Elsevier

Sexual Medicine Reviews

Volume 5, Issue 1, January 2017, Pages 87-102
Sexual Medicine Reviews

Review
Benign Prostatic Hyperplasia Treatment Options and Their Effects on Sexual Function

https://doi.org/10.1016/j.sxmr.2016.05.006Get rights and content

Abstract

Introduction

The goal of any medical or surgical treatment for benign prostatic hyperplasia (BPH) is to improve quality of life. It is important to consider the sexual side effects of these treatments, which can directly affect quality of life.

Aim

To review the published literature on the sexual side effects of different medical and surgical treatments for BPH.

Methods

A literature review was performed of the various approved medical and surgical treatments for BPH and their respective sexual side effects.

Main Outcome Measures

The main outcome measure was sexual dysfunction associated with different treatments in the form of ejaculatory dysfunction, erectile dysfunction, decreased libido, and sexual dissatisfaction.

Results

The most common side effect for medical and surgical treatments of BPH is ejaculatory dysfunction, although its prevalence after any individual treatment varies greatly. Surgical therapies have a greater relative impact on erectile dysfunction compared with medical therapies; the exact mechanism of this erectile dysfunction has yet to be fully elucidated. The degree of decreased libido and sexual dissatisfaction associated with most treatments is poorly described in the literature and often contradictory.

Conclusion

There are numerous medical and surgical therapies available for treating BPH. Most of these therapies have sexual side effects that can negatively affect a patient's quality of life. It is important for physicians to consider these sexual side effects and to discuss them with their patients before initiating treatment.

Introduction

Benign prostatic hyperplasia (BPH) is common in aging men and is an important cause of lower urinary tract symptoms (LUTS).1 The main goals of medical and surgical treatments of BPH are to alleviate bother symptoms, halt disease progression, and improve overall quality of life (QoL). Increasing attention is being directed to the effects of these various therapies on sexual dysfunction.

Sexual dysfunction, which includes ejaculatory dysfunction (EjD), erectile dysfunction (ED), decreased libido, and sexual dissatisfaction, increases as men age and significantly affects QoL. EjD broadly describes any disturbance of normal ejaculation. EjD includes premature ejaculation, delayed ejaculation, retrograde ejaculation, anejaculation, and painful ejaculation. The link between BPH and EjD has been investigated and the Multinational Survey of the Aging Male study documented that EjD increases significantly with LUTS severity, regardless of a patient's age and comorbidities.2 A review by Becher and McVary3 recognized that although the association between ED and BPH is consistent, it is difficult to establish a causal relation.

The aim of this communication is to review the literature on the sexual side effects of medical and surgical therapies for BPH.

Section snippets

Medical management of BPH and sexual dysfunction

BPH medical management generally includes five broad classes of pharmaceutical agents: α-1-adrenergic receptor blockers (α-blockers), 5-α-reductase inhibitors (5-ARIs), phosphodiesterase type 5 inhibitors (PDE5Is), phytotherapy, and anticholinergics.

With the exception of the more selective silodosin and tamsulosin, α-blockers show low rates of EjD and ED comparable to 5-ARIs. Silodosin and tamsulosin produce notably higher rates of EjD. Combination therapy of α-blocker and 5-ARI is associated

α-1-Adrenergic receptor blockers

The α-blockers are a common first-line pharmacotherapy for BPH and are considered the most effective monotherapy regardless of prostate size.4 The α-blockers induce relaxation of the prostate and bladder neck smooth muscle by blocking adrenergic receptors that modulate tone through endogenously released norepinephrine. The α-blockers induce an American Urological Association (AUA) Symptom Index score decrease of 4.5 to 9 points.5 The predominant receptor subtype, α1a, is localized in the

