Microsurgical Subinguinal Varicocele Repair of Grade II-III Lesions Associated with Improvements of Testosterone Levels

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1 Original Paer DOI: / Received: Setember 1, 2015 Acceted: February 9, 2016 Published online: March 30, 201 Microsurgical Subinguinal Varicocele Reair of Grade II-III Lesions Associated with Imrovements of Testosterone Levels Saad Elzanaty a,c Claus Johansen b a,c Deartment of Translational Medicine, Division of Urological Research, Skåne University Hosital, Lund University, Malmö; b Deartment of Radiology, Ystad Hosital, Ystad, Sweden Key Words Hyogonadism Microsurgery Varicocele reair Testosterone Abstract Introduction: The results of reorts on the association between varicocele reair and testosterone levels were conflicting. The aim of the resent study is, therefore, to investigate the imact of varicocele reair on testosterone levels. Materials and Methods: The study is based on 20 men who exerienced microsurgical subinguinal varicoceles reair because of chronic dull scrotal ain. All hormonal rofiles available in the clinical records were reviewed. Follow-u evaluation was done at 1 and 12 months after surgery. Men were classified into grous based on the reoerative testosterone levels: euogonadal (serum levels of testosterone > 12 nmol/l), hyogonadal men (serum levels of testosterone 12 nmol/l). Results: Microsurgical subinguinal varicocele reair was associated with a significant imrovements of testosterone levels at 1 and 12 months after surgery as comared to the reoerative levels ( nmol/l vs. 18 nmol/l, = 0.03; nmol/l vs. 15 nmol/l, = ). The same trend was seen in men who were classified as being hyogonadal (.0 nmol/l vs. 15 nmol/l, = ;.0 nmol/l vs. 10 nmol/l, = 0.02). No significant imrovements in testosterone levels were observed in euogonadal men ( > 0.05). Conclusion: Microsurgical subinguinal varicocele reair was associated with a significant imrovements of testosterone levels in men with grade II III lesions and low reoerative testosterone values. Coyright 2016 S. Karger AG, Basel Introduction Varicocele defined as dilatation of the aminiform lexus of veins surrounding the testis is observed in % of the general male oulation, in % of the infertile men [1], and in 2 14 % of men with scrotal ain [2, 3]. Several studies have reorted significant imrovements in semen quality and regnancy rate [4, 5], and scrotal ain [6 8] following reair of clinical varicoceles. The association between clinical varicocele and hyogonadism has been acceted, although the exact athogohysiology of the rocess remains uncertain. However, the rimary hyotheses involved hyerthermia, venous ressure, toxin substances, and aotosis [9 12]. Moreover, the results of reorts on the association between varicocele reair and testosterone levels were conflicting, indicating no association [ 16] or a ositive association [1 21]. This contradictory could be attributed Fax karger@karger.ch S. Karger AG, Basel Accessible online at: Saad Elzanaty Deartment of Translational Medicine Division of Urological Research, Skåne University Hosital Jan Waldenströms Gata Malmö (Sweden) saad.elzanaty@med.lu.se

