Effects of Varicocelectomy on Serum Testosterone Levels among Infertile Men with Varicocele

The relationship between varicocele and male infertility was first noted in the late 1800s when Bennet reported an improvement in semen quality after correction for bilateralvaricoceles in a patient (1, 2). Varicocele is an abnormaldilatation of the pampiniform plexus of the veins that drain the testis. Restoration of this abnormality has been shown to cause positive effects on the spermatogenesis process (2-4). According to a number of studies, varicocelectomy improves semen parameters, hormonal profiles, and pregnan. cy rates (5-8). However, the process by which varicocele and its repair affects testicular Leydig cell function, semen quality, and the resultant changes in testosterone produc. tion levels are less understood and intensely debated. Many studies have reported that varicocelectomy promotes Leydig cell function based on testosterone levels. In addition, research indicates that ageing in men can induce a reduction in serum testosterone levels (2, 9, 10).

Among mechanisms involved in controlling testicular testosterone level, temperature has been highlighted. Animal models showed that both varicocele and increased testicular temperatures impede sperm production (5, 11). Disruption in the cooling system in veins of the scrotum during varicocele results in an increase in temperature of the scrotum. This phenomenon can be overcome by varicocelectomy (5, 8, 11). High temperatures can reduce the activity of the 17-a hydroxyl progesterone aldolase en. zyme, which results in decreased testosterone production. Thus, it is believed that treatment of varicocele may improve the function of Leydig cells, reactivate this enzyme, and increase testosterone production (12-14). In light of this understanding, we aim to assess the effects of varicocelectomy on serum testosterone levels and semen quality in infertile men with varicocele.

A total of 355 men participated in the study-240 control and 115 infertile men with varicocele. Fertile men had higher mean testosterone levels (583 ± 263 ng/dl) compared to infertile men (567 ± 222 ng/dl) before the operation, however this was not a statistically significant difference (P=0.558). The mean ages of infertile (32.2 ± 5.23 years) and fertile men (32.8 ± 5.27 years) were not significantly different (P=0.328). There was a significant linear relationship observed between age and testosterone level among the control group (Fig .1, r=-0.28, P<0.0001), but we did not observe this in the varicocele group (r=- 0.17, P=0.07). The mean size of the left testes (18.58 ± 4.98) was statistically lower than the right testes (19.01 ± 4.75, P=0.017). Pearson correlation showed a significant correlation between total testosterone and right testis size (r=0.21, P=0.026) in infertile men with varicocele before surgery (Fig .2). There was no relationship between grade of varicocele and testosterone level (r=-0.05, P=0.58). Varicocelectomy resulted in an insignificant rise in testosterone levels from 567 ± 222 ng/dl to 594 ± 243 ng/dl (P=0.27, Table 1).

Semen parameters that included including: volume, motility, and concentration were assessed before and after surgery. Both volume and motility of the sperm nonsignificantly increased after surgery. However, sperm concentration significantly (P<0.001) increased after surgery. Linear regression was used to show the effects of the variables (age, grade, and testis size) on total testosterone before surgery (Table 2). The other model was selected using the backward method (Table 3). The regression coefficient for age and right testis size compared to testosterone as the dependent variable was significant (P=0.036).

The relationship between varicocele and disorder in the function of testosterone production was not clearly understood in that work. To the best of our knowledge, few or no studies have assessed the effect of varicocelectomy upon Leydig cell function and testosterone production. Treatment of varicocele may lead to a suitable condition on total testosterone levels (2). As shown in our research, despite the increased testosterone level in infertile men after varicocelectomy, the difference was not significant.

Other researchers reported the negative impact of varicocele on spermatogenesis. In order to improve the quality of sperm parameters, varicocelectomy was used to treat male infertility. Therefore, we evaluated the other parameters that supposedly affect total testosterone levels. These parameters included age, grade, and testis size. We determined that the difference in the sizes of the left and right testes impacted total testosterone level in infertile men. According to previous studies, the probability of varicocele increased with increased age (15-17). Hsiao et al. (18) showed that the testosterone levels lower than 400 ng/dl improved considerably in individuals after varicocele treatment. However, it has been shown in earlier works that varicocelectomy may improve testosterone production even if it is not significant in addition to semen quality, particularly sperm concentration and motility (8, 9, 19). The present research has shown that the preoperative testosterone levels in infertile men were lower compared to fertile men. After surgery, testosterone levels increased in infertile men with varicocele. However, this increase was not significant. Other sperm parameters such as volume, motility and concentration were analyzed pre- postoperative. Although all parameters increased, only the increase in sperm concentration was statistically significant.

In addition to statistical analysis of the mentioned components, we assessed multivariable linear regression coefficients for testosterone before surgery by taking into consideration age and right testis size. Although the coefficient regression related to age stood negative, it was not significant. There was a significant relation between right testis size and total serum testosterone level.

Resorlu et al. (20) recently reported no changes in serum testosterone levels after varicocele repair. Notably, low-normal testosterone values were recorded both before and after the repair with no significant change in serum testosterone levels for any of their study groups. Preoperative and 6-month postoperative subjects were evaluated by Rodriguez Peña et al. (21), in which hormonal profiles and other data showed an increase in the serum testosterone after surgery, but this increase was not significant. Zohdy et al. (22) reported that patients who underwent varicocelectomy demonstrated a significant postoperative improvement in serum testosterone levels. Considering that varicocele has been universally accepted to negatively impact testis function, including paracrine and endocrine functions of the Leydig cells, the relationship between varicocele and diminished androgen levels appears to be reversed with varicocele repair. However, further studies are needed to better understand the multifactorial pathophysiology of varicocele-mediated Leydig cell dysfunction (23).

The results of this study show that varicocelectomy could improve sperm parameters such as sperm concentration and increase the testosterone level of blood serum although the increase is statistically insignificant. Nevertheless, it appears that this treatment is necessary to improve function in testes afflicted with varicocele.