5-α-Reductase Inhibitors

The 5-ARIs prevent the conversion of testosterone to dihydrotestosterone (DHT) by inhibiting 5-α-reductase enzymes. Type II 5-AR is the dominant isozyme in the prostate and genitalia and DHT is the active androgen metabolite primarily responsible for prostate enlargement.10 Dutasteride, an inhibitor of type I and II isozymes, suppresses serum and intraprostatic DHT significantly more than finasteride, an inhibitor of exclusively type II isozyme.42, 43, 44, 45 Clinical efficacy of the two 5-ARIs

Combination therapy of α-blockers and 5-ARIs

Treatment with combination α-blocker and 5-ARIs is well established and endorsed by all major BPH guidelines for men with moderate to severe symptoms and a higher risk of disease progression.44, 58

Multiple studies have associated combination therapy with more significant side effects.14, 59 A recent meta-analysis of RCTs involving combination therapy found a threefold increase in the risk of EjD compared with either monotherapy, regardless of treatment duration.14 Kaplan et al53 examined the

Phosphodiesterase type 5 inhibitors

The PDEIs work by inhibiting the PDE5 enzyme, causing cyclic guanosine monophosphate concentrations to increase, leading to nitric oxide-mediated detrusor, prostate, and urethra smooth muscle relaxation. PDE5Is include tadalafil, sildenafil, and vardenafil and are first-line ED therapy approved for the treatment of BPH. It has been suggested that the therapeutic effect in ED and BPH might be independent.61, 62 No data have suggested a negative impact on ejaculatory function.

A recent

Phytotherapy

More than 30 phototherapeutic compounds have been described for BPH management, with saw palmetto being the most widely used and studied. Complementary and alternative medical therapy for BPH is currently more prevalent in Europe than in the United States.74 Evidence to support complementary and alternative medical efficacy is limited in most cases and there are many contradictory study results.75, 76, 77, 78, 79 One important barrier to evaluation is lack of standard formulations, leading to

Anticholinergics

Bladder smooth muscle contractions are induced by acetylcholine binding to postsynaptic muscarinic receptors, primarily M3.81 Anticholinergics are commonly used to treat overactive bladder symptoms attributed to detrusor overactivity. Detrusor overactivity, which can be induced by bladder outlet obstruction, has been identified in approximately 50% of men with BPH and up to 90% in men with more severe urinary obstruction. Other anticholinergic medications include tolterodine, flavoxate,

Surgical management of BPH and sexual dysfunction

In the most recent guidelines, the AUA recommends surgical management of BPH for men with renal insufficiency secondary to BPH, recurrent urinary tract infection, gross hematuria owing to BPH and bladder stones, and LUTS refractory to other therapies. Transurethral resection of the prostate (TURP) is recognized as the benchmark surgical procedure, with different alternative technologies also available.

Compared with medical management, surgical management of BPH is associated with much higher

Transurethral resection of the prostate

TURP is an endoscopic procedure that uses a resectoscope outfitted with a wire-loop electrode to remove prostatic tissue impinging on the urethra, thereby relieving outlet obstruction. It is considered the gold standard surgical treatment for BPH. Studies have repeatedly confirmed that TURP is associated with EjD. This can be explained by resection of the bladder neck smooth muscle and prostatic tissue during the procedure.

It has been established that TURP is associated with a 65% rate of EjD

Open prostatectomy

OP has been largely replaced by TURP as the main surgical treatment for BPH. OP is currently recommended for patients with large prostate glands (>80–100 g). Owing to the morbid nature of this surgical procedure, it is expected to cause higher rates of sexual dysfunction.

