Impact of Treatment of BPH on Sexuality

C Schulman1* 1Department of Urology, Erasme Hospital, University Clinics of Brussels, Belgium

Benign prostatic hyperplasia (BPH) can have a profound affect on a patient’s quality of life and sexual function and is considered by patients to be one of the most important aspects affected by the disease. Different treatments can produce a variable response in terms of the patient’s quality of life, including sexual activity and satisfaction. Varying rates of erectile dysfunction (ED) and retrograde ejaculation following surgery for BPH have been reported. In general, the incidence of these side-effects is less after minimally invasive therapies, such as interstitial laser coagulation and transurethral microwave therapy, but the data available are limited. The lowest rates of sexual dysfunction are reported with medical therapies. The 5a-reductase inhibitor, finasteride, can result in ED in 5 – 9% of patients and ejaculation disorders in 0.8 – 2.0%. With the exception of tamsulosin, a1 blockers are associated with a low rate of sexual dysfunction. No cases of ED have been reported with alfuzosin and abnormal ejaculation with terazosin or alfuzosin is negligible. Indeed, early research suggests a beneficial effect of a1 blockers on sexual function. In addition to information on the efficacy of a particular therapy, patients should be informed of side effects, in particular those relating to sexual function, in order that they can make informed treatment decisions. Prostate Cancer and Prostatic Diseases (2001) 4, Suppl 1, S12–S16.

Keywords: benign prostatic hyperplasia; sexual function; a1 blockers; ﬁnasteride; surgical therapy

Introduction activities, but above all sexual activities and satisfaction with sexual relationships. Although not considered to be a life-threatening disease, benign prostatic hyperplasia (BPH) can seriously affect the patient’s normal physical and social activities, and Evaluation of sexual function may have a profound effect on quality of life.1,2 From the urologist’s point of view, this impact of treatment on The most useful and comprehensive study of the epide- sexuality, be it medical, surgical or instrumental, has miology of erectile dysfunction (ED) at present is the often been poorly investigated and neglected. Massachusetts Male Aging Study (MMAS), which was From the patient’s perspective, one of the major aspects conducted between 1987 and 1989.4 This cross-sectional, of quality of life is sexuality following treatment for BPH.3 random sample survey of health status and related issues A recent study evaluated which aspects of quality of life was conducted in men between the ages of 40 and 70 y. were most affected by prostatic symptoms and those Analysis of data on 1209 men indicated that the mean which the patient considered most important.3 A self- probability of some degree of ED was 52.0%. Between the administered questionnaire composed of 89 items was fifth and seventh decades, the probability of complete ED completed by 117 patients with an International Prostate almost tripled from 5.1% to 15%. Symptom Score (IPSS) > 7. The aspects reported to be Helgason et al showed that only 17% of men over 50 y most affected and the most important were sleep, anxiety reported that they could live without a sex life.5 Another and worry about the disease, mobility, leisure, daily study evaluated the sexual function of an unselected population referred for hospital treatment for clinical BPH.6 A total of 401 patients completed a questionnaire, which included three questions on sexuality: erection, ejaculation volume and pain/discomfort during ejacula- *Correspondence: C Schulman, Department of Urology, Erasme Hospital, University Clinics of Brussels, Route de Lennik 808, B-1070 tion. Analysis of the results showed that the incidence of Brussels, Belgium. ED increased with age and related bother was much [email protected] greater in younger males. Treatment of BPH and sexuality C Schulman S13 An important issue when discussing BPH and sexu- completed a questionnaire on personal evaluation of ality is to identify what specific aspects of sexual function sexual function, including erection, ejaculation, libido are being considered; whether it is ED, ejaculation dys- and satisfaction. Of the responders, 54% stated that function, decreased libido or overall decreased sexual there was deterioration in all of these factors and impor- satisfaction. Assessment of sexual function is another tantly, 50% attributed this to the surgery they had under- important concern. Sexual dysfunction often occurs in gone, ie TURP. the same subpopulation of men who are affected by symptomatic BPH. Consequently, the direct or indirect side effects of treatment for BPH on sexual function may Minimally invasive therapies be difficult to assess. The lack of reproducible instruments to measure sexual A number of minimally invasive treatments have been function is another obstacle. Several different question- developed for symptomatic BPH, including transurethral naires are available including: needle ablation (TUNA), transurethral microwave thermotherapy (TUMT), interstitial laser coagulation (ILC). 7 The Brief Sexual Function Inventory (SFI) The effect on sexual function of these therapies has been 8 The International Index of Erectile Function (IIEF) evaluated; however, a variety of assessment methods 9 Urolife Scale were used. 10,11 The Danish Prostatic Symptom Score (DAN-PSS) With regard to ILC, retrograde ejaculation was Of these, the SFI and the IIEF have been developed reported in 6% of patients in a study by Arai et al17 and specifically to measure male sexual function. 0 – 11.9% in others;18 no cases of ED have been described with ILC.18,19 The incidence of sexual dysfunction is negligible after TUNA; several studies reported no ED or retrograde ejaculation.20 – 22 Only one study, a prospec- Impact of treatment on sexual function tive multicentre trial in the US, found less than 1 and 2% of retrograde ejaculation and ED, respectively.23 Different treatments can have the same impact on symp- Limited data are available on TUMT. Francisca et al toms but may produce a variable response in terms of the studied 50 patients treated with TUMT or by sham and patient’s quality of life, which is influenced by the found that 20% of patients treated with either modality patient’s preferences and values. For example, some had a worsened sexual function at 26 weeks post-treat- patients with BPH may be more concerned about preser- ment.24 The overall incidence of retrograde ejaculation ving or improving their actual sexuality than decreasing was 11% and for lack of orgasms, 14%. Interestingly, at their potential risk of acute urinary retention by a mod- baseline and at 12 and 26 weeks post-treatment, there was erate percentage. For some patients, retrograde ejacula- no statistically significant difference between TUMT and tion following transurethral resection of the prostate sham treatment with regard to quality of life related to (TURP) may be an acceptable side effect of surgery if it sexual function. has been properly discussed beforehand, while for others it represents a major issue. The actual impact that the various treatments have on sexual function is discussed Medical therapy below.

