Advertisement

Current Urology Reports

, 19:69 | Cite as

Is Tamsulosin Linked to Dementia in the Elderly?

  • Jason K. Frankel
  • Yinghui Duan
  • Peter C. Albertsen
Benign Prostatic Hyperplasia (K McVary, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Benign Prostatic Hyperplasia

Abstract

Purpose of Review

Lower urinary tract symptoms (LUTS) result from age-related changes in detrusor function and prostatic growth that are driven by alterations in the ratio of circulating androgens and estrogens. Alpha-adrenergic receptor blockers are commonly used to treat LUTS because they influence urethral tone and intra-urethral pressure. Molecular cloning studies have identified three α1-adrenergic receptor subtypes (α1A, α1B, and α1D). The α1A subtype is predominant in the human prostate but is also present in many parts of the brain that direct cognitive function. Tamsulosin is the most widely used α1-adrenergic receptor antagonist with 12.6 million prescriptions filled in 2010 alone. When compared to the other common types of α1-adrenergic receptor antagonists (i.e., terazosin, doxazosin, and alfuzosin), tamsulosin is 10- to 38-fold more selective for the α1A versus the α1B subtype.

Recent Findings

Duan et al. have recently shown that men taking tamsulosin have a higher risk of developing dementia when compared to men taking other α-adrenergic antagonists or no α-adrenergic antagonists at all (HR 1.17; 95% CI 1.14–1.21).

Summary

Based upon this retrospective analysis, we believe that tamsulosin, because of its unique affinity for α1A-adrenergic receptors, may increase the risk of developing dementia when used for an extended period of time. If these findings are confirmed, they carry significant public health implications for an aging society.

