The effects of microsurgical varicocelectomy performed for infertility on premature ejaculation

The effects of microsurgical varicocelectomy performed for infertility on premature ejaculation

Yalcin Kizilkan1 · Mesut Berkan Duran2 · Mehmet Vehbi Kayra3 · Bahadir Sahin4 · Serdar Toksoz5 ·

Mehmet Hamza Gultekin6 · Omer Yildirim7 · Murat Gul8 · Nebil Akdogan9 · Kagan Turker Akbaba10 · Iyimser Ure11 ·

Eray Hasirci12 · Oguzhan Kahraman13 · Erman Ceyhan12 · Abdulmecit Yavuz14 · Ugur Akgun15 · Onder Cinar16 ·

Umit Gul17 · Hasan Deliktas18 · Hamdi Ozkara6 · Tahsin Turunc19

Received: 11 November 2024 / Accepted: 17 December 2024 / Published online: 21 December 2024

© The Author(s), under exclusive licence to Springer Nature B.V. 2024

Abstract

Purpose To investigate the effects of varicocelectomy on premature ejaculation (PE) in patients with varicocele and infertility. Methods A total of 82 sexually active patients aged 18 years or over who had undergone microscopic subinguinal varicocelectomy with a clinical diagnosis of varicocele in 14 urology clinics between October 2021 and March 2023 with primary infertility were evaluated prospectively Patients were evaluated using the Turkish validated form of the ‘Premature Ejaculation Diagnostic Tool’ (PEDT) scale. A PEDT score of 11 or above was taken to indicate the presence of PE. Turkish validated forms of PEDT and International Index of Erectile Function-5 (IIEF-5) were completed in all patients pre-operatively and at 3 and 6 months post-operatively. Intravaginal ejaculatory latency time (IELT) and serum testosterone measurements were also recorded. Results Left varicocelectomy was performed in 70.7% and bilateral varicocelectomy in 29.3% of the participants. A significant difference was found between pre- and post-operative PEDT scores (× 2 (2) = 130.1, p < 0.001). A significant difference was observed between pre- and post-operative IELT time (× 2 (2) = 143.2, p < 0.001). IIEF-5 scores differed before and after surgery (× 2 (2) = 59.5, p < 0.001). A difference was found between the testosterone levels measured before and after surgery (× 2 (2) = 40.9, p < 0.001). No statistically significant difference was observed between the third- and sixth-month testosterone values (p = 0.183). Testosterone levels (p = 0.001) and IELT scores (p < 0.001) were significantly higher, while

PEDT scores (p < 0.001) were significantly lower in the bilateral varicocelectomy group at the sixth post-operative month. Conclusion In light of our findings, it is recommended that infertile patients with varicocele be informed of the positive effects of varicocelectomy on PE.

Keywords Erection ・ Infertility ・ Premature ejaculation ・ Varicocelectomy

Introduction

Varicocele represents the most common cause of reversible male infertility. It is characterised by dilatation of the plexus pampiniformis, which drains the testis, and may lead to impaired spermatogenesis. The prevalence of this condition is estimated to be between 15 and 20% in the general population and 35% in males with primary infertility. Premature ejaculation (PE) is the most prevalent sexual dysfunction among men, affecting approximately 20–30% of sexually active individuals. Inflammatory diseases of the prostate, pelvic nerve injury, urogenital malformations, erectile dysfunction (ED), hyperthyroidism, circumcision, monosymptomatic enuresis, use of some medications including pseudoephedrine, and varicocele may contribute to PE. The relationship between varicocele and PE is a complex

one, and the precise nature of the link remains unclear. It has been reported that the local increase in temperature/ stimulus in the genital area and hormonal changes in the hypothalamic-pituitary–gonadal axis caused by varicocele may be involved in PE formation. Despite the abundance of research examining the high prevalence of PE in patients with varicocele, there is a paucity of studies investigating the impact of varicocelectomy on PE. To the best of our knowledge, only five studies have explored this topic.

This study aimed to investigate the effects of varicocelectomy on PE in patients with varicocele and infertility. Currently, this is the sixth study in the literature to address

this topic.