Finasteride. Finasteride is a selective 5a-reductase inhibi- Surgery tor that reduces the conversion of testosterone to dihy- Potential late sequelae of surgery for BPH include retro- drotestosterone. It has been shown to improve symptoms grade ejaculation and ED. Dependent on the series, 25 – in patients with BPH over a period of 3 – 6 months, and 99% of men lose ejaculation after surgery.12 The impact of the efficacy of the drug appears to be related to prostate 25 surgery on sexual function is difficult to assess and is also size over 40 ml. The effect of finasteride on sexual 26 – 28 dependent on the patient’s perception of his sexual ability function is summarised in Table 1. Increased risk of before and after surgery, as well as on the presence of a various side effects related to sexual function were sexual partner. This is also reflected by the variable rates demonstrated with finasteride. of ED that have been reported to occur after TURP or open prostatectomy. Phytotherapy. There are very few placebo controlled The American Urological Association (AUA) Coopera- studies on phytotherapy for BPH evaluating the impact tive Study reported a 13% incidence of ED following on sexual function. A 6 month study compared the effects TURP.13 A comparative study was conducted in which of Serenoa repens, a plant extract, with finasteride in 1098 men were randomised to treatment with TURP or trans- men with moderate BPH.29 The effect on sexual function urethral vaporisation of the prostate (TUVP). Postopera- was assessed in a sexual questionnaire and indicated that tive ED was reported in 17 and 11% and retrograde Serenoa repens resulted in fewer complaints of decreased ejaculation in 72 and 89% of patients treated with TURP libido and ED, although the percentages reported were and TUVP, respectively.14 A second comparative trial low. resulted in retrograde ejaculation in 68 and 35% of patients undergoing TURP and transurethral incision of a1 blockers. Avarietyofa1 blockers are available and their the prostate (TUIP), respectively.15 use generally results in a 6 – 31% improvement in symptom Follow-up after TURP with regard to sexual function score within the first 2 – 3weeks.30,31 Maximum urinary was studied by Kinn and associates.16 A total of 127 men flow rate can also be increased by up to 3.9 ml/s.30

Prostate Cancer and Prostatic Diseases Treatment of BPH and sexuality C Schulman S14 Table 1 The effect of ﬁnasteride on sexual function

VA Study26 PROWESS Study27 PLESS Study28 Follow-up 1 y 2 y 4 y

Placebo (%) Fin (%) Placebo (%) Fin (%) Placebo (%) Fin (%) (n ¼ 305) (n ¼ 310) (n ¼ 1591) (n ¼ 1577) (n ¼ 1376) (n ¼ 1384)

Decreased libido 1.0 5.0 2.8 4.0 2.6 2.6 Erectile dysfunction 5.0 9.0* 4.7 6.6* 5.1 5.1 Decreased ejaculation NA NA NA NA 0.5 1.5* Ejaculation disorder 1.0 2.0 0.6 2.1* 0.1 0.8

NA ¼ not applicable; Fin ¼ ﬁnasteride. *Statistically signiﬁcant: P < 0.05.

