Lower UrinaryTract Symptoms (LUTS) and Sexual Function in Both Sexes

European Urology European Urology 46 (2004) 229 234 Lower UrinaryTract Symptoms (LUTS) and Sexual Function in Both Sexes Bjarne Lühr Hansen * Research Unit of General Practice, University of Southern Denmark, Winsløwparken 19, 5000 Odense C, Denmark Accepted 14 April 2004 Available online 3 May 2004 Abstract Objectives: It has been stated that lower urinary tract symptoms (LUTS) do not affect sexual function to any significant degree, but a recent study has suggested that there might be an association in men. The present study was conducted to investigate the relationship between LUTS and sexual problems in both men and women aged 40 65 years. Methods: The survey was conducted in Denmark between May and June 2003. Detailed questionnaires were mailed to a random sample of 15,000 men and women aged 40 65 years. LUTS and sexual function were assessed by validated symptom scales. Multivariate regression analysis was performed using logistic regression for dichotomous dependent variables of sexual function. The independent variables for both sexes were age, LUTS, partner status, body mass index (BMI), alcohol consumption and co-morbidities. Results: A total of 15,000 questionnaires were mailed out, 8491 were completed and returned, and 7741 were deemed valuable and included in the analysis. LUTS and sexual dysfunction were common in both men and women. Logistic regression analysis of items related to erection problems and satisfaction with sex life in men and sexual function in women showed that LUTS are an independent risk factor for sexual dysfunction in both men and women aged 40 65 years. Significant effects on sexual function were also found for the independent variables of partner status and co-morbidities. Conclusions: The presence of LUTS is an independent risk factor for sexual dysfunction in men and women. These results highlight the clinical importance of evaluating LUTS in patients with sexual dysfunction, and the need to consider sexual issues in the management of patients with LUTS. # 2004 Elsevier B.V. All rights reserved. Keywords: Lower urinary tract symptoms; Men; Sexual function; Women 1. Introduction Aging is associated with profound structural and functional alterations in the lower urinary tract which can ultimately lead to lower urinary tract symptoms (LUTS) [1,2]. The mean increase in LUTS from the age of 20 is 3.9%/decade for women and 7.3%/decade in men [3]. A strong relationship between aging and sexual function is also found, with sexual activity being higher in younger age groups [4]. * Tel. þ45-6550-3030; Fax: þ45-6311-1642. E-mail address: bhli@post9.tele.dk (B.L. Hansen). LUTS in men are usually assumed to be caused by benign prostate hypertrophy (BPH). Symptoms vary on an individual level, but generally fall into three groups: (i) voiding (also known as obstructive) includes reduced stream, hesitancy, and straining; (ii) storage (also known as irritative) includes frequency, nocturia, and symptoms of incontinence, and (iii) mixed voiding and storage [5]. Studies using validated symptom scales, such as the International Prostate Symptom Score, have shown an overall prevalence rate of LUTS of 20% to 50% in men aged >50 years [6,7]. The prevalence of LUTS in women defined as urinary leakage, associated with social or hygienic problems, 0302-2838/$ see front matter # 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2004.04.005

230 B.L. Hansen / European Urology 46 (2004) 229 234 has been reported as high as 19% and 22% in two Danish studies [8,9]. In a Swedish survey of 10,000 women, aged 46 86 years, the prevalence of LUTS increased in a linear fashion, from 12% in the 46-yearolds to 25% in 86-year-olds [10]. The prevalence of sexual dysfunction in women is not well known, but it has been estimated that 40% of women complain of at least one sexual problem [4]. Prevalence of sexual problems in incontinent women is even higher and varies from 41% to 71% and is most common in women with urge incontinence [11]. Until now, no study has been conducted to investigate the relationship between LUTS and sexual problems in women. The Massachusetts Male Aging Study showed that 35% of men aged 40 70 years had erectile dysfunction, which was strongly related to age, diabetes, depression and cardiovascular disease [12]. While the Massachusetts Male Aging Study stated that neither BPH itself nor LUTS affect sexual function in men to any significant effect, a number of recent studies have suggested that there might be such an association [13 18]. Even though the pathogenetic relationship between LUTS and erectile dysfunction is not yet completely understood, a recent study postulates a direct association between these two symptom complexes in the aging male [19]. If an association between LUTS and sexual function exists, this will have implications for the management of LUTS. This study was conducted to investigate the relationship between LUTS and sexual dysfunction in both men and women aged 40 65 years. 