Effects of Beta-Blockers on Sexual Performance in Men with Coronary Heart Disease

Effects of beta-blockers on sexual performance in men with coronary heart disease. A prospective, randomized and double blinded study

D Franzen1*, A Metha1, N Seifert1, M Braun2 and HW Ho¨pp1

1III Department of Medicine, Cardiology, Universita¨tskliniken Ko¨ln, Germany; and 2Department of Urology, Universita¨tskliniken Ko¨ln, Germany

In a prospective trial assessing the effects of beta-blockers on sexual function men with coronary heart disease were randomized to a 4 month treatment with sustained release metoprolol 95 mg or placebo. A standardized and validated self-report questionnaire (KEED ¼ Ko¨lner Erhebungsbogen der Erektilen Dysfunktion) dealing with several aspects of sexual performance in men had to be answered at the beginning and at the end of the study. Based on 65 patients completing the study, sex life seemed unaffected by metoprolol treatment. International Journal of Impotence Research (2001) 13, 348–351.

Keywords: impotence; beta-blockers; coronary heart disease

Introduction placebo controlled trial on the effect of beta-blockers on restenosis following PTCA and on the effect on erectile dysfunction. Pending a successful angio- Compliance with the prescribed medication is a key plasty, treatment with the study medication was problem in all disciplines of medicine. Among other continued for 4 months. drugs, this holds true in particularly for beta- A total of 192 male patients were randomized to blockers in the treatment of coronary heart disease treatment with 95 mg sustained release metoprolol 1 and hypertension. Although proven beneficially in once a day or placebo beginning at least 1 day before primary and secondary prevention, both, patients PTCA. Pending a successful angioplasty and in- and even physicians tend to avoid the prescription formed consent, patients received an anonymous of beta-blockers because of potential interference and standardized questionnaire (KEED ¼ Ko¨lner with their sex life. Beta-blockers seem to disturb the Erhebungsbogen der Erektilen Dysfunktion) at study delicate balance between alpha- and beta-adrenergic entry and after 4 months of treatment. The KEED is 2 nerve fibers. However, it is surprising and unclear an 18-item questionnaire for the evaluation of why not all or the majority of patients experience erectile dysfunction, which has been developed such side effects. In the following we report on a and validated in German.3,4 It is aimed to identify prospective, randomized and placebo controlled symptoms of erectile dysfunction and its effects on trial on the effect of beta-blockers on the sexual quality of life. Questions 1 to 8 assess sociodemo- performance in men with coronary artery disease. graphic characteristics, medical history and medication, smoking and alcohol consumption habits. Questions 9 and 10 refer to sexual desire and frequency of sexual activities. Questions 11 to 16 Methods assess erectile and orgasmic function on a 5-point scale, allowing calculation of an Erectile Dysfunc- Consecutive male patients undergoing elective cor- tion (ED) Score. Satisfaction with sex life and onary angioplasty (PTCA) at Cologne University general well-being is covered by the last two were asked to participate in a randomized and questions. Apart from the standardized questionnaire a specific question at study end addressed the issue whether the study medication had affected sex life negatively, positively or not at all. *Correspondence: D Franzen, Berrenrather-Str. 296, 50937 Patients with prior treatment using any beta- Ko¨ln, Germany. Tel: 0049-221-4201100; blocker within the last 12 months were considered Fax: 0049-221-4201110. inappropriate candidates for study participation. In Received 7 June 2001; accepted 26 September 2001 addition, exclusion criteria for enrollment were Beta-blockers and impotence D Franzen et al 349 cardiac conductance disturbances, presence of asth- Table 2 Demographic data of the study participants ma or chronic obstructive lung disease. Metoprolol Placebo (n ¼ 38) (n ¼ 27)

Age (y) 56 Æ 957Æ 11 Statistics Profession worker 12 (32%) 6 (22%) public servant 0 0 employee 5 (13%) 8 (30%) Statistical analysis was based on an intention-to- self-employed 3 (7%) 1 (4%) treat analysis. However, both questionnaires were without work 1 (3%) 0 needed to evaluate the treatment effects of metopro- retired 17 (45%) 12 (44%) lol and placebo on erectile dysfunction. Continuous Marital status married 28 (73%) 22 (82%) data were presented as mean plus standard devia- unmarried 6 (16%) 2 (7%) tion (s.d.) and compared using student’s t-test. divorced 3 (8%) 2 (7%) Cross-tabulation was applied for categorical and widowed 0 1 (4%) numerical data. Covariance analysis was performed to assess the relevance of individual parameters. Statistics were calculated using the SPSS software.

Table 3 Inﬂuence of metoprolol or placebo on sexual Results performance Changes in sex life