Materials and methods

This multicentre and prospective study was prepared following of the principles of the Declaration of Helsinki and approved by the Ankara Bilkent City Hospital Ethics Committee

(approval number: E1-20-1074). Written informed constants were obtained from each patient. Forms and data about the patients were recorded and archived in a way that 3rd parties can not access them. The study population comprised sexually active patients aged 18 years or over. Patients who had undergone microscopic subinguinal varicocelectomy with a clinical diagnosis of varicocele in 14 urology clinics between October 2021 and March 2023 with primary infertility were evaluated prospectively. Patients were evaluated using the Turkish validated form of the ‘Premature Ejaculation Diagnostic Tool’ (PEDT) scale [10]. A PEDT score of 11 or above was taken to indicate the presence of PE. All patients included in the study exhibited clinical varicocele and at least one sperm parameter abnormality. Impaired sperm parameters were confirmed by at least two spermiograms. Turkish validated forms of PEDT and International Index of Erectile Function-5 (IIEF-5) were completed in all patients pre-operatively and at 3 and 6 months post-operatively [11]. Intravaginal ejaculatory latency time (IELT) and serum testosterone measurements were also recorded. Exclusion criteria included a PEDT score of less than 11, sexually inactive patients younger than 18 years, non-microscopic varicocelectomy, surgery for reasons other than infertility, hyperprolactinaemia, thyroid dysfunction, hypogonadotropic hypogonadism, 3 months prior antidepressant use, oral, topical or behavioural treatment for PE, external genital malformation or recurrent varicocele, urological infection and history of pelvic surgery, and these patients were excluded from the study accordingly. All surgeons had performed at least 50 subinguinal microscopic varicocelectomy procedures before starting the study. The standard microsurgical subinguinal approach was applied to all patients. Briefly, a 2-cm horizontal incision was made 1 cm below the external inguinal ring, the overlaying opening the spermatic fascia, all of the identified arteries were counted and dissected free from the adjacent veins and lymphatics. The internal spermatic veins were counted and separated, ligated and divided. All of the identified lymphatics and arteries were carefully preserved.

Statistical analysis

 Data were analysed using SPSS version 22. Quantitative data were analysed descriptively (median-min–max). Frequencies and percentages were calculated for categorical and nominal data. Data were tested for normality using the Shapiro–Wilk test and Kolmogorov–Smirnov test. The Mann–Whitney U test was used to compare the two independent groups for testosterone levels, PEDT, IELT, and IIEF-5 scores. Friedman's repeated measures test was used to compare variables within groups in testosterone levels, PEDT, IELT, and IIEF-5 scores. The Wilcoxon test was performed to test the significance of pairwise differences using Bonferroni correction to adjust for multiple comparisons. A p-value ≤ 0.05

was considered significant.

Results

 A total of 82 patients were included in the study, with a median age of 31 (21–42) years. Left varicocelectomy was performed in 70.7% and bilateral varicocelectomy in 29.3% of the participants. The demographic and clinical characteristics of the patients enrolled in the study are shown in. A significant difference was found between pre- and postoperative PEDT scores (× 2 (2) = 130.1, p < 0.001). While the median PEDT score pre-operatively was 14 (11–18),

the PEDT score at 3 months post-operatively was 10 (7–15) (p < 0.001) and at 6 months 10.5 (7–13) (p < 0.001). A significant difference was observed between pre- and postoperative IELT time (× 2 (2) = 143.2, p < 0.001). While the median IELT time prior to surgery was 50 (40–110) seconds, it increased to 90 (45–180) seconds at 3 months postoperatively (p < 0.001) and to 120 (15–300) seconds at 6 months (p < 0.001). IIEF-5 scores differed before and after surgery (× 2 (2) = 59.5, p < 0.001). While the median IIEF-5 score pre-operatively was 20 (15–24), the IIEF-5 score at 3 months post-operatively was 22 (15–24) (p = 0.02) and at 6 months 22 (17–24) (p < 0.001). A difference was found between the testosterone levels measured before and after surgery (× 2 (2) = 40.9, p < 0.001). While the median testosterone

level was 422 ng/dl (43–599) pre-operatively, it increased to 476 ng/dl (319–781) at 3 months post-operatively (p < 0.001) and to 500 ng/dl (420–925) at 6 months (p < 0.001). No statistically significant difference was observed between the third- and sixth-month testosterone values (p = 0.183). When fascia was opened, exposing the spermatic cord, which

subsequently was grasped with a pusher and surrounded by a Penrose drain. Operating microscope with 8–15 magnification was brought into the operative field. After the internal spermatic cord was grasped, the vas deferens, vasal veins, and arteries were identified and preserved. All identifiable external spermatic veins were then ligated and divided. After the subgroups were examined, in the left varicocelectomy group; there were significant differences between the preoperative values and the postoperative 3rd and 6th month values

for testosterone, PEDT, IELT, IIEF. While there was no significant difference between the values of the postoperative 3rd and 6th months except IIEF scores. In patients with bilateral varicocelectomy, there were significant differences between the preoperative values and the postoperative 3rd and 6th month in all four parameters except preoperative and 3rd month testosterone levels. Moreover, there were significant differences between postoperative 3rd

