|Year : 2014 | Volume
| Issue : 1 | Page : 164-168
Varicocele repair outcome with respect to hormonal profile and spermogram pattern
Alaa Eldin M Almahdy, Ahmed A Gamal Eldin, Mohammed M. Abdullah, Mohammed I. Abuzaid
Urology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||04-Jul-2013|
|Date of Acceptance||04-Oct-2013|
|Date of Web Publication||20-May-2014|
Mohammed I. Abuzaid
MBBCh, Urology Department, Faculty of Medicine, Menoufia University, Menoufia, 11160
Source of Support: None, Conflict of Interest: None
This study aims to evaluate the outcome of varicocelectomy on the hormonal and spermatogenic function of the testis.
Varicocele of the testis is the most common male factor causing subfertility. The harmful effect of varicocele on the testis has been documented, and the value of varicocelectomy in improving spermatogenesis has also been confirmed. However, the effect of varicocele on steroidogenesis and the role of varicocelectomy in improving testicular testosterone production are still under evaluation.
Patients and methods
This prospective study included 46 patients with bilateral varicocele. Semen analysis was carried out and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were obtained preoperatively. Bilateral inguinal varicocelectomy was performed in all 46 patients. All patients were followed up 3 months postoperatively by semen analysis and serum levels of FSH, LH, and testosterone. Only 32 patients were followed up 6 months postoperatively, also by semen analysis and serum levels of FSH, LH, and testosterone.
There was no statistically significant change in the levels of FSH, LH, and testosterone postoperatively even after 6 months of follow-up. However, a significant increase in the testosterone level was found in patients with preoperative low testosterone level (≥3 ng/ml) both at 3 months (P = 0.005 ) and at 6 months (P = 0.004) from the operation. Both sperm concentration and progressive sperm motility showed statistically significant increases both at 3 months (P = 0.0003 and 0.0001, respectively) and 6 months (P = 0.0001 and 0.002, respectively) of follow-up. Normal morphology of sperm showed a statistically significant improvement only after 3 months of follow-up (P = 0.008).
Varicocelectomy improves the spermatogenic function of the testis. In addition, it has a favorable effect on testosterone production in patients with varicocele and low serum testosterone.
Keywords: Hormone, infertility, testosterone, varicocele
|How to cite this article:|
Almahdy AM, Gamal Eldin AA, Abdullah MM, Abuzaid MI. Varicocele repair outcome with respect to hormonal profile and spermogram pattern. Menoufia Med J 2014;27:164-8
|How to cite this URL:|
Almahdy AM, Gamal Eldin AA, Abdullah MM, Abuzaid MI. Varicocele repair outcome with respect to hormonal profile and spermogram pattern. Menoufia Med J [serial online] 2014 [cited 2019 Mar 25];27:164-8. Available from: http://www.mmj.eg.net/text.asp?2014/27/1/164/132792
| Introduction|| |
Varicocele is one of the highly controversial issues in urology. Although its harmful effect on the testis has been documented, the indications for varicocele repair and the outcome of varicocelectomy are still points of debate . In men with a varicocele, increased levels of reactive oxygen species and sperm DNA damage can be found. Seminal oxidative stress is believed to be the source of sperm DNA damage .
After varicocelectomy, sperm parameters significantly improve and sperm DNA fragmentation shows a significant decrease. Low DNA fragmentation index values are associated with a higher pregnancy rate (spontaneous and with assisted reproductive technique) .
The increased risk for subfertility in men with varicocele is well established. Yet, varicocele pathophysiology is poorly understood, and potential implications for testosterone production are less clear. Evidence suggests that varicocele may result in lower serum testosterone levels and that varicocelectomy may, in turn, correct this deficit .
In an animal study conducted on rats, induced varicocele has resulted in impairment of the Leydig cell function by increasing apoptosis and suppressing the expression of the StAR protein. This was associated with a decrease in both serum testosterone and intratesticular testosterone .
| Patients and methods|| |
This is a prospective study that was conducted at the Urology Department in Menoufia University Hospital between February 2011 and December 2012. The study included 46 patients who were presented with bilateral varicocele and who were indicated for repair because of subfertility or pain.
