Venous leg symptoms in patients with varicocele: A multicenter assessment study (VEIN-TURKEY study)

Abstract

Objective

The aim of this study is to evaluate chronic venous disease symptoms by using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms (VEINES-QoL/Sym) questionnaire in varicocele patients.

Material and methods

The study was designed as a prospective, case controlled study and conducted in four hospitals from Turkey. A total of 600 patients who admitted to urology outpatient clinic were enrolled to the study. After the exclusion of 44 patients who do not match the inclusion criteria, the remaining 556 patients were examined for the presence and grade of varicocele and subsequently examined clinically for the presence of chronic venous disease findings. Finally, patients were asked to answer the VEINES-Sym questionnaire consisting of 10 items. All patients’ demographic parameters, cardiovascular risk factors, other co-morbid diseases and drug usage were noted.

Results

Patients were classified into two groups: varicocele (+) group (n = 269) and varicocele (−) group (n = 287). VEINES-Sym scores of varicocele patients were lower compared to patients without varicocele (41.41 ± 5.21, 43.19 ± 3.22, respectively, p < 0.001). Grades of varicocele significantly but inversely correlated with VEINES-Sym score (r = 0, −206, p = 0.001). Logistic regression analysis revealed that presence of varicocele irrespective of grading significantly and independently associated with the presence of aching (odds ratio: 2.054, 95% confidence interval: 1.265–3.338, p = 0.004) and throbbing (odds ratio: 2.586, 95% confidence interval: 1.353–4.943, p = 0.004).

Conclusion

Varicocele patients have lower VEINES-Sym scores compared to patients without varicocele and this finding is inversely correlated with the degree of the varicocele. This association supports the hypothesis that there may be a systemic vessel wall abnormality in venous disease patients. Patients with symptoms related to vascular dilatation in any territory may deserve to be assessed systematically with the support of further clinical studies.

Keywords

Symptoms varicocele chronic venous disease leg diseases

Introduction

Chronic venous disease (CVD) is very common in the Western countries¹ and an important mortality and morbidity factor depending on the effected vascular region.² It is often overlooked by healthcare professionals due to the underestimation of the prevalence and impact of the disease. Besides, variations in clinical presentations of CVD contribute to underdiagnosis of the disease. It represents a spectrum of conditions varying from simple telangiectasia or reticular veins to skin fibrosis and venous ulceration. The main clinical characteristics are dilated veins, edema, leg pain, and cutaneous alterations in the legs. Varicose veins are dilating superficial veins, which become more tortuous and enlarged, continuously.^2,3

Varicocele is defined as the dilatation, elongation and tortuosity of the scrotal portion of the internal spermatic venous system, which drains the testicle.⁴ Its prevalence varies between 7% and 20% in healthy adolescents and young men and 75% and 90% of varicocele is left sided. It is associated with male infertility and it can be treated surgically. Diagnosis of varicocele can be made by physical examination easily.⁵ Absence or deficiency of venous valves, increased venous pressure, and vascular wall pathologies are suspected pathophysiological mechanisms for varicocele formation.²

Besides affecting the morbidity and mortality, CVD have an impact on the life quality of patients suffering from the disease, which can be measured with quality-of-life (QoL) reports. These questionnaires are important for the clinicians to evaluate the symptom severity, its impacts on daily life and response to treatment.^1,6 Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms (VEINES-QoL/Sym) questionnaire is patient based, designed for self-completion instrument to measure both the symptom severity and quality of life. VEINES-QOL measures life quality and VEINES-Sym provides an overall estimate of CVD symptom frequency. Lower VEINES-Sym scores indicate more severe symptoms and higher VEINES-QoL/Sym scores indicate better QoL.^7,8

Recently, chronic venous diseases such as varicocele and varicose veins have been defined as ‘Dilating venous diseases’ by Yetkin et al. due to the fact that they have similar pathophysiological mechanisms.² Besides, presence of peripheral varicose veins was shown to be associated with varicocele in a study published by Kılıç et al., previously.⁵ However, CVD symptoms, which are also included in the VEINES-Sym questionnaire, have never been evaluated in varicocele patients. In this context, in this study we have aimed to investigate the CVD symptoms in varicocele patients.

