Stesura Seveso


Archivio Italiano di Urologia e Andrologia 2020; 92, 2158

ORIGINAL PAPER

Evaluation of the influence of subinguinal varicocelectomy
procedure on seminal parameters, reproductive hormones
and testosterone/estradiol ratio

Ünal Öztekin, Mehmet Caniklioğlu, Sercan Sarı, Volkan Selmi, Abdullah Gürel, Mehmet Şakir
Taşpınar, Levent Işıkay

Bozok Unıversıty Faculty of Medicine, Department of Urology, Yozgat, Turkey.

Objective: Varicocele is the most commonly
surgically curable cause of male infertility.

However, the mechanisms related to the effect of reducing fer-
tility potential have not been clearly identified. The aim of this
study was to investigate the effects of varicocelectomy on
semen parameters, reproductive hormones and testosterone /
estradiol ratio.
Matherial and methods: Fifty seven patients outcomes were
evaluated before and 6 months after subinguinal microsurgical
varicocelectomy. Semen parameters, reproductice hormones
and testosteron/estradiol ratio results of patients were com-
pared retrospectively.
Results: The mean age was 26.8 years.  Fifty four (94.7%)
patients had grade 3 and  3 (5.3%) patients had grade 2 varic-
ocele. There was a significant increase in semen parameters
except semen volume. There was a statistically significant
increase in serum testosterone levels, but not on testosterone/
estradiol ratio.
Conclusions: According to our results, microsurgical subin-
guinal varicocelectomy can be recommended for both improv-
ing semen parameters and hormonal recovery.

KEY WORDS: Varicocele; Testosterone; Testosterone/Estradiol 
ratio; Semen parameters; Reproductive hormones.

Submitted 14 September 2019; Accepted 23 December 2019 

Summary

No conflict of interest declared.

DOI: 10.4081/aiua.2020.2.158

INTRODUCTION
Varicocele is a genital abnormality that disrupts the
growth and development of the ipsilateral testis and can
also reduce the quality of life due to pain symptoms. 
It is seen in 11.7% of adult males and 25.4% of whose
with abnormal sperm parameters. It is thought to cause
hypogonadism and to be associated with male subfertil-
ity (1). Varicocele is the most commonly surgically cur-
able cause of male infertility (2). Pain and feeling of scro-
tal fullness are also indications for surgical treatment (3).
Factors such as reflux of kidney and adrenal metabolites,
hypoxia, endocrine disorders, increased sperm DNA
fragmentation, oxidative stress, increased intratesticular
apoptosis, and  disruption of  intratesticular enzymes
due to temperature increase have been implicated in the
etiology (4). However, the mechanisms related to the
effect of reducing fertility potential have not been clear-

ly identified (1). There is also limited evidence of how
Leyding cells and testosterone production are affected
after varicocelectomy and how much it changes  testos-
terone production (5).
In the literature, it is generally indicated that Leydig cell
function is negatively affected in varicocele patients with
decreased testosterone production and that also hor-
mone level is improved by varicocelectomy (4, 6, 7).
Studies on rats have shown pathological changes such as
increased apoptosis of Leydig and Sertoli cells causing
decreased viability and testosterone synthesis due to
varicocele (8, 9). However, there are studies advocating
that varicocelectomy has no effect on serum testosterone
levels in human studies (3, 10, 11).
Local hormonal balance between testicular testosterone
and estradiol ratio is effective on spermatogenesis.
Impairment of this balance in semen and serum can cause
infertility by disrupting normal spermatogenesis. 
Varicocelectomy can positively affect the balance between
testosterone and testosterone/estradiol ratio (T/E) (4).
Therefore, evaluating T/E ratio changes may provide more
useful information (12).
The aim of this study was to investigate the effects of
varicocelectomy on sperm parameters, reproductive
hormones and T/E ratio.

