Comorbid LUTS and Erectile Dysfunction: Optimizing Their Management

By Kaminetsky, Jed C

Key words: α^sub 1^-Adrenergic receptor antagonists – Benign prostatic hyperplasia – Erectile dysfunction – Lower urinary tract symptoms – 5α-Reductase inhibitors – Sexual dysfunction

ABSTRACT

Background and scope: Lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasla (BPH), and sexual dysfunction such as erectile dysfunction (ED), are highly prevalent in men over the age of 50. LUTS and ED have a negative impact on sexual function and when comorbid, result in reduced quality of life. The goal of this article is to discuss the relationship between ED and LUTS, describe the diagnostic workup of these disorders, explore the current treatment options, and examine how treatments may affect this population. Medline (1980-2006), Cochrane reviews, and the American Urotogteal Association 2006 General Meeting abstracts were searched for relevant clinical trials and reviews with the terms: benign prostatic hyperplasia, lower urinary tract symptoms, erectile dysfunction, sexual dysfunction, α-adrenerglc receptor antagonists, α-blockers, 5α-reductase inhibitors, phosphodiesterase type-5 inhibitors, transurethral resection of the prostate, transurethral microwave thermotherapy, transurethral needle ablation, adverse events, alfuzosin, doxazosin, tamsutosin, terazosin, dutasteride, finasteride, sildenafil, tadatafil, vardenafil. However, because of the volume of literature, this article is not a systematic review.

Findings: Although age is an independent risk factor for both LUTS and ED, studies report that LUTS is also an independent risk factor for ED. Treatments for LUTS include pharmacologic, minimally invasive, and surgical therapies. Among pharmacologic options, α^sub 1^-adrenergic receptor (α^sub 1^-AR) antagonists provide effective treatment with a tow risk of sexual side-effects; some of these drugs have been reported to improve sexual function. The treatment of LUTS may improve ED. Phosphodiesterase type 5 inhibitors (PDE-5s) are considered first-line therapy for ED. Comorbid LUTS and ED are treated with an α^sub 1^-AR antagonist and a PDE-5; however, this combination must be used with caution because of vasodilatory adverse events associated with both classes of drugs.

Conclusions: Optimal management includes screening to identify patients with comorbid LUTS and ED, and the use of treatments that minimize both vasodilatory and sexual side-effects.

Introduction

Two of the most common changes noted by men as they grow older are changes in sexual function and voiding patterns; either of these conditions may have a negative impact on quality of life (QoL)1. Men who remain sexually active notice diminished penile rigidity, longer latency periods, decreased sensation, and less intense orgasm and pleasure. Other men may become sexually inactive either because of decreased libido (hypoactive sexual desire) or erectile dysfunction (ED). Until recently, no particular association was made between sexual dysfunction and lower urinary tract symptoms (LUTS), apart from an age-related simultaneity. Indeed, ED, diminishment in libido (i.e., hypoactive sexual desire), and LUTS were considered an inevitable result of increasing age2. Yet, these symptoms often are now known to be associated with a number of treatable conditions such as hypertension, heart disease, diabetes, depression, and benign prostatic hyperplasia (BPH)3-5. More recently, studies have demonstrated that the presence of LUTS is strongly associated with an increased likelihood of ED, and that sexual dysfunction, while common, is not a necessary consequence of aging2,6-9.

The understanding of both ED and LUTS secondary to BPH has increased substantially in recent years, with advances in treatment options improving the QoL and sexual satisfaction of many men. The goal of this article is to discuss the relationship between ED and LUTS, describe the diagnostic workup of these disorders, explore the current treatment options for men with comorbid LUTS and ED, and examine how these treatments may affect this particular population.

Methods

A Medline literature search was conducted for relevant medical literature published between 1980 and 2006. The search terms employed included: benign prostatic hyperplasia, lower urinary tract symptoms, erectile dysfunction, sexual dysfunction, α- adrenergic receptor antagonists, α-blockers, 5α-reductase inhibitors, phosphodiesterase type-5 inhibitors, transurethral resection of the prostate, transurethral microwave thermotherapy, transurethral needle ablation, adverse events, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, sildenafil, tadalafil, vardenafil. The search was limited to controlled clinical trials, meta-analyses, systematic reviews, and key review articles. Non-English references were excluded. A Cochrane Review search was also conducted using the same search terms. In addition, abstracts from the American Urological Association (AUA) 2006 Annual Meeting were searched using the above search terms to determine whether newer data relevant to this review had recently emerged. Finally, bibliographies of located articles were examined for other viable sources of data.