Materials and methods

Study design

This study was designed as a prospective, case controlled study. The study consisted of patients admitted in the urology clinic with varying complaints between June 2015 and October 2016. The patients were enrolled to the study in four clinics in Turkey: Başkent University Ankara Hospital, Başkent University Konya Hospital, Private Malatya Gözde Hospital, Private Batman Dünya Hospital.

The Ethics Committee of Başkent University Faculty of Medicine approved the study protocol (KA15/297). All study procedures were conducted according to the principles of Good Clinical Practice and Helsinki Declaration. Written informed consent was obtained from the patients who accepted to participate in the study.

Study population

The study group consisted of 600 consecutive patients who admitted the outpatient urology clinic with any symptom regardless of associated with varicocele. The main inclusion criterion was the willingness of patients to be involved in the study. Exclusion criteria were the history of malignancy, active infection or drug usage for infection at the time of enrollment, hematological disease, collagen tissue disease, history of heart failure, atrial fibrillation, history of a respiratory disease, rheumatic disease, history of lower extremity orthopedic disease/surgery and elephantiasis. The flow chart diagram of the study including exclusion criteria is also shown in Figure 1.

Figure 1.

Flow-chart diagram of the study.

Physical examination of the patients

All the patients included in the study were examined for the presence of varicocele by an experienced urologist in each clinic. Patients were examined in a warm room after a 5-min resting. The scrotum was examined with palpation and each spermatic cord in the supine and upright positions with and without the Valsalva maneuver. The varicocele was graded according to the Dubin and Amelar system: Grade 1, varicocele palpable only during the Valsalva maneuver; grade 2, varicocele palpable in standing position; and grade 3, varicocele detectable by visual scrutiny alone.⁹

The patients were then examined clinically for lower extremity venous system according to CVD guidelines and categorized according to clinical component of CEAP (clinical, etiological, anatomical and pathological) classification as follows: grade 0, no visible signs of venous disease; grade 1, telangiectasias or reticular veins; grade 2, varicose veins; grade 3, edema; grade 4, skin changes due to CVD; grade 5, skin changes with healed ulceration; and grade 6, skin changes with active ulceration.¹⁰ Patients with CEAP ≥ 2 were considered as positive for the peripheral varicose vein. All patients’ demographic parameters, cardiovascular risk factors, venous diseases, occlusive diseases and drug usage were recorded on our database. Duplex ultrasonography for the assessment of CVD and ultrasonographic grading of varicocele were not performed in all patients due to design of study. On the other hand, further ultrasonographic evaluation of varicocele was performed when clinically needed in selected patients. Finally, patients were asked to answer the VEINES-Sym questionnaire. VEINES-Sym consists of 10 items including nine venous symptoms (heavy legs, aching legs, swelling, night cramps, heat/burning sensation, restless legs, throbbing, itching and tingling sensation) in five different frequencies (1 = everyday, 2 = several times a week, 3 = about once a week, 4 = less than once a week, 5 = never). The tenth question concerning at what time of the day these symptoms are most intense is not included in calculation and is only used for descriptive information. Kutlu and her colleagues studied the validity and reliability of the VEINES-QoL/Sym questionnaire in the Turkish population.⁷

Statistical analysis

All statistical analyses were performed using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA). Categorical variables were determined as counts and percentages and compared between the groups using the chi-squared test. Continuous variables were expressed as mean value ± standard deviation for parametric variables. The Kolmogorov–Smirnov test was applied for the assessment of normality. Differences between the means were compared by unpaired t-test when the continuous variables showed normal distribution or by the Mann–Whitney U-test when they did not. Relationship between the varicocele grade and VEINES-Sym score was tested by Spearman’s correlation analysis. One-way ANOVA and post-hoc Bonferroni test was performed to compare the VEINES-Sym scores according to the grade of varicocele. Logistic regression analysis was applied to identify the possible association of venous leg symptoms and mean VEINES-Sym scores with varicocele. All of the venous leg symptoms mentioned in the VEINES-Sym questionnaire were included in the regression analysis. Two-tailed p < 0.05 was considered as statistically signiﬁcant in all tests.

