Lower urinary tract symptoms and its potential relation with late-onset hypogonadism

Abstract

The study of the health status of the aging male takes presently a more integrative approach and it appears that ailments typical of male aging, such as lower urinary tract symptoms (LUTS), (visceral) obesity, metabolic syndrome and erectile failure are significantly interrelated. A common denominator of the above ailments is lower-than-normal testosterone levels occurring in a significant proportion of elderly men. This review addresses the potential connections between LUTS and late-onset hypogonadism. In animal studies there appear to be androgen and estrogen receptors in the urothelium and smooth muscle cells of the urethra and bladder of the rat and rabbit, as well as in the neurons in the autonomic ganglia of the prostatic plexus of the male rat. Upon castration electrically evoked relaxations of the smooth muscle of the prostatic urethra were decreased. There is a Rho-kinase activation/endothelin pathway; possibly involved in the increased smooth muscle activity found in both LUTS/benign prostate hyperplasia. Nitric oxide (NO) appears to have a smooth muscle relaxing effect in the urogenital organs. Studies in humans have convincingly shown that phosphodiestererase inhibitors have a beneficial effect on LUTS. More intervention studies should be undertaken to test the clinical validity of the theoretically plausible interrelationship between LUTS and late-onset hypogonadism.

Effect of testosterone therapy on the urinary bladder in experimental hypogonadism of rats

“…Castration decreases noticeably the activities of the mitochondria specific enzyme, citrate synthase of the UB muscle and mucosa (Juan et al 2007) which could be corrected by TRT. Nitric oxide (NO) is also one of the mediators of dilatation of the bladder neck and urethra (McVary 2006) by its smooth muscle relaxing effect in the urogenital system (Pradidarcheep 2008). It was suggested that TRT could improve the urinary symptoms by increasing NO production by modulatory effect on NO synthase (Chamness et al 1995) or phosphodiesterase which might be linked to TRT effect on the penile tissues in hypogonadal men (Kalinchenko et al 2008).…”

“…AR have been widely identified in UB including its urothelium, smooth muscle cells and neurons (Pradidarcheep 2008). Activation of AR by androgen may stimulate stromal precursor cells to differentiate into smooth muscle cells (Traish et al 2007).…”

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit

“…Pimonidazole (hypoxyprobe) is a water soluble substituted 2-nitrominidazole that is rapidly distributed to all tissues in the body, but it only forms adducts with proteins in hypoxic cells, which are at an oxygen pressure equal to or lower than 10 mmHg. Hypoxic cells are thereafter easily detected by immunohistochemistry, using a monoclonal antibody (Hypoxyprobe-1Mab1) that recognizes hypoxyprobe protein adduct (Durand & Raleigh 1998, Bennewith et al 2002; Pimonidazole as a probe for the in vivo detection of hypoxia has been validated previously (Arteel et al 1995, Vignozzi et al 2006, 2008, 2009, Bouchentouf et al 2008, Via et al 2008, Morelli et al 2010a. Rabbit ventral prostate samples were rapidly removed and fixed in 4% neutral buffered formalin, dehydrated, and embedded in paraffin.…”

“…Tissue oxygenation has been analyzed as described previously (Vignozzi et al 2006, 2008, 2009, Morelli et al 2010a). Briefly, 1 h before being killed, rabbits of each experimental group were intraperitoneally injected with the bioreductive drug pimonidazole hydrochloride (Hypoxyprobe-1, 60 mg/kg).…”

“…MetS appears, therefore, related to the development of LUTS. Potential common etiological factors include hyperglycemia, insulin resistance, low-grade chronic inflammation (Moul & McVary 2010), and also hypogonadism (Pradidarcheep 2008). Recent data have in fact suggested that low testosterone in males might be considered an additional MetS component (Corona et al 2009, Zitzmann 2009, Corona et al 2011a,b, Traish et al 2011.…”