Impact of LUTS on sexual functioning

Sexual dysfunction such as ED, ejaculatory dysfunction (EjD), and hypoactive sexual desire occur commonly in men over 40. According to the Massachusetts Male Aging Study, some degree of ED, the persistent inability to achieve and maintain an erection, affects 52% of men over the age of 40; the prevalence of complete impotence triples from 5% to 15% between the ages of 40 and 70 years3. ED is estimated to afflict 26 out of 1000 men per year, with incidence rates strongly related to age10,11. The National Health and Social Life Study revealed that sexual dysfunction occurred in 31% of men, and that the odds of having ED increases with age and the presence of LUTS12.

BPH is characterized by histological changes associated with a benign enlargement of the prostate that may cause bladder outlet obstruction (BOO). In turn, BOO may lead to functional and structural alterations in the bladder wall and nerve supply, leading to manifestations of LUTS such as urinary frequency, hesitancy, nocturia, and poor urinary flow13,14. It should be noted that LUTS may also result from other causes, including urinary tract infection, heart failure, and diabetes and not necessarily to BOO or BPH15. The prevalence of BPH among men between the ages of 31 and 40 years is approximately 8%, rising to 50% in men aged 51-60 years, about 70% in men between 61 and 70, and 90% of men aged 81-90(16). BPH is not exclusively a disease of older men; approximately 17% of men between the ages of 40 and 50 have reported that urinary dysfunction associated with BPH negatively affected their activities of daily living17.

Varying degrees of sexual dysfunction have been associated with BPH/LUTS, although there is a consistent pattern of increased sexual dysfunction correlated with increased occurrence of LUTS1,9. The Cologne Male Survey examined ED and comorbidities in approximately 4500 men12. While 31.2% of all men surveyed described having LUTS, the rate of LUTS in those with ED was considerably higher6. Men suffering from ED experienced LUTS at a rate of 72.2%, compared to 37.7% for those without ED. Statistical analysis of these data determined that LUTS is an independent risk factor – distinct from the influence of age – for the development of ED (p < 0.001).

A variety of hypotheses has been put forward to explain the ways in which LUTS and ED may be associated. However, these hypotheses, while widely reported, remain largely speculative. One theory suggests that diminished QoL, apart from being a consequence of ED, may in fact have a role in promoting it18,19. Girman et al. found that decreases in QoL scores resulting from worsening LUTS were particularly apparent in the areas of hypoactive sexual desire and sexual satisfaction, and concluded that the global decrease in QoL from LUTS had a detrimental effect on sexual function19. In addition, there are multiple physiologic pathways by which LUTS affect sexual function, and the particular manifestations of sexual dysfunction may vary to some extent from patient to patient. Such variation may be related to a particular patient’s comorbidities.

Patients with cardiovascular disease and the metabolic syndrome (a cluster of associated metabolic risk factors including hyperlipidemia, central adiposity, hypertension, and insulin resistance or glucose intolerance) may be predisposed to sexual dysfunction; this is likely related to altered endothelial function and consequent impairments in vasodilation associated with these disorders1,18,20. Metabolic syndrome may also be a linchpin in the relationship between LUTS and ED. Firstly, metabolic syndrome is itself a risk factor for ED through an increase in sympathetic tone; the latter may also be a causative factor in the development of BPH21-23. Secondly, prostate growth has been correlated with other aspects of the metabolic syndrome, including hyperlipidemia and hypertension, as well as type 2 diabetes21. The metabolic syndrome may also be a factor in the development of atherosclerosis, which may induce ED by a reduction of blood flow into the corpus cavemosum24.

Another explanation that links comorbidLUTS and ED is the presence of α-adrenergic receptors (α-ARs) in the smooth muscle of both the prostate and corpus cavernosum of the penis, suggestive of a common source of dysfunction and a common target of treatment25,26. The presence of α^sub 1A^-ARs in the smooth muscle of the prostate has been well described; blockade of this receptor subtype has been demonstrated to relax prostatic smooth muscle and, as a consequence, promote better urinary flow rates and the amelioration of LUTS25,27. Similarly, blockade of α^sub 1^- AR-mediated smooth muscle contraction in the corpus cavernosum facilitates penile erection28.