Keywords

Benign prostatic hyperplasia Tamsulosin Dementia Alpha-blockers 

Notes

Compliance with Ethical Standards

Conflict of Interest

Jason K. Frankel, Yinghui Duan, and Peter C. Albertsen each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    McConnell JD. Prostatic growth: new insights into hormonal regulation. Br J Urol. 1995;76(Suppl 1):5–10.PubMedGoogle Scholar
  2. 2.
    Peters CA, Walsh PC. The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia. N Engl J Med. 1987;317(10):599–604.CrossRefPubMedGoogle Scholar
  3. 3.
    Isaacs JT. Antagonistic effect of androgen on prostatic cell death. Prostate. 1984;5(5):545–57.CrossRefPubMedGoogle Scholar
  4. 4.
    Kyprianou N, Isaacs JT. Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. Mol Endocrinol. 1989;3(10):1515–22.CrossRefPubMedGoogle Scholar
  5. 5.
    Shapiro E, Becich MJ, Hartanto V, Lepor H. The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia. J Urol. 1992;147(5):1293–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Roehrborn CG, Schwinn DA. Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004;171(3):1029–35.CrossRefPubMedGoogle Scholar
  7. 7.
    Lepor H, Tang R, Meretyk S, Shapiro E. Alpha 1 adrenoceptor subtypes in the human prostate. J Urol. 1993;149(3):640–2.CrossRefPubMedGoogle Scholar
  8. 8.
    Lepor H, Tang R, Shapiro E. The alpha-adrenoceptor subtype mediating the tension of human prostatic smooth muscle. Prostate. 1993;22(4):301–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Honda K, Miyata-Osawa A, Takenaka T. Alpha 1-adrenoceptor subtype mediating contraction of the smooth muscle in the lower urinary tract and prostate of rabbits. Naunyn Schmiedeberg's Arch Pharmacol. 1985;330(1):16–21.CrossRefGoogle Scholar
  10. 10.
    Lepor H, Gup DI, Baumann M, Shapiro E. Laboratory assessment of terazosin and alpha-1 blockade in prostatic hyperplasia. Urology. 1988;32(6 Suppl):21–6.PubMedGoogle Scholar
  11. 11.
    Michel MC, Vrydag W. Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol. 2006;147(Suppl 2):S88–119.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Caine M, Perlberg S, Meretyk S. A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction. Br J Urol. 1978;50(7):551–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Berthelsen S, Pettinger WA. A functional basis for classification of alpha-adrenergic receptors. Life Sci. 1977;21(5):595–606.CrossRefPubMedGoogle Scholar
  14. 14.
    Hedlund H, Andersson KE, Ek A. Effects of prazosin in patients with benign prostatic obstruction. J Urol. 1983;130(2):275–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Andersson KE, Lepor H, Wyllie MG. Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997;30(3):202–15.CrossRefPubMedGoogle Scholar
  16. 16.
    Price DT, Schwinn DA, Lomasney JW, Allen LF, Caron MG, Lefkowitz RJ. Identification, quantification, and localization of mRNA for three distinct alpha 1 adrenergic receptor subtypes in human prostate. J Urol. 1993;150(2 Pt 1):546–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Kobayashi S, Tang R, Wang B, Opgenorth T, Stein E, Shapiro E, et al. Localization of endothelin receptors in the human prostate. J Urol. 1994;151(3):763–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Walden PD, Durkin MM, Lepor H, Wetzel JM, Gluchowski C, Gustafson EL. Localization of mRNA and receptor binding sites for the alpha 1a-adrenoceptor subtype in the rat, monkey and human urinary bladder and prostate. J Urol. 1997;157(3):1032–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Perez DM, Doze VA. Cardiac and neuroprotection regulated by alpha(1)-adrenergic receptor subtypes. J Recept Signal Transduct Res. 2011;31(2):98–110.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Rokosh DG, Simpson PC. Knockout of the alpha 1A/C-adrenergic receptor subtype: the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proc Natl Acad Sci U S A. 2002;99(14):9474–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Cavalli A, Lattion AL, Hummler E, Nenniger M, Pedrazzini T, Aubert JF, et al. Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor. Proc Natl Acad Sci U S A. 1997;94(21):11589–94.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Tanoue A, Nasa Y, Koshimizu T, Shinoura H, Oshikawa S, Kawai T, et al. The alpha(1D)-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction. J Clin Invest. 2002;109(6):765–75.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lapiz MD, Morilak DA. Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability. Neuroscience. 2006;137(3):1039–49.CrossRefPubMedGoogle Scholar
  24. 24.
    Rommelfanger KS, Edwards GL, Freeman KG, Liles LC, Miller GW, Weinshenker D. Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proc Natl Acad Sci U S A. 2007;104(34):13804–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Stone EA, Quartermain D. Alpha-1-noradrenergic neurotransmission, corticosterone, and behavioral depression. Biol Psychiatry. 1999;46(9):1287–300.CrossRefPubMedGoogle Scholar
  26. 26.
    Sirvio J, MacDonald E. Central alpha1-adrenoceptors: their role in the modulation of attention and memory formation. Pharmacol Ther. 1999;83(1):49–65.CrossRefPubMedGoogle Scholar
  27. 27.
    Doze VA, Papay RS, Goldenstein BL, Gupta MK, Collette KM, Nelson BW, et al. Long-term alpha1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity. Mol Pharmacol. 2011;80(4):747–58.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Knauber J, Muller WE. Decreased exploratory activity and impaired passive avoidance behaviour in mice deficient for the alpha(1b)-adrenoceptor. Eur Neuropsychopharmacol. 2000;10(6):423–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Spreng M, Cotecchia S, Schenk F. A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities. Neurobiol Learn Mem. 2001;75(2):214–29.CrossRefPubMedGoogle Scholar
  30. 30.
    Sadalge A, Coughlin L, Fu H, Wang B, Valladares O, Valentino R, et al. Alpha 1d adrenoceptor signaling is required for stimulus induced locomotor activity. Mol Psychiatry. 2003;8(7):664–72.CrossRefPubMedGoogle Scholar
  31. 31.
    Nalepa I, Kreiner G, Bielawski A, Rafa-Zablocka K, Roman A. Alpha1-adrenergic receptor subtypes in the central nervous system: insights from genetically engineered mouse models. Pharmacol Rep. 2013;65(6):1489–97.CrossRefPubMedGoogle Scholar
  32. 32.
    McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793–803.CrossRefPubMedGoogle Scholar
  33. 33.
    Lepor H. Alpha-blockers for the treatment of benign prostatic hyperplasia. Urol Clin North Am. 2016;43(3):311–23.CrossRefPubMedGoogle Scholar
  34. 34.
    Food and Drug Administration. Pediatric focused safety review: Flomax®(tamsulosin hydrochloride). Center for Drug Evaluation and Research; 2012 [Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM289947.pdf.
  35. 35.
    Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I. Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997;282(1):228–35.PubMedGoogle Scholar
  36. 36.
    Andersson KE, Wyllie MG. Ejaculatory dysfunction: why all alpha-blockers are not equal. BJU Int. 2003;92(9):876–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Giuliano F. Impact of medical treatments for benign prostatic hyperplasia on sexual function. BJU Int. 2006;97(Suppl 2):34–8. discussion 44-5CrossRefPubMedGoogle Scholar
  38. 38.
    Nikolic K, Filipic S, Smolinski A, Kaliszan R, Agbaba D. Partial least square and hierarchical clustering in ADMET modeling: prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands. J Pharm Pharm Sci. 2013;16(4):622–47.CrossRefPubMedGoogle Scholar
  39. 39.
    Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA. Changes in adrenoreceptors in the prefrontal cortex of subjects with dementia: evidence of compensatory changes. Neuroscience. 2007;146(1):471–80.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40••.
    Duan Y, Grady JJ, Albertsen PC, Helen Wu Z. Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia. Pharmacoepidemiol Drug Saf. 2018;27(3):340–8. This is the first report linking tamsulosin to the risk of developing dementia. The authors outline a plausible mechanism of action and provide support from Medicare claims data Google Scholar
  41. 41.
    Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimers Dement. 2016;12(3):216–24.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Jorm AF, Jolley D. The incidence of dementia: a meta-analysis. Neurology. 1998;51(3):728–33.CrossRefPubMedGoogle Scholar
  43. 43•.
    Gill SS, Bai AD. Beta testing the potential link between the alpha antagonist tamsulosin and dementia. Pharmacoepidemiol Drug Saf. 2018;27(3):349–50. This editorial comment accompanied reference #40. The authors support the idea of a causal link between tamsulosin and dementia and encourage future trials to prove this relationship CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jason K. Frankel
    • 1
  • Yinghui Duan
    • 2
  • Peter C. Albertsen
    • 1
  1. 1.Department of SurgeryUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Department of Community Medicine and Health CareUniversity of Connecticut Health CenterFarmingtonUSA

Personalised recommendations