TESTICULAR HYPOTROPHY DOES NOT CORRELATE WITH GRADE OFADOLESCENT VARICOCELE

JOSEPH P. ALUKAL,* DAVID ZURAKOWSKI, ANTHONY ATALA, STUART B. BAUER,JOSEPH G. BORER, BARTLEY G. CILENTO, JR., JAMES MANDELL, CRAIG A. PETERS,

HARRIET J. PALTIEL, ALAN B. RETIK AND DAVID A. DIAMONDFrom the Department of Urology, Children’s Hospital Boston, Boston, Massachusetts

ABSTRACT

Purpose: Testicular hypotrophy is the most widely accepted indication for correcting adolescentvaricocele. Previous studies in adolescents have shown a relationship between increasing gradeof varicocele and the likelihood of testicular hypotrophy. As this relationship has significantclinical implications, we studied the correlation between grade and testicular volume dispropor-tion in our adolescent varicocele population.

Materials and Methods: We reviewed the adolescent varicocele database at our institution. Atotal of 168 patients 8 to 21 years old were studied. We routinely calculated testis volumes usingscrotal ultrasound. Testicular disproportion was calculated using the equation [(size of unaf-fected testis) � (size of affected testis)]/(size of unaffected testis) � 100%. Disproportion wascategorized as less than 10%, 10% to 20% and more than 20%. Varicoceles were graded by anattending urologist with the patient standing, using the system of Dubin and Amelar. Analysisof variance and Pearson chi-square indicated no significant differences in volume differentialbetween varicocele grades.

Results: Mean � SD volume differential was 18% � 15% for grade I, 25% � 20% for grade IIand 19% � 14% for grade III. ANOVA revealed no significant difference in mean volumedifferential between the 3 varicocele grades (p � 0.10). When categorizing patients into 3 levelsof volume differential (less than 10%, 10% to 20%, more than 20%) no significant correlation wasobserved between varicocele and volume differential (p � 0.48, chi-square test).

Conclusions: Grade of varicocele does not correlate with presence or severity of testiculardisproportion in adolescent boys with varicocele as measured by scrotal ultrasound.

KEY WORDS: varicocele, adolescent, testis, growth and development

Varicocele is a common condition in adolescent boys, withan incidence of 15%.1 In adolescents testicular growth failurehas been the most widely accepted indication for surgicalrepair of varicocele, and reversal of testicular size discrep-ancy in the majority of boys has been observed followingspermatic vein ligation.2

Management of varicocele in adolescents remains contro-versial. The relationship between grade of varicocele, inci-dence of testicular growth arrest and further likelihood ofdecreased fertility has not been clearly elucidated.3–5 Someinvestigators are proponents of repairing severe varicoceles,regardless of the presence or absence of testicular growtharrest. Severe (grade III) varicoceles are presumed to bemore injurious to the testis, and, therefore, potentially morelikely to cause growth arrest and impairment of testicularfunction.2, 3, 6

A recent report by Thomas and Elder demonstrated a cor-relation between varicocele grade in adolescents and likeli-hood of testicular growth arrest.6 This retrospective analysiscompared testicular hypotrophy, defined as 15% volume dif-ferential based on caliper measurements, with grade of var-icocele as measured on physical examination. In an effort tostudy further the relationship between varicocele grade inadolescents and testicular hypotrophy we reviewed the data-base of patients with varicoceles at our institution.

MATERIALS AND METHODS

We retrospectively considered 168 boys with varicoceletreated at our institution between June 1996 and January2004. Mean patient age was 14.9 years (SD 2.5, range 8 to21). Varicoceles were graded by 1 of 8 attending urologists,with the patient standing. Grade III varicoceles were visibleto the examiner, grade II varicoceles were easily palpable butnot visible and grade I varicoceles were palpable with theValsalva maneuver.

Testis volumes were calculated using scrotal ultrasound byan attending radiologist, using a technique described previ-ously.7 Testicular disproportion was determined using theformula [(size of unaffected testis) � (size of affected testis)]/(size of unaffected testis) � 100%. Testicular volume differ-ential was categorized as less than 10%, 10% to 20% orgreater than 20%.

Boys with bilateral varicocele on examination or solitarytestis were excluded from consideration. Those boys in whomthe testis on the affected side was larger than the contralat-eral side on ultrasound were included in the less than 10%differential category (based on the reasoning that the af-fected testis was not arrested in size despite the presence ofvaricocele). Because some boys underwent only 1 ultrasound,for those boys in whom multiple ultrasounds were obtainedultrasound at time of initial presentation was used.