Another theory purported to explain the link between ED and LUTS is that of reduced levels of nitric oxide synthesis in the pelvis and prostate, which would result in altered neurogenic influence and smooth muscle contractility in LUTS and impaired smooth muscle relaxation in ED29. This hypothesis is supported by the presence of phosphodiesterase (PDE) in the prostate and corpus cavemosum of the penis29,30. Finally, bladder outlet obstruction may induce ED by an upregulation of Rho kinase in the penis, resulting in increased penile smooth muscle tone and decreased relaxation, leading to increased penile flaccidity31. Nevertheless, a causal relationship between LUTS and ED based on the available data has been disputed by some authors who suggest a less rigorous association32. An understanding of the underlying pathologic mechanisms common to both ED and LUTS may lead to novel treatment paradigms; emerging treatments will be discussed later in this review.

Diagnosis of LUTS severity and sexual function in BPH

The diagnosis of BPH-related LUTS is predicated on the presence of symptoms, including urinary frequency, nocturia, urgency, hesitancy, weak or intermittent urine stream, straining to void, and the sensation of incomplete voiding. The initial assessment should also include symptom scoring using the AUA Symptom Index (AUA-SI) (Table 1)33. Nevertheless, it should be remembered that symptom score severity does not correlate with objective measures of BPH34. Also, patients may minimize symptoms, as they sometimes do in many medical conditions. Symptom scores do correlate well with patient perception of QoL and degree of bother, which is what the decision to treat is mostly based on34. Mild LUTS are categorized as those with AUA-SI scores ≤7 points, while moderate LUTS scores range from 8 to 19, and those of severe LUTS from 20 to 35(33). Because LUTS are a risk factor for sexual dysfunction, and patients and physicians are often not aware of the relationship between the two1,7,19, clinicians should also evaluate sexual function in patients who present with LUTS. Ironically, because of the high visibility of ED treatments in the last several years, some men may be more willing to discuss symptoms of sexual dysfunction with their physicians; this may be especially true among younger patients who wish to remain sexually active. Given that LUTS are a risk factor for ED, physicians should take the opportunity to evaluate patients who present with ED for LUTS and treat them appropriately if symptoms are present. A consideration of comorbid LUTS and ED is particularly important in the case of primary care physicians, who often are the sole Healthcare provider. As with any treatment selection, the choice of therapy for LUTS in patients with comorbid LUTS and ED should aim toward a minimal effect on sexual functioning35.

Several questionnaires are currently used to determine levels of sexual function. These include the International Index of Erectile Function (IIEF), also known as the Sexual Health Inventory for Men, which evaluates sexual desire, orgasmic function, intercourse satisfaction, and overall satisfaction36,37. Five questions from this survey are also used to assess ED (Table 2)36-38. Other surveys include the Male Sexual Health Questionnaire (MSHQ), which assesses ED, ejaculatory function, and sexual satisfaction39, and the Danish Prostate Symptom Score Sex Questionnaire (DANPSSex), which assesses ED, EjD, pain or discomfort during ejaculation, and associated level of bother for each40. Patient information gleaned from any of these surveys and the AUA-SI may be useful in selecting a course of treatment that will optimize the management of comorbid disorders.

Table 1. The American Urological Association Symptom Index (AUA- SI) (reprinted with permission30)

Table 2. International Index of Erectile Function-5 for assessing erectile function* (2006, with permission from Excerpta Medica, Inc.33)

Optimizing sexual function In the treatment of LUTS/ED

Watchful waiting

Patients with only mild symptoms of LUTS (AUA-SI/ IPSS ≤ 7) may be monitored by watchful waiting. Patients with moderate symptoms scores (AUA-SI/ IPSS ≥8) and a low degree of symptom bother are usually not treated if symptoms do not affect their QoL. Watchful waiting may be useful even for those with higher symptom scores, as some patients can tolerate a high degree of symptom bother. In these patients, bothersome symptoms may be managed with minor lifestyle modifications, such as decreasing fluid intake at bedtime33. However, if a patient has comorbid ED, it is likely that further therapy will be required.

