Association Between Lower Urinary Tract Symptoms and Serum Levels of Sex Hormones in Men

Miwa, Yoshiji; Kaneda, Taisei; Yokoyama, Osamu

doi:10.1016/j.urology.2008.04.023

Cited by 36 publications

(33 citation statements)

References 15 publications

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“…9,10,29 However, such associations were not observed in other studies. 8,30,31 In our study, T þ E2 treatment resulted in a lower incidence of severe BOO (as characterized by urinary retention, bladder outlet luminal sizes and amounts of collagen deposit) than E2-alone treatment in both WT and 12.1DMT1 mice. The T supplement appeared to alleviate BOO symptoms in mice having elevated E2 exposures.…”

Section: Discussionsupporting

confidence: 48%

Increased susceptibility of estrogen-induced bladder outlet obstruction in a novel mouse model

Tam

Zhang

Xiao

et al. 2015

Laboratory Investigation

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Disorders of the prostate and lower urinary tract are common in elderly men. We investigated the role of metallothionein-1 (MT1) in prostate carcinogenesis by generating a prostate-specific, MT1-expressing mouse. Unexpectedly, genomic analyses revealed that a 12.1-kb genomic region harboring several conserved noncoding elements was unintentionally deleted, upstream of the transgene integration site in the mouse, which we named it 12.1DMT1. Male 12.1DMT1 mice chronically treated with testosterone (T) plus 17b-estradiol (E2) to induce prostate cancer exhibited no evidence of precancerous or cancerous lesions. Instead, most of them exhibited a bladder outlet obstruction (BOO) phenotype not observed in treated wild-type (WT) mice. Thus, we hypothesized that 12.1DMT1 is a novel model for studying the hormonal requirement for BOO induction. Adult male 12.1DMT1 and WT mice were treated with T, E2, bisphenol A (BPA), T þ E2, or T þ BPA for up to 6 months. Histologic and immunohistochemical analysis of the prostate, bladder, and urethra were performed. No significant prostate pathologies were observed in WT or 12.1DMT1 mice treated with any of the hormone regimens. As expected, prostatic regression occurred in all E2-treated animals (WT and 12.1DMT1). Of great interest, despite a small prostate, 100% of E2-treated 12.1DMT1 mice, but only 40% of E2-treated WT mice, developed severe BOO (Po0.01). In contrast, T þ E2 treatment was less effective than E2 treatment in inducing severe BOO in 12.1DMT1 mice (68%, Po0.05) and was completely ineffective in WT animals. Similarly, T, BPA, and T þ BPA treatments did not induce BOO in either WT or 12.1DMT1 mice. The BOO pathology includes a thinner detrusor wall, narrowing of bladder neck and urethral lumen, and basal cell hyperplasia in the bladder body and urethra. These findings indicate that 12.1DMT1 mice exhibit enhanced susceptibility to E2-induced BOO that is independent of prostate enlargement but that is attenuated by the conjoint treatment with T. (2015) 95, 546-560; doi:10.1038/labinvest.2015 published online 23 February 2015 Bladder outlet obstruction (BOO) is regarded as a major cause of bothersome lower urinary tract symptoms (LUTS) in men. LUTS encompass a range of urinary morbidities, including those of storage, voiding, and postmicturition. 1 The incidence and prevalence of LUTS increase with age. 2 The etiologies of LUTS are multifactorial, and the pathophysiology is not well understood. 1,3 LUTS has often been attributed to benign prostatic hyperplasia (BPH), which narrows the urethral lumen and ultimately leads to BOO. However, a number of studies have suggested that BOO is not always caused by BPH. [4][5][6] Factors or organs other than the prostate have been proposed as contributors to BOO or modifiers of the severity of its symptoms. 3,7 An imbalance between androgens and estrogens has been implicated in the development of LUTS in men, including BOO. Higher levels of circulating 17b-estradiol (E2) were associated with an increased risk of LUTS in older men,...

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Section: Discussionsupporting

confidence: 48%

Increased susceptibility of estrogen-induced bladder outlet obstruction in a novel mouse model

Tam

Zhang

Xiao

et al. 2015

Laboratory Investigation

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“…These concerns are based on the concept that androgens are essential for prostate growth, which potentially can worsen LUTS. 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: Introductionmentioning

confidence: 99%

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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“…No significant association between LUTS and FT were found in the present analysis. Interestingly, some authors have also reported inverse relationships between LUTS and FT levels (22,23).…”

Section: Discussionmentioning

confidence: 99%

Obesity may influence the relationship between sex hormones and lower urinary tract symptoms

et al. 2014

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ARTICLE INFO ______________________________________________________________ ______________________Purpose: The effects of serum testosterone in the lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) are not well established. The objective of the study is to evaluate the association of sex hormones with LUTS and control the results by patient weight. Materials and Methods:The study comprised a cross-sectional analysis of 725 men included in a prostate cancer screening program at University of Sao Paulo Medical School. The serum concentrations of total testosterone (TT), free testosterone (FT) and sex hormone binding globulin (SHBG) were measured. Variables analyzed were age, American Urological Association (AUA) symptom score, storage symptoms, voiding symptoms, quality of life score, prostate specific antigen levels and prostate volume. Obesity was measured through the calculation of body mass index (BMI). A regression analysis model was performed.Results: Median patient age was 65 years (48 to 94). A higher TT level was significantly associated with a severe AUA symptom score only among patients with a BMI ≥ 25. Median TT was 371, 370 and 427ng/dL (p = 0.017) in patients with mild, moderate and severe LUTS respectively. The multivariate regression analysis in patients with BMI ≥ 25 showed that only age, TT and sex score were related to LUTS. Conclusions: A higher TT is associated with a severe AUA score symptom index only in obese patients. Further analysis are necessary to evaluate the mechanisms through which testosterone may influence LUTS in these patients.

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Association Between Lower Urinary Tract Symptoms and Serum Levels of Sex Hormones in Men

Cited by 36 publications

References 15 publications

Increased susceptibility of estrogen-induced bladder outlet obstruction in a novel mouse model

Increased susceptibility of estrogen-induced bladder outlet obstruction in a novel mouse model

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

Obesity may influence the relationship between sex hormones and lower urinary tract symptoms

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