Each patient underwent a thorough medical and reproductive history taking. In the present study, clinical varicoceles were graded according to the criteria of Dubin and Amelar : grade 1, palpable venous distension only during a Valsalva maneuver; grade 2, palpable intrascrotal venous distension without a Valsalva maneuver but not visible; and grade 3, the distended venous plexus bulges visibly through the scrotal skin and is easily palpable without a Valsalva maneuver. Subclinical varicoceles were detected using a color Doppler-flow imaging, (Trading Company, Guangdong, China) system and a 7.5-MHz linear array transducer. The diagnostic criteria of a subclinical varicocele include that the spermatic veins are impalpable on a careful physical examination during a Valsalva maneuver, with reversal of blood flow in the internal spermatic veins and the presence of internal spermatic veins of at least 3 mm during a Valsalva maneuver .
Bilateral inguinal varicocelectomy is performed in all patients included in this study. Under spinal anesthesia, a 3-5 cm oblique skin incision is made above and parallel to the inguinal ligament, initiating from the level of the external inguinal ring. The external oblique aponeurosis is opened to expose the spermatic cord in the inguinal canal. The spermatic cord is then mobilized and elevated, and the cremasteric muscle and the internal spermatic fascia are then opened. The dilated internal spermatic veins are then doubly clamped, transected, and ligated. The incision is then closed in layers.
Semen specimens were collected by masturbation after a minimum of 3 days of abstinence, and the samples were examined within 1 h of collection. Manual semen analysis was performed for sperm concentration, percent motility, viability, and Kruger/strict morphology using the WHO, 4th ed., methodologies . Preoperative and postoperative semen analysis parameters were separately averaged and used as the mean values for concentration, motility, and morphology of all semen analyses (preoperatively and postoperatively) for each patient.
Serum hormone levels
Total circulating testosterone levels, serum follicle-stimulating hormone (FSH), and luteinizing hormone (LH) measurements were determined using commercial radioimmunoassay kits. Serum FSH and LH were determined using the Immulite automated analyzer (Immulite; Diagnostic Products Corporation, Los Angeles, California, USA). Serum total testosterone was measured using the electrochemiluminescence immunoassay method (Elecys 1010; Boehringer Mannheim, Mannheim, Germany). Preoperative and postoperative testosterone determination were performed between 8 and 10 a.m. Preoperative and postoperative serum hormone levels were separately averaged and used as the mean values of testosterone, FSH, and LH for each patient.
Statistical analyses were performed using the two-sample paired t-test and the Wilcoxon signed-rank test. Statistics for two-sample comparisons were reported as mean plus or minus SEM. All statistical calculations were performed using computer program SPSS version 15 for Microsoft Windows (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
Patients demographic data
Forty-six patients with varicocele were assessed in our hospital and were included in this study. Their ages ranged from 17 to 59 years, with a mean age of 29.8 years. Eighteen of our patients were manual workers, 19 had governmental jobs, six had skilled jobs, and three were students. As for smoking, 24 were smokers, whereas the other 22 were nonsmokers. Only eight of our patients were singles and 38 were married.
Change in hormones levels
The mean level of FSH was decreased 3 months postoperatively from 6.6 to 6.4 mIU/ml (P = 0.122). In 32 patients who were followed up after 6 months, the mean level of FSH was decreased from 6.4 preoperatively to 6.19 mIU/ml postoperatively (P = 0.247). Similarly, the mean level of LH was decreased 3 months postoperatively from 6.9 to 6.6 mIU/ml (P = 0.09); in 32 patients who were followed up after 6 months, the level was decreased from 6.7 to 6.4 mIU/ml (P = 0.129) [Table 1].
In contrast, the mean level of testosterone was increased 3 months postoperatively from 4.9 to 5.2 ng/ml (P = 0.133); in 32 patients who were followed up after 6 months, the level was increased from 4.1 to 4.8 ng/ml (P = 0.106).
Effect of baseline testosterone
Patients were stratified according to the level of preoperative testosterone (≥3 vs. >3 ng/ml). In 13 patients with preoperative serum testosterone of 3 ng/ml or less, a mean increase in testosterone level was found from 2.3 ± 0.5 to 3.2 ± 1 ng/ml after 3 months of operation (P = 0.005). In 10 patients who were followed up after 6 months, there was a mean increase in the level from 2.5 ± 0.5 ng/ml preoperatively to 3.7 ± 1.2 ng/ml after 6 months of operation (P = 0.004) [Figure 1].