In a retrospective meta-analysis of 3,304 men treated by OP, TURP, or transurethral incision of the prostate (TUIP), it was observed that OP was associated with the highest rates of sexual dysfunction, and rates of EjD were

Transurethral incision of the prostate

TUIP is a much less aggressive procedure that has been recommended for small prostates (<30 g); it incises through prostate tissue rather than resecting it as in TURP. Lengthwise internal incisions are made in the prostate close to the bladder neck to open the bladder neck and prostate and this subsequently lowers pressure on the urethra. According to the European Urological Association and AUA BPH panel meta-analyses, TUIP was associated with an 18% rate of EjD.98 Of note, TUIP has been shown

Photoselective vaporization of the prostate

Greenlight photoselective vaporization of the prostate (PVP) uses a light wavelength of 532 to 1064 nm, a wavelength preferentially absorbed by hemoglobin, to vaporize prostatic tissue. There is concern that using a higher-energy laser could cause bladder neck damage leading to EjD. Some surgeons prefer to use a lower-wattage setting in the region of the bladder neck.101 Postulated mechanisms for de novo ED include energy dispersion caused by deterioration of the laser fibers and thermal energy

Holmium laser enucleation of the prostate

Considering the damage that occurs to the bladder neck, HoLEP might be expected to incur EjD. Current data appear to support this. According to the AUA BPH guidelines, HoLEP is associated with 59% EjD and 3% ED. As previously noted, the speculation is whether the amount of energy delivered relative to prostate volume removed could affect EF.110, 111

These rates were confirmed in one recent study and EF was not observed to change from baseline.112 Four other RCTs mentioned EjD rates for HoLEP of

Thulium laser enucleation of the prostate

Multiple studies have reported similar rates of EjD for thulium laser enucleation of the prostate (ThuLEP) and TURP. In one randomized prospective trial, EjD was reported in 55% and 65% of ThuLEP and TURP groups, respectively.119 In another retrospective comparison, rates of EjD and decrease in IIEF orgasmic function domain were not significantly different between the ThuLEP and TURP arms.120 Furthermore, a recent meta-analysis of five RCTs comparing ThuLEP with TURP demonstrated similar

Intraprostatic drug injections

Intraprostatic ethanol injection is currently the most widely studied intraprostatic injectable therapy. Multiple studies have repeatedly documented that this technique is associated with significantly lower rates of sexual dysfunction.

In one small prospective study, at 4-year follow-up there were no detectable occurrences of EjD.124 Similar results were noted in four previous studies evaluating a total of 38 men.125, 126, 127, 128 Most recently, a 3-month study also showed no detectable EjD

Prostatic urethral lift

UroLift (NeoTract Inc, Pleasanton, CA, USA) is a non-ablative non-resecting technique that uses sutures deployed transurethrally to mechanically open the prostatic urethral lumen. It has been repeatedly shown to be efficacious for BPH symptom improvement while preserving EF and ejaculatory function. PUL has been suggested to be ideal for the subset of men for whom preservation of EF and ejaculatory function is critical.135, 136

The landmark Luminal Improvement Following Prostatic Tissue

Plasmakinetic enucleation of the prostate

Much like TURP, PKEP can affect EF by thermal damage to the erectile nerves.148 Zhao et al149 conducted a 3-year prospective study comparing PKEP with TURP using the IIEF-5 questionnaire and concluded that EF was comparable at all time points.

In contrast, another recent prospective trial found PKEP to have no negative impact on EF, a 49% incidence of EjD, and a statistically significant decrease in orgasmic function domain scores at 3, 6, and 12 months. Nonetheless, no decrease in overall

High-intensity focused ultrasound

HIFU uses ultrasonic energy that is focused within the prostate to heat the prostatic tissues and induce thermal coagulative necrosis. The limited literature available on the effect of HIFU on sexual function has shown an increased risk of hematospermia. This therapy is not approved by the Food and Drug Administration for BPH or prostate cancer.