Pharmacotherapy

Pharmacologic treatment of BPH/LUTS consists primarily of two classes of drugs: α^sub 1^-AR antagonists and 5α- reductase inhibitors (5-ARIs). The former are used for the treatment of LUTS secondary to BPH, while the latter are applicable in patients with significant prostatic enlargement (Table 3)33,41. These two drug types may be used individually or in combination to reduce the risk of clinical progression of BPH. The combination will have the advantages of both classes of drugs – immediate symptom relief (α^sub 1^-AR antagonists) and reduction of prostate size (5-ARIs)33. However, side-effects will reflect the combined profile and thus be greater than with either agent alone33.

α^sub 1^-AR antagonists

α^sub 1^-AR antagonists act by blocking smooth muscle contraction in the prostate and bladder neck, resulting in the relaxation of the bladder neck, improvement in urinary flow, and generally an amelioration of LUTS42. Four α^sub 1^-AR antagonists are widely available for the treatment of BPH: alfuzosin, doxazosin, tamsulosin, and terazosin. All have equivalent efficacy for the treatment of BPH-related LUTS but different side- effect profiles33. Most of the currently available α^sub 1^-AR antagonists are non-subtype-selective for α^sub 1^-ARs. The exception is tamsulosin, which is more selective for the α^sub 1A^ subtype, the predominant adrenoreceptor found in prostatic smooth muscle43,44. The differences in side-effect profiles appear to be in part a consequence of α^sub 1B^ blockade by non- subtype-selective α^sub 1^-AR antagonists. α^sub 1B^-ARs increase in expression with aging and are mostly found in vascular smooth muscle associated with blood pressure regulation45. This may explain why vasodilatory side-effects (e.g., orthostatic hypotension) are minimized in BPH/LUTS patients treated with tamsulosin46.

Table 3. Pharmacologic options for moderate-to-severe symptoms of benign prostatic kyperplasia/lower urinary tract symptoms (reprinted with permission30)

The use of α^sub 1^-AR antagonists is also associated with several types of sexual side-effects. Safety data from a meta- analysis of six placebo-controlled trials reported that patients receiving terazosin were more likely to develop ED than were those receiving placebo47. Speculation by the author is that minimal hypotension caused by α^sub 1^-blockade may render a marginally potent man impotent47. EjD (e.g., retrograde ejaculation, ejaculation failure) is also associated with some α^sub 1^-AR antagonists. An analysis of three randomized trials of tamsulosin (two trials of tamsulosin vs. placebo and one of tamsulosin 0.4 mg daily vs. alfuzosin 2.5mg three times daily) showed that in the two studies comparing the effects of tamsulosin with those of placebo, abnormal ejaculation occurred at a higher rate among tamsulosin- treated subjects (p = 0.01)48. This effect of tamsulosin appears to be dose-related from studies that compared 0.4 mg to 0.8mg doses43. When the effects of tamsulosin were compared with those of alfuzosin, no significant differences were observed for any of the sexual parameters between the two drugs48. (These parameters were defined as a change from baseline based on a life-style questionnaire completed at the beginning and end of the study.) Interestingly, this analysis revealed that total sexual function scores for tamsulosin were significantly superior to those of placebo (p = 0.042), which suggests that the abnormal ejaculation associated with tamsulosin did not interfere with the patients’ overall sexual satisfaction, and that improvements in LUTS resulting from treatment with tamsulosin had a beneficial effect on patients’ sexual functioning48. In a subsequent study, both alfuzosin and tamsulosin were found to have identical rates of ejaculation failure (1.3%); however, no measures of sexual satisfaction were performed. Retrograde ejaculation was also observed in 1.9% of tamsulosintreated subjects49. Earlier alfuzosin studies have shown lower rates of abnormal ejaculation50. While abnormal ejaculation may be associated with these drugs, it does not seem to be bothersome to patients; counseling patients with regard to potential side-effects in advance may further mitigate these events51. More comparative studies between α^sub 1^-AR antagonists are needed to fully evaluate the sexual side-effect profile associated with drugs and to determine their potential benefits in patients with comorbid LUTS and ED.