In 33 patients with preoperative serum testosterone greater than 3 ng/ml, a nonsignificant increase in the mean testosterone level was noted from 5.6 ± 0.9 to 5.7 ± 1 ng/ml 3 months after varicocelectomy (P = 0.446). In 22 patients who were followed after 6 months, mean testosterone level was increased from 5.4 ± 0.8 ng/ml preoperatively to 5.5 ± 1 ng/ml after 6 months of operation (P = 0.776).
Change in semen parameters
Sperm concentration, sperm progressive motility, and sperm form were improved after varicocelectomy. After 3 months of operation, mean sperm concentration increased from 17.6 to 23.7 million/ml (P = 0.0003); mean progressive motility increased from 26.9 to 34.9% (P = 0.0001); and abnormal forms declined from 33.8 to 27.5% (P = 0.008). In 32 patients who were followed up after 6 months, mean sperm concentration increased from 16.8 to 24.78 million/ml (P = 0.0001); mean progressive motility increased from 28.6 to 34.4% (P = 0.002); and abnormal forms declined from 33.6 to 31.6% (P = 0.158) [Table 2].
| Discussion|| |
The negative impact of varicocele on spermatogenesis has long been recognized. For clinically significant varicoceles, varicocele ligation is performed with the goal of improving semen parameters in the setting of subfertility. The association between clinically significant varicocele and impaired testosterone production is less well established. Furthermore, the utility of varicocelectomy for optimizing the Leydig cell function and testosterone production has not yet been studied .
Several hypotheses have been suggested to explain how varicocele has a deleterious effect on the testis function. The most widely accepted of these theories relates to alterations in the testicular thermal environment. Under normal scrotal conditions, a countercurrent heat-exchange mechanism between the outflow of the pampiniform plexus and testicular arterial inflow supports the cooler temperature required for optimal sperm production .
Varicocele has been implicated in altered function of 17-͍-hydroxyprogesterone aldolase, which converts 17-hydroxyprogesterone to testosterone. Heat effects related to varicocele could have a negative effect on the enzyme's action, thus resulting in decreased testosterone production .
In our study, we noted a decrease in the levels of both FSH and LH after varicocelectomy was performed. However, this decrease did not reach statistical significance even after 6 months of follow-up.
Our results are in agreement with those published by Su et al.  and by Sathya Srini and Belur Veerachari in 2011 . Both demonstrated a decrease in FSH and LH levels postoperatively, but the decrease was not statistically significant after 6 months of follow-up ,.
As for serum level of testosterone, in our study it was increased by 0.3 ng/dl following varicocelectomy. However, this improvement was not statistically significant. When we divided the patients into two groups according to the preoperative serum testosterone level, we found that the group with preoperative low testosterone had improved remarkably, with an improvement from 2.5 ng/dl preoperatively to 3.7 ng/dl postoperatively after 6 months of follow-up (P = 0.004).
Similar to our results, Su et al.  found an improvement in serum testosterone after varicocelectomy. Furthermore, similar to our results, they found that patients with low preoperative testosterone had more postoperative improvement.
In another study published in 2013, there was a significant improvement in serum testosterone level after varicocelectomy after a mean follow-up of 7 months. All patients in this study had preoperative serum testosterone less than 4 ng/ml .
From these results, we can observe that varicocele repair is effective in improving serum testosterone level in selected patients with varicocele and low testosterone.
Mean sperm concentration in 46 patients who were included in our study increased after 3 months of operation by 6.1 million/ml (from 17.6 to 23.7 million/ml) (P = 0.0003), and in 32 patients who were followed up after 6 months the concentration increased by 8 million/ml (from 16.8 to 24.8 million/ml) (P = 0.0001). The mean percent of progressive sperm motility in the 46 patients increased by 8% after 3 months (from 26.9 to 34.9%) (P = 0.0001), and in 32 patients who were followed up after 6 months it increased by 5.8% (from 28.6 to 34.4%) (P = 0.002). The mean percent of abnormal forms decreased from 33.8 to 27.5% after 3 months of follow-up in all 46 patients (P = 0.008). In 32 patients who were followed up after 6 months it decreased from 33.6 to 31.6% (P = 0.158).