MATERIALS AND METHODS
Data of patients who presented with infertility and/or
pain and then underwent microsurgical subinguinal
varicocelectomy between November 2017 and July 2019
were evaluated retrospectively. After approval from the
local ethics committee, patients aged 18 and over were
included in the study and the study was conducted in
accordance with the Declaration of Helsinki. Fifty seven
patients who met the study criteria were evaluated. 
All patients were examined while standing and evaluat-
ed with Valsalva maneuver and then color flow doppler
ultrasonography (CFDU) was performed. Patients were
classified according to clinical grading system. 
Grade 0 (subclinical): cannot be detected by inspection
or palpation but can only be detected by CFDU. Grade
I: only palpable on Valsalva maneuver. 



159Archivio Italiano di Urologia e Andrologia 2020; 92, 2

Varicocelectomy and hormones 

Grade II: palpable without Valsalva maneuver. Grade III:
visible with no need for palpation. Patients with known or
detected hormonal pathology (hypo/hypergonadism,
hypo/hyperthyroidism, hyperprolactinemia), azoospermia
and cryptozoospermia (≤ 1 million/mL), body mass index
(BMI) ≥ 30 kg/m2, genital tract infection (orchitis, epi-
didymitis, urethritis) and patients who had used
chemotherapeutic drugs were excluded from the study.
Semen analyses were performed after 3-7 days of absti-
nence using the 2010 criteria of the World Health
Organization (13). Semen volume, sperm concentration,
total sperm count, progressive motility and
total motility data were recorded as semen
parameters before and 6 months after varicoc-
electomy.  Age, body mass index, hormone
profiles including follicle stimulating hormone
(FSH), luteinizing hormone (LH), prolactin
(PRL), estradiol (E2) and total testosterone (T)
results and T/E ratios were recorded.
Subinguinal incision was performed and
microsurgical varicocelectomy procedure
was performed by defining spermatic cord
from external inguinal ring in all patients.
Preoperative and postoperative results of
patients were compared retrospectively. 

Statistical analysis
All statistical tests were performed using the
Statistics Package for Social Sciences version
25 (IBM SPSS®, Chicago, IL). Kolmogorov-
Smirnov test was used to determine the nor-
mal distribution of data. Paired-sample T-test
was used for pre-postoperative comparison of
parametric data and Wilcoxon Signed Ranks
Test was used for pre-postoperative compari-
son of non-parametric data. A value p < 0.05
was considered statistically significant.

RESULTS
A total of 57 patients aged 18-41 (mean: 26.8) were
included in the study. The mean BMI value was 24.77
(18.31-29.41) kg/m2. The varicocele grade was grade 2
in 3 (5.3%) patients who underwent varicocelectomy.
Fifty four (94.7%) patients had grade 3 varicocele. 
In 21 (36.8%) of the patients, no increase was observed
according to the preoperative testosterone values, while
31 (54.3%) had less than 50% and 5 (8.7%) had more
than 50% change (Table 1).
There was no significant difference between preoperative
and postoperative semen volumes. There was a statisti-
cally significant improvement in sperm concentration,
total sperm count, progressive and total sperm motility
compared to preoperative period (p < 0.05) (Table 2).
There were no significant changes in serum FSH, LH, E2,
PRL values compared to preoperative values. There was
a statistically significant increase in serum testosterone
levels 507.63 ± 174.27, 547.01 ± 184.59 ng/dl preoper-
atively and postoperatively, respectively (p = 0.003).
However, T/E ratios (preoperative and postoperative
22.36 ± 9.46, 22.87 ± 11.10, respectively) were not sig-
nificantly changed (p = 0.978) (Table 3). 

DISCUSSION
Varicocele is an abnormal dilation of the plexus
pampiniformis and testicular spermatic veins in the sper-
matic cord (14). It is often caused by left side veins and
is a venous dilatation disorder characterized by increased
pressure within the internal spermatic vein (6). It affects
male fertility by creating anatomical and functional dam-
age within the testis (15). It has been reported that
patients with varicocele have higher degree of sperm
DNA fragmentation when compared to healthy individ-
uals. Also, varicocele patients with abnormal sperm
parameters have higher fragmentation levels than those
with normal sperm parameters (16). More severe dam-
age to the testicle has been reported as the degree of
varicocele increases (17). Increased venous pressure in
the varicocele, which is a dilated venous disease, can
cause venous stasis by delaying vascular washout, result-
ing in impaired thermal regulation leading to hyperther-
mia and accumulation of toxins (18). As a result of
hyperthermia, it has been suggested that after germ cell
apoptosis, inhibition of enzymes involved in spermato-
genesis (19) and steroid biosynthesis decreases conver-

Table 1. 
Overall and specific course rating.

