Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: A pilot study

Калинченко, С. Ю.; El, Vishnevskiy; An, Koval'; Gj, Mskhalaya; Saad, Farid

doi:10.1080/13685530801953994

Cited by 68 publications

(45 citation statements)

References 30 publications

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“…However, some prospective (Kristal et al 2008, Trifiro et al 2010 and cross-sectional studies (Schatzl et al 2000, Tan et al 2003, Roberts et al 2004, Miwa et al 2008, St Sauver et al 2011 have demonstrated an inverse association between serum testosterone and LUTS or BPH. Consistent with these observations, testosterone replacement therapy has been reported to relieve LUTS in hypogonadal men with both BPH (Holmäng et al 1993, Saad et al 2007, Kalinchenko et al 2008, Karazindiyanoglu & Ç ayan 2008, Amano et al 2010, Shigehara et al 2011 and MetS (Haider et al 2009).…”

Section: Introductionsupporting

confidence: 62%

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

Vignozzi¹,

Morelli²,

Sarchielli³

et al. 2011

Journal of Endocrinology

172

174

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Metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) are often associated. One of their common denominators is hypogonadism. However, testosterone supplementation is limited by concerns for potential prostatic side effects. The objective was to determine whether MetS-associated prostate alterations are prevented by testosterone supplementation. We used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks. Subsets of HFD rabbits were treated with testosterone or with the farnesoid X receptor agonist INT-747. Rabbits fed a standard diet were used as controls. HFD-animals develop hypogonadism and all the MetS features: hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. In addition, HFD-animals show a prostate inflammation. Immunohistochemical analysis demonstrated that HFD-induced prostate fibrosis, hypoxia, and inflammation.The mRNA expression of several proinflammatory (IL8, IL6, IL1b, and TNFa), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR gt), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGFb, SM22a, aSMA, RhoA, and ROCK1/ROCK2) markers was significantly increased in HFD prostate. Testosterone, as well as INT-747, treatment prevented some MetS features, although only testosterone normalized all the HFD-induced prostate alterations. Interestingly, the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and the majority of inflammatory markers analyzed. These data highlight that testosterone protects rabbit prostate from MetS-induced prostatic hypoxia, fibrosis, and inflammation, which can play a role toward the development/progression of BPH/LUTS.

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Section: Introductionsupporting

confidence: 62%

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

Vignozzi¹,

Morelli²,

Sarchielli³

et al. 2011

Journal of Endocrinology

172

174

View full text Add to dashboard Cite

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“…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). In addition, as increased rho-kinase activity coincides with the development of LUTS in elderly men, therefore TRT-induced inhibition of rho-kinase is thought to decrease smooth muscle cell proliferation and to decrease adrenergic contractions (Rees et al 2003).…”

Section: Discussionmentioning

confidence: 96%

“…However, it is not known whether these beneficial effects of TRT can be continued in the long term (Yassin et al 2014). Moreover, the significance of low T as well as the exact mechanism of TRT-induced improvement of LUTS are not well-understood (Kalinchenko et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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

Abdel-Hamid

Ali

2015

J Mol Hist

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Testosterone (T) deficiency is prevalent particularly in elderly men and lead to physical and sexual morbidities. Although low levels of T are associated with low urinary tract symptoms, the correlation between T deficiency and bladder dysfunction is not clearly identified. The aim of this study was to investigate the effect of high dose testosterone replacement therapy (TRT) on the histological structure of the UB in castrated rats. Twenty-five adult male rats were divided into three groups: control, castrated and castrated + TRT. T was administrated in high dose (100 mg/kg) two intramuscular injections/week for 60 days. UB sections were prepared and stained with H&E, Masson's trichrome and immunohistochemical detection of Cytokeratin 20 (Ck20). All data were morphometrically and statistically analyzed. In castrated group, significant atrophy of the urothelium (P < 0.001) accompanied with widening of the corium were observed. The smooth muscle appeared thin with marked increase in the collagen fibers. On treating the castrated group with TRT, atypical Ck20 expression as well as significant increase in urothelial thickness (P < 0.05) and smooth muscle/collagen ratio (P < 0.001) were detected. In castrated rat model, high dose TRT has a positive effect on the UB smooth muscle rather than the urothelium which acquired atypical patterns.