Results

A total of 600 consecutive male patients who admitted to the urology clinic were enrolled in the study prospectively. Among them, 44 patients who do not match the inclusion criteria were excluded from the analysis. Patients were classified into two groups: Varicocele (+) group (n = 269) and varicocele (−) group (n = 287).

The baseline demographics, clinical characteristics, and admission complaints of the study population are shown in Table 1. Patients in varicocele (+) group were younger and thinner compared to patients in varicocele (−) group. The height was not comparable between the groups; however, body mass index of the varicocele (+) group was lower compared to varicocele (−) group. The percentage of patients with peripheral varicose vein was higher in varicocele (+) group compared to varicocele (−) group (26.3%, 14.9%, respectively, p = 0.008); however, the percentage of patients with hemorrhoids was lower in varicocele (+) group (13.3%, 20.9%, p = 0.04). Sexual complaints, micturition complaints, and other admission complaints were significantly higher in patients without varicocele, whereas pain and infertility complaints were significantly higher in patients with varicocele.

Table 1.

Baseline demographics, clinical characteristics and admission complaints of the study population.

Variable	Varicocele		p Value
Variable	No (n = 287)	Yes (n = 269)	p Value
Age (years)	36 ± 12	30 ± 9	<0.001
Weight (kg)	77.9 ± 10.6	75.4 ± 10.7	0.001
Height (cm)	174.8 ± 6.1	174.5 ± 6.5	0.60
Body mass index (kg/m²)	25.3 ± 3.0	24.5 ± 2.9	0.001
Hypertension	11 (3.8%)	5 (1.8%)	0.02
Diabetes mellitus	8 (2.7%)	0 (0%)	0.01
Hypercholesterolemia	17 (5.9%)	10 (3.7%)	0.21
Current smoker	115 (40.0%)	139 (51.6%)	0.13
Peripheral varicose vein	43 (14.9%)	71 (26.3%)	0.008
Hemorrhoids	60 (20.9%)	36 (13.3%)	0.04
Deep venous thrombosis	0 (0%)	0 (0%)	–
Pulmonary embolism	0 (0%)	0 (0%)	–
Pain	71 (26.3%)	123 (42.8%)	0.001
Infertility	45 (16.7%)	108 (37.6%)	0.001
Sexual complaints	40 (14.8%)	30 (10.4%)	0.01
Micturition complaints	34 (12.6%)	9 (3.1%)	0.001
Other	82 (30.4%)	49 (17.0%)	0.005

Symptom evaluation and VEINES-Sym scores of the study population are shown in Table 2 and Figures 2 and 3. Among the venous leg symptoms, which are included in the VEINES-Sym questionnaire, the percentages of patients indicating aching legs, swelling, night cramps, restless legs and throbbing were significantly higher in patients with varicocele than those without varicocele. Likewise, mean VEINES-Sym scores of the heavy legs, aching legs, swelling, night cramps, restless legs, throbbing, and itching were significantly lower in patients with varicocele than those without varicocele. Total mean VEINES-Sym score was found to be significantly lower in varicocele (+) group compared to varicocele (−) group (41.41 ± 5.21, 43.19 ± 3.22, respectively, p < 0.001).

Table 2.

Symptom evaluation and VEINES-Sym score assessment of the study population.