Testicular volume differential was compared between var-icocele grades by analysis of variance (ANOVA) with Bonfer-roni correction.8 No significant departure from normalcy wasdetected for volume differential based on the Kolmogorov-Smirnov goodness-of-fit statistic. Therefore, the mean and

Submitted for publication March 4, 2005.*Correspondence: Department of Urology, Children’s Hospital

Boston, Hunnewell-3, 300 Longwood Ave., Boston, Massachusetts02115 (e-mail: joseph.alukal@bmc.org, david.diamond@childrens.harvard.edu).

0022-5347/05/1746-2367/0 Vol. 174, 2367–2370, December 2005THE JOURNAL OF UROLOGY® Printed in U.S.A.Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000180418.23208.1d

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standard deviation were used to summarize the data. Inaddition, the association between varicocele grade and vol-ume differential category was evaluated using the Pearsonchi-square test. A power analysis indicated that a minimumsample size of 25 patients within each varicocele grade would

provide 90% power to detect a difference of 10% in differen-tial volume among the 3 grades (nQuery Advisor®, version5.0). Two-tailed values of p �0.05 were regarded as statisti-cally significant. Analysis of the data was conducted usingSPSS® version 12.0.

A, comparison of testicular volume differential among patients with varicocele grades I, II and III. Mean volume differential was notsignificantly different among groups based on F test in ANOVA (p � 0.10). Mean values � SD were 18% � 15% for grade I, 25% � 20% forgrade II and 19% � 14% for grade III varicoceles. B, comparison of testicular volume differential among patients younger than 15 years withvaricocele grades I, II and III. Mean volume differential was not significantly different among groups based on ANOVA (p � 0.27). Meanvalues were 23% � 17% for grade I, 27% � 22% for grade II and 20% � 15% for grade III varicoceles. C, comparison of testicular volumedifferential among patients 15 years or older with varicocele grades I, II and III. Mean volume differential was not significantly differentamong groups based on ANOVA (p � 0.13). Mean values were 11% � 9% for grade I, 23% � 21% for grade II and 17% � 15% for grade IIIvaricoceles.

TESTICULAR HYPOTROPHY DOES NOT CORRELATE WITH VARICOCELE GRADE2368

RESULTS

Among the patients 26 (15%) had grade I, 61 (36%) hadgrade II and 81 (48%) had grade III varicocele. ANOVAdisplayed no significant differences in mean volume differen-tial between the 3 varicocele grades (F � 2.47, p � 0.10). Asshown in part A of the figure, mean volume differential was18% � 15% for grade I, 25% � 20% for grade II and 19% �14% for grade III. Bonferroni comparisons indicated no dif-ference in volume differential between grades I and II(p � 0.32), grades I and III (p � 0.98) or grades II and III(p � 0.11).

When segregating the data according to patient age lessthan 15 years versus 15 years or greater there were 92patients younger than 15 years and 76 who were 15 or older.Of the younger group 18 (20%) had grade I, 29 (32%) hadgrade II and 45 (49%) had grade III varicocele. ANOVArevealed no significant differences in mean volume differen-tial between the 3 varicocele grades (F � 1.34, p � 0.27). Asdemonstrated in part B of the figure, mean volume differen-tial was 23% � 17% for grade I, 27% � 22% for grade II and20% � 15% for grade III.

Of the older group 8 (11%) had grade I, 32 (42%) had gradeII and 36 (47%) had grade III varicocele. ANOVA displayedno significant differences in mean volume differential be-tween the 3 varicocele grades (F � 2.12, p � 0.13). As shownin part C of the figure, mean volume differential was 11% �9% for grade I, 23% � 21% for grade II and 17% � 15% forgrade III.

When categorizing patients into 3 levels of volume differ-ential (less than 10%, 10% to 20%, more than 20%) no sig-nificant difference was observed between varicocele grades,indicating that volume differential is independent of gradefor all patients (Pearson chi-square 3.51 on 4 df, p � 0.48),patients younger than 15 years (Pearson chi-square � 5.90on 4 df, p � 0.21) and patients 15 years or older (Pearsonchi-square � 4.15 on 4 df, p � 0.39, see table). Considering allpatients, volume differential was less than 10% in 91, 10% to20% in 23 and more than 20% in 54.

The most clinically significant volume differential was de-fined as more than 20% between involved and uninvolvedtestes. This finding was identified in 32% of patients overall(54 of 168), with no significant differences between grades(grade I 31%, grade II 39%, grade III 27%, see table). Com-pared to grades II and III, a higher percentage of boys withgrade I varicocele had testicular volume differentials lessthan 10%, although this relationship was not statisticallysignificant.