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“…When comparing with the previous treatment period consisting of intramuscular injections of T cypionate 200-300 mg over 8 weeks, the quality-of-life surveys for the patients treated with the T gel showed a trend toward greater physical and emotional wellbeing and cognitive function (mean increase: 10%). T-gel therapy in 88 HIV-positive men with abdominal obesity and low T was associated with greater decrease in whole body, total and subcutaneous abdominal fat mass and a greater increase in lean mass compared with placebo [121]. Beneficial effects of topical T gel were also observed in patients with end-stage liver disease [122].…”

Section: Additional Potential Therapeutic Uses Of Testosterone Gelsmentioning

confidence: 95%

Therapeutic Potential of Testosterone Gels

Lunenfeld

Oettel

2009

Aging Health

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Aging Health (2009) 5(2), 227-245 of male primary hypogonadism is due to testicular failure, with Klinefelter's syndrome accounting for the majority of cases. Abnormalities at the testicular level result in hypergonadotropic hypogonadism (primary hypogonadism) and at the hypothalamic-pituitary level result in hypogonadotropic hypogonadism (secondary h ypogonadism) (Figure 1).In addition, it has been clearly demonstrated that aging is associated with a decline in both total T and free T levels, with a 20 and 35% incidence of hypogonadism in men aged 60 years and in those over 80 years of age, respectively [2,9]. This decline in T is the result of a combination of a primary steroidogenic defect in the aging Leydig cells [10], decreased pituitary secretory capacity and responsiveness to gonadotropin-releasing hormone [11]. This type of testicular deficiency has been termed late-onset hypogonadism (LOH). Aging is also asso ciated with an increase in sex hormone-binding globulin levels and, consequently, with a slower decline in total T than in free T [12]. The normal diurnal rhythm of T secretion observed in young men is partially lost with aging [13]. Aging is also associated with a decrease in lean body mass, muscle mass and strength, diminished libido, erectile function, decreased bone mass, increased fracture risk and diminished sleep quality -symptoms similar to those observed in hypogonadism, which may need treatment with T. Per definition, male hypogonadism is a clinical syndrome characterized by a reduction in circulating androgens and the presence of signs and symptoms of androgen deficiency. The existence of clinical symptoms is In demographic terms, the global population is estimated to grow from the current 6.5 billion to approximately 9 billion by the year 2050. However, owing to the worldwide prolongation of the mean life expectancy and the drastic reduction of fertility rate, it is projected that the elderly (>60 years) will double during the same period from 688-1964 million [1].Approximately 30% of men aged 60-70 years and 70% of men aged 70-80 years have low bioavailable or free testosterone (T) levels [2]. Symptoms and findings of T deficiency are more or less similar to those associated with aging. They include loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strength, increased fat mass, frailty, osteopenia and osteoporosis [3]. Clinical trials indicate that T therapy can improve many of these findings [4][5][6][7][8].Testosterone is the principal androgen in men, as well as the prohormone for the biosynthesis of two other sexual steroids: 5α-dihydrotestosterone (DHT) and 17β-estradiol. In human males, T 6-7 mg is secreted by the testes in a circadian rhythm with a nocturnal rise in T followed by a decline during the day. T is necessary for spermatogenesis, penile function, to induce and maintain secondary sexual characteristics, lean muscle mass, bone density and for normal sexual behavior and cognitive function.The administration of T is appropri...

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Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: A pilot study

Cited by 68 publications

References 30 publications

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

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

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

Therapeutic Potential of Testosterone Gels

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