Table 2 The effect of a1 blockers on sexual function

Drug Study No. of patients Dose (mg/day) Abnormal ejaculation (%)

Alfuzosin Buzelin et al31 89 10 0.3 Terazosin HYCAT Trial32 2084 1 – 10 1.4 VA Study26 610 10 0.3 Tamsulosin Abrams et al33 295 0.4 4.0 Chapple et al34 575 0.4 4.5 Schulman et al35 515 0.4 4.3 Lepor H36 254 0.4 6 248 0.8 18 Lepor H37 139 0.4 10 139 0.8 26

In terms of sexual function, the effect of the different an erection, whereas erectile function decreased with 26,31 – 37 a1 blockers on ejaculation is shown in Table 2. finasteride therapy and with the combination of the two The European Tamsulosin Group reported that at 3 y drugs, presumably due to the contribution of finasteride. follow-up, 2.9% of patients had ED and 4.3% ejaculation With regard to ejaculation, again, only finasteride and the 35,38 disorders. In contrast to the other a1 blockers, combination had a detrimental effect. doxazosin has been poorly studied with regard to sexual It has been suggested that a1 blockers may improve satisfaction. sexual function in patients with BPH. A study of 2829 Clearly, a1 blockers do not have the adverse effect on patients with BPH treated with alfuzosin 2.5 mg t.i.d. or sexual function that certain other therapies exhibit. The 5 mg b.i.d. for 1 y was conducted in the primary care ALFIN Study in addition to comparing the efficacy of setting.41 Sex drive, erections and overall sexual satisfac- alfuzosin and finasteride and their combination in BPH, tion were assessed using the Urolife2 BPHQoL9. Data also examined the effect of these therapies on erection and were analysed according to patient age and symptom ejaculation using the DAN-PSS questionnaire.39,40 A total severity and baseline patient characteristics are shown in of 1051 patients aged 50 – 75 y were enrolled in the study. Table 3. Following treatment with alfuzosin, particularly in The effects of therapy on ED and ejaculatory function are the younger age group, there was an appreciable improve- shown in Figures 1 and 2.39,40 Results showed that ment in overall sex life in patients with moderate and alfuzosin had very little effect on the ability to achieve severe symptoms (Figures 3 and 4).41

Figure 1 Effect of therapy on the ability to achieve an erection in the Figure 2 Effect of therapy on ejaculatory function in the ALFIN ALFIN Study.37,38 Study.37,38

Prostate Cancer and Prostatic Diseases Treatment of BPH and sexuality C Schulman S15 Table 3 Baseline characteristics of patients treated with alfuzosin Evidence exists for the potential benefits of other a1 2.5 mg t.i.d. or 5 mg b.i.d. for 1 y in the primary care setting39,40 blockers on sexual function. In one study, patients with BPH were treated with doxazosin for up to 8 weeks and Age (y) assessed at weeks 4 and 8 using a sexual function ques- 42 < 65 65 – 70 > 70 tionnaire. Results showed that doxazosin significantly improved overall sexual function compared with baseline No. of patients (%) 1098 (41%) 764 (29%) 787 (30%) values and, in particular, the ability to gain and keep an Sexual score according to symptom severity: erection. A 10% improvement in overall sexual function Moderate (I-PSS 8 – 19) 12.62 9.89 6.78 was noted at week 4 (P ¼ 0.002) and a 15% improvement Severe (I-PSS 20 – 35) 9.56 7.26 4.55 at week 8 (P < 0.001). Perhaps the strongest evidence for the benefits of a1 blockers in improving sexual function comes from their intracavernous use in patients with ED. Colson conducted a retrospective study on 1001 patients with total or partial ED treated with three different vasoactive preparations: moxisylyte (n ¼ 476), PGE1 (n ¼ 195) or papaverine (n ¼ 170); 160 patients were given a mixture of monother- apy and combined therapy.43 Results indicate that moxisylyte was superior to the other intracavernous treatments with regard to: return of satisfactory sexual activity after discontinuation of therapy; reappearance and improvement of spontaneous erections; and return of the penis to its usual size. Intracavernosal injection of phenoxybenzamine, another a1 blocker, has also been shown to produce full erections lasting for over 30 min in men with ED.44

Conclusion In making treatment decisions for BPH it is necessary to Figure 3 Improvement in sexual score in patients with moderate symptoms of BPH after 1 y of treatment with alfuzosin.39,40 consider the balance between efﬁcacy, side effects and the potentially beneﬁcial effect of treating patients at an early stage, where the impact on voiding and sexual function may be greater. Quality of life for patients is clearly of great importance to them and the impact of treatment on sexual function should be considered more carefully. By improving patients’ symptoms, a1 blockers bring about a general improvement in the patient’s wellbeing and a likely improvement in his sex drive. It is also essential to provide the patient with information on the consequences of therapy for the disease, in particular the effects on quality of life and sexual function, in order that their treatment preferences and priorities can be taken into account.

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