Variable	Varicocele				p Value
Variable	No (n = 287)		Yes (n = 269)		p Value
Symptoms	n (%)	Mean score ± SD	n (%)	Mean score ± SD	n (%)	Mean score ± SD
Heavy legs	43 (14.9%)	4.81 ± 0.53	47 (17.4%)	4.68 ± 0.76	0.33	0.02
Aching legs	63 (21.9%)	4.63 ± 0.86	110 (40.8%)	4.10 ± 1.28	<0.001	<0.001
Swelling	25 (8.7%)	4.87 ± 0.49	41 (15.2%)	4.74 ± 0.72	0.01	0.01
Night cramps	45 (15.6%)	4.76 ± 0.63	71 (26.3%)	4.47 ± 0.98	0.006	<0.001
Heat/burning sensation	48 (16.7%)	4.79 ± 0.72	50 (18.5%)	4.67 ± 0.81	0.26	0.07
Restless legs	31 (10.8%)	4.82 ± 0.61	68 (25.2%)	4.53 ± 0.95	<0.001	<0.001
Throbbing	22 (7.6%)	4.90 ± 0.39	59 (21.9%)	4.57 ± 0.90	<0.001	<0.001
Itching	40 (13.9%)	4.83 ± 0.52	56 (20.8%)	4.66 ± 0.78	0.08	0.003
Tingling	31 (10.8%)	4.82 ± 0.63	44 (16.3%)	4.74 ± 0.74	0.10	0.16
VEINES-Sym score	–	43.19 ± 3.22	–	41.41 ± 5.21	–	<0.001

Figure 2.

Mean VEINES-Sym score of symptoms in patients with and without varicocele. Lower VEINES-Sym scores indicate more severe symptoms.

Figure 3.

Proportion of patient reported symptoms among patients with and without varicocele.

Variance analyses of VEINES-Sym scores of each individual symptom and cumulative VEINES-Sym scores regarding the grade of varicocele are shown in Table 3 and VEINES-Sym score was shown to be significantly correlated with the grades of varicocele (r = 0, −206, p = 0.001) as shown in Figure 4.

Table 3.

Variance analysis of symptoms regarding the grade of varicocele.

	0 (n = 287)	1 (n = 54)	2 (n = 131)	3 (n = 84)	p Value
Heavy legs	4.81 ± 0.53	4.75 ± 0.70	4.71 ± 0.73	4.59 ± 0.83	0.04
Aching legs	4.63 ± 0.86	4.22 ± 1.31	4.25 ± 1.23	3.98 ± 1.24	<0.001
Swelling	4.87 ± 0.49	4.86 ± 0.50	4.74 ± 0.78	4.65 ± 0.77	0.003
Night cramps	4.76 ± 0.63	4.71 ± 0.78	4.56 ± 0.92	4.14 ± 1.08	<0.001
Heat/burning sensation	4.79 ± 0.72	4.76 ± 0.56	4.66 ± 0.87	4.51 ± 0.94	0.02
Restless legs	4.82 ± 0.61	4.64 ± 0.92	4.57 ± 0.94	4.52 ± 0.89	<0.001
Throbbing	4.90 ± 0.39	4.83 ± 0.56	4.64 ± 0.89	4.41 ± 0.95	<0.001
Itching	4.83 ± 0.52	4.74 ± 0.73	4.70 ± 0.75	4.63 ± 0.74	0.05
Tingling	4.82 ± 0.63	4.88 ± 0.49	4.77 ± 0.72	4.60 ± 0.80	0.02
VEINES-Sym score	43.19 ± 3.22	42.58 ± 4.16	41.59 ± 5.66	40.34 ± 4.96	<0.001

Figure 4.

Error bar graphic of VEINES-Sym score of patients without varicocele and patients with different grades of varicocele. “r” represents the correlation coefficient between the VEINES-Sym scores and varicocele grades.

Logistic regression analysis, which was performed to determine the symptoms and VEINES-Sym scores related with varicocele, are shown in Tables 4 and 5, respectively. Among the nine symptoms, which are present in VEINES-Sym questionnaire, presence of aching legs (odds ratio: 2.054, 95% confidence interval: 1.265–3.338, p = 0.004) and throbbing (odds ratio: 2.586, 95% confidence interval: 1.353–4.943, p = 0.004) were independently and positively associated with varicocele. In addition, VEINES-Sym scores of these symptoms were independently and positively associated with varicocele (odds ratio: 1.456, 95% confidence interval: 1.183–1.792, p < 0.001; odds ratio: 2.431, 95% confidence interval: 1.521–3.886, p < 0.001; respectively).