2 Table 1. Descritive statistics of the study oulation Number of atients Age (years) Testicular volume (ml) Left Right Varicocele grade I II III Varicocele laterality Unilateral Left Right Bilateral to the different methods of classification of men based on their reoerative testosterone levels among different studies. Many studies that failed to demonstrate a ositive association between varicocele reair and testosterone levels did not characterize atients with low reoerative testosterone levels. The aim of the resent study is to investigate the imact of microsurgical varicocele reair on testosterone levels based on data from 20 men who had the microsurgical subinguinal varicoceles reair because of chronic dull scrotal ain. All hormonal rofiles available in the clinical records were reviewed. Materials and Methods Value (18 66) 19 (15 25) 21 (18 25) 0 (0%) 8 (40%) 12 (60%) 20 (100%) 19 (95%) 1 (5.0%) 0 (0%) The resent study was based on 20 men who had the microsurgical subinguinal varicoceles reair because of chronic dull scrotal ain from Aril 2014 to August 2014 at the Deartment of Urology, Ystad hosital. evaluation was including detailed medical history; assessment of scrotal ain; scrotal examination including measurement of testicular size using orchidometer, assessment of the eididymis with resect to its consistency and any ain on alation, and evaluation of the sermatic cord for the resence of varicocele and its location (left, right, bilateral). Varicoceles were assigned to grades I III during examination while the atients in a standing osition according to the criteria [22] as follow: grade I, alable only with Valsalva; grad II, alable without Valsalva; and grade III, visible from distance. Patients who had other causes of scrotal ain such as testicular trauma, testicular torsion, eididymitis, rostatitis, and sexually transmitted dieses were excluded. Only atients with clinical varicocele and chronic dull scrotal ain were included and were scheduled for microsurgical subinguinal varicocele reair. None of the men were taking hormonal or other kinds of treatment for male infertility or hyogonadism. Our technique of microsurgical subinguinal varicocele reair was reviously described []. All hormonal rofiles available in the clinical records including testosterone, luteinizing hormone (LH), sex-hormone-binding (SHBG), and testosterone/shbg ratio were reviewed. Testosterone was obtained before 10 a.m. Follow-u was done at 1 and 12 months after surgery. Statistical Analyses Statistical analyses were done using the SPSS software version 16 (SPSS, Inc; Chicago, IL). For the comarison of the reoerative and ostoerative levels of LH, testosterone, SHBG, and testosterone/shbg ratio aired-samle t tests were used. In order to estimate factors that could affect testosterone changes after surgery, the analyses were stratified for varicocele grade (grade II vs. grade III) and the age of men (< 40 vs. 40 years). Thereafter, men were classified according to the reoerative testosterone values into 2 grous: eugonadal (serum levels of testosterone > 12 nmol/l) and hyogonadal men (serum levels of testosterone 12 nmol/l), based on the cutoff level set by [23], and ostoerative changes in testosterone levels were comared to the reoerative values using aired-samle t tests. P-values less than 0.05 were considered statistically significant. Results Descritive statistics of the study oulation is resented in table 1. Overall, microsurgical subinguinal varicocele reair was associated with a statistically significant higher levels of testosterone at 1 and 12 months after surgery as comared to the reoerative levels ( vs. 18 nmol/l, = 0.03; vs. 15 nmol/l, = ). The same trend was found regarding serum levels of LH (3.0 vs. 5.0 IE/l, = ; 3.0 vs. 5.0 IE/l, = 0.04). On the other hand, no significant differences were found when comaring the ostoerative serum levels of SHBG and testosterone/shbg ratio with the reoerative values ( > 0.05). Postoerative testicular volume did not differ significantly when comared with the volume measured before surgery ( > 0.05) (table 2). When stratified by the clinical grade of varicocele and the age of subjects, no significant difference was found in the mean reoerative testosterone levels among the 2 grades (Grade II and III) or the age of subjects (< 40 years vs. 40 years) ( > 0.05) (table 3). For the euogonadal men, no significant imrovements in testosterone levels were observed at 1 and 12 months after surgery as comared to the reoerative values ( > 0.05). When looking to the hyogonadal men, testosterone levels were significantly imroving following varicocele reair at 1 and 12 months after surgery as comared to the reoerative values (.0 vs. 15 nmol/l, = ;.0 vs. 10 nmol/l, = 0.02) (table 4). 46 Elzanaty/Johansen

3 Table 2. Pre- and ost-oerative LH, testosterone, SHBG, and testosterone/shbg ratio levels; and testicular volume obtained from 20 men who had microsurgical subinguinal varicoceles reair because of chronic dull scrotal ain. Postoerative 1 month 12 months * ** LH (IE/l) Testosterone (nmol/l) SHBG (nmol/l) Testosterone/SHBG ratio Right testicular volume (ml) Left testicular volume (ml) 3.0 (± 2.0) (±.0) 36 (± 15) 0.4 (± 0.2) 21 (± 3.0) 19 (± 3.0) 5.0 (± 2.0) 18 (± 6.0) 38 (± 15) 0.5 (± 0.2) 20 (± 3.0) 1 (± 3.0) 5.0 (± 3.0) 15 (±.0) 35 (± ) 0.4 (± 0.2) 21 (± 3.0) 18 (± 3.0) Data are mean (± SD). LH = Luteinizing hormone, SHBG = sex-hormone-binding globulin. * indicates statistical difference between reoerative values and values measured at 1 month ostoerative. ** indicates statistical difference between reoerative values and values measured 12 months ostoerative is considered statistically significant. Table 3. Pre- and ost-oerative testosterone levels stratified by the age of men and varicocele grade obtained from 20 men who had microsurgical subinguinal varicoceles reair because of chronic dull scrotal ain. Number Postoerative 1 month 12 months * ** Age (years) < 40 years 40 years Varicocele grade Grade II Grade III (± 8.0) 12 (± 5.0) (± 9.0) 14 (± 4.0) 19 (± 6.0) 15 (± 4.0) 1 (±.0) 1 (± 9.0) 12 (± 3.0) 10 (± 4.0) 18 (±.0) Data are mean (± SD). Statistical analyses were done using t aired-samle t tests. * indicates statistical difference between reoerative values and values measured at 1 month ostoerative. ** indicates statistical difference between reoerative values and values measured 12 months ostoerative is considered statistically significant. Table 4. Pre- and ost-oerative testosterones levels obtained from euogonadal and hyogonadal men who undergone microsurgical subinguinal varicoceles reair because of chronic dull scrotal ain. Number Postoerative 1 month 12 months * ** Eugonadal Hyogonadal.0 (± 3.0) 15 (± 6.0) 1 (± 4.0) 10 (± 3.0) Data are mean (±SD). Statistical analyses were done using t aired-samle t tests. * indicates statistical difference between reoerative values and values measured at 1 month ostoerative. ** indicates statistical difference between reoerative values and values measured 12 months ostoerative is considered statistically significant. Discussion Based on 20 men who had undergone microsurgical subinguinal varicocele reair of grade II-III lesions because of chronic scrotal ain, varicocele reair was associated with a significant imrovements of testosterone levels in men with low reoerative testosterone levels. Therefore, microsurgical subinguinal varicocele reair may benefit atients with grade II-III lesions and low testosterone levels. Microsurgical Varicocele Reair and Testosterone Levels 4

