Serum testosterone and prostate-specific antigen levels are major risk factors for prostatic volume increase among benign prostatic hyperplasia patients

doi:10.1016/j.ajur.2020.06.001

Asian Journal of Urology, 2021, 8 (3): 289-297 doi: 10.1016/j.ajur.2020.06.001

Original Article

Serum testosterone and prostate-specific antigen levels are major risk factors for prostatic volume increase among benign prostatic hyperplasia patients

Gede Wirya Kusuma Duarsa^a,*(

),Yudit Anastasia Sari^b,Anak Agung Gde Oka^a,Kadek Budi Santosa^a,I Wayan Yudiana^a,Pande Made Wisnu Tirtayasa^a,Ida Bagus Putra Pramana^a,Yudhistira Pradnyan Kloping^c

^a Department of Urology, Sanglah General Hospital, Faculty of Medical and Health Sciences of Udayana University, Denpasar, Bali, Indonesia
^b General Surgery Department, Faculty of Medicine Udayana University, Denpasar, Bali, Indonesia
^c Medical Faculty, Universitas Airlangga, Surabaya, East Java, Indonesia

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Abstract

Objective: Benign prostatic hyperplasia (BPH) is one of the most common diseases found among elderly men. Even though multiple risk factors of BPH have been identified in the past, the risk factors which have a direct impact on prostate volume have not been identified. In this study, we aim to determine the most significant contributing risk factors to prostate volume enlargement by analyzing possible associated risk factors previously studied.
Methods: This is a quantitative study with an analytical observational design, performed using a retrospective cohort approach. Total sampling was performed on 83 patients who underwent transurethral resection of the prostate (TURP) in Sanglah General Hospital from January to February 2019. Bivariate analysis is performed to examine each variable's association with prostate volume followed by a multivariate analysis. All variables were reassessed with path analysis to measure the direct effects, indirect effects, and total effects on prostate volume.
Results: Bivariate analysis shows that serum testosterone (R=0.208; p=0.059) and prostate-specific antigen (PSA) level (R=0.626; p=0.001) have a significant association with prostate volume. Multivariate analysis shows that serum PSA (B=1.4; p=0.001; 95% confidence interval [95% CI]=1.039-1.770) and testosterone (B=0.024; p=0.005; 95% CI=0.008-0.041) levels are significant among all the analyzed risk factors. There is a significant and strong effect of PSA to prostate volume (c=0.636; p=0.001) whereas testosterone has a significant albeit weak effect to prostate volume (c=0.246; p=0.009) based on the total effect of the path analysis.
Conclusion: Serum testosterone and PSA levels are significantly associated with prostatic volume increase among BPH patients.

Key words： Testosterone Prostate-specific antigen Prostate volume Benign prostatic hyperplasia

Received: 18 January 2020 Available online: 07 July 2020

Corresponding Authors: Gede Wirya Kusuma Duarsa E-mail: gwkurology@gmail.com

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	Yudit Anastasia Sari
	Anak Agung Gde Oka
	Kadek Budi Santosa
	I Wayan Yudiana
	Pande Made Wisnu Tirtayasa
	Ida Bagus Putra Pramana
	Yudhistira Pradnyan Kloping

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Cite this article:

Gede Wirya Kusuma Duarsa,Yudit Anastasia Sari,Anak Agung Gde Oka, et al. Serum testosterone and prostate-specific antigen levels are major risk factors for prostatic volume increase among benign prostatic hyperplasia patients[J]. Asian Journal of Urology, 2021, 8(3): 289-297.

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http://www.ajurology.com/EN/10.1016/j.ajur.2020.06.001 OR http://www.ajurology.com/EN/Y2021/V8/I3/289

Subjects’ characteristics.

Bivariate analysis results between risk factors and prostate volume.

Linier regression results of risk factors regarding prostate volume.