Combination therapy (α^sub 1^-AR antagonists and PDE-5 inhibitors)

PDE-5 inhibi\tors are used as first-line treatment for ED, unless they are contraindicated. In patients with LUTS comorbid with ED, treatment with α^sub 1^-AR antagonists in addition to PDE-5 inhibitors might also be of benefit52. Hypotheses that the vasodilatory effects of α^sub 1^-AR antagonists could be beneficial for treating ED, while the smooth muscle effects of PDE- 5 inhibitors may help ameliorate LUTS, have driven recent studies investigating this type of combination therapy52. As both PDE-5 inhibitors and α^sub 1^-AR antagonists have vasodilatory properties to some extent, the concomitant use of PDE-5 inhibitors with α^sub 1^-AR antagonists should be managed with caution53- 55. Recent pilot studies have investigated the use of α^sub 1^- AR antagonists in conjunction with PDE-5 inhibitors. Two of these studies found that patients treated with a combination of an α^sub 1^-AR antagonist and a PDE-5 inhibitor had concomitant improvements in both LUTS and ED52. Other pilot studies have reported that the incidence of vasodilatory adverse events was sometimes higher when PDE-5 inhibitors were taken in combination with non-subtype-selective α^sub 1^-AR antagonists than with the subtype-selective agent tamsulosin56-58. A placebo-controlled trial in 22 patients with BPH found that combination therapy with the PDE-5 inhibitor vardenafil and tamsulosin resulted in no clinically significant hypotension and no serious adverse events56. Two parallel randomized controlled trials, each in 18 patients, evaluated combination therapy with the PDE-5 inhibitor tadalafil plus doxazosin or tamsulosin57. Patients given doxazosin plus tadalafil experienced significantly greater postural hypotension than did those given placebo plus doxazosin (95% confidence interval did not contain 0), while no significant blood pressure effects were seen with tamsulosin plus tadalafil57. A retrospective safety evaluation of tamsulosin-treated patients (n = 1002) and terazosin- treated patients (n = 981) found that the addition of sildenafil produced a higher rate of dizziness in the latter group (beyond the increased rate of hypotension of terazosin monotherapy) than in the group treated with tamsulosin59. Recently published data from a trial in 18 patients, however, showed no additive hypotension in patients receiving tadalafil plus alfuzosin59.

5-ARIs

The use of the 5-ARIs dutasteride and finasteride in treating BPH/ LUTS is based upon their inhibition of the 5α-reductase enzyme, which catalyzes the formation of dihydrotestosterone (DHT) from testosterone. DHT is the most important androgen in promoting prostate growth2. Both medications therefore act as anti-androgenic agents. Unlike α^sub 1^-AR antagonists, this class of drugs is only recommended for men with significant prostatic enlargement diagnosed by digital rectal exam (≥ 30mL)33,41. In addition, symptomatic relief usually parallels the onset of efficacy, which requires several months to become apparent41. Large-scale trials suggest that finasteride is effective in reducing the risks of clinical progression of BPH and acute urinary retention, although its ability to improve BPH symptoms and flow rate is inconsistent in clinical trials and may be dependent on prostate size, with greater efficacy seen in patients with larger prostates41,60,61.

Both finasteride and dutasteride have been associated with sexual side-effects, which are likely due to reductions in circulating androgens. In the Medical Treatment of Prostatic Symptoms (MTOPS) trial, finasteride-treated patients had a significantly higher incidence of ED, EjD, and decreased libido compared with those given placebo (p < 0.05 for each). Similarly, the Proscar Long-term Efficacy and Safety Study (PLESS), a 4-year, placebo-controlled trial of 3040 men with BPH, found that 15% of finasteride-treated subjects experienced drug-related sexual dysfunction during the first year of the study, compared with 7% of placebo-treated men (p < 0.001)62. Pooled data from three large-scale trials of dutasteride also showed an association with sexual dysfunction, including a 7% rate of ED (vs. 4% for placebo-treated subjects), a 2% rate of EjD (vs. 1% for the placebo arm of the study), and a 4% rate of decreased libido (vs. 2% for those treated with placebo)63. Thus, while these medications are effective in reducing prostatic volume and also have been shown to decrease the risk of progression of BPH60, their use may not produce optimal outcomes in patients with ED or other sexual dysfunction.

