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Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia

Abstract

The aetiology of benign prostatic hyperplasia (BPH) remains unclear. The objective of the present study was to test the insulin, oestradiol and metabolic syndrome hypotheses as promoters of BPH. The design was a risk factor analysis of BPH in which the total prostate gland volume was related to endocrine and anthropometric factors. The participants studied were 184 representative men, aged 72–76 years, residing in Göteborg, Sweden. Using a multivariate analysis, BPH as measured by the total prostate gland volume correlated statistically significantly with fasting serum insulin (β=0.200, P=0.028), free oestradiol (β=0.233, P=0.008) and lean body mass (β=0.257, P=0.034). Insulin and free oestradiol appear to be independent risk factors for BPH, confirming both the insulin and the oestradiol hypotheses. Our findings also seem to confirm the metabolic syndrome hypothesis. The metabolic syndrome and its major endocrine aberration, hyperinsulinaemia, are possible primary events in BPH.

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References

  1. Guess HA . Benign prostatic hyperplasia: antecedents and natural history. Epidemiol Rev 1992; 14: 131–153.

    Article  CAS  Google Scholar 

  2. Partin AW, Oesterling JE, Epstein JI, Horton R, Walsh P . Influence of age and endocrine factors on the volume of benign prostatic hyperplasia. J Urol 1991; 145: 405–409.

    Article  CAS  Google Scholar 

  3. Walch PC, Retic AB, Stamey TA, Vaughan ED . Campbell's Urology, 6th edn. W.B. Saunders: Philadelphia, 1992, pp 1014–1015.

    Google Scholar 

  4. Suzuki K, Ito K, Ichinose Y, Kurokawa K, Suzuki T, Imai K et al. Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol 1995; 29: 65–68.

    Article  CAS  Google Scholar 

  5. Schatzl G, Brossner C, Schmid S, Kugler W, Roehrich M, Treu T et al. Endocrine status in elderly men with lower urinary tract symptoms: correlation of age, hormonal status, and lower urinary tract function. The Prostate Study Group of the Austrian Society of Urology. Urology 2000; 55: 397–402.

    Article  CAS  Google Scholar 

  6. Hammarsten J, Högstedt B, Holthuis N, Mellström D . Components of the metabolic syndrome—risk factors for the development of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 1998; 1: 157–162.

    Article  CAS  Google Scholar 

  7. Hammarsten J, Högstedt B . Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. Blood Press 1999; 8: 29–36.

    Article  CAS  Google Scholar 

  8. Hammarsten J, Högstedt B . Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia. Eur Urol 2001; 39: 151–158.

    Article  CAS  Google Scholar 

  9. Hammarsten J, Högstedt B . Calculated fast-growing benign prostatic hyperplasia—a risk factor for developing clinical prostate cancer. Scand J Urol Nephrol 2002; 36: 330–338.

    Article  Google Scholar 

  10. Nandeesha H, Koner BC, Dorairajan LN, Sen SK . Hyperinsulinaemia and dyslipidaemia in non-diabetic benign prostatic hyperplasia. Clin Chim Acta 2006; 370: 89–93.

    Article  CAS  Google Scholar 

  11. Ozden C, Ozdal OL, Urgancioglu G, Koyuncu H, Gokkaya S, Memis A . The correlation between metabolic syndrome and prostatic growth in patients with benign prostatic hyperplasia. Eur Urol 2007; 51: 199–206.

    Article  Google Scholar 

  12. Rohrmann S, De Marzo AM, Smit E, Giovannucci E, Platz EA . Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey (NHANES III). Prostate 2005; 62: 27–33.

    Article  CAS  Google Scholar 

  13. DeFronzo RA, Ferrannini E . Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14: 173–194.

    Article  CAS  Google Scholar 

  14. Dahle SE, Chokkalingam AP, Gao Y-T, 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.

    Article  CAS  Google Scholar 

  15. Mellström D, Johnell O, Ljunggren Ö, Eriksson A-L, Lorentzon M, Mallmin H et al. Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J Bone Miner Res 2006; 4: 529–535.

    Article  Google Scholar 

  16. Vermeulen A, Verdonck L, Kaufman JM . A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666–3672.

    Article  CAS  Google Scholar 

  17. Van den Beld AW, De Jong FH, Grobbee DE, Pols HAP, Lamberts SWJ . Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab 2000; 85: 3276–3282.

    CAS  PubMed  Google Scholar 

  18. Littrup PJ, Williams CR, Egglin TK, Kane RA . Determination of prostate volume with transrectal US for screening—Part II. Accuracy of in vitro and in vivo techniques. Radiology 1991; 179: 49–53.

    Article  CAS  Google Scholar 

  19. Terris MK, Stamey TA . Determination of prostate volume by transrectal ultrasound. J Urol 1991; 145: 984–987.

    Article  CAS  Google Scholar 

  20. Giovannucci E . Nutrition, insulin, insulin-like growth factors and cancer. Horm Metab Res 2003; 35: 694–704.

    Article  CAS  Google Scholar 

  21. Stattin P, Kaaks R, Riboli E, Ferrari P, Dechaud H, Hallmans G . Circulating insulin-like growth factor-I and benign prostatic hyperplasia—a prospective study. Scand J Urol Nephrol 2001; 35: 122–126.

