Effects of Holmium Laser Enucleation of the Prostate on Sexual Function

Introduction

The prevalence and severity of erectile dysfunction (ED) increases progressively with age, as do lower-urinary-tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). ¹ Numerous studies have convincingly demonstrated that the presence of LUTS poses an increased risk for the development of ED, regardless of age, medications, or underlying diseases. ² Further compounding the issue, the treatment for patients with LUTS due to BPH may negatively impact sexual function quality. ³

Holmium laser enucleation of the prostate (HoLEP) is one of the most promising surgical techniques for the relief of bladder outlet obstruction (BOO) caused by BPH. Numerous series and prospective randomized clinical trials have demonstrated the safety and efficacy of HoLEP. ^{4 –8} HoLEP leads to significant and lasting improvements in flow rates and symptoms, but its effects on sexual function have not been extensively studied. ^{9 –12} The objective of this study was to evaluate the effects of HoLEP on sexual function. In particular, we aimed to ascertain how postoperative erection and ejaculation alterations are perceived by patients. Secondarily, we sought to identify whether any clinical factors are involved in erection impairment after HoLEP.

Patients and Methods

All patients who underwent HoLEP by a single, experienced practitioner between 2008 and 2013 were included in this retrospective analysis. Clinical data were captured in prospectively prior to surgery and maintained in a database. Signed informed consent was obtained from all patients. The indications for surgery were refractory urinary retention and LUTS due to BPH. Inclusion criteria for this study were maximal flow rate (Q _max) ≤15 mL/second and/or moderate-to-severe LUTS that did not improve with medical treatment. All included patients were sexually active prior to surgery. Patients with neurogenic bladder, previous prostatic or urethral surgery, urethral stricture, or prostate cancer were excluded. Patients who were not sexually active, whose postoperative follow-ups were <1 year, who did not have complete clinical data, or who were being treated with phosphodiesterase type 5 inhibitors (PDE5i) or testosterone were also excluded. The procedures were performed using a 100-W holmium:YAG laser (Lumenis), following Gilling's technique, with minimal variations. ^13,14

The preoperative work-up included medical history, digital rectal examination, urine culture, prostate volume measurement via transrectal or abdominal ultrasonography, uroflowmetry, postvoid residual urine volume (PRV) measurement, serum determination of testosterone and prostate-specific antigen (PSA), and symptom evaluation. As cardiovascular diseases are a major cause of ED, the preoperative evaluation also included an estimation of the 10-year general cardiovascular disease risk score according to the Framingham study, ¹⁵ as well as the American Society of Anesthesiologists (ASA) classification status. All patients were reassessed 3 and 12 months after surgery.

Symptoms were evaluated using self-administered questionnaires: the five-item version of the International Index of Erectile Function (IIEF-5), the ICIQ-male sexual matters associated with LUTS (ICIQ-MLUTSsex), the American Urological Association symptom score (AUA-SS), and the single-question quality of life (QoL) score. The IIEF-5 is designed to assess the presence and severity of ED, ¹⁶ and the ICIQ-MLUTSsex is used to evaluate sexual matters associated with male LUTS. ¹⁷

To confirm the ability of HoLEP to treat BOO and reduce LUTS, and to examine the influence of HoLEP on sexual function, the preoperative values of Q _max, average flow rate (Q _ave), PRV, AUA-SS, QoL score, IIEF-5, and ICIQ-MLUTSsex were compared with those obtained 3 and 12 months after surgery. The IIEF-5 questionnaire used 3 months after surgery was modified to refer only to the previous month's situation. With the aim of identifying any clinical factors that could be involved in the deterioration of erections after HoLEP, the roles of several clinical variables and perioperative parameters were compared between patients with and without erection impairment. For this study, a change of more than five points in either direction on the IIEF-5 was necessary to indicate improvement or deterioration in erection quality. This cutoff point, which represents 20% of the total questionnaire score, has been used in other studies to ensure that only clinically relevant changes are taken into account. ¹⁸

As most variables did not follow a normal distribution, the continuous variables are presented as median value [interquartile range], the categorical variables are expressed as absolute numbers and percentages, and nonparametric tests were used. The Wilcoxon signed-rank test for related samples was used to assess variations in the studied parameters over time. A marginal homogeneity test was used to assess equality between the proportions of patients with ejaculatory or ED at follow-up. The Mann–Whitney U test, Fisher's exact test, or chi-squared tests were used to identify risk factors associated with the deterioration of erection following HoLEP. Bonferroni's correction was used in multiple comparisons. p-Values<0.05 were considered to be statistically significant. Statistical analysis was performed using IBM^® SPSS^® Statistics v20.