and 6th month in all parameters. The clinical changes in the pre-operative and post-operative periods are presented in Table 2. The pre- and post-operative variables of the bilateral varicocelectomy and left varicocelectomy groups at three and six months are presented in Table 3. Testosterone levels (p = 0.001) and IELT scores (p < 0.001) were significantly higher, while PEDT scores (p < 0.001) were significantly lower in the bilateral varicocelectomy group at the sixth post-operative month. Discussion The objective of this study was to analyse the effects of varicocelectomy on PE in patients who were evaluated for infertility and diagnosed with varicocele and also had PE. The findings of this study revealed significant implications for the field. The first notable outcome is the significant improvement in PEDT score and IELT at three and six months post-operatively. Secondly, and more interestingly,patients with bilateral varicocele (grade 2–3) and PE demonstrate a significantly greater improvement in PEDT score, IELT time at the six-month mark following varicocelectomy than patients who underwent only left varicocelectomy. To the best of our knowledge, this is the sixth study in the existing literature to investigate the effects of varicocelectomy on PE. Although previous studies have demonstrated a significant association between PE and varicocele, the underlying mechanism remains complex and poorly understood. The first study examining the relationship between varicocele and PE in patients with sexual dysfunction was reported by Lotti et al. in 2009. It was proposed that varicocele, associated with venous abnormalities, could lead to pelvic congestion through an increase in the diameter of the prostatic venous plexus and venous reflux into the prostatic plexus. The presence of pelvic congestion has been suggested to predispose individuals to prostatitis and cause changes in the ejaculatory reflex, thereby contributing to the development of PE.It has been suggested that an increase in local temperature and hormonal changes in the genital area of a varicocele may be a contributing factor in the PE formation. The underlying causes of PE were initially presumed to be rooted in psychological factors for an extended period. The majority of the conditions that have been considered in the context of aetiology are not evidence-based. The psychological theories that have been proposed to explain sexual behaviour include early sexual experience, anxiety, sexual technique and frequency of sexual activity . The underlying psychological premise posits that heightened sympathetic nervous system activation with anxiety results in earlier emission and ejaculation. In studies examining the relationship with anxiety, it was observed that the prevalence of PE was higher. The organic theories encompass penile hypersensitivity, hyperexcitability of the ejaculatory reflex (rapid emission and rapid expulsion phase, increased bulbocavernosus reflex), genetic predisposition (more prevalent in first-degree relatives) and central 5-HT receptor sensitivity (potentially diminished 5-HT neurotransmission, 5-HT2C receptor hypo-sensitivity and/or 5-HT1A receptor hypersensitivity). Due to the progressive nature of varicocele, in addition to its negative effects on spermatogenesis, dysfunction in Leydig cells, decreased androgen production, and testicular volume loss can be observed. Increasing evidence has shown that dysfunction in Leydig cells may lead to disruptions in the hypothalamic-pituitary–gonadal axis. Reduced testosterone levels can lead to ED. Furthermore, it has been reported that surgical repair of varicocele can result in an increase in testosterone levels and testicular volume. Saylam et al. performed microscopic varicocelectomy on 202 hypogonadal varicocele patients and found significant increases in IIEF scores and testosterone levels. They also reported that 52% of the patients had their testosterone levels return to the normal range, transitioning out of the hypogonadal state. It has been suggested that the relationship between varicocele and ED may also be due to factors other than testosterone. In a study by Liu et al., it was reported that treating varicocele and associated pain with Transcutaneous Neuromuscular Electrical Stimulation resulted in improvements in both PE and ED. This supports the Notion that the relationship between varicocele and ED is not solely dependent on testosterone levels.