2. Material and methods This survey was conducted in Denmark between May and June 2003. Questionnaires were mailed to a randomly selected age- and sex-stratified population of 15,000 persons between 40 and 65 years of age, reflecting Danish sex and age structure. The questionnaire was sent by post; in case of non-response, study subjects were sent a reminder. A total of 8491 questionnaires were completed and returned, and 7741 (52%) were deemed valuable and included in the analysis. With a view to assess possible selection bias, a telephone interview was carried out with 200 women and 200 men in the group of non-responders, where the frequency of LUTS and sexual dysfunction was registered. There was no difference in the frequency of LUTS and sexual dysfunction among responders and non-responders. Symptoms of LUTS and sexual dysfunction were measured using a standardised, self-report questionnaire. To standardise the assessment of LUTS in men a validated symptom scoring system (International Prostate Symptom Score) was used [20]. A total score >1 was defined as LUTS and depending on type of symptoms defined as voiding, storage or mixed type of LUTS. If a person answered yes to questions about voiding symptoms and no to questions about storage symptoms, voiding LUTS were defined. Storage LUTS were defined the other way around. If the question about both voiding and storage symptoms was answered affirmatively, mixed LUTS were defined. The Bristol Female Lower Urinary Tract Symptoms questionnaire characterised symptom severity and impact on quality of life in case of LUTS in women. The Bristol Female Lower Urinary Tract Symptoms questionnaire was chosen for two reasons mainly: (i) previous extensive psychometric testing, and (ii) the fact that each question regarding symptoms was followed by a quality of life question [21]. Depending on type of symptoms, LUTS were defined as stress, urge or mixed type. If the women answered yes to questions about stress symptoms and no to questions about urge symptoms, stress LUTS were defined. Urge LUTS were defined the other way around. If the question about both urge and stress symptoms was answered affirmatively, mixed LUTS were defined. Male sexual function was assessed using standardised, validated questionnaires from the Danish Prostate Symptom Score and included the frequency of erectile problems, and satisfaction with sex life [22]. Various aspect of female sexual function was assessed using the Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores, a standardised, validated and reliable instrument developed to evaluate sexual function in women with urinary incontinence [23]. Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire was developed as a condition-specific, reliable, validated, and self-administered instrument to evaluate sexual function in women with pelvic organ prolapse or urinary incontinence. Domains assessed included the frequency of sexual activity, sexual desire, painful intercourse, incontinent of urine during sexual activity, and overall sexual satisfaction. Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores are highly correlated with both the Sexual History Form- 12 and the Incontinence Impact Questionnaire. For the classification of sexual dysfunction, a Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire cut-off value <17 was used. The presence of lifestyle factors (BMI and alcohol consumption), medical conditions (diabetes, depression, and cardiovascular disease) and partner status (partner yes, partner no) were also assessed to determine their potential confounding effects on sexual function. Statistical procedures were calculated by the computer software SPSS. Multivariate regression analysis was performed using logistic regression for dichotomous variables. For men the dependent dichotomous variables was erectile dysfunction (yes/no) and satisfaction with sex life (high/low) and for women the Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores (cut-point ¼ 17) was used. The independent variables in the logistic regression analysis were age, LUTS, partner status, BMI, alcohol consumption and co-morbidities (diabetes, depression, and cardiovascular disease). 3.Results A random selection of 7500 women (49:8 10:5 years; range 40 65 years) and 7500 men (49:1 11:0 years; range 40 65 years) were recruited for this study. The age distribution of the female and male

