 Shyper women. In a longitudinal analysis, we evaluated the relationship between baseline plasma TSH, FT3 and FT4 and the 3-year change in SPPB score in 304 men and 409 women who were euthyroid at enrolment. Results: At the cross-sectional analysis, Shyper men, but not women, had a significantly (p?=?0.02) lower SPPB score than Eut controls, although with comparable CMA, grip strength and NCV, and were more likely to have poor physical performance (odds ratio?=?2.97, p?<?0.05). Longitudinal analysis showed that in Eut men higher baseline FT4 was significantly (p?=?0.02) predictive of a lower SPPB score at the 3-year follow-up. Conclusion: Even a modest thyroid hormone excess is associated with a reduced physical function in elderly men.     

Decline of serum levels of free testosterone in aging healthy Chinese men

Objective.?To investigate the age-related change of serum androgen levels in healthy men and to define a cut-off value of serum testosterone for the diagnosis of androgen deficiency in the aging male.

Method.?1080 healthy men aged 20 to ?70 years old were enrolled in Beijing, Shanghai, Xian and Chongqing. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), calculated free testosterone (cFT), sex hormone binding globulin (SHBG), 17beta-oestradiol (E2), the T/LH ratio, and T/SHBG as a free testosterone index (FTI) were all determined.

Results.?Serum total T did not significantly decline, but the cFT, T/LH and FTI progressively decreased with aging. To determine androgen deficiency, the 10th percentile value of men <40 years was defined as the lower cut-off value for cFT, T/LH or FTI, which were 0.3 nmol/L, 2.8 nmol/IU, and 0.4 nmol/IU respectively. With the median value of cFT of men aged between 20 and 49 years as the criterion, the level of cFT was lower in 2.82% of men from 40 to 49 years, in 19.53% from 50 to 59 years, in 22.57% from 60 to 69 years, and in 33.19% of men ?70 years. Taking the above value of cFT as the cut-off point, the prevalence of androgen deficiency in men 40–49 years was 13.0%, 31.8% in men 50–59 years, 30.1% in men 60 to 69 years, and 46.7% in men >70 years.

Conclusions.?(i). While serum total T values do not decline with aging, the levels of cFT gradually decline with aging; (ii) when using the value of cFT of the 10th percentile of men aged 20 to 39 years as the cut-off point, the prevalence of androgen deficiency was <15% before the age of 50 years, and about 30% thereafter, approaching 45% after the age of 70 years; and (iii) in this study the values of T/LH paralleled those of cFT closely; therefore, T/LH could serve as a surrogate for cFT.     

Testosterone supplementation's effects on age-related bladder remodeling – experimental study in rats

Abstract

Objective: This study was designed to evaluate the effect of testosterone replacement on the fibrotic process of the detrusor bladder muscle during the normal aging process.

Methods: 15 Wistar senile rats, aged between 18 and 20 months were divided into two groups: testosterone group – 11 animals submitted to the administration of testosterone undecanoate (50?mg/kg intramuscular), once per month; and, Control group – four animals underwent a sham procedure. At the end of eight weeks, animals from both groups were sacrificed; bladders were removed and subsequently stereologically evaluated to determine the volumetric density of collagen fibers. The success of testosterone administration was confirmed by the measurement of serum testosterone at the beginning and end of the experiment.

Results: In the replacement group, testosterone average was 3.2?ng/ml, whereas in the control group, the mean testosterone at the end of the experiment was 0.64?ng/ml (p?<?0.05). Analysis of stereological collagenous fiber showed higher density in the control group compared to the testosterone group I (56% versus 37.02%, respectively). The difference of volume concentration of collagen between both groups was statistically significant (p?<?0.000).

Conclusion: Bladder wall fibrosis was reduced in senile rats subjected to testosterone replacement.     

Prevalence,incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania

Objective.?Low total testosterone levels (TT) have been associated with increased morbidity and mortality. However, the prevalence and incidence of testosterone deficiency (TD) in association with its risk has not been assessed systematically to date.

Methods.?Data from the prospective population-based Study of Health in Pomerania were used. From the 2117 men aged 20–79 years at baseline, 1490 men with complete TT data were analysed. Crude and age-specific prevalence and incidence rates of TD were estimated by TT levels below the age-specific 10th percentile. Analysis of covariance and Poisson regression models were used to assess the association of socio-demographic characteristics, health-related lifestyle, as well as somatometric, medical and laboratory measures with risk of incident TD.

Results.?TD baseline prevalence was 10.4% (N?=?155) and incidence 11.7 per 1000 person-years. TT levels showed a significant age-related decline with an unadjusted rate of 0.05 nmol/l per year. Obesity, metabolic syndrome, diabetes and dyslipidaemia were identified as risk factors of incident TD. Subpopulations of men without the revealed risk factors at both examinations maintained constant TT levels over time.

Conclusions.?Besides aging alone, lifestyle and different comorbidities were associated with TT level decline, suggesting that the age-related TT decline may be at least partly prevented through the management of potentially modifiable risk factors and health related behaviour.