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 (
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 (
We conducted this prospective research on 115 infertile men with clinical varicocele grades II and III and 240 fertile men as the control group. The study received approval from the Ethical Committee (number: EC/91/1114) of Royan Institute (Tehran, Iran) and was conducted from August, 2012 to February, 2015. The subjects were men, ages 21-46 years, who were not affected by diabetes and did not take medications known to elicit imbalanced androgen levels. The control group included men who had one or more children, did not suffer from varicocele and diabetes, and did not take medications known to elicit changes in androgen levels. Prior to performing the study, consent letters were received from the patients which informed them of all the study procedures. We included another control group, called the witness group, as the positive control that compared testosterone hormone levels between non-varicocele treated fertile men (had at least one child in the recent year or had more children during their coupling life) against infertile men diagnosed with varicocele.
Patients and fertile males provided blood samples and we compared their serum testosterone levels. The blood samples of infertile men were taken 3-6 months after surgery in order to reassess the changes in serum testosterone levels. Semen parameters (concentration, motility, and morphology) were assessed according to WHO guidelines. In infertile men, prior to varicocelectomy, we assessed the effects of age, testis size (left-right), and grade on the mean total testosterone level. Semen samples were obtained by masturbation after 3-5 days of sexual abstinence. Accordingly, the patient’s samples were taken before and after varicocelectomy to evaluate the effects of varicocele repair upon the quality of the sperm parameters.
Blood samples were taken from fertile and infertile men.
The level of total testosterone was evaluated by an Elisa Kit
(AccuBind® Microwell ELISA Kit, Monobind Inc., Lake
Forest, CA, USA) before and after (
The Pearson correlation was applied to specify the relationship between continuous variables, and the independent t test was used to compare testosterone levels, age, and semen parameters between infertile men with varicocele and fertile men. The unit of testosterone is ng/dl. SPSS 16 software was used to analyze the data. The paired t test was performed to compare the pre- and post-operative testosterone levels, semen volumes, sperm concentrations, and motility. All results of the continuous variables were reported as mean standard deviation. Statistical significance was set at a P<0.05. Multiple linear regression analysis was applied to identify potential factors that affected the changes in mean testosterone levels before surgery.
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 (
Scatter plot that demonstrates the relationship between testosterone and age in the control group (P<0.05).
Comparison of testosterone and semen parameters before and after varicocelectomys
|Variable||Before surgery Mean ± SD||After surgery Mean ± SD||P value|
|Testosterone (ng/dl)||567 ± 223||594 ± 243||0.27|
|Volume||3.29 ± 1.67||3.39 ± 1.80||0.47|
|Sperm concentration (×106/ml)||19.10 ± 23.50||28.90 ± 31.90||0.00|
|Sperm motility (%)||31.60 ± 24.60||32.30 ± 25.60||0.66|
Scatter plot that demonstrates the relationship between testosterone and right testis size in infertile men with varicocele before surgery (P<0.05).
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 (
Correlation between testosterone concentrations before surgery with age, grade of varicocele, and left and right testis sizes
|Left testis size||0.177||0.063|
|Right testis size||0.211||0.026|
Multivariable linear regression coefficients for testosterone before surgerys
|Variable||Coefficient||Standard error||P value|
|Right testis size||0.087||0.041||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 (
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 (
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. (
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.