Results

A total of 419 patients underwent HoLEP during the study period; only 275 had completed the preoperative and postoperative questionnaires and met the inclusion criteria. Seventy-three of those patients had no sexual activity before surgery (IIEF-5<5). As 80.8% of such patients remained without sexual activity 1 year after surgery, we excluded them from analysis, leaving 202 evaluable patients. The small amount of missing data was irrelevant. Median patient age was 66.7 years [61.9–71.3]. Median prostate volume was 84.4 cm³ [63.6–107.2], and the median weight of the enucleated adenoma was 57.2 g [35.2–81.9]. Prior to surgery, 187/202 patients (92.6%) were taking α-adrenergic blockers and 84/202 (41.6%) 5α-reductase inhibitors. About 46/202 patients (22.8%) had an indwelling catheter before surgery. At the time of surgery, 41/202 patients (20.3%) had diabetes mellitus, 124/197 (62.9%) had hypertension, and 108/196 (55.1%) were taking drugs with known adverse effects on erection (antihypertensives, diuretics, β-blockers, antidepressants, antipsychotics, antihistamines, etc.). ASA status was class I in 22 patients, class II in 154, class III in 23, class IV in 2, and unknown in one. The median Framingham general cardiovascular disease risk scores were 29.3% [21.2–36.6] using lipids and 36.9% [26.8–43.7] using body mass index.

There was an improvement in the scores of the questionnaires assessing LUTS and QoL after the patients underwent HoLEP (Table 1). There was also an improvement in flow rates, a reduction in PRV, and a decrease in PSA levels. All changes observed were statistically significant and were maintained or further improved throughout follow-up. There were no significant differences between the preoperative and postoperative scores on the questionnaires that evaluated erection quality or between the proportions of patients with varying degrees of ED (Tables 2 and 3). Nevertheless, 12 months after HoLEP, 6.9% (14/202) of the patients reported improvement in erection quality, and 12.4% (25/202) reported deterioration. The greatest loss of erectile function after surgery, and the only significant one, was seen in the subgroup without preoperative ED (IIEF-5>21). Deterioration in erectile function in this subgroup occurred in 12.8% (5/39) of patients 12 months after surgery. In patients with preoperative ED (IIEF-5 5–21), postoperative deterioration was lower and nonsignificant. All of the IIEF-5 questions contributed similarly to the changes in the questionnaire scores observed after surgery.

An analysis of the factors that might be involved in erection deterioration after surgery was conducted, but no significant differences were found between patients in whom erection quality worsened 12 months after surgery and those in whom erection quality remained unchanged or improved (Table 4). Thus, erection deterioration after surgery was not associated with differences in the baseline characteristics of the patients, the surgery, or the postoperative outcome. Despite these findings, the importance that the patients attached to their erection problems diminished with surgery.

The majority of the patients (80%; 156/195) experienced near complete or complete lack of ejaculation after surgery. One year after surgery, ejaculation was present in normal amounts in 16.7% (8/48) of patients who had normal ejaculation before surgery and in 6.3% (9/142) of those in whom ejaculation was previously absent or in whom the amount was diminished. The presence of ejaculation in normal amounts after surgery was not related to patient age, prostate volume, or enucleated tissue weight. However, the number of patients with pain during ejaculation also decreased with surgery, from 52/198 (26.3%) before surgery to 17/195 (8.7%) 1 year after surgery. Similarly, the importance represented by ejaculatory dysfunction and the influence of LUTS on sexual activity declined after surgery.

