PPARγ: A molecular link between systemic metabolic disease and benign prostate hyperplasia

Jiang, Ming; Strand, Douglas W.; Franco, Omar E.; Clark, Peter E.; Hayward, Simon W.

doi:10.1016/j.diff.2011.05.008

Cited by 41 publications

(34 citation statements)

References 201 publications

(286 reference statements)

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“…Furthermore, animal studies have demonstrated that pioglitazone decreased prostate weight in response to a high-fat diet 12 . These observations suggest that PPARγ signaling is an important factor driving the insulin resistance/diabetes and BPH association 8 .…”

Section: Introductionmentioning

confidence: 91%

“…Along with chronic inflammation, it also appears that diabetes mellitus may be associated with an increased risk for developing BPH 5 . Possible mechanisms for such an association include the hyperinsulinemic state observed in type 2 diabetes mellitus, the mitogenic effect of insulin-like growth factor, 6, 7 and chronic obesity-induced inflammation 8 .…”

Section: Introductionmentioning

confidence: 99%

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Thiazolidinedione and Metformin Use and the Risk of Benign Prostate Hyperplasia in Veterans with Diabetes Mellitus

Murff

Roumie

Greevy

et al. 2014

Journal of Men's Health

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Background Chronic inflammation is important in the development of benign prostatic hyperplasia (BPH) and certain oral antidiabetic medications have anti-inflammatory properties. The purpose of this study was to determine if use of thiazolidinediones or metformin was associated with a reduced risk of requiring medical or surgical treatment for BPH compared to sulfonylureas among diabetic men. Methods We constructed a retrospective cohort of 192,457 male veterans newly prescribed either rosiglitazone, pioglitazone, metformin, or a sulfonylurea. We used Cox proportional hazard regression to assess the association between thiazolidinedione or metformin use and the risk of requiring medical or surgical treatment for BPH compared to sulfonylurea use. New BPH treatment was defined by either a new prescription for a α-1 blocker or 5α-reductase inhibitors or a surgical procedure indicated for severe BPH. Results In 259,995 person-years of follow up we identified 14,690 new treatments for BPH. After adjusting for covariates including age, HbA1c, and body mass index, we found no association between rosiglitazone (adjusted hazard ratio [aHR] 1.02, 95% CI 0.86, 1.20), pioglitazone (aHR 0.79, 95% CI 0.45, 1.38), or metformin use (aHR 0.99, 95% CI 0.94, 1.03) and risk of new medical or surgical treatment for BPH compared to sulfonylureas. Analyses ignoring prescriptions for non-selective α-1 blockers (terazosin, doxazosin, prazosin) from our BPH case definition (n = 11,079), yielded similar results. Conclusions In this large cohort, we observed no association between the use of thiazolidinediones or metformin and new medical or surgical treatment for BPH compared to sulfonylureas.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Thiazolidinedione and Metformin Use and the Risk of Benign Prostate Hyperplasia in Veterans with Diabetes Mellitus

Murff

Roumie

Greevy

et al. 2014

Journal of Men's Health

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“…Although the precise mechanisms by which obesity influences the risk of BPH/LUTS remain unclear, a theory of causation can be supported by animal studies which provide biological underpinnings for the association between the two disorders [5]. Obesity is characterized by enlarged depots of adipose tissue, which are hormonally active and secrete pro-inflammatory cytokines and chemokines that can influence local adipocyte biology as well as prostate health [6].…”

Section: Introductionmentioning

confidence: 99%

Urine chemokines indicate pathogenic association of obesity with BPH/LUTS

et al. 2015

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Objectives High prevalence of lower urinary tract symptoms (LUTS) consistent with benign prostate hyperplasia (BPH) is associated with obesity and prostatic inflammation. Here, we investigated whether chemokines associated with obesity and prostatic inflammation can be measured in normally voided urine of BPH/LUTS patients to demonstrate the mechanistic association between obesity and BPH/LUTS. Methods Frozen urine specimens of BPH/LUTS patients enrolled in the Nashville Men's Health Study were sent for blinded analysis to University of Pittsburgh. Thirty patients were blocked by their AUA-SI (>7 or ≤7) and prostatic enlargement (<40, 40–60, >60 cc). Clinical parameters including age, prostate size, and medications were derived from chart review. CXC chemokines (CXCL-1, CXCL-8, and CXCL-10), CC chemokines (CCL2 and CCL3), and sIL-1ra were measured in thawed urine using Luminex™ xMAP® technology and ELISA for NGF. Results Urinary CCL2 levels were several fold higher compared with the other six proteins, of which CCL3 was detectable in less than one-fourth of patients. Urine levels of sIL-1ra and CXCL-8 were significantly associated with increasing BMI and waist circumference in BPH patients. CXCL-8 showed a marginal association with overall AUA-SI scores, as well as obstructive (p = 0.08) symptom sub-scores. Prostate volume was inversely and marginally associated with urinary CXCL-10 (p = 0.09). Conclusions Urine levels of CXCL-8, CXCL-10, and sIL-1ra were associated with varying degrees with LUTS severity, prostate size, and obesity, respectively. These findings in urine are consistent with past studies of chemokine levels from expressed prostatic secretions and demonstrate the potential of noninvasively measured chemokine in urine to objectively classify BPH/LUTS patients.

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“…The possibility of a link between MetS and BPH has been explored for almost 20 years [7,8,9,10,11]. Our previous study suggested that MetS is highly prevalent in the BPH population and that it is associated with an increase in total volume and annual prostate growth rate.…”

Section: Introductionmentioning

confidence: 99%

Association of Metabolic Syndrome and Benign Prostatic Hyperplasia in Chinese Patients of Different Age Decades

Pan¹,

Jiang²,

Luo³

et al. 2013

Urol Int

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Objectives: To evaluate the relationship between metabolic syndrome (MetS) and annual prostate growth rates in Chinese patients of different age decades with benign prostatic hyperplasia (BPH). Methods: We retrospectively analyzed the clinical data obtained from 1,052 Chinese men with BPH. Overnight fasting venous blood specimens were collected and serum levels of prostate-specific antigen, fasting blood glucose, high-density lipoprotein cholesterol, total cholesterol and triglyceride were recorded. We divided age into four groups: 50 ≤ age ≤ 60, 60 < age ≤ 70, 70 < age ≤ 80 and 80 < age ≤ 90. Pearson's correlation coefficient was used to test the linearity of the relationships between each of the MetS components and prostate volume and annual prostate growth rates generally and in different age decades. Results: The median total prostate volume (69.01 ml) and median annual prostate growth rate (1.92 ml/year) were significantly higher in the MetS group compared with the non-MetS group (57.26 ml and 1.23 ml/year). Significant positive correlations were also found in total prostate volume and different age decades, while negative correlations were seen in annual prostate growth rate and different age decades. Conclusions: MetS is associated with an increased risk of total volume and annual prostate growth rate in BPH patients of different age decades.

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PPARγ: A molecular link between systemic metabolic disease and benign prostate hyperplasia

Cited by 41 publications

References 201 publications

Thiazolidinedione and Metformin Use and the Risk of Benign Prostate Hyperplasia in Veterans with Diabetes Mellitus

Thiazolidinedione and Metformin Use and the Risk of Benign Prostate Hyperplasia in Veterans with Diabetes Mellitus

Urine chemokines indicate pathogenic association of obesity with BPH/LUTS

Association of Metabolic Syndrome and Benign Prostatic Hyperplasia in Chinese Patients of Different Age Decades

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