B.L. Hansen / European Urology 46 (2004) 229 234 231 study population was comparable to the Danish population. TheprevalenceofLUTSinmenwas39.1%andin women 41.3%. Prevalence of LUTS was associated with age in both sexes; the highest prevalence was in the age group 50 59 years. Erectile dysfunction was significantly increasing with age and the total prevalence was 28.8%. Satisfaction with sex life was significantly decreasing with age, and 19.1% of all the men reported low satisfaction. The Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores were significantly decreasing with age, and overall 58.2% women reported low (<17) scores. The relationship between sexual dysfunction and LUTS is shown in Tables 1 3. Logistic regression analysis of Danish Prostate Symptom Score items related to erection problems and satisfaction with sex life showed a high degree of association between LUTS and sexual dysfunction. Men with mixed LUTS were almost three times as likely to experience erection difficulties or low satisfaction with sex life, than men without LUTS. Significant effects were also found for the independent variables partner status and co-morbidities. Age and LUTS showed a higher degree of association with sexual dysfunction than co-morbidities. For women the same results were observed for Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores. The strongest predictors of sexual dysfunction in women were age and LUTS, but partner status and co-morbidities were also significant predictors. BMI and alcohol consumption Table 1 Logistic regression analyses for sexual dysfunction and LUTS Independent variables Odds ratio Confidence interval p Age 40 49 1.00 50 59 2.35 1.95 2.83 <0.000 60 65 4.08 3.26 5.11 <0.000 LUTS No LUTS 1.00 Voiding 2.07 1.52 2.82 <0.000 Storage 1.55 1.25 1.93 <0.000 Mixed 2.82 2.31 3.44 <0.000 Partner No partner 1.00 Yes partner 0.63 0.51 0.77 <0.000 Co-morbidities a No 1.00 Yes 1.91 1.51 2.41 <0.000 The dependent variable is erectile dysfunction. N ¼ 3442 men. a Diabetes, depression and cardiovascular disease. Table 2 Logistic regression analyses for sexual dysfunction and LUTS Independent variables Odds ratio Confidence interval p Age 40 49 1.00 50 59 0.90 0.73 1.10 0.276 60 65 0.71 0.55 0.91 0.007 LUTS No LUTS 1.00 Voiding 0.55 0.38 0.78 0.001 Storage 0.50 0.40 0.64 <0.000 Mixed 0.36 0.29 0.45 <0.000 Partner No partner 1.00 Yes partner 2.08 1.68 2.60 <0.000 Co-morbidities a No 1.00 Yes 0.49 0.39 0.63 <0.000 The dependent variable is high satisfaction with sex life. N ¼ 3451 men. a Diabetes, depression and cardiovascular disease. Table 3 Logistic regression analyses for sexual dysfunction and LUTS Independent variables Odds ratio Confidence interval p Age 40 44 1.00 45 49 0.85 0.70 1.03 0.106 50 54 0.69 0.56 0.83 <0.000 55 59 0.38 0.31 0.47 <0.000 60 65 0.30 0.29 0.38 <0.000 LUTS No LUTS 1.00 Stress 0.57 0.47 0.68 <0.000 Urge 0.68 0.51 0.90 0.008 Mixed 0.36 0.30 0.43 <0.000 Partner No partner 1.00 Yes partner 1.41 1.18 1.68 <0.000 Co-morbidities a No 1.00 Yes 0.69 0.55 0.85 <0.000 The dependent variable is high Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores (>17). N ¼ 4052 women. a Diabetes, depression and cardiovascular disease. were not significant predictors of sexual dysfunction ( p > 0:05). 4. Discussion This study showed that LUTS and sexual dysfunction are very common disorders and that LUTS are an independent risk factor for sexual dysfunction in both men and women aged 40 65 years.

232 B.L. Hansen / European Urology 46 (2004) 229 234 This study is the largest study to date on the prevalence of LUTS and sexual dysfunction in a representative sample of both men and women aged 40 65 years. In addition to the large sample size, the study is noteworthy for the use of standardised, validated scales of LUTS and sexual dysfunction. These scales provided sensitive and reliable measures of the major variables of interest. It is also the first study of both sexes to control for the effects of age, medical comorbidities, and lifestyle factors in evaluating the relationship between LUTS and sexual dysfunction. Erectile dysfunction was reported by 28% of the men in this study. This high rate of erection problems observed is similar to other recent population-based studies [12,16]. Erection problems were significantly more common in men with LUTS independent of the effects of age, partner status and co-morbidities. Rosen et al. have recently reported the same results in a largescale, multinational study of men aged >50 years [16]. Similarly, in a representative population sample of 8000 German men aged 30 80 years, the prevalence of LUTS was 72.2% in patients with erectile dysfunction compared with 38.7% in patients without erectile dysfunction [13]. In my study, low satisfaction with sex life was reported by 19% and LUTS were an independent risk factor for low satisfaction with sex life. The potential mechanisms responsible for increased sexual problems in men with LUTS are not well understood at present. Hormone factors as increased noradrenergic nerve activity associated with bladder outlet obstruction may interfere with the normal process of erection [24]. Anatomic factors may play a role, as the enlarged prostate could impinge on local nerves on local nerves of blood supply [25]. Psychological factors should also be taken into account in view of the high level of stress and anxiety that may accompany severe urinary symptoms in some men [26]. Data on female sexual dysfunction are limited. Laumann et al. estimated that 43% of women complain of at least one sexual problem [4]. In different clinical female samples 11 33% falls within specific sexual problems. Desire, arousal and orgasm phase disorders are among the most commonly presented problems [4]. In this study sexual dysfunction (Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores <17) were reported by 58%. Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire scores included the frequency of sexual activity, sexual desire, painful intercourse, incontinent of urine during sexual activity, and overall sexual satisfaction [23]. Sexual dysfunction is often present in women with urinary symptoms. Prevalence of sexual problems in incontinent women varies between 21% and 71% and is most common in women with urge incontinence [11]. In an interview study of 208 women, who attended an incontinence clinic, 43% thought their urinary problems had adversely affected their sexual life. They complained of less frequency of intercourse because of dyspareunia, leakage during coitus and wetness at night [27]. My study is the first to confirm the importance of LUTS as an independent risk factor for sexual dysfunction in women. The potential mechanisms responsible for increased sexual problems in women with LUTS are not well understood. LUTS and sexual dysfunction can be considered to be aspects of the urogenital ageing symptoms because of decreasing level of estrogens, which generally attributed to atrophy in the epithelium of vagina, urethra, trigonum of the bladder, and in the pelvic floor muscles. LUTS may also cause sexual dysfunction because of embarrassment, psychological distress or the occurrence of urinary incontinence during sexual activity [28]. Several limitations of the present study are worth noting. First, despite the large sample size potential effects of selection bias cannot be completely eliminated from consideration. For example, it is theoretically possible that respondents with lesser degrees of LUTS or sexual function declined to participate in the study. This is unlikely because the prevalence of LUTS and sexual function was similar in the respondents and non-respondents, as shown by the telephone interviews. Another possible limitation concerns the use of selfreport questionnaires for assessing LUTS and sexual dysfunction. This introduces a potential for response bias, as respondents may inaccurately report their urinary or sexual dysfunction symptoms. In the absence of a physical examination, this possibility cannot be excluded. However, the questionnaires selected for the present study have all been previously validated in clinical and non-clinical samples and are widely used in research and practice. Finally, conclusions should be drawn cautiously regarding the direction of causality. It is generally assumed that LUTS is a risk factor for sexual dysfunction, rather than the reverse. However, in the absence of a clearer understanding of the mechanisms involved, we cannot be certain that LUTS directly or indirectly increase the likelihood of sexual problems. It is possible, for example, that both disorders are caused by a third, as yet unidentified, factor. Further longitudinal studies are needed to establish this problem. The clinical implication of the present study is significant. Male and female patients who present with urinary symptoms should be carefully evaluated for the

B.L. Hansen / European Urology 46 (2004) 229 234 233 presence of sexual problems. The presence or absence of sexual problems should be taken into account when selecting appropriate management of LUTS. In particular, patients should be informed about the potential adverse effects of treatment on all aspects of sexual function. Acknowledgements Distribution and collection of the questionnaires were carried out by the Mentor Institute, Copenhagen, Denmark. Funding support for the study was provided by an unrestricted grant from Pfizer. References [1] Fultz NH, Herzog A. Epidemiology of urinary symptoms in the geriatric population. Urol Clin North Am 1996;23:1 10. [2] Elbadawi A, Diokno AC, Millard RJ. The aging bladder: Morphology and urodynamic. World J Urol 1998;16(Suppl 1):10 34. [3] Schatzl G, Temml C, Waldmüller J, Thürridl T, Haidinger G, Madersbacher S. A comparative cross-sectional study of Lower Urinary Tract Symptoms in both sexes. Eur Urol 2001;40:213 9. 