Discussion

Many surgical techniques have recently been developed for the surgical relief of BPH. While most of these procedures are associated with less morbidity than conventional surgery, their effectiveness is under debate. In contrast, several series and prospective randomized studies have proven the safety and clinical efficacy of HoLEP, leading many to suggest that this procedure should be considered the new gold standard. HoLEP achieves an immediate disappearance of BOO, with fewer complications than traditional surgery. ^{4 –8} Although HoLEP produces a significant and sustained improvement in flow rates and symptom scores, its effects on sexual function have not been well documented thus far.

In a prospective randomized study of 120 patients comparing HoLEP with transurethral resection of the prostate (TURP), no significant differences in IIEF questionnaire scores were observed over the first 2 years of follow-up. ⁹ However, more than 75% of patients had no ejaculation post-HoLEP, and over 15% experienced a reduction in ejaculatory volume; only 3.3% of the patients complained of transient pain or discomfort during ejaculation. No changes were reported in erectile function, satisfaction with intercourse, sexual desire, or overall satisfaction.

Another study, which investigated 108 patients, reported no differences in Danish Prostate Symptom Score Sexual Function questionnaire scores 6 months after HoLEP. ¹⁰ Although the percentage of patients with retrograde ejaculation or early morning erections increased after surgery, no differences were observed in the number of patients with ED or those who were satisfied with their sex life, libido, erection, or orgasm. A third study, involving 75 patients, confirmed that the average IIEF-5 questionnaire score remained unchanged 1, 3, and 12 months after undergoing HoLEP. ¹¹ However, 13% of the patients experienced an improvement in erections, while 20% had a transient or permanent worsening of erections after surgery.

A recent prospective study that included 191 patients compared changes in sexual function after HoLEP, holmium laser ablation of the prostate, and photoselective vaporization of the prostate (PVP) using a GreenLight laser. ¹² The results showed a significant improvement in the total scores of the IIEF questionnaire and all its subdomains after HoLEP. In that study, only 17.2% of the patients reported a decrease in erection quality after HoLEP, whereas 60.2% reported an improvement. The risk of erection deterioration was greater in patients with smaller prostates, higher preoperative IIEF scores, preoperative IIEF score >55, or a higher ratio of laser energy to prostate size. Similar to other studies, the majority of patients (77.3%) reported postoperative retrograde ejaculation. Apart from these studies, the evidence that exists is limited and comes from a few studies that included a small number of patients or used nonvalidated instruments. ^7,8

The scarcity of studies aimed at analyzing the influence of HoLEP on sexual function prompted us to perform this study. We excluded all patients who had taken PDE5i at some point during the study period to avoid the confounding effect that it might cause. We initially investigated the patients' baseline situations and realized that the vast majority had ED. Only 19.3% of the patients reported normal erections during the 6 months prior to surgery, with 27.8% reporting moderate-to-severe ED. These findings are similar to those of other studies, which included patients who underwent TURP or laser vaporization of the prostate. ^{19 –22} The reasons are diverse and include, among others, aging, medication, smoking, diabetes mellitus, cardiovascular diseases, hypertension, dyslipidemia, late-onset hypogonadism, and psychological factors. ² In our study, 27.7% of the patients were over 70 years of age, 20.3% had diabetes mellitus, 34.2% presented low total testosterone levels (<350 mg/dL), 12.4% had high ASA scores, and 55.1% had been treated with drugs that affected erection.

We used specific questionnaires in order to determine whether erectile function, as determined by the patient, was somehow altered with surgery. We did not find any significant differences in the scores of the questions assessing erection quality or in the distribution of patients according to the IIEF-5 grading system. Despite this, 12.4% of the patients did report a decline in erection quality, while 6.9% reported an improvement. The greatest decline in IIEF-5 questionnaire scores, and the only one in which erection deterioration was significant, was in the subgroup of patients without preoperative ED (12.8%). These findings prompted us to conduct an analysis of the clinical and surgical factors that might be involved in the worsening of erections after HoLEP. However, we were not able to identify any factors associated with erection impairment after surgery. In fact, age, presence of diabetes mellitus, capsular perforation, and amount of laser energy applied were not associated with the risk of erection impairment. Interestingly, the importance that the patients placed upon their erection problems diminished after surgery.