The initial study to investigate the correlation between varicocelectomy and PE was conducted by Li et al. which assessed the effects of spermatic vein ligation and IELT. In this study, which included eighty-one patients, the subjects were divided into two groups based on their IELT times, with the groups comprising those with IELT times below and above 2 min, respectively. It was observed that the IELT time increased significantly in both groups following varicocelectomy. The authors also reported that improved VAS is negatively correlated with prolonged IELT. The present study revealed that the IELT time was significantly higher in both the third and sixth months post-operatively than pre-operatively. Additionally, patients were evaluated for PE during follow-ups using PEDT score in addition to IELT time. Unlike this study, VAS scores were not assessed in our study. In the other study by Ahmed et al., patients with PE who had varicocele were divided into two groups: those who underwent microscopic varicocelectomy and those who did not want or could not be operated on for any reason, who were designated as the control group. The group that had undergone varicocelectomy demonstrated a statistically significant reduction in PEDT scores, an increase in testosterone levels and a statistically significant improvement in IIEF-5 scores. Additionally, an increase in testicular volume was observed; however, this difference was not statistically significant. The results of our study indicate a reduction in the PEDT score, an increase in IELT time, and a significant increase in testosterone and IIEF-5 scores following varicocelectomy. Nevertheless, it should be noted that the effect of the operation on testicular volume was not analysed in this study. In light of the findings of another study, the authors suggested that high-grade varicocele may be a potential intervention for improving spermiogram parameters and for treating PE in cases where medical treatment has remained ineffective. We also believe that varicocelectomy may benefit varicocele patients with PE; however, we think that there is not yet sufficient evidence to justify performing varicocelectomy solely for the indication of PE and there is a need for further research on this topic. Noting that dopamine is an important regulator of male sexual health and behaviour, Hosseini et al. measured 24-h urinary dopamine levels in PE patients with high-grade varicocele. It was reported that urinary dopamine levels doubled in the first month after varicocelectomy, but no significant difference was found at the time of the IELT. The authors

reported that this may be related to the short-term results of the study (1 month). The most recent study in the literature was conducted in 2020 and comprised a cohort of patients who had undergone bilateral varicocelectomy. In the sixth month following varicocelectomy, a significant improvement in PEDT score and IELT time was observed, in accordance with the results of our study. However, in contrast to our findings, a significantly higher increase in testicular volume and satisfaction score was noted. Our study included patients with both unilateral and bilateral varicocele. Patients who underwent bilateral varicocelectomy showed significantly greater improvements in IELT time, PEDT score, and testosterone levels at the 6-month postoperative follow-up compared to those who underwent unilateral varicocelectomy. The secondary outcome of the study was an increase in testosterone levels and IIEF-5 scores in patients who had undergone varicocelectomy. It is established that varicocele is associated with Leydig cell dysfunction and related hypogonadism. In a study of 141 patients, Zohdy et al. reported that 75% of those who had undergone varicocelectomy and were hypogonadic reached normal testosterone levels. Furthermore, a significant increase in IIEF-5 scores was observed in the cohort with hypogonadism . In our study, postoperative testosterone level and IIEF-5 scores increased significantly. Additionally, testosterone levels

were observed to be significantly greater in patients who underwent bilateral varicocelectomy compared to those who received unilateral varicocelectomy at the sixth postoperative month. As the preoperative testosterone levels and IIEF-5 scores of nearly all patients included in the study were within normal limits, we can not conclude that varicocelectomy has positive effects on erection and testosterone levels. The limitations of the study comprise the estimated duration of IELT, the fact that the operations were performed by different surgeons, the insufficient number of patients enrolled in the study, and the absence of questioning about partner satisfaction.

 Conclusion

In consideration of the data obtained from our study, varicocelectomy in patients presenting with PE and varicocele stands to significantly improve PE. Additionally, significant increases in testosterone levels and IIEF-5 scores can be considered secondary gains. It is recommended that infertile patients with varicocele be informed of the positive effects of varicocelectomy on PE. A larger, randomized controlled trial series is required in this regard. Author contributions Y.K., M.B.D., and B.S. conceptualized the study and designed the research. S.T. and M.H.G. were responsible for data collection. O.Y., M.G., and N.A. performed the statistical analysis, while K.T.A. and I.U. interpreted the results. E.H., O.K., and E.C. contributed to drafting the manuscript. M.V.K., A.Y., and U.A. prepared tables and figures. O.C., U.G., and H.D. reviewed the manuscript critically for important intellectual content. H.O. and T.T. supervised the research process and provided final approval of the manuscript. All authors reviewed and approved the final version and agree to be accountable for all aspects of the work. Data availability No datasets were generated or analysed during the current study.

Declarations

Conflict of interest The authors declare no competing interests.

Authors and Affiliations

Yalcin Kizilkan1 · Mesut Berkan Duran2 · Mehmet Vehbi Kayra3 · Bahadir Sahin4 · Serdar Toksoz5 · Mehmet Hamza Gultekin6 · Omer Yildirim7 · Murat Gul8 · Nebil Akdogan9 · Kagan Turker Akbaba10 · Iyimser Ure11 · Eray Hasirci12 · Oguzhan Kahraman13 · Erman Ceyhan12 · Abdulmecit Yavuz14 · Ugur Akgun15 · Onder Cinar16 · Umit Gul17 · Hasan Deliktas18 · Hamdi Ozkara6 · Tahsin Turunc19

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