Improvement Of Metabolic Syndrome And Lower Urinary Tract Symptoms Upon Normalisation Of Plasma Testosterone Levels In Hypogonadal Elderly Men

Main Category: Urology / Nephrology
Also Included In: Men's health
Article Date: 01 Mar 2009 - 1:00 PDT

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UroToday.com - It is becoming clear that many age-related health problems of men, hitherto regarded as distinct clinical diagnostic categories and treated by different medical disciplines, are actually inter-related and require a more integrative approach to advance health care of the aging male. At the epidemiological level, an association between central obesity in adulthood, the metabolic syndrome, erectile failure and lower urinary tract symptoms (LUTS) has been established.

A common denominator of the above ailments is lower-than-normal testosterone levels occurring in a significant proportion of elderly men. Epidemiological associations suggest but do not prove a causal relationship, and intervention studies are required to make a causal relationship plausible. In a recent study we could, indeed, demonstrate a concurrent improvement of features of the metabolic syndrome and of lower urinary tract symptoms (LUTS) upon administration of testosterone to men with lower-than-normal serum testosterone levels.

The first mention of effects of testosterone on bladder function was reported by Holmang et al. finding an increase in peak urinary flow and mean urine volume voided in a testosterone treated group of men compared to placebo treatment. Recently, beneficial effects of testosterone administration on LUTS have also been reported by other authors.

A few studies have analyzed the relationship between circulating testosterone and LUTS symptoms. One study found that hypogonadism was seen in approximately one fifth of elderly men with LUTS, but it had no impact on symptom status. Another study found a relation between symptoms of LUTS and plasma total and bioavailable testosterone but this relationship disappeared after statistical adjustment for age. No consistent correlations were found between total and calculated free testosterone and symptoms of LUTS in other reports.

But a recent study reported that low testosterone levels in clinical bladder outlet obstruction correlated negatively with detrusor pressure at urethral closure and detrusor pressure at maximum flow, while promoting detrusor overactivity. So, the possibility must be considered that the potential beneficial effects of normalization of serum testosterone on symptoms of LUTS are indirect. In fact, the findings of our study support this assumption. While occurring concurrently, a statistically significant correlation between the improvement of features of the metabolic syndrome and the improvements in the IPSS and residual bladder volume could not be established. A number of modes of actions of the indirect effect of testosterone on LUTS may be considered.

The relationship between the metabolic syndrome and LUTS may be due to overactivity of the autonomic nervous system for which hyperinsulinemia, a key element of the metabolic syndrome, might be responsible. While not being responsible for the development of LUTS it may play a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary anatomical/pathophysiological characteristics of other ailments leading to LUTS. Another recent study provided evidence that stress conditions could be associated with the development and aggravation of prostatic disease. It was found that body mass index, and age, greater diastolic blood pressure reactivity were associated with a greater transition zone volume, greater total prostate gland volume, greater postvoid residual bladder volume, and more severe LUTS.

Inflammatory infiltrates are frequently found in and around nodules in benign prostate hyperplasia (BPH) in symptomatic BPH. The presence of the metabolic syndrome might be a mediator of this association because it is associated with elevated serum C-reactive protein (CRP) concentration, a non-specific marker of inflammation. Testosterone administration leads to an improvement in the levels of inflammation markers such as CRP.

Nitric oxide (NO) exerts a smooth muscle relaxing effect in the urinary tract. NO is a mediator of erection but also of dilatation of the bladder neck and urethra. In humans 72-96% of neurons in the wall of the bladder appear to contain nitric oxide synthase, and clinical studies have convincingly shown that phosphodiesterase inhibitors have a beneficial effect on LUTS. NO-synthase appears to be androgen dependent. Several clinical studies indicate that the phosphodiesterase-inhibitors are not very efficacious when circulating levels of testosterone are low.

In summary: Testosterone itself might not be the 'prime mover' of the effects of testosterone on those structures of the urinary tract anatomically and functionally related to LUTS. Testosterone might exert an indirect effect mediated by the effects on features of the metabolic syndrome, its anti-inflammatory effects, and its effects on nitric oxide/cGMP signaling.

Written by Farid Saad, PhD as part of Beyond the Abstract on UroToday.com

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