KARI A. O. TIKKINEN Epidemiology of Nocturia Results from the FINNO Study ACADEMIC DISSERTATION To be presented, with the permission of the Faculty of Medicine of the University of Tampere, for public discussion in the Small Auditorium of Building M, Pirkanmaa Hospital District, Teiskontie 35, Tampere, on March 5th, 2010, at 12 o’clock. UNIVERSITY OF TAMPERE ACADEMIC DISSERTATION University of Tampere, Medical School Tampere University Hospital, Department of Urology University of Tampere, School of Public Health Helsinki University Central Hospital, Department of Urology Clinical Research Institute HUCH Ltd., Helsinki Finland Supervised by Reviewed by Professor Anssi Auvinen Adjunct Professor Pekka Hellström University of Tampere University of Oulu Finland Finland Professor Teuvo Tammela Professor Jaakko Kaprio University of Tampere University of Helsinki Finland Finland Distribution Tel. +358 3 3551 6055 Bookshop TAJU Fax +358 3 3551 7685 P.O. Box 617 [email protected] 33014 University of Tampere www.uta.fi/taju Finland http://granum.uta.fi Cover design by Juha Siro Acta Universitatis Tamperensis 1504 Acta Electronica Universitatis Tamperensis 942 ISBN 978-951-44-8019-5 (print) ISBN 978-951-44-8020-1 (pdf) ISSN-L 1455-1616 ISSN 1456-954X ISSN 1455-1616 http://acta.uta.fi Tampereen Yliopistopaino Oy – Juvenes Print Tampere 2010 Dedicated to the FINNO Study participants Table of contents Table of contents ....................................................................................................................... 4 List of original contributions ..................................................................................................... 6 Abbreviations ............................................................................................................................ 7 Abstract ..................................................................................................................................... 8 Tiivistelmä ............................................................................................................................... 11 Introduction ............................................................................................................................. 14 1. Literature review ................................................................................................................ 18 1.1 Terms and definitions .................................................................................................. 18 1.1.1 Epidemiology .................................................................................................... 18 1.1.2 Lower urinary tract symptoms and nocturia ..................................................... 20 1.2 Prevalence of nocturia ................................................................................................. 22 1.3 Bother and impact of nocturia ..................................................................................... 23 1.4 Risk factors of nocturia ............................................................................................... 24 2. Aims of the study ............................................................................................................... 31 3. Materials and methods ....................................................................................................... 32 3.1 Design .......................................................................................................................... 32 3.2 Exclusions ................................................................................................................... 33 3.3 Assessment of urinary symptoms, their impact and potential risk and confounding factors .................................................................................................... 34 3.3.1 Measures of lower urinary tract symptoms and bother..................................... 34 3.3.2 Measures of health-related quality of life ......................................................... 37 3.3.3 Assessment of potential risk and confounding factors ..................................... 37 3.4 Statistical analysis ....................................................................................................... 43 3.5 Controlling for confounding ........................................................................................ 46 4 3.6 Effect modification ...................................................................................................... 47 3.7 Estimating bias due to selective participation ............................................................. 47 4. Results ................................................................................................................................ 49 4.1 Participation in the FINNO Study ............................................................................... 49 4.2 Prevalence of nocturia ................................................................................................. 51 4.3 Bother, health-related quality of life and nocturia ....................................................... 55 4.4 Prevalence of overactive bladder and its relation with nocturia .................................. 60 4.5 Risk factors of nocturia ............................................................................................... 63 4.5.1 Conditions, medications, lifestyle and nocturia ................................................ 63 4.5.2 Reproductive factors and nocturia .................................................................... 68 4.5.3 Relation of nocturia to obesity .......................................................................... 71 5. Discussion .......................................................................................................................... 73 5.1 Prevalence of nocturia ................................................................................................. 74 5.2 Prevalence of overactive bladder ................................................................................. 75 5.3 Bother, health-related quality of life and nocturia ....................................................... 81 5.4 Risk factors of nocturia ............................................................................................... 83 5.5 Strengths of the FINNO Study .................................................................................... 91 5.6 Representativeness of the study population ................................................................ 91 5.7 Limitations ................................................................................................................... 93 5.7.1 Study design and study population ................................................................... 94 5.7.2 Self-reporting .................................................................................................... 94 5.7.3 Limitations related to potential risk or confounding factors ............................ 95 5.8 Use of questionnaire for assessment of nocturia ......................................................... 97 5.9 Future aspects ............................................................................................................ 101 6. Conclusions ...................................................................................................................... 102 Acknowledgements ............................................................................................................... 103 References ............................................................................................................................. 106 Appendices ............................................................................................................................ 123 Original communications ...................................................................................................... 166 5 List of original contributions I Tikkinen KAO, Tammela TLJ, Huhtala H, Auvinen A. Is nocturia equally common among men and women? A population based study in Finland. J Urol 2006;175:596- 600. II Tikkinen KAO, Tammela TLJ, Rissanen AM, Valpas A, Huhtala H, Auvinen A. Is the prevalence of overactive bladder overestimated? A population-based study in Finland. PLoS ONE 2007;2:e195. III Tikkinen KAO, Johnson TM 2nd, Tammela TLJ, Sintonen H, Haukka J, Huhtala H, Auvinen A. Nocturia frequency, bother and quality of life – How often is too often? A population-based study in Finland. Eur Urol 2010;57:488-498. IV Tikkinen KAO, Auvinen A, Huhtala H, Tammela TLJ. Nocturia and obesity: A population-based study in Finland. Am J Epidemiol 2006;163:1003-11. V Tikkinen KAO, Auvinen A, Tiitinen A, Valpas A, Johnson TM 2nd, Tammela TLJ. Reproductive factors associated with nocturia and urinary urgency in women: a population-based study in Finland. Am J Obstet Gynecol 2008;199:153:e1-12. VI Tikkinen KAO, Auvinen A, Johnson TM, 2nd, Weiss JP, Keränen T, Tiitinen A, Polo O, Partinen M, Tammela TLJ. A systematic evaluation of factors associated with nocturia – The population-based FINNO Study. Am J Epidemiol 2009;170:361-8. The original publications, as well as the roundtable discussion and editorial comments, are reproduced with permission of the copyright holders. 6 Abbreviations AHI apnea-hypopnea index AUA-SI American Urological Association Symptom Index BMI body mass index BPE benign prostatic enlargement BPH benign prostatic hyperplasia BPO benign prostatic obstruction CAD coronary