Correlation	r-score	p-Value	95% CI
Two-sided correlation
Age ↔ UTI	-0.076	0.511	-0.303-0.151
Age ↔ T2DM	-0.157	0.114	-0.351-0.038
Age ↔ Obesity	-0.187	0.094	-0.407-0.032
Age ↔ Dyslipidemia	-0.123	0.311	-0.362-0.115
Age ↔ TNF	-0.021	0.862	-0.255-0.213
Age ↔ TGF	0.023	0.818	-0.174-0.221
UTI ↔ T2DM	-0.086	0.368	-0.274-0.101
UTI ↔ Obesity	-0.018	0.861	-0.224-0.187
UTI ↔ Dyslipidemia	-0.033	0.745	-0.229-0.163
UTI ↔ TNF	0.174	0.182	-0.081-0.429
UTI ↔ TGF	0.003	0.972	-0.184-0.190
T2DM ↔ Obesity	0.191	0.005	0.057-0.325
T2DM ↔ Dyslipidemia	0.323	<0.001	0.155-0.490
T2DM ↔ TNF	-0.085	0.395	-0.279-0.110
T2DM ↔ TGF	-0.127	0.066	-0.262-0.008
Obesity ↔ Dyslipidemia	0.071	0.504	-0.138-0.281
Obesity ↔ TNF	-0.182	0.167	-0.440-0.076
Obesity ↔ TGF	-0.101	0.361	-0.317-0.116
Dyslipidemia ↔ TNF	0.154	0.121	-0.041-0.349
Dyslipidemia ↔ TGF	0.157	0.108	-0.034-0.348
TNF ↔ TGF	0.515	<0.001	0.352-0.678
One-sided correlation
PSA ← Age	0.089	0.341	-0.094-0.271
PSA ← UTI	-0.018	0.856	-0.216-0.179
PSA ← T2DM	-0.227	0.001	-0.360-0.094
PSA ← Obesity	-0.000	0.998	-0.222-0.221
PSA ← Dyslipidemia	-0.004	0.968	-0.213-0.204
PSA ← TNF	0.050	0.700	-0.207-0.308
PSA ← TGF	-0.018	0.888	-0.266-0.230
Prostate volume ← PSA	0.636	0.001	0.471-0.802
Prostate volume ← Testosterone	0.246	0.013	0.051-0.440
Prostate volume ← Age	0.036	0.593	-0.097-0.170
Prostate volume ← UTI	-0.038	0.606	-0.183-0.107
Prostate volume ← T2DM	-0.006	0.957	-0.213-0.201
Prostate volume ← Obesity	0.082	0.296	-0.071-0.235
Prostate volume ← Dyslipidemia	0.099	0.191	-0.049-0.247
Prostate volume ← TNF	-0.019	0.852	-0.215-0.178
Prostate volume ← TGF	0.039	0.655	-0.131-0.208
Testosterone ← Age	-0.017	0.881	-0.252-0.216
Testosterone ← UTI	-0.045	0.734	-0.304-0.214
Testosterone ← T2DM	-0.171	0.101	-0.376-0.033
Testosterone ← Obesity	0.087	0.397	-0.114-0.288
Testosterone ← Dyslipidemia	-0.078	0.616	-0.383-0.227
Testosterone ← TNF	-0.014	0.918	-0.282-0.253
Testosterone ← TGF	-0.085	0.458	-0.309-0.140

Correlation between two risk factor variables.

Direct and indirect effects of evaluated risk factors.

Total effect of risk factors to prostate volume.

Risk factors for prostatic volume increase path analysis. PSA, prostate-specific antigen; TNF, tumor necrosis factor; TGF, transforming growth factor; UTI, urinary tract infection; T2DM, type 2 diabetes mellitus.