    Article  CAS  Google Scholar 

  22. Chokkalingam AP, Gao YT, Deng J, Stanczyk FZ, Sesterhenn IA, Mostofi FK et al. Insulin-like growth factors and risk of benign prostatic hyperplasia. Prostate 2002; 52: 98–105.

    Article  CAS  Google Scholar 

  23. Roberts RO, Jacobson DJ, Girman CJ, Rhodes T, Klee GG, Lieber MM et al. Insulin-like growth factor I, insulin-like growth factor binding protein 3, and urologic measures of benign prostatic hyperplasia. Am J Epidemiol 2003; 157: 784–791.

    Article  Google Scholar 

  24. Cohen PG . The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone–estradiol shunt—a major factor in the genesis of morbid obesity. Med Hypothesis 1999; 52: 49–51.

    Article  CAS  Google Scholar 

  25. McNeal J . Pathology of benign prostatic hyperplasia: insight into etiology. Urol Clin North Am 1990; 17: 477–486.

    CAS  PubMed  Google Scholar 

  26. Peirson EL . A study of the effect of stilbestrol therapy on the size of the benignly hypertrophied prostate gland. J Urol 1946; 55: 73–78.

    Article  CAS  Google Scholar 

  27. Campbell M, Harrison J . Urology, 6th edn. W.B. Saunders: Philadelphia, 1970, pp 1100.

    Google Scholar 

  28. Gingell JC, Knonagel H, Kurth KH, Tunn UW . Placebo controlled double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia not requiring operation. The Schering 90062 Study Group. J Urol 1995; 154: 399–401.

    Article  CAS  Google Scholar 

  29. Radlmaier A, Eickenberg HU, Fletcher MS, Fourcade RO, Reis Santos JM, van Aubel OG et al. Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trail using two doses of the aromatase-inhibitor atamestane. Atamestane Study Group. Prostate 1996; 29: 199–208.

    Article  CAS  Google Scholar 

  30. Tivesten Å, Hulthe J, Wallenfeldt K, Wikstrand J, Ohlsson C, Fagerberg B . Circulating estradiol is an independent predictor of progression of carotide artery intima-media thickness in middle-aged men. J Clin Endocrin Metab 2006; 91: 4433–4437.

    Article  CAS  Google Scholar 

  31. Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen T-P, Valkonen V-P et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 2003; 149: 601–608.

    Article  CAS  Google Scholar 

  32. Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen T-P, Valkonen V-P et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004; 27: 1036–1041.

    Article  CAS  Google Scholar 

  33. Fejes I, Koloszar S, Zavaczki Z, Daru J, Szollosi J, Pal A . Effect of body weight on testosterone/estradiol ratio in oligozoospermic patients. Arch Androl 2006; 52: 97–102.

    Article  CAS  Google Scholar 

  34. Muller M, Grobbee DE, den Tonkelaar I, Lamberts SWJ, van der Schouw YT . Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 2005; 90: 2618–2623.

    Article  CAS  Google Scholar 

  35. Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, Sims EAH et al. What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J Clin Endocrinol Metab 2001; 86: 1020–1025.

    CAS  PubMed  Google Scholar 

  36. You T, Ryan AS, Nicklas BJ . The metabolic syndrome in obese postmenopausal women: relationship to body composition, visceral fat, and inflammation. J Clin Endocrinol Metab 2004; 89: 5517–5522.

    Article  CAS  Google Scholar 

  37. Lee S, Min HG, Choi SH, Kim YJ, Oh SW, Kim YJ et al. Central obesity as a risk factor for prostatic hyperplasia. Obesity (Silver Spring) 2006; 14: 172–179.

    Article  Google Scholar 

  38. Kahn R, Buse J, Ferrannini E, Stern M . The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetolgia 2005; 48: 1684–1699.

    Article  CAS  Google Scholar 

  39. Hald T . Urodynamics in benign prostatic hyperplasia: a survey. Prostate Suppl 1989; 2: 69–77.

    Article  CAS  Google Scholar 

  40. Leveillee RJ, Patel VR, Bird VG . Prostate hyperplasia, Benign. http://www.emedicine.com/med/topic1919.htm; 2004.

  41. Parsons JK, Carter HB, Partin AW, Windham BG, Metter EJ, Ferrucci L et al. Metabolic factors associated with benign prostatic hyperplasia. J Clin Endocrinol Metab 2006; 91: 2562–2568.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by an unconditional grant from Sanofi-Aventis, the Swedish Research Council, the Swedish Foundation for Strategic Research, the ALFA/LUA research grant in Gothenburg, the Novo Nordisk Foundation, Wilhelm and Martina Lundgrens Forskningsfond and Alice Swenzons Stiftelse.

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Correspondence to J Hammarsten.

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Hammarsten, J., Damber, JE., Karlsson, M. et al. Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 12, 160–165 (2009). https://doi.org/10.1038/pcan.2008.50

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