The most widely accepted theory to explain the erection impairment that sometimes presents after TURP is chemical or thermal injury to the neurovascular bundles. Although rare, this adverse effect is more frequent among patients with preexisting ED, advanced age, diabetes mellitus, small-sized prostate, hypertension, or cardiovascular disease, or when there is profuse hemorrhage or capsular perforation. ^19,23,24 Nevertheless, most studies that used validated tools did not observe a decrease in erection quality following TURP. ^21,22 It has therefore been postulated that the major contributor involves psychological factors experienced after surgery. In fact, it has been suggested that the anxiety associated with TURP, the presence of pain or bothersome symptoms, complications, and the confounding effect generated by the loss of ejaculation might contribute to the perception that erection quality was diminished by the surgery. ^25,26 This concern is further compounded if patients have not been properly informed about the possible side effects of the surgery prior to undergoing TURP. ²⁶

In the case of PVP with GreenLight laser, recent studies have reported a postoperative reduction in erection quality in patients with preoperative IIEF-5 scores ≥19. ^20,27 However, the reasons for these changes are unknown. In our study, we examined a set of variables that might be related with erection impairment, but none of those factors was associated with that risk. We did not find any relationship between erection impairment and the amount or density of laser energy applied, previous use of a urethral catheter, prostate size, or patient age. Similarly, erection worsening was not associated with the development of complications, degree of ejaculatory dysfunction, or changes experienced in LUTS. Moreover, the “much-feared” capsular perforation that can occur during HoLEP had no negative effect on erection.

As expected, erection quality was not altered in the majority of our patients. It is unlikely, given its properties, that holmium laser energy could damage nerves traveling just beneath the prostatic capsule; various features of HoLEP support this supposition. The holmium laser operates in ultrapulsed mode and has a narrow (0.4 mm) optical penetration depth. ²⁸ In the human prostate, it causes a rim of coagulated tissue (1000–2000 μm) ²⁹ that is smaller than the thickness of the pseudocapsule. ³⁰ During HoLEP, a large part of the dissection is mechanical, and the laser is usually reserved for coagulating blood vessels. Further, dissection of the apical lobes is performed by reducing laser energy to prevent the transmission of heat to the external sphincter and neurovascular bundles. There is also no risk of chemical neuropraxia, as HoLEP is performed with saline instead of glycine as an irrigation fluid.

Not surprisingly, complete enucleation of the prostatic adenoma led to more than 70% of the patients having no semen ejaculation and to a reduction in the amount of ejaculate in 21%. Because only 24.9% of the patients had normal semen quantities before surgery, the postoperative reduction in semen was less significant. Although the majority of the patients in the study group experienced a change in semen, the patients seemed less concerned by the change after surgery compared with prior to surgery. Similarly, both the presence of pain or discomfort during ejaculation and the worry associated with it decreased after surgery. Finally, the study results demonstrated that the interference of LUTS on the patient's sex life diminished with surgery.

Limitations of our study include its retrospective design, the lack of control over psychological factors, and the lack of assessment by the partner. Unfortunately, there is no way of knowing whether the deterioration in erectile function that some patients reported was real, as we did not use objective tools to assess erection quality, such as vascular or neurophysiologic tests. Despite this limitation, the results show that erections can be altered after surgery in a small percentage of patients. Although the percentage may be overestimated, as only sexually active patients were included in the study, we should not forget to counsel patients prior to surgery regarding the risks of negative changes in sexual function.

Conclusions

In summary, our results confirm that erection quality is not significantly impaired after HoLEP. Although 19% of the patients showed either improvement or deterioration in erectile function, it was not altered at all in the vast majority of the patients. However, in patients without preoperative ED, there was a statistically significant deterioration in the quality of the erection. In fact, 12.8% of them reported some degree of ED 1 year after surgery. Interestingly, patient concerns regarding ED and ejaculatory abnormalities diminished with HoLEP.