ReviewBenign Prostatic Hyperplasia Treatment Options and Their Effects on Sexual Function
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 Conception and Design Faysal Yafi; Wayne Hellstrom
Acquisition of Data
Igor Voznesensky; Eric Shaw
Analysis and Interpretation of Data
Igor Voznesensky; Eric Shaw; Kenneth J. DeLay
- (a)
Drafting the Article
Igor Voznesensky
- (b)
Revising It for Intellectual Content
Eric Shaw; Kenneth J. DeLay; Faysal Yafi; Wayne Hellstrom
- (a)
Final Approval of the Completed Article
Igor Voznesensky; Eric Shaw; Kenneth J. DeLay; Faysal Yafi; Wayne Hellstrom
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Prostatic Artery Embolization and Sexual Function: Literature Review and Comparison to Other Urologic Interventions
2020, Techniques in Vascular and Interventional RadiologyCitation Excerpt :Because of the complex pelvic vasculature, nontarget embolization to the penis may increase the risk of developing ED 7. Conversely, because of symptom reduction after PAE, discontinuation of medications or catheter liberation may contribute to the IIEF improvements.13,14 In the meta-analysis by Uflacker et al, none of the evaluated studies found an association between PAE and ED.15
Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results
2019, Sexual Medicine ReviewsCitation Excerpt :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.
Comparing Sexual Dysfunction Following Open Prostatectomy and Transurethral Resection of the Prostate
2022, Journal of Mazandaran University of Medical Sciences
Conflict of Interest: The author reports no conflicts of interest.
Funding: None.