[1]	Lim KB. Epidemiology of clinical benign prostatic hyperplasia. Asian J Urol 2017; 4:148-51.
[2]	Wei JT, Calhoun E, Jacobsen SJ. Urologic diseases in America project: benign prostatic hyperplasia. J Urol 2005; 173:1256-61. doi: 10.1097/01.ju.0000155709.37840.fe
[3]	Mochtar CA, Umbas R, Soebadi DM, Purnomo BB, Widjanarko S, Tarmono, et al. Panduan penatalaksanaan klinis pembesaran prostat jinak (benign prostatic hyperplasia/BPH). 2nd ed. Jakarta: Ikatan Ahli Urologi Indonesia; 2015. p. 1-27.
[4]	Duarsa GWK, Lesmana R, Mahadewa TG. High serum prostate specific antigen as a risk factor for moderate-severe prostate inflammation in patient with benign prostatic hyperplasia. Bali Med J 2016; 4:148-51.
[5]	Chen Z, Miao L, Gao X, Wang G, Xu Y. Effect of obesity and hyperglycemia on benign prostatic hyperplasia in elderly patients with newly diagnosed type 2 diabetes. Int J Clin Exp Med 2015; 8:11289-94. pmid: 26379937
[6]	Taylor BC, Wilt TJ, Fink HA, Lambert LC, Marshall LM, Hoffman AR, et al. Prevalence, severity, and health correlates of lower urinary tract symptoms among older men: the MrOS study. Urol Times 2006; 68:804-9.
[7]	Bosch J, Tilling K, Bohnen A, Bangma C, Donovan J. Establishing normal reference ranges for prostate volume change with age in the population-based Krimpen-study: prediction of future prostate volume in individual men. Prostate 2007; 67:1816-24. pmid: 17935157
[8]	Loeb S, Kettermann A, Carter HB, Ferrucci L, Metter EJ, Walsh PC. Prostate volume changes over time: results from the Baltimore longitudinal study of aging. J Urol 2009; 182:1458-62. doi: 10.1016/j.juro.2009.06.047
[9]	Schaeffer AJ. Infections of the urinary tract. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell-walsh urology tenth edition. Philadelphia: Elsevier- Saunders; 2012. p257-326.
[10]	Heyns C. Urinary tract infection associated with conditions causing urinary tract obstruction and stasis, excluding urolithiasis and neuropathic bladder. World J Urol 2012; 30:77-83. doi: 10.1007/s00345-011-0725-9 pmid: 21720861
[11]	Wang S, Mao Q, Lin Y, Wu J, Wang X, Zheng X, et al. Body mass index and risk of BPH: a meta-analysis. Prostate Cancer Prostatic Dis 2012; 15:265. doi: 10.1038/pcan.2011.65
[12]	Lee SH, Kim JC, Lee JY, Kim JH, Oh CY, Lee SW, et al. Effects of obesity on lower urinary tract symptoms in Korean BPH patients. Asian J Androl 2009; 11:663-8. doi: 10.1038/aja.2009.62
[13]	Parsons JK. Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Curr Bladder Dysfunct Rep 2010; 5:212-8. doi: 10.1007/s11884-010-0067-2
[14]	Kim JM, Song PH, Kim HT, Moon KH. Effect of obesity on prostate-specific antigen, prostate volume, and international prostate symptom score in patients with benign prostatic hyperplasia. Korean J Urol 2011; 52:401-5. doi: 10.4111/kju.2011.52.6.401
[15]	Dahle SE, Chokkalingam AP, Gao YT, Deng J, Stanczyk FZ, Hsing AW. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol 2002; 168:599-604. doi: 10.1016/S0022-5347(05)64687-3
[16]	Kok ET, Schouten BW, Bohnen AM, Groeneveld FP, Thomas S, Bosch JR. Risk factors for lower urinary tract symptoms suggestive of benign prostatic hyperplasia in a community based population of healthy aging men: the Krimpen Study. J Urol 2009; 181:710-6.
[17]	Wong SY, Woo J, Leung JC, Leung PC. Depressive symptoms and lifestyle factors as risk factors of lower urinary tract symptoms in Southern Chinese men: a prospective study. Aging Male 2010; 13:113-9. doi: 10.3109/13685530903440432
[18]	Pelton K, Di Vizio D, Insabato L, Schaffner CP, Freeman MR, Solomon KR. Ezetimibe reduces enlarged prostate in an animal model of benign prostatic hyperplasia. J Urol 2010; 184:1555-9. doi: 10.1016/j.juro.2010.05.083
[19]	Lekili M, Müezzinoğlu T, Uyanık BS, Büyüksu C. Serum lipid levels in benign prostatic hyperplasia. World J Urol 2006; 24:210-3. pmid: 16506048
[20]	Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes 2000; 24:S64. https://doi.org/10.1038/sj.ijo.0801281.
[21]	Gupta A, Gupta S, Pavuk M, Roehrborn CG. Anthropometric and metabolic factors and risk of benign prostatic hyperplasia: a prospective cohort study of Air Force veterans. Urol Times 2006; 68:1198-205.
[22]	Zucchetto A, Tavani A, Dal Maso L, Gallus S, Negri E, Talamini R, et al. History of weight and obesity through life and risk of benign prostatic hyperplasia. Int J Obes 2005; 29:798-803. doi: 10.1038/sj.ijo.0802979
[23]	Bourke J, Griffin J. Diabetes mellitus in patients with benign prostatic hyperplasia. Br Med J 1968; 4:492-3.
[24]	Safarinejad MR. Prevalence of benign prostatic hyperplasia in a population-based study in Iranian men 40 years old or older. Int Urol Nephrol 2008; 40:921-31. doi: 10.1007/s11255-008-9338-7 pmid: 18246438
[25]	Vikram A, Tripathi D, Ramarao P, Jena G. Intervention of Dglucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat. Toxicol Appl Pharmacol 2008; 226:84-93. doi: 10.1016/j.taap.2007.09.006