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The prevalence of sexual problems in women attending for urodynamic investigation. Int Urogynecol J 1993;4:212 5. [12] Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54 61. [13] Braun M, Wassmer G, Klotz T, Reifenrath B, Maters M, Engelmann U. Epidemiology of erectile dysfunction: results of the Cologne Male Survey. Int J Impot Res 2000;12:305 11. [14] MacFarlane GJ, Botto H, Sagnier PP, Twillac P, Richard F, Boyle P. The relationship between sexual function and urinary condition in the French community. J Clin Epidemiol 1996;49:1171 6. [15] Blanker MH, Bohnen AM, Groenveld FPMJ, Bernsen RMD, Prins A, Thomas S. Correlates for erectile and ejaculatory dysfunction in older Dutch men: a community-based study. J Am Geriatr Soc 2001;49:436 42. [16] Rosen R, Altwein J, Boyle P, Kirby RS, Lukacs B, Meulemann E, et al. Lower Urinary Tract Symptoms and male sexual dysfunction: the Multinational Survey of the Aging Male (MSAM-7). Eur Urol 2003;44:637 49. [17] Gordon D, Groutz A, Sinai T, Wiezman A, Lessing JB, David MP, et al. Sexual function in women attending a urogynecology clinic. Int Urogynecol J 1999;10:325 8. [18] Vallancien G, Einberton M, Harvig N, van Moorslaar RJ. Sexual dysfunction in 1.274 European men suffering from lower urinary tract symptoms. J Urol 2003;169:2257 61. [19] Braun MH, Sommer F, Haupt G, Mathers MJ, Reifenrath B, Engelmann UH. Lower urinary tract symptoms and erectile dysfunction: co-morbidity or typical aging male symptoms? Results of the Cologne male survey. Eur Urol 2003;44:588 94. [20] Chute CG, Panser LS, Girman CJ, Oesterling JE, Guess HA, Jacobsen SJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol 1993;150:85 9. [21] Jackson S, Donovan J, Brooks S, Eckford S, Swithinbank L, Abrams P. The Bristol Female Lower Urinary Tract Symptoms questionnaire: development and psychometric testing. Br J Urol 1996;77:805 12. [22] Schou J, Holm NR, Meyhoff HH. Sexual function in patients with symptomatic benign prostates hyperplasia. Scand J Urol Nephrol Supll 1996;179:119 22. [23] Rogers GR, Kammerer-Doak D, Villarreal A, Coates K, Qualls C. A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse. Am J Obstet Gynecol 2001;184:552 8. [24] Steers WD, Clemow DB, Persson K, Sherer TB, Andersson KE, Tuttle JB. The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostates hyperplasia and young anxious males. Exp Physiol 1999;84:137 47. [25] Chang S, Hypolite JA, Zderic SA, Wein AJ, Chacko S, DiSanto ME. Enhanced force generation by corpus cavernosum smooth muscle in rabbits with partial bladder outlet obstruction. J Urol 2002;167: 2636 44. [26] Goldstein I. The mutually reinforcing triad of depressive symptoms, cardiovascular disease, and erectile dysfunction. Am J Cardiol 2000;86:41F 5F. [27] Suthest J, Brown M. Sexual dysfunction associated with urinary incontinence. Urol Int 1980;35:377 81. [28] Mauritsen L. Sex and urogynecological problems a survey. Nordisk Sexologi 1997;15:89 98. Editorial Comment R. Rosen, New Brunswick, NJ, USA rosen@umdnj.edu Symptoms of LUTS are highly prevalent and bothersome in both men and women. LUTS in men is most frequently associated with benign prostatic hypertrophy (BPH), and has also been associated recently with symptoms of sexual dysfunction, including both erectile and ejaculatory disturbances in men over 50 [1]. The mechanism for this association has not been established definitively to date. In women, the symptoms of LUTS include urinary leakage, a highly prevalent and bothersome disorder in women occurring in more than 25% of women over the age of 70. In the above paper by Hansen, LUTS in women have now

234 B.L. Hansen / European Urology 46 (2004) 229 234 been reported to be associated with sexual dysfunction problems in a new epidemiological study. Approximately 50% response rate was obtained in this large, random sample of Danish women. More than half reported sexual problems, consisting of problems with desire, pain during intercourse and lack of sexual satisfaction. It is likely that different mechanisms might be mediating the sexual responses of men and women with LUTS, particularly since the etiology of the various urinary disorders are likely to be different in men and women with LUTS. In men, the underlying processes involved include hormonal and neurotransmitter (e.g. alpha-adrenergic) effects, which might also mediate changes in sexual function. Smooth muscle activators, rho-kinase inhibitors, or alpha adrenergic blockade could all be important mediating factors. On the other hand, infectious or inflammatory mechanisms might be more important in women. For both sexes, psychological mechanisms are likely important in mediating the degree of bother commonly associated with both sexual and urinary distress. This aspect (bother) of both sexual and urinary distress is not well understood at the present time. Hopefully, further research will evaluate this important dimension (psychological mechanisms) of both urinary and sexual dysfunction. Reference [1] Rosen R, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol 2003;44(6):637 49.