Of 192 randomized patients angioplasty was Metoprolol (n ¼ 38) Placebo (n ¼ 27) successful in 136 patients who continued taking the study medication and were asked to return for Negative influence 9 (24%) 10 (37%) No influence 19 (50%) 15 (56%) a control angiography after 4 months. Table 1 Undecided 9 (24%) 2 (7%) illustrates the breakdown of the fate of study Positive influence 1 (3%) 0 participants. Pending on a successful coronary angioplasty patients were asked to participate in a prospective and placebo controlled study on the effects of beta- blockers on erectile dysfunction. Of 50 patients Erectile Dysfunction (ED) scores were similar in the in each treatment group at study entry a total of metoprolol and in the placebo group at study entry 38 patients in the metoprolol group and 27 in and did not changed significantly while taking the the placebo group completed both sets of study medication (Table 4). It is of note that about questionnaires. 60% of the study participants had no problems Baseline demographic data were tabulated in achieving a sufficient erection of their penis and Table 2. Most patients were in their 50s, married reaching orgasm. According to specific questioning and retired from work. The frequency of sexual at study end most patients felt unaffected in their intercourse per month in the metoprolol group sex life by either metoprolol or placebo treatment averaged to 6.8 Æ 3.0 times at study entry and (Table 3). decreased not significantly to 6.0 Æ 3.6 times at study end. In the placebo group the frequency Æ decreased from 7.4 4.6 times at study entry to Discussion 5.5 Æ 3.6 at study end. All differences were statisti- cally not significant when using Fischer’s exact test. Beta-blockers have been gaining a key role in the treatment of various cardiovascular disorders.5,6 Apart from side effects predominantly affecting Table 1 Flowchart of study participants cardiac and lung function most patients are afraid Randomization of negative interference with their sex life while n ¼ 192 taking beta-blockers.1 In the present prospective, randomized and placebo-controlled study patients Metoprolol Placebo in their fifties suffering from atherosclerotic heart n ¼ 97 n ¼ 95 Successful PTCA Successful PTCA disease were asked to evaluate their sexual perfor- n ¼ 72 n ¼ 64 mance before and after treatment with low dose Control evaluation after Control evaluation after beta-blockers or placebo. According to an anon- 4 months n ¼ 54 4 months n ¼ 43 ymous standardized questionnaire questions deal- Completion of the Completion of the questionnaire n ¼ 38 questionnaire n ¼ 27 ing with various aspects of erectile dysfunction had to be answered at the beginning and at the end of the

International Journal of Impotence Research Beta-blockers and impotence D Franzen et al 350 Table 4 Details of sexual performance

metoprolol group placebo group start end start end

Sex partner Yes 17 24 13 16 No 13 12 7 10 Coitus possible Yes 29 35 22 21 No2 215 Number of coitus per month 6.8 Æ 3.0 6.0 Æ 3.6 7.4 Æ 4.6 5.5 Æ 3.6 Impaired erection Yes 2 4 2 7 Not always 3 6 3 3 Rare 5 6 3 3 No 20 19 14 14 Erection possible Yes 15 20 10 13 Not always 2 6 2 2 Rare 0 0 0 1 No1 001 Complete erection Yes 10 19 7 9 Not always 5 6 5 3 Rare 0 0 0 2 No2 102 Slow erection Yes 5 6 5 5 Not always 1 4 0 1 Rare 1 3 1 0 No 9 13 6 12 Spontaneous erection in the morning Yes 5 6 6 9 Not always 3 4 3 3 Rare 2 7 1 0 No4 836

study.3,4 Overall, in this selected cohort success and blockers on the erectile function in different and larger frequency of the sexual intercourse seemed unaf- populations. fected by metoprolol treatment. In several other studies antihypertensive agents seem to exert a negative effect on the erectile Acknowledgement function of the penis7,8 but the mechanisms in- volved remain unclear. It is of note that the prevalence of impotence in patients with vascular The present study is supported by ASTRA Pharma- diseases and=or hypertension is far greater than in ceutical Company, Germany supplying the study the average population and may be related to medication somatic and psychological factors.9,10 Our results are in agreement with studies in untreated hypertensive patients as compared to those treated with References propanolol or other beta-blockers.11,12 Studies using various dosages of propanol showed that sexual 1 Rosen RC, Kostis JB. Biobehavioral sequelae associated with dysfunction might be related to higher doses of beta- adrenergic-inhibiting antihypertensive agents: a critical re- blocking agents.13 view. Health Psychology 1985; 4 579 – 604. The discrepancy of the effects of various beta- 2 Meinhardt W, Kropman RF, Vermeij P, Lycklama A, Nijeholt blockers and dosages may be related to a differential AAB, Zwartendijk L. The inﬂuence of medication on erectile = function. Int J Impot Res 1997; 9:17– 26. action on peripheral structures and or on the central 3 Braun M, Klotz T, Reifenrath B, Wassmer G, Engelmann U. 14 nervous system. Apart from potential disadvanta- KEED-erster deutschsprachig validierter Fragebogen zur Erfas- geous effects of the drop in blood pressure following sung der ma¨nnlichen sexuellen Funktion. Akt Urol 1998; 29: beta-blocker treatment the local balance of alpha and 300 – 305. beta-adrenergic function may be pertubated and 4 Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, 2,15,16 Engelmann U. Epidemiology of erectile dysfunction: results of interfer with the vascular events during erection. the ‘Cologne Male Survery’. Int J Impot Res 2000; 12: 305 – 311. According to the results of our study educational, 5 Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade social as well as psychological factors might play the during and after myocardial infarction: an overview of the dominant role in the development of impotence as has randomized trials. Progr Cardiovac Dis 1985; 27: 335 – 371. 6 Wikstrand J, Warnold I, Olsson G, Tuomilehto J, Elmfeldt D, been indicated in other studies dealing with quality of Berglund G. Primary prevention with metoprolol in patients 1,17 life in patients with coronary heart disease. Further with hypertension. Mortality results from the MAPHY study. work is however needed to clarify the role of beta- JAMA 1988; 259: 1976 – 1982.

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