DISCUSSION

Adolescent varicocele is a common problem that may leadto future fertility issues.3, 9, 10 Surgical correction during ad-olescence has been reserved for those patients who exhibitsignificant hypotrophy of the affected testis, pain or an ab-normal semen analysis. Others have attempted to find acorrelation between varicocele grade and likelihood of hypo-trophy of the affected testis,6 implying that grade III varico-celes should be corrected prophylactically because of the in-creased likelihood of growth arrest developing with time.

The purpose of our study was to determine whether acorrelation exists between grade of varicocele and testicularhypotrophy in adolescents. Ultrasound measurements wereused to assess testicular size discrepancy, as this method haspreviously been found in dogs to provide a more accuratemeasurement of testicular size differential than orchidom-eter.7 Size discrepancy was separated into 3 categories, ieless than 10%, 10% to 20% and greater than 20%. These 3categories were chosen because previous studies have re-vealed that 10% size variance between testes without asso-ciated abnormalities is normal.11 In addition, a previousstudy at this institution demonstrated that a 10% differenceis the minimum that can be reliably determined on ultra-sound.7

In a previous study of 117 patients Thomas and Elderfound a correlation between grade III (as opposed to grade II)varicocele and likelihood of hypotrophy.6 In that series pa-tient age ranged from 7 to 18 years. Testicular size meas-urements were performed using calipers, and hypotrophywas defined as a size differential greater than 15%. In addi-tion, in patients with multiple measurements size differen-tials were calculated based on the caliper measurementshowing greatest discrepancy.

Another series by Sigman and Jarow looked retrospec-tively at 611 adults with left varicocele, of whom 50% hadipsilateral hypotrophy.12 In that study hypotrophy was de-fined as a 3 cc difference in the size of the testes, and testic-ular size was measured using a Takihara orchidometer. Ofpatients with large (grade III) varicoceles 73% exhibited ip-silateral hypotrophy, compared to 55% of patients with gradeII and 49% of those with grade I varicocele. While the pa-tients with grade III varicocele had a statistically higherlikelihood of hypotrophy, there was no difference betweenpatients with grade I and grade II varicocele.

Our series did not reveal a direct correlation between var-icocele grade and testicular hypotrophy. Our series differedfrom previously published series most notably in the use ofultrasound for measurement of testicular volumes, which is

Comparison of testicular volume differential according to varicocele grade

Varicocele Grade Less Than 10%Differential Category

10%–20% More Than 20% Totals

No. all pts (%):Grade I 16 (62) 2 (8) 8 (31) 26Grade II 29 (48) 8 (13) 24 (39) 61Grade III 46 (57) 13 (16) 22 (27) 81

Totals 91 (54) 23 (14) 54 (32) 168No. pts younger than 15 yrs (%):

Grade I 11 (61) 0 (0) 7 (39) 18Grade II 11 (38) 6 (21) 12 (41) 29Grade III 25 (56) 7 (16) 13 (29) 45

Totals 47 (51) 13 (14) 32 (35) 92No. pts 15 yrs old or older (%):

Grade I 5 (63) 2 (25) 1 (13) 8Grade II 18 (56) 2 (6) 12 (38) 32Grade III 21 (58) 6 (17) 9 (25) 36

Totals 44 (58) 10 (13) 22 (29) 76Percentages may total more than 100 due to rounding.

TESTICULAR HYPOTROPHY DOES NOT CORRELATE WITH VARICOCELE GRADE 2369

potentially more accurate. The study by Sigman and Jarowdemonstrated testicular size differential in 50% of a largeseries of adult patients. This percentage is significantlyhigher than that in the series by Thomas and Elder6 or in ourseries, both of which studied adolescent populations. It ispossible that hypotrophy in relation to varicocele requires along period to develop. In addition, it is possible that factorsas yet unidentified may influence testicular growth in ado-lescents.

Our results showed no difference in relationship of varico-cele severity to hypotrophy based on age. This analysis wasperformed using a cutoff of 15 years, beyond which mostadolescents are considered postpubertal. In the younger andolder patients no significant association between grade ofvaricocele and hypotrophy was identified. This finding ar-gues against the possibility that the effect of a varicoceleneeds to be present during specific periods of pubertal devel-opment for clinically significant hypotrophy to occur.

Limitations of our study include low number of grade Ivaricoceles, referral bias and observer variability. First, 26patients with grade I varicocele were included in our analy-sis, and although this number was adequate in terms of thestatistical power of our conclusions, more patients in thiscohort would have been ideal. With regard to referral bias, itseems likely that many cases of low grade varicoceles withoutassociated hypotrophy would have remained undiagnosed orwould not have been referred for further evaluation. Finally,8 attending urologists and several radiologists and techni-cians were called on to grade varicoceles and to measuretesticular size, introducing the possibility of interobservervariability.