Table 4.

Logistic regression analysis of venous leg symptoms for varicocele.

	p Value	Odds ratio	95% Confidence interval
Heavy legs	0.14	0.622	0.327–1.182
Aching legs	0.004	2.054	1.265–3.338
Swelling	0.85	1.069	0.512–2.235
Night cramps	0.85	0.949	0.540–1.667
Heat/burning sensation	0.14	0.638	0.349–1.166
Restless legs	0.10	1.638	0.898–2.989
Throbbing	0.004	2.586	1.353–4.943
Itching	0.97	0.991	0.586–1.678
Tingling	0.54	1.188	0.679–2.081

Table 5.

Logistic regression analysis of VEINES-Sym scores for the presence of varicocele.

	p Value	Odds ratio	95% Confidence interval
Heavy legs	0.69	0.932	0.658–1.321
Aching legs	<0.001	1.456	1.183–1.792
Swelling	0.76	1.063	0.712–1.586
Night cramps	0.76	1.046	0.776–1.410
Heat/burning sensation	0.08	0.751	0.540–1.044
Restless legs	0.47	1.113	0.830–1.493
Throbbing	<0.001	2.431	1.521–3.886
Itching	0.63	1.081	0.786–1.487
Tingling	0.69	.942	0.698–1.271

Discussion

To the best of our knowledge, this is the first study in the literature evaluating the CVD symptoms with VEINES-Sym questionnaire in varicocele patients. In the present study, we have demonstrated for the first time that score is significantly low in patients with varicocele and independently associated with the presence of varicocele. Besides, we have shown that varicocele grade significantly correlated with the VEINES-Sym score.

CVD is a widespread but overlooked problem of lower extremity veins and is frequently linked with varicose veins.³ The spectrum of CVD ranges from varicose veins to leg edema and serious skin changes such as hyper-pigmentation, eczema, lipodermatosclerosis, and venous ulceration.¹¹ In the Western populations, the prevalence of varicose veins varies between 25% and 33% in females and 10–20% in males.^2,12 CVD is a very common problem affecting the Western adult population with a prevalence of up to 57% and 77% in men and women, respectively. It may also be associated with other clinical manifestations.^12–15 Symptoms of varicose vein patients vary between aching, burning, pain, cramps, heaviness, swelling, throbbing, tiredness, leg ulcers, tightness, and ecchymosis.^6,8,16,17 Interestingly, ecchymosis has been shown to be a sign of varicose vein and associated with muscle cramps.¹⁸ Aging, female gender, race differences, pregnancy, family history, obesity, limited physical activity, prolong standing, genetic and chromosomal abnormalities are traditional risk factors.^3,19 Although various mechanisms have been proposed, the main mechanism causing varicose vein and CVD is not fully understood. Varicocele, which is a life debilitating disease and associated with male infertility, is abnormal dilatation of the veins within the scrotum and shares similar pathophysiological mechanisms with varicose veins.² Besides having similar pathogenetic mechanisms, a high coexistence of these diseases was shown, previously. In their study, Kılıç et al. showed that the prevalence of peripheral varicose veins in patients suffering from varicocele is significantly higher than patients without varicocele.⁵ In our study, we have found a symptomatic association between these two diseases, which was also related with the degree of the disease. Although prevalence of CVD is lower in male patients regarding the female counterpart, significant association of VEINES-Sym score with varicocele in our case control study underlines the common pathophysiological mechanism on two distinct vascular territories.