Various studies have described rates of EjD and short-term hematospermia after HIFU ranging from 0% to 13.4% and from 13% to 36%, respectively.152, 153,

Transurethral Radiofrequency Needle Ablation

Transurethral radiofrequency needle ablation (TUNA) uses directly applied radiofrequency energy to heat and ablate hyperplastic prostate tissue. Current studies have suggested that although TUNA has higher long-term retreatment rates, it carries a low risk of sexual dysfunction.44

In a meta-analysis of 35 studies of TUNA, 26 non-comparative studies found minimal rates of ED, EjD, and hematospermia. In three comparative studies, rates of ED, EjD, and loss of libido were significantly less after

Prostatic Artery Embolization

Prostatic artery embolization (PAE) uses pelvic angiography to embolize prostatic arteries selectively to achieve vascular stasis. Recent data have shown that PAE could have a role in treating BPH in men with large prostates refractory to other treatment modalities.166, 167 One RCT comparing the efficacy of PAE with TURP in treating BPH found no statistical difference in long-term symptom improvement.168

The impact PAE has on sexual function is not well studied. Current data have suggested PAE

Infertility and BPH

The relation between infertility and BPH is an area of great interest and ongoing research. Inflammation has been implicated in BPH and likely is involved in deterioration of semen quality and formation of antisperm antibodies.176 Interestingly, a recent study by Hoover and Naz177 concluded that BPH does not induce antibodies to spermatozoa, sperm-specific antigens, or seminal plasma components.

There are data suggesting that some BPH therapies contribute to male infertility. One study found

Conclusion

There are a multitude of treatments for LUTS associated with BPH, each with its own sexual side effect profile (Tables 1 and 2).19, 181 The exact mechanism underlying the association between BPH and sexual dysfunction is not yet fully understood and continues to be an area of active research.

When initiating BPH therapy, it is important for physicians to counsel patients about possible adverse sexual events associated with each treatment. Medical management of BPH is associated with lower rates

Statement of authorship

Category 1

  1. (a)

    Conception and Design

    • Faysal Yafi; Wayne Hellstrom

  2. (b)

    Acquisition of Data

    • Igor Voznesensky; Eric Shaw

  3. (c)

    Analysis and Interpretation of Data

    • Igor Voznesensky; Eric Shaw; Kenneth J. DeLay

Category 2
  1. (a)

    Drafting the Article

    • Igor Voznesensky

  2. (b)

    Revising It for Intellectual Content

    • Eric Shaw; Kenneth J. DeLay; Faysal Yafi; Wayne Hellstrom

Category 3
  1. (a)

    Final Approval of the Completed Article

    • Igor Voznesensky; Eric Shaw; Kenneth J. DeLay; Faysal Yafi; Wayne Hellstrom

References (181)

  • S. Leungwattanakij et al.

    Sexuality and management of benign prostatic hyperplasia with alfuzosin: SAMBA Thailand

    J Sex Med

    (2010)
  • P. Narayan et al.

    Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia

    Urology

    (2001)
  • L.S. Marks et al.

    Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month, open-label extension study

    Urology

    (2009)
  • C.R. Chapple et al.

    Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe

    Eur Urol

    (2011)
  • O. Bozkurt et al.

    Silodosin causes impaired ejaculation and enlargement of seminal vesicles in sexually active men treated for lower urinary tract symptoms suggestive of benign prostatic hyperplasia

    Urology

    (2015)
  • K.T. McVary et al.

    Update on AUA guideline on the management of benign prostatic hyperplasia

    J Urol

    (2011)
  • J.L. Tenover et al.

    Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group

    Clin Ther

    (1997)
  • M.J. Marberger

    Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group

    Urology

    (1998)
  • H. Wessells et al.

    Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia

    Urology

    (2003)
  • S.A. Kaplan et al.

    Time course of incident adverse experiences associated with doxazosin, finasteride, and combination therapy in men with benign prostatic hyperplasia: the Medical Therapy of Prostatic Symptoms (MTOPS) trial

    J Urol

    (2016)
  • P.B. Hudson et al.

    Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group

    Urology

    (1999)
  • C.G. Roehrborn et al.

    Efficacy and safety of dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia

    Urology

    (2002)
  • C.G. Roehrborn et al.

    Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia

    Urology

    (2004)
  • M. Oelke et al.

    Eau guidelines on the treatment and follow-up of nonneurogenic male lower urinary tract symptoms including benign prostatic obstruction

    Eur Urol

    (2013)
  • C.G. Roehrborn et al.