Combination therapy (α^sub 1^-AR antagonists and 5-ARIs)

Combination therapy with an α^sub 1^-AR antagonist and a 5- ARI is recommended in patients with bothersome LUTS and significant prostatic enlargement33. Several studies have investigated the efficacy of combination therapy on symptom relief61,64. The MTOPS trial compared the effects of doxazosin and finasteride, alone and in combination, with placebo on the risk of overall BPH progression60. The cumulative 4-year incidence of overall clinical progression in MTOPS was 17%, 10%, and 10% in the placebo, doxazosin, and finasteride groups, respectively, compared with 5% in the combination therapy arm (p < 0.001 vs. placebo or either agent alone). Symptomatic relief as assessed by the AUA-SI was also significantly greater in the combination therapy group compared with the finasteride (p < 0.001) or doxazosin (p = 0.006) groups. All adverse events, except allergic reaction, were significantly increased compared to placebo with combination therapy (Table 4), and, as expected, sexual side-effects such as ED and decreased libido occurred at a higher rate among patients treated with combination therapy and finasteride than in patients treated with doxazosin alone. Despite the increase in adverse events, the percentage of patients discontinuing both drugs by study end was not greater in the combination arm compared with either monotherapy arm of the study60.

Minimally invasive treatments

Two minimally invasive treatments for LUTS due to BPH are currently approved by the AUA. The best-known treatment that falls into this category is transurethral needle ablation (TUNA), which uses radiofrequency waves administered through two 18-gauge needles to heat prostatic tissue33. While generally less effective than transurethral resection of the prostate (TURP), TUNA has been shown to have a failiure rate of about 23% after 5 years and is performed on an outpatient basis33,65. TUNA is, however, associated with temporary side-effects, including irritative urinary symptoms and urinary retention33.

Table 4. Ten most frequently reported adverse events in the Medical Therapy ofProstatic Symptoms study treatment arms (reprinted with permission51)

Transurethral microwave thermotherapy (TUMT) employs a microwave antenna that is inserted into the prostate via the urethra, where microwave energy is directed at the prostate and destroys targeted tissue”. TUMT is associated with varying degrees of side-effects and a recovery period following the procedure, during which catheterization may be necessary and side-effects may be considerably more pronounced33.

In a single-arm meta-analysis, TUNA and TUMT had a similar rate of ED as sham-operated controls33. However, patients treated with TUMT have a 16% rate of EjD, compared with 4% of those treated with TUNA and 2% of controls33. In fact, patients treated with TUNA have been reported to experience negligible adverse events related to sexual function66-69. Thus, TUNA may be considered the minimally invasive surgical technique of choice in patients wishing to minimize sexual-related side-effects.

Interstitial laser coagulation (ILC) employs a fiberoptic probe that is inserted into the prostate via a cytoscope. Heat energy from the fiberoptic probe coagulates the targeted prostate tissue in about 3 minutes, after which the device may be moved to target another section of the prostate. While ILC has been widely used in BPH, and is regarded as a viable alternative to surgical intervention, a 2004 Cochrane Review deemed the available data insufficient for comparison with other minimally invasive techniques70.

Transurethral incision of the prostate (TUIP) is usually an outpatient procedure and is performed in patients with smaller prostates. TUIP involves making longitudinal incisions in the prostate and bladder neck to improve urine flow. A case review of 300 patients receiving TUIP (285 with BPH) found a high rate of success in improving urinary flow and relieving symptoms71. One of the advantages of TUIP over TURP, apart from the fact that the procedure requires no removal of prostatic tissue, is a significantly lower rate of retrograde ejaculation seen among TUIP patients, according to randomized prospective trial data72.

A new technique known as photoselective vaporization (PW) of the prostate employs the use of a highpower potassium-titanyl-phosphate laser to precisely ablate the prostate, creating a prostatic cavity similar to that created by standard TURP73. A prospective, non- randomized bi-center trial of 101 patients, 64 undergoing PVP and 37 undergoing TURP, suggested that PVP was as effective as TURP in improving flow rate and reducing IPSS symptom scores74. Additionally, a 3-year multi-center clinical evaluation of 139 patients who underwent PW indicated sustained BPH symptom improvement 3 years after treatment, suggesting the treatment is adequately durable73.