Venous diseases which were proven to share similar pathophysiological mechanisms such as peripheral varicose veins, varicocele, hemorrhoids, and pelvic congestion syndrome have been named as ‘Dilating venous diseases’ by Yetkin et al., recently.² Besides, it is known from previous reports that there is a close linkage between these diseases. Sakamoto found that men with bilateral varicoceles have increased mean diameter, and peak retrograde and antegrade flow velocity in the prostatic venous plexus.²⁰ Besides, Holdstock et al. found that there is a frequent association between pelvic vein varices and hemorrhoids.²¹ Kilciler et al. reported an association between varicocele and hemorrhoids.²² According to these reports, it is reasonable to suggest that dilating venous diseases are closely linked to each other and venous reflux or dilatation of the venous vessels in different vascular systems might have originated from a systemic vascular wall pathology rather than being a local disease.^2,23 Surprisingly, similar association has also been demonstrated between dilating venous and arterial vessel diseases. This association has been demonstrated between coronary artery ectasia and varicocele,²⁴ and coronary artery ectasia and varicose veins²⁵ in previous studies. In light of these studies, we can speculate that venous reflux or dilatation in various vascular regions share a common pathogenetic mechanism, which causes all vessels prone to dilate or reflux.

VEINES-QoL/Sym questionnaire measures the effect of CVD on the life quality of patients and is currently the most appropriate and applicable choice for patient evaluation. It is the only self-reported test that covers the whole spectrum of patients’ considerations about leg-related venous disease, varying in a wide spectrum from uncomplicated varicose vein dilatations to deep venous thrombosis. Its psychometric and statistical characteristics seem to be scientific for translation to various demographic environments. VEINES-QoL provides an overall prediction of QoL, and the VEINES-Sym gives information about symptom frequency.²⁶ Therefore, the validity and reliability of this questionnaire in varicose vein and CVD patients has been studied in different countries.^7,27,28 However, symptoms, which are also present in this questionnaire, have not been studied in varicocele patients previously. Due to the fact that VEINES-Sym is the most extensive and complete questionnaire on symptom type and frequency,²⁶ we have preferred to apply this questionnaire in our study. Even so, there are some contrary reports about the feasibility of VEINES-Sym questionnaire in some studies. Van der Velden et al. found that existence of venous symptoms was slightly more often in CVD patients but the difference was small and statistically non-significant. They concluded that symptoms, which are present in VEINES-Sym questionnaire, are less specific for patients suffering from CVD and refluxing veins than is usually thought and the VEINES-QOL/Sym questionnaire is not suitable to use as a diagnostic or screening tool.²⁹

CVD represents a wide spectrum of clinical conditions depending on the effected vascular region.^2,3 Therefore, symptoms of these patients and clinical presentations may vary. In some studies, it has been concluded that patient-reported lower limb symptoms are not specific to CVD. The Bonn Vein Study, which is a population-based trial, indicated that 62.1% of women and 49.1% of men complained from leg symptoms; however, only 27.8% of men and 34.1% of women had CVD above clinical classification C2 and only 35.3% had pathological reflux in the duplex sonographic examination.³⁰ According to the results of the Edinburgh Vein Study, only certain lower limb symptoms such as swelling, cramps, itching in men, and aching and cramps in women were related to the venous reflux on duplex ultrasound examination. The authors concluded that using duplex ultrasound scanning is not suitable to identify the patients with real venous symptoms.³¹ In our study, the percentage of patients suffering from aching, swelling, night cramps, restless legs, and throbbing were found to be higher and mean VEINES-Sym score of these symptoms was found to be significantly lower in varicocele patients. In addition, as previously demonstrated by Kılıç and his colleguaes,⁵ frequency of patients with peripheral varicose vein was higher in varicocele patients compared to patient group without varicocele. However, such an association was not observed in terms of hemorrhoids in our study. We think this contrary result originates from insufficient patient reports. Due to the fact that this is a symptom-based study, we did not perform rectal examination to the patients. Moreover, independent association between varicocele grade and VEINES-Sym has been documented. On the other hand, it is difficult to make a conclusive or definite pathophysiological statement on the causal relationship between the varicocele and CVD. This clinical and symptomatical association between the varicocele and CVD underlines the presence of population who are prone to dilate due to vascular wall abnormality. Since considerable number of patients without varicocele has also CVD and leg symptoms in our study, contributing factors^3,19 such as race differences, family history, obesity, limited physical activity, prolong standing, genetic and chromosomal abnormalities should also be considered in the pathophysiologic course and presentation of venous diseases. Likewise, hip pain due to pelvic venous reflux has been described without leg varicose veins.³² Additionally, any superficial venous reflux without clear clinical signs and non-saphenous leg vein reflux from sources including the pelvic veins^32,33 might have led us to overlook the diagnosis of CVD.

