Frailty and the aging male

Frailty occurs in aging males for a variety of reasons. It is less common in males than females. Diseases which are particularly associated with frailty are diabetes mellitus, atherosclerosis, anemia and chronic obstructive pulmonary disease. Insulin resistance syndrome plays a pathogenetic role in the “fat-frail” syndrome. Sarcopenia occurs predominantly because of hormone deficiency and cytokine excess. Pain and anorexia are also associated with frailty. Stem cell research represents a potential promise for the treatment of frailty.     

Cross-sectional analysis between prostate volumes and serum sex hormones in Japanese men attending a urological clinic

Aim: To evaluate epidemiologically the association between measured prostate volume and sex hormones.

Methods: Between December 2012 and September 2014, 226 patients attending the urological clinic were assessed for the relationship between prostate volume (PV) and, serum sex hormones, physical size, personal habits, etc. Prostate volume was measured by using transabdominal ultrasonography. Statistically, the Pearson correlation coefficients test was used.

Results: Total cases, the cases of PV?≤?25?ml, and the cases of PV?>?25?ml were evaluated respectively. Total cases and the cases of PV?>?25?ml showed a positive significant correlation with testosterone (T), but the cases of PV?≤?25?ml showed no such correlation. The cases of PV?>?25?ml had a positive significant correlation with estradiol (E2), but total cases and cases of PV?≤?25?ml did not. Dehydroepiandrosterone sulfate (DHEAS) showed no correlation with any case of PV, however it decreased significantly with age and had a correlation with alopecia. The E2/T ratio had no correlation with any case of PV, but on the other hand, the T/DHEAS and E2/DHEAS ratios had significant positive correlation with PV?>?25?ml.

Conclusions: Serum T and E2 had significant positive correlation with measured PV especially in larger prostates. This result seems to correspond with the conventional theory that T and E2 have an etiological effect on benign prostatic hyperplasia. DHEAS did not show direct correlation with PV, however it appeared to suppress the role of T and E2 on benign prostatic hyperplasia growth. DHEAS might be a key to understanding the etiology of benign prostatic hyperplasia with aging.     

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.     

Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function

Abstract

Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males.     

LOH–pitfalls of an ambiguous abbreviation

Osteoporosis in elderly men is becoming an important health issue with the aging society. Elderly men with androgen deficiency are exposed to osteoporosis and can be treated with testosterone replacement. In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-deficient osteoporotic aged rat as alternative to testosterone. Aged 12 months old Sprague-Dawley rats were divided into groups of normal control (NC), sham-operated (SO), orchidectomised-control (OrxC), orchidectomised and supplemented with EL (Orx?+?El) and orchidectomised and given testosterone (Orx?+?T). After 6 weeks of treatment, serum osteocalcin, serum terminal C-telopeptide Type 1 collagen (CTX) and the fourth lumbar bone calcium were measured. There were no significant differences in the osteocalcin levels before and after treatment in all the groups. The CTX levels were also similar for all the groups before treatment. However, after treatment, orchidectomy had caused significant elevation of CTX compared to normal control rats. Testosterone replacements in orchidectomised rats were able to prevent the rise of CTX. Orchidectomy had also reduced the bone calcium level compared to normal control rats. Both testosterone replacement and EL supplementation to orchidectomised rats were able to maintain the bone calcium level, with the former showing better effects. As a conclusion, EL prevented bone calcium loss in orchidectomised rats and therefore has the potential to be used as an alternative treatment for androgen deficient osteoporosis.     

Recommendations on the diagnosis,treatment and monitoring of late-onset hypogonadism in men – a suggested update

Abstract

Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men were first published by ISSAM in 2002 In 2005, and, in 2008, updated recommendations were published in the International Journal of Andrology, the Journal of Andrology, the Aging Male and European Urology. Towards discussions at the next ISSAM/ESSAM meeting in Moscow, 29 November 2013, we suggest the following update.     

Androgen effect on body composition and fat metabolism

Reproduced with permission     

Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia

Abstract

Purpose: We examined the prevalence of low testosterone (LT) and its relationship with body mass index (BMI) in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), who were enrolled in a clinical trial of drug therapy, the Medical Therapy of Prostatic Symptoms (MTOPS) Study.

Materials and methods: MTOPS enrolled 3047 men, and of these, 1896 had total testosterone (TT) measured at baseline. LT was defined as a single measurement of TT of <300?ng/dL.

Results: The overall prevalence of LT was 25.7%. Prevalence increased with increasing BMI; 14.7% among men who were normal weight (BMI <25?kg/m²) and 24.2% and 39.3% among overweight (BMI 25 to <30?kg/m²), and obese (baseline BMI ≥30?kg/m²) men, respectively.

Conclusions: LT was observed in about one in four MTOPS study participants with baseline TT measurements. The prevalence of LT increased markedly with increasing BMI. Our findings suggest a high prevalence of LT in obese men with LUTS/BPH. Physicians should be alert to the possibility of symptoms of hypogonadism in this population.     

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.