Surgical treatments

Several different surgical interventions are available for the treatment of BPH/LUTS, including TURP. TURP involves the surgical removal of a portion of the prostate via an endoscope through the urethra33. This procedure remains the gold standard of surgical options for the treatment of complications of BPH such as urinary retention and hydronephrosis33. Current treatment guidelines do not regard alternative surgical proced\ures as having any outcome advantage over TURP33. Nevertheless, TURP is a significant surgical procedure requiring a hospital stay and is associated with TURP syndrome, as well as irritative voiding symptoms, sexual dysfunction, bladder neck contracture, the need for blood transfusions, urinary tract infection, and hematuria33,75.

Studies have found that patients treated with TURP for LUTS due to BPH had a sexual performance equivalent to that of patients who chose watchful waiting33,76. This may be due to a negative effect on sexual functioning following treatment with TURP; one study found that nearly 100% of patients treated with this procedure experienced retrograde ejaculation66. Thus, while TURP has an important place among treatment options for BPH, it may not be an entirely satisfactory choice in the context of BPH/LUTS-related sexual dysfunction.

Limitations

The present article is a review of the epidemiologic and pathophysiologic data regarding the relationship between comorbid BPH/LUTS and ED, as well as the hypotheses regarding the etiology of, diagnostic criteria for, and the available treatment options for comorbid LUTS/ED, with special attention being paid to issues of safety and tolerability associated with these treatment options. The key clinical trials relevant to these issues have been reviewed and, where appropriate, reported with the goal of providing practical information for optimizing the management of comorbid LUTS/ED. This article may, however, be seen to be limited by the fact that it is neither a systematic review nor a metaanalysis of the data. That is, this review is confined to an analysis of data identified as central to its goals, but does not attempt to compile or report on all available clinical data in a comprehensive fashion.

Conclusions

LUTS and ED are highly prevalent in men as they age and are frequently observed as comorbid conditions. In fact, the presence of LUTS is associated with an increased risk for ED. Although neither condition is life-threatening, both have a highly significant effect on QoL individually and especially when they occur together. While patients with LUTS are likely to seek medical care when bothersome symptoms arise, many men are reluctant to discuss issues of sexual dysfunction with their physicians. Because of its effect on the lives of its sufferers, its potential as a marker for undiagnosed medical and psychological comorbidities, and its treatable nature, it is important that Healthcare practitioners include questions about ED when evaluating their patients, particularly those over the age of 50.

The treatment of LUTS may improve sexual dysfunction, and so the treatment approach selected for a patient with comorbid LUTS and ED should be one that is most likely to have a beneficial effect on ED and minimizes side-effects that would meaningfully impact sexual health. In addition, treatment of older patients should take into account other comorbidities often seen in this patient population. The risk of vasodilatory adverse events, in particular, should be evaluated when determining which medical therapies are most appropriate.

The use of α^sub 1^-AR antagonists are recommended for the treatment of comorbid LUTS and ED, with 5-ARIs appropriate for monotherapy or in combination with an α1-AR antagonist for men with bothersome LUTS and significantly enlarged prostates (≥ 35 mL). The addition of a PDE-5 inhibitor to ≥^sub 1^-AR antagonist therapy should also be considered as long as the specific drug combination is not associated with adverse hypertensive effects.

Acknowledgment

Declaration of interest: Dr Kaminetsky serves on speakers’ bureaus for Lilly ICOS, Pfizer, GlaxoSmithKline, Sanofi-Aventis, Boehringer Ingelheim, Auxilium, and Astellas. The author wishes to thank Susan DePetris and David Ferreiro of Insight Medical Communications Inc. for advice and review of the manuscript.

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CrossRef links are available in the online published version of this paper: http://www.cmrojoumal.com

Paper CMRO-3505_3, Accepted far publication: 13 October 2006

Published Online: 15 November 2006

doi:10.1185/030079906X154141

Jed C. Kaminetsky

Department of Urology, New York University School of Medicine, New York, NY, USA

Address for correspondence: Jed C. Kaminetsky, MD, Department of Urology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. Tel.: +1 212-686-9015; Fax: +1 212-686- 8607; email: jckammd@att.net

Copyright Librapharm Dec 2006

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