The present study has a few limitations. First, due to the fact that this is a symptom and clinical examination-based study, we did not perform ultrasonographic examination in our study population. Since we did not examine the patients with venous duplex ultrasound, silent superficial venous reflux without any clinical signs might have been missed. Second, our patient group comprised partially younger patients. So these results cannot be attributed to older populations.

In conclusion, we have demonstrated for the first time that varicocele patients have lower VEINES-Sym scores compared to patients without varicocele and this is inversely correlated with the degree of the varicocele. This association supports the hypothesis that there may be a systemic vessel wall abnormality in venous disease patients and warrants further studies to elucidate the pathophysiologic mechanisms. Patients with symptoms related to vascular dilatation in any territory may deserve to be assessed systematically with the support of further clinical studies.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by Vascular and Molecular Cardiology Society.

Ethical approval

The study protocol was approved by The Ethics Committee of Baskent University Faculty of Medicine.

Guarantor

EY.

Authors’ contributions

SO, KTA, EY, SK, LP, MI, IT contributed to the conception and design; EY, KTA, SK, TC, LP, IT, AG, OA, MI were involved in acquisition, analysis and interpretation of data; SO, EY, KTA, TC, LP, IT, AG, SK, OA, MI, EY were involved in drafting the article; SO, EY, LP, IT, KTA, TC, MI were involved in revising it critically for important intellectual content.

Acknowledgements

We would like to thank Ebru Kayadelen for her skillful help on collecting and editing data of patients enrolled in the study.

References

Meissner

. What is effective care for varicose veins? Phlebology 2016; 31: 80–87.

Yetkin

Ileri

. Dilating venous disease: pathophysiology and a systematic aspect to different vascular territories. Med Hypotheses 2016; 91: 73–76.

Eberhardt

Raffetto

. Chronic venous insufficiency. Circulation 2014; 130: 333–346.

Greenfield

Seville

Wan

. Experience with varicoceles in children and young adults. J Urol 2002; 168: 1684–1688. discussion 8.

Kilic

Aksoy

Sincer

et al.

Cardiovascular evaluation of young patients with varicocele. Fertil Steril 2007; 88: 369–373.

Paty

Elash

Turner-Bowker

. Content validity for the VVSymQ(R) Instrument: a new patient-reported outcome measure for the assessment of varicose veins symptoms. Patient 2017; 10: 51–63.

Kutlu

Yilmaz

Cecen

et al.

The Turkish validity and reliability of the venous insufficiency epidemiological and economic study-quality of life/symptoms scales. Angiology 2011; 62: 329–37.

Lamping

Abenhaim

Kurz

et al.

Measuring quality of life and symptoms in chronic venous disorders of the leg: development and psychometric evaluation of the VEINES-QOL/VEINES-SYM questionnaire. Quality Life Res 1998; 7: 621–622.

Dubin

Amelar

. Varicocele. Urol Clin North Am 1978; 5: 563–572.

10.

Padberg

Jr . CEAP classification for chronic venous disease. Dis Mon 2005; 51: 176–182.

11.

Eklof

Rutherford

Bergan

et al.

Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg 2004; 40: 1248–1252.

12.

Beebe-Dimmer

Pfeifer

Engle

et al.

The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol 2005; 15: 175–184.

13.

Robertson

Evans

Fowkes

. Epidemiology of chronic venous disease. Phlebology 2008; 23: 103–111.