CONCLUSIONS

Our findings suggest that varicocele grade and volumedifferential in adolescents are independent variables. Long-term sequential study of individual patients should help todetermine whether a relationship between these factors de-velops in adulthood.

REFERENCES

1. Akbay, E., Cayan, S., Doruk, E., Duce, M. N. and Bozlu, M.: Theprevalence of varicocele and varicocele-related testicular atro-phy in Turkish children and adolescents. BJU Int, 86: 490,2000

2. Kass, E. J. and Belman, A. B.: Reversal of testicular growthfailure by varicocele ligation. J Urol, 137: 475, 1987

3. Sawczuk, I. S., Hensle, T. W., Burbige, K. A. and Nagler, H. M.:Varicoceles: effect on testicular volume in prepubertal andpubertal males. Urology, 41: 466, 1993

4. Kass, E. J., Chandra, R. S. and Belman, A. B.: Testicular histol-ogy in the adolescent with a varicocele. Pediatrics, 79: 996,1987

5. Paduch, D. A. and Niedzielski, J.: Semen analysis in young menwith varicocele: preliminary study. J Urol, 156: 788, 1996

6. Thomas, J. C. and Elder, J. S.: Testicular growth arrest andadolescent varicocele: does varicocele size make a difference?J Urol, suppl., 168: 1689, 2002

7. Diamond, D. A., Paltiel, H. J., DiCanzio, J., Zurakowski, D.,

Bauer, S. B., Atala, A. et al: Comparative assessment of pedi-atric testicular volume: orchidometer versus ultrasound.J Urol, 164: 1111, 2000

8. Armitage, P., Berry, G. and Matthews, J. N. S.: Statistical Meth-ods in Medical Research, 4th ed. Oxford: Blackwell ScienceLtd., pp. 208–227, 2002

9. Pryor, J. L. and Howards, S. S.: Varicocele. Urol Clin North Am,14: 499, 1987

10. Takihara, H., Cosentino, M. J., Sakatoku, J. and Cockett, A. T.:Significance of testicular size measurements in andrology: II.Correlation of testicular size with testicular function. J Urol,137: 416, 1987

11. Zachmann, M., Prader, A., Kind, H. P., Hafliger, H. andBudliger, H.: Testicular volume during adolescence. Cross-sectional and longitudinal studies. Helv Paediatr Acta, 29: 61,1974

12. Sigman, M. and Jarow, J. P.: Ipsilateral testicular hypotrophy isassociated with decreased sperm counts in infertile men withvaricoceles. J Urol, 158: 605, 1997

EDITORIAL COMMENT

This is an important retrospective analysis showing that varico-cele grade does not correlate with presence or severity of testiculardisproportion. Varicocele management is still a challenge. Of adultswith primary infertility 40% have a varicocele,1 and correction canlead to improved semen analysis in 60% (reference 9 in article). Onthe other hand, most varicoceles in healthy adolescents and adultsare obviously not causing significant problems in terms of fertility orpain. Unfortunately, different studies have used a variety of methodsfor volume assessment, and whenever different observers are per-forming sonographic volume measurement the interobserver vari-ability may be quite high.

It is a fact that after successful varicocele repair a reversal oftesticular size discrepancy can be observed. However, is this findingreally a catch-up growth phenomenon, or maybe only testicularedema due to division of lymphatic vessels during surgery?2 Onemajor issue would be to look at the function of these testes. Isfunction (endocrine and exocrine) really a matter of size in a certainmanner? Functional results (semen analysis) would help to deter-mine the answer. Prospective longitudinal observation with func-tional analysis is mandatory to rule out a possible relationshipbetween varicocele grade and volume differential.

Christian RadmayrDepartment of Pediatric UrologyMedical University InnsbruckInnsbruck, Austria

1. Gorelick, J. I. and Goldstein, M.: Loss of fertility in men withvaricocele. Fertil Steril, 59: 613, 1993

2. Kocvara, R., Dolezal, J., Hampl, R., Povysil, C., Dvoracek, J.,Hill, M. et al: Division of lymphatic vessels at varicocelectomyleads to testicular oedema and decline in testicular functionaccording to the LH-RH analogue stimulation test. Eur Urol,43: 430, 2003

REPLY BY AUTHORS

We agree that functional assessment of this patient population isan important next step in determining the impact of adolescentvaricocele on fertility. To that end, we are currently accumulatingsemen analysis data from patients presenting to our institution.

TESTICULAR HYPOTROPHY DOES NOT CORRELATE WITH VARICOCELE GRADE2370