Table 2. 
Comparison of semen parameters before and after varicocelectomy.

Table 3. 
Comparison of hormonal data before and after varicocelectomy.

Age (mean) (min-max) 26.8 (18-41)
BMI kg/m2 (mean)(min-max) 24.77 (18.31-29.41)

Testosterone change
No increase (n) 21 (36.8%)
0-50% increase (n) 31 (54.3%)
50-100% increase (n) 5 (8.7%)
BMI: Body Mass Index.

Preoperative Postoperative P value

Semen volume, ml (mean ± SD) 3.12 ± 1.39 3.33 ± 1.56 0.105b

Sperm concentration (mil/ml) (mean ± SD) 35.54 ± 24.76 45.13 ± 23.76 0.001a

Total sperm count, (mil) (mean ± SD) 113.44 ± 98.54 153.84 ± 115.98 < 0.001b

Progressive motility (Type A) (%) 24.71 ± 10.57 28.95 ± 9.95 0.001a

Total motility (Type A+B) (%) 41.96 ± 16.00 45.14 ± 14.63 0.011b

a Calculated using Paired-sample T-test. b Calculated using Wilcoxon Signed Ranks Tests. SD: standard deviation. 

Preoperative Postoperative P valueb

Serum FSH, mIU/ml (mean ± SD) 3.69 ± 2.69 3.73 ± 2.50 0.689

Serum LH, mIU/ml (mean ± SD) 3.33 ± 1.51 3.32 ± 1.68 0.161

Serum PRL, ng/ml (mean ± SD) 10.20 ± 3.96 9.86 ± 3.35 0.609

Serum E2, ng/L (mean ± SD) 24.88 ± 8.78 26.48 ± 9.02 0.445

Serum T, ng/dl (mean ± SD) 507.63 ± 174.27 547.01 ± 184.59 0.003

T/E2 (mean ± SD) 22.36 ± 9.46 22.87 ± 11.10 0.978
b Wilcoxon Signed Ranks Tests. SD: Standard deviation. FSH: Follicle stimulating hormone. LH: Luteinizing hormone. PRL: Prolactin.
E2: Estradiol and T: Total testosterone T/E2: Testosterone/Estradiol ratio.



Archivio Italiano di Urologia e Andrologia 2020; 92, 2

Ü. Öztekin, M. Caniklioğlu, S. Sarı, V. Selmi, A. Gürel, M. Şakir Taşpınar, L. Işıkay