4 A growing body of evidence suggests that varicocele adversely affects leydig cell function and testosterone roduction. Tanrikut et al. [20] measured testosterone levels in 325 men with clinical varicoceles and in 510 men without clinical varicoceles who served as a comarison grou. Men with clinical varicoceles had significantly lower testosterone levels than the comarison grou, the difference ersisted when analysed by age of men. In the same line, Hurtado et al. [24] reorted significantly lower testosterone levels in 36 infertile men with unilateral left varicocele and 33 age-aired fertile controls. Luo et al. [25] studied the morhology and function of Leydig cells in the rat testis between 40 male Srague-Dawley rats which were divided into 2 grous: the exerimental grou underwent surgery to create a left varicocele, and the control grou underwent a sham oeration. The mean aotosis index of Leydig cells in the exerimental grou was significantly higher than that in the control grou after 4 or 8 weeks. Steroidogenetic acute regulatory (StAR) rotein mrna levels in the Leydig cells of the exerimental grou were significantly lower comared to those of the control grou. The authors suggested that varicocele imairs Leydig cell function by increasing aotosis and suressing the exression of the StAR rotein. Sirini et al. [26] analysed testosterone levels in 200 infertile men with clinical varicoceles who were divided into two grous, 100 men with clinical varicoceles who had microsurgical varicocele reair and 100 age-matched men with clinical varicoceles who underwent assisted reroduction rocedures served as the control grou. Testosterone levels imroved significantly after varicoceles reair as comared to the control grou. Abdel-Meguid et al. [1] recently reorted significant imrovements in testosterone levels after varicocele reair in men with low reoerative levels. A similar significant change was observed by others [2, 28]. In accordance, we demonstrated significant imrovements in testosterone levels following reair of clinical varicoceles in men with low reoerative testosterone levels. In an attemt to elucidate factors that could affect changes in testosterone levels after surgery, we considered varicocele grade and age of the men as determining factors. However, neither the varicocele grade nor the age of the men seems to determine the imrovement in testosterone levels in our study and others [1, 19, 28]. We believe, therefore, that varicocele grade and the age of atients are not redicting factors for how testosterone changed following varicocele reair. Zohdy et al. [21] reorted that serum LH decreases significantly following varicocele reair in the hyogonadal atients and this may be attributed to imrovement in Leydig cell function. We failed to observe such changes in our study in accordance with revious reorts [28]. We were not able to exlain this contradictory. Our study has some limitations; the study is retrosective in design and based on a small number of selected grou, namely men who undergone varicocele reair because of chronic dull scrotal ain and testosterone imrovement was a secondary outcome. Therefore, our results might not reresenting men from the general oulation and/or men under infertility assessment. However, our results are still valid and suort the nation that varicocele reair associated with imrovement of testosterone in men with low reoerative testosterone values. Our study did not involve atients with grade I varicocele and/or atients with bilateral varicocele. Therefore, we could not make a conclusion whether reair of small varicocele and/or bilateral varicocele can imrove testosterone levels. In conclusion, our results have shown that microsurgical subinguinal reair of varicocele grade II-III was associated with a significant imrovements of testosterone levels in men with low reoerative values. Therefore, microsurgical varicocele reair may benefit men with grade II-III lesions and low reoerative testosterone values. 48 Elzanaty/Johansen

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