[26]	Keda K, Wada Y, Foster HE, Wang Z, Weiss RM, Latifpour J. Experimental diabetes-induced regression of the rat prostate is associated with an increased expression of transforming growth factor-b. J Urol 2000; 164:180-5. doi: 10.1016/S0022-5347(05)67491-5
[27]	Haffner S. Sex hormones, obesity, fat distribution, type 2 diabetes and insulin resistance: epidemiological and clinical correlation. Int J Obes 2000; 24:S56-8. https://doi.org/10.1038/sj.ijo.0801279.
[28]	Hammarsten J, Högstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia. Eur Urol 2001; 39:151-8. pmid: 11223674
[29]	Rohrmann S, Smit E, Giovannucci E, Platz EA. Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey (NHANES III). Int J Obes 2005; 29:310-6. doi: 10.1038/sj.ijo.0802881
[30]	Sarma AV, Parsons JK, McVary K, Wei JT. Diabetes and benign prostatic hyperplasia/lower urinary tract symptomsdwhat do we know? J Urol 2009; 182:32e7.
[31]	Sarma AV, Burke JP, Jacobson DJ, McGree ME, Sauver JS, Girman CJ, et al. Associations between diabetes and clinical markers of benign prostatic hyperplasia among communitydwelling Black and White men. Diabetes Care 2008; 31:476-82. doi: 10.2337/dc07-1148
[32]	Burke JP, Jacobson DJ, McGree ME, Roberts RO, Girman CJ, Lieber MM, et al. Diabetes and benign prostatic hyperplasia progression in Olmsted County, Minnesota. Urol Times 2006; 67:22-5.
[33]	Rastrelli G, Vignozzi L, Corona G, Maggi M. Testosterone and benign prostatic hyperplasia. Sex Med Rev 2019; 7:259-71. doi: S2050-0521(18)30143-4 pmid: 30803920
[34]	Schenk JM, Kristal AR, Neuhouser ML, Tangen CM, White E, Lin DW, et al. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol 2010; 171:571-82. doi: 10.1093/aje/kwp406
[35]	Robert G, Descazeaud A, Allory Y, Vacherot F, Taille ADLA. Should we investigate prostatic inflammation for the management of benign prostatic hyperplasia? Eur Urol Suppl 2009; 8:879-86. doi: 10.1016/j.eursup.2009.11.004
[36]	Yalcinkaya FR, Gokcei A, Davarci M, Guven EO, Inci M, Karta S. The impact of NIH-IV prostatitis on early post-operative outcomes of transurethral resection of the prostate in patients with symptomatic benign prostate hyperplasia. Turk J Med Sci 2011; 41:515-9.
[37]	Wang X, Lin WJ, Izumi K, Jiang Q, Lai KP, Xu D, et al. Increased infiltrated macrophages in benign prostatic hyperplasia (BPH) role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation. J Biol 2012; 287:18376-85.
[38]	Gandaglia G, Briganti A, Gontero P, Mondaini N, Novara G, Salonia A, et al. The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). BJU Int 2013; 112:432-41. doi: 10.1111/bju.12118 pmid: 23650937
[39]	Duarsa GW, Oka AA, Maliawan S, Soebadi DM, Astawa P, Bakta M, et al. Elevated tumor necrosis factor-a and transforming growth factor-b in prostatic tissue are risk factors for lower urinary tract symptoms after transurethral resection of the prostate in benign prostatic hyperplasia patients with urinary retention. Open Urol Nephrol J 2018; 11:46-53. doi: 10.2174/1874303X01811010046
[40]	Huang X, Lee C. Regulation of stromal proliferation, growth arrest, differentiation and apoptosis in benign prostatic hyperplasia by TGF-beta. Front Biosci 2003; 8:s740-9. https://doi.org/10.2741/1093. doi: 10.2741/1093
[41]	Schauer IG, Rowley DR. The functional role of reactive stroma in benign prostatic hyperplasia. Differentiation 2011; 82:200-10. doi: 10.1016/j.diff.2011.05.007 pmid: 21664759
[42]	van der Sluis TM, Vis AN, van Moorselaar RJA, Bui HN, Blankenstein MA, Meuleman EJ, et al. Intraprostatic testosterone and dihydrotestosterone. Part I: concentrations and methods of determination in men with benign prostatic hyperplasia and prostate cancer. BJU Int 2012; 109:176-82. doi: 10.1111/j.1464-410X.2011.10651.x pmid: 21992222
[43]	Jarvis TR, Chughtai B, Kaplan SA. Testosterone and benign prostatic hyperplasia. Asian J Androl 2015; 17:212-6. doi: 10.4103/1008-682X.140966
[44]	Dias JP, Melvin D, Shardell M, Ferrucci L, Chia CW, Gharib M, et al. Effects of transdermal testosterone gel or an aromatase inhibitor on prostate volume in older men. J Clin Endocrinol Metab 2016; 101:1865-71. doi: 10.1210/jc.2016-1111
[45]	Dell’Atti L, Galosi AB. The role of the serum testosterone levels as a predictor of prostate cancer in patients with atypical small acinar proliferation at the first prostate biopsy. Asian J Androl 2018; 20:15-8. doi: 10.4103/aja.aja_17_17
[46]	Deori R, Das B, Rahman MA. A study of relationship of prostate volume, prostate specific antigen, and age in benign prostatic hyperplasia. Int J Contemp Med Res 2017; 4:1582-6.
[47]	Putra IBO, Hamid AR, Mochtar CA, Umbas R. Relationship of age, prostate-specific antigen, and prostate volume in Indonesian men with benign prostatic hyperplasia. Prostate Int 2016; 4:43-8. doi: 10.1016/j.prnil.2016.03.002