160

sion to intratesticular testosterone and synthesis (20). In
support of this theory, studies advocating increased
testosterone levels after varicocelectomy are presented.
In the study of Tanrıkut et al. (6), they reported the
results of testosterone before and after varicocelectomy
as 416 ng/dL and 469 ng/dL respectively in their series
of 325 patients with palpable varicocele. They showed a
significant increase in testosterone level in two thirds of
patients after varicocelectomy. The results of our study
were 507.63 ± 174.27 and 547.01 ± 184.59 ng/dl before
and after surgery respectively and there was a significant
increase (p = 0.003). Similarly, two-thirds of our patients
had increased testosterone. In the study by Sathya S. et al,
testosterone levels increased from 1.77 ± 0.18 ng/ml to
3.01 ± 0.43 ng/ml after varicocelectomy (21). Hsiao et al.
likewise stressed that there was a significant increase in
testosterone level and sperm concentration and total
sperm count in all varicocelectomy patients, including
the 5th and 6th decade age group (22). In a meta-analysis
evaluating 814 patients, it was concluded that surgical
treatment of varicocele significantly increased Leyding
cell function and testosterone production (23).
Numerous studies have shown that testosterone levels
are elevated after varicocelectomy, but there are also
studies advocating that it does not cause any changes. In
the study by Rodriguez et al., there was no relationship
between varicocele and low testosterone. It was also
argued that there was no improvement in semen profile
in treated varicoceles (10). Similarly, Panach-Navarrete
et al. showed that there was no correlation between the
presence of varicocele and decreased serum testosterone
level (11). Zheng et al. detected that there is not signifi-
cant change in testosterone levels compared to preoper-
ative values in 104 infertile patients after left or bilateral
varicocelectomy procedure (24). 
Although the prevalence of varicocele is widespread
worldwide and associated with low testosterone levels,
this relationship has not been clearly demonstrated. 
In this context, it is considered that T/E ratio evaluation
can provide more useful information (12). Simorangkir et
al. concluded that the T/E2 ratio in pampiniform plexus
was significantly lower than in the control group in their
study by creating varicocele in a rabbit model (25).
Although there are limited studies on this subject in the
literature, the pre and postoperative T/E ratio was found
to be 19 ± 7.7 and 27.5 ± 1.2 in the prospective study
conducted by Gomaa et al. (4). They emphasized that
there was a significant postoperative decrease in E2 level
(26.9 ± 3.2 and 22.9 ± 3.1 pg/ml p < 0.001, respective-
ly). In our study, T/E2 ratios were 22.36 ± 9.46 and
22.87 ± 11.10, before and after surgery, respectively (p =
0.978). There was an increase in postoperative serum E2
values but it was not statistically significant (p = 0.445).
When we evaluated only 36 patients with increased
testosterone levels, the mean preoperative and postoper-
ative E2 levels were 23.85 ± 9.17 and 26.92 ± 9.57 ng/L
(p = 0.104), respectively. There was an increase in E2
values with increasing T levels. However, it was not sta-
tistically significant. In addition, there was no significant
increase in T/E ratios in this patient group (p = 0.470).
No significant difference was found between the two
groups whose T level increased and showed no change

(p = 0.212). Therefore, it is suggested that these changes
may be in the testicular cells regardless of peripheral aro-
matase activity. Although these results suggest that
improvement in Leydig cell functions after varicocelecto-
my may increase estradiol production, further prospec-
tive randomized studies with more patients and long-
term follow-up are needed. 
A meta-analysis of 548 patients evaluating seven studies
emphasized that varicocelectomy provided significant
improvement, particularly on progressive sperm motility
(26). In another meta-analysis, the varicocelectomy group
was compared to the untreated group in terms of semen
parameters in adolescents, but no difference was observed
between the two groups (27). In general, it is seen that
microsurgical varicocelectomy increases sperm concentra-
tion and motility (28). Also, there was a significant
increase in semen volume, sperm concentration and total
number, progressive and total motility after varicocelecto-
my in our study. 
Retrospective design of our study is a limitation. Other
limitations include low number of study population and
short follow-up, collection of single-centered data, and
failure to evaluate pregnancy outcomes.

CONCLUSIONS
When the data of our study were evaluated, we conclud-
ed that subinguinal varicocelectomy procedure with
microsurgical method provided significant improvement
on semen parameters and testosterone levels. However,
we did not find a significant relationship between T/E2
ratio and surgery. According to our results, microsurgical
subinguinal varicocelectomy can be recommended for
both improving semen parameters and hormonal recov-
ery. However, multicenter prospective randomized stud-
ies are needed to clarify relationship with reproductive
hormones and semen parameters, including more patients
with long-term follow-up and pregnancy rate evaluation.

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Correspondence
Ünal Öztekin, MD (Corresponding Author)
dr_unal@hotmail.com
Mehmet Caniklioğlu, MD
dr.mehmetcaniklioglu@gmail.com
Sercan Sarı, MD
sercansari92@hotmail.com
Volkan Selmi, MD
volkanselmi@hotmail.com
Abdullah Gürel, MD
abdullahgurel@hotmail.com
Mehmet Şakir Taşpınar
mehmetsakirtaspinar@hotmail.com
Levent Işıkay, MD
isikay@gmail.com
Yozgat Bozok University, Research and Application Hospital, 
Urology Department, Yozgat, Turkey