In a recent meta-analysis evaluating the role of varicocelectomy in the treatment of male factor infertility, 22 prospective studies reporting on sperm concentration before and after varicocele repair were identified. The mean improvement in sperm concentration in these studies ranged from 4 to 60 million/ml, with an overall improvement of 12.32 million/ml. The improvement was statistically significant in 15 of them. Only five prospective studies reporting on the change in percent progressive sperm motility before and after varicocele repair were identified. The mean improvement in progressive sperm motility ranged from 5 to 15.7%, with an overall improvement of 9.69%. The improvement was statistically significant in four of the five studies .
In another study comparing open inguinal, laparoscopic, and subinguinal microscopic varicocelectomy, 40 patients underwent open inguinal varicocelectomy. The mean sperm concentration in those 40 patients increased from 22 to 40 million/ml (P<0.01). The mean sperm motility increased from 33 to 48% (P<0.01). The mean normal forms increased from 34 to 36% (P = 0.4). The mean follow-up in this study was 18 months (range from 11 to 26 months) .
| Conclusion|| |
Varicocele has a negative impact on testicular function that in turn affects male fertility. Varicocele repair is indicated in subfertile men with subnormal semen parameters, as after varicocelectomy a significant improvement in semen parameters is observed. In addition, in selected patients with varicocele and low serum testosterone, varicocelectomy is noted to be associated with improved serum testosterone postoperatively.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Will MA, Swain J, Fode M, Sonksen J, et al. The great debate: varicocele treatment and impact on fertility. Fertil Steril 2011; 95 :841-852. |
|2.||Zini A, Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation? Fertil Steril 2011; 96 :1283-1287. |
|3.||Smit M, Romijn JC, Wildhagen MF, Veldhoven JL, et al. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol 2013; 189 :S146-S150. |
|4.||Tanrikut C, McQuaid JW, Goldstein M. The impact of varicocele and varicocele repair on serum testosterone. Curr Opin Obstet Gynecol 2011; 23 :227-231. |
|5.||LuoDY, Yang G, Liu JJ, Yang YR, et al. Effects of varicocele on testosterone, apoptosis and expression of StAR mRNA in rat Leydig cells. Asian J Androl 2011; 13 :287-291. |
|6.||Dubin L, Amelar RD. Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil Steril 1970; 21 :606-609. |
|7.||Jarow JP, Ogle SR, Eskew LA. Seminal improvement following repair of ultrasound detected subclinical varicoceles. J Urol 1996; 155 :1287-1290. |
|8.||Cao XW, Lin K, Li CY, Yuan CW. A review of WHO Laboratory Manual for the Examination and Processing of Human Semen (5th edition). Zhonghua Nan Ke Xue 2011; 17 :1059-1063. |
|9.||Tanrikut C, Goldstein M, Rosoff JS, Lee RK, et al. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU Int 2011; 108 :1480-1484. |
|10.||1Zorgniotti AW. Testis temperature, infertility, and the varicocele paradox. Urology 1980; 16 :7-10. |
|11.||1Ando S, Giacchetto C, Colpi G, Panno ML, et al. Plasma levels of 17-OH-progesterone and testosterone in patients with varicoceles. Acta Endocrinol (Copenh) 1983; 102 :463-469. |
|12.||1Su LM, Goldstein M, Schlegel PN. The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles. J Urol 1995; 154 :1752-1755. |
|13.||1Sathya Srini V, Belur Veerachari S. Does varicocelectomy improve gonadal function in men with hypogonadism and infertility? Analysis of a prospective study. Int J Endocrinol 2011; 2011:916380. |
|14.||1Hsiao W, Rosoff JS, Pale JR, Powell JL, et al. Varicocelectomy is associated with increases in serum testosterone independent of clinical grade. Urology 2013; 81 :1213-1217. |
|15.||1Baazeem A, Belzile E, Ciampi A, Dohle G, et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol 2011; 60 :796-808. |
|16.||1Al Bakri A, Lo K, Grober E, Cassidy D, et al. Time for improvement in semen parameters after varicocelectomy. J Urol 2012; 187 :227-231. |
[Table 1], [Table 2]