14.

Serra

Buffone

de Franciscis

et al.

A genetic study of chronic venous insufficiency. Ann Vasc Surg 2012; 26: 636–642.

15.

Serra

Grande

Butrico

et al.

Epidemiology, diagnosis and treatment of chronic venous disease: a systematic review. Chirurgia-Italy 2016; 29: 34–45.

16.

Yetkin

. Images in vascular medicine. A new or overlooked finding of varicose veins: ecchymosis. Vasc Med 2016; 21: 75–76.

17.

Yetkin

Öztürk

Ileri

. Varicose vein and ecchymosis: a case report. Int Archives Med 2017, pp. 10. doi: 10.3823/2508.

18.

Yetkin

Ileri

Waltenberger

. Ecchymosis: a novel sign in patients with varicose vein. Clin Hemor Microcirc 2018; 68: 413–419. DOI: 10.3233/CH-170320.

19.

Castro-Ferreira

Cardoso

Leite-Moreira

et al.

The role of endothelial dysfunction and inflammation in chronic venous disease. Ann Vasc Surg 2018; 46: 380–393.

20.

Sakamoto

Ogawa

. Is varicocele associated with underlying venous abnormalities? Varicocele and the prostatic venous plexus. J Urol 2008; 180: 1427–31.

21.

Holdstock

Dos Santos

Harrison

et al.

Haemorrhoids are associated with internal iliac vein reflux in up to one-third of women presenting with varicose veins associated with pelvic vein reflux. Phlebology 2015; 30: 133–139.

22.

Kilciler

Sancaktutar

Avci

et al.

Chronic constipation: facilitator factor for development of varicocele. World J Gastroenterol 2011; 17: 2641–2645.

23.

Yetkin

. Hemorrhoid, internal iliac vein reflux and peripheral varicose vein: Affecting each other or affected vessels? Phlebology 2015; 30: 145–145.

24.

Yetkin

Kilic

Acikgoz

et al.

Increased prevalence of varicocele in patients with coronary artery ectasia. Coron Artery Dis 2005; 16: 261–264.

25.

Androulakis

Katsaros

Kartalis

et al.

Varicose veins are common in patients with coronary artery ectasia. Just a coincidence or a systemic deficit of the vascular wall?

Eur J Vasc Endovasc Surg 2004; 27: 519–524.

26.

Catarinella

Nieman

Wittens

. An overview of the most commonly used venous quality of life and clinical outcome measurements. J Vasc Surg Venous Lymphat Disord 2015; 3: 333–340.

27.

Sinabulya

Bergstrom

Hagberg

et al.

Cultural adaptation and validation of the Swedish VEINES-QOL/Sym in patients with venous insufficiency. Phlebology 2018; 33: 540–546.

28.

van der Velden

Biemans

Nijsten

et al.

Translation and validation of the Dutch VEINES-QOL/Sym in varicose vein patients. Phlebology 2014; 29: 227–235.

29.

Van der Velden

Shadid

Nelemans

et al.

How specific are venous symptoms for diagnosis of chronic venous disease?

Phlebology 2014; 29: 580–586.

30.

Maurins

Hoffmann

Losch

et al.

Distribution and prevalence of reflux in the superficial and deep venous system in the general population–results from the Bonn Vein Study, Germany. J Vasc Surg 2008; 48: 680–687.

31.

Bradbury

Evans

Allan

et al.

The relationship between lower limb symptoms and superficial and deep venous reflux on duplex ultrasonography: the Edinburgh Vein Study. J Vasc Surg 2000; 32: 921–931.

32.

Dos Santos

Whiteley

. Pelvic congestion syndrome masquerading as osteoarthritis of the hip. SAGE Open Med Case Rep 2016; 4: 2050313X16683630–2050313X16683630.

33.

Labropoulos

Tiongson

Pryor

et al.

Nonsaphenous superficial vein reflux. J Vasc Surg 2001; 34: 872–877.