    The effects of combination therapy with duatsteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study

    Eur Urol

    (2010)
  • A. Haddad et al.

    Phosphodiesterase type 5 inhibitors for treating erectile dysfunction and lower urinary tract symptoms secondary to benign prostatic hyperplasia: a comprehensive review

    Arab J Urol

    (2015)
  • A. Descazeaud et al.

    [Negative effects on sexual function of medications for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia]

    Prog Urol

    (2015)
  • M. Gacci et al.

    A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia

    Eur Urol

    (2012)
  • M. Oelke et al.

    Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial

    Eur Urol

    (2012)
  • H. Porst et al.

    Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: analyses of pooled data from four randomized, placebo-controlled tadalafil clinical studies

    J Sex Med

    (2013)
  • K.T. McVary et al.

    Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial

    J Urol

    (2007)
  • S.A. Kaplan et al.

    Combination of alfuzosin and sildenafil is superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction

    Eur Urol

    (2007)
  • C.G. Stief et al.

    A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

    Eur Urol

    (2008)
  • H. Helmy et al.

    Vardenafil improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind, placebo-controlled trial

    Eur Urol

    (2009)
  • O. Allkanjari et al.

    What do we know about phytotherapy of benign prostatic hyperplasia?

    Life Sci

    (2015)
  • A.R. Zlotta et al.

    Evaluation of male sexual function in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon1), tamsulosin or finasteride

    Eur Urol

    (2005)
  • C. Gratzke et al.

    EAU guidelines on the assessment of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction

    Eur Urol

    (2015)
  • K.T. McVary

    BPH: epidemiology and comorbidities

    Am J Manag Care

    (2006)
  • C.G. Roehrborn et al.

    Medical therapy options for aging men with benign prostatic hyperplasia: focus on alfuzosin 10 mg once daily

    Clin Interv Aging

    (2008)
  • H. Lepor et al.

    α-Blockers for benign prostatic hyperplasia: the new era

    Curr Opin Urol

    (2012)
  • J.R. Bell et al.

    Update on the sexual impact of treatment for benign prostatic hyperplasia

    Curr Urol Rep

    (2012)
  • F. Giuliano

    Impact of medical treatments for benign prostatic hyperplasia on sexual function

    BJU Int

    (2006)
  • N.I. Osman et al.

    Silodosin: a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia

    Expert Opin Pharmacother

    (2012)
  • A. Sanbe et al.

    α1-Adrenoceptors are required for normal male sexual function

    Br J Pharmacol

    (2007)
  • W.J. Hellstrom et al.

    Effects of alfuzosin and tamsulosin on sperm parameters in healthy men: results of a short-term, randomized, double-blind, placebo-controlled, crossover study

    J Androl

    (2009)
  • A.C.L. Pompeo et al.

    A randomised, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia in Brazil

    Int J Clin Pract

    (2006)
  • R.S. Kirby et al.

    Efficacy of extended-release doxazosin and doxazosin standard in patients with concomitant benign prostatic hyperplasia and sexual dysfunction

    BJU Int

    (2005)
  • K. McKeage et al.

    Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia

    Drugs

    (2002)
  • R.J. van Moorselaar et al.

    Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction

    BJU Int

    (2005)
  • S. Yoon et al.

    Efficacy of long-term daily dosage of alfuzosin 10 mg upon sexual function of benign prostatic hypertrophy patients: two-year prospective observational study

    World J Mens Health

    (2014)

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      We found no credible evidence to suggest that finasteride or dutasteride increases testicular de novo T biosynthesis. In a recent review by Voznesensky et al,64 it was reported that in men with BPH treated with finasteride, the drug-related adverse events profile remained independent of normal physiological T levels, suggesting that finasteride treatment did not produce significant changes in serum T levels. This supports our contention that 5α-RIs do not increase serum T levels.

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    • A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency

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    Conflict of Interest: The author reports no conflicts of interest.

    Funding: None.

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