BJU International (1999), 84, 1046–1049

The eVect of microsurgical varicocelectomy on serum folliclestimulating hormone, testosterone and free testosteronelevels in infertile men with varicoceleS. CAYAN, A. KADIOGLU*, I . ORHAN*, E . KANDIRALI*, A. TEFEKLI* and S. TE LLALOGLU*Departments of Urology, Faculty of Medicine, Mersin University, Mersin, and *Faculty of Medicine, Istanbul University, Istanbul,Turkey

Objectives To analyse the eCects of varicocelectomy on 32.83 (4.37) pg/mL (P<0.001). In contrast to thesignificant diCerence in sperm motility before and afterserum follicle-stimulating hormone (FSH), testosterone

and free testosterone levels, and to investigate the surgery of all patients (P<0.01), the diCerence insperm count was insignificant (P>0.05). Thirty-sixinterrelationships between seminal and hormonal

variables. patients with high serum FSH levels before surgeryhad significantly lower levels afterward (P=0.001).Patients and methods The records were retrospectively

evaluated for 78 infertile patients who underwent In this group, the sperm concentration and motilityalso increased, from 17.66 (4.35) to 20.76 (4.37)microsurgical inguinal varicocelectomy, with docu-

mented serum FSH, testosterone, free testosterone million/mL (P=0.05) and from 30.9 (4.4)% to37.5 (4.34)%, respectively (P=0.01). In the remain-levels, sperm concentration and sperm motility before

and after surgery. Left and bilateral varicoceles were ing 42 patients who had normal preoperative serumFSH levels, there was a slight decrease after surgerydetected in 40 and 38 patients, respectively. In

addition, serum hormonal values of 10 fertile men in (P=0.02). Their sperm concentration increasedslightly (P=0.04), and motility also increased (P=whom physical examinations and Doppler ultrasono-

graphy revealed no evidence of varicocele were 0.001). Sixty patients had a significantly higher testos-terone level after surgery; in this group the spermrecorded and used as a control group.

Results The mean (sd) serum FSH levels of all patients concentration and motility increased (P=0.01).Conclusion Varicocelectomy promotes Sertoli and Leydigdecreased from 15.21 (3.34) before surgery to

10.82 (2.93) mIU/mL afterward (P=0.01), and serum cell function. The significant increase in serum freetestosterone level results in a significant improvementtestosterone levels increased from 5.63 (1.40) to

8.37 (2.2) ng/mL (P=0.01), whereas free testos- in sperm concentration and motility.Keywords Varicocele, infertility, hormones, surgeryterone levels increased from 23.13 (3.19) to

celectomized patients were statistically insignificant inIntroduction

some studies, while some have reported that serumtestosterone levels have become normal after varico-Although the incidence of varicocele in the general male

population is #15%, it has been implicated as a factor celectomy [7–10].Thus the objective of the present study was to assessresponsible for infertility in about a third of the infertile

population [1,2]. Theories relevant to the pathogenesis the eCects of microsurgical varicocelectomy on serumFSH, testosterone and free testosterone levels, and toof varicocele are hyperthermia, hormonal dysfunction,

increased or decreased testicular blood flow rates, reflux investigate the interrelationships between seminal andhormonal variables.of renal or perirenal metabolites and hypoxia [3].

Weiss et al. [4] reported that in vitro testosteronesynthesis in men with varicoceles was depressed. Other

Patients and methodsstudies have shown that the development of hormonaldysfunction of the Leydig cells was caused by compensa- The study included 78 patients (mean 29.5 years,

sd 6.21, range 21–40) evaluated between January 1994tory proliferation and hyperplasia of the Leydig cells[5,6]. Increases in serum testosterone levels in varico- and January 1996 and who were referred to the out-

patient clinic because of infertility; they were diagnosedas having varicoceles using a detailed history, physicalAccepted for publication 21 July 1999

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MICROSURGICAL VARICOCELECTOMY 1047

Table 1 Sperm quality, FSH, testosteroneand free testosterone levels for all patientsand the subgroups with various levels ofFSH and testosterone

Variable Before surgery After surgery Mean (sem) diCerence

Mean (sem) for all 78 patientsSperm count (million/mL) 23.6 (4.56) 25.6 (4.67) 1.94 (3.2)Motility (%) 29.2 (4.45) 38.5 (4.4)† 9.31 (4.4)FSH (mIU/mL) 15.2 (3.34) 10.8 (2.93)† 4.39 (1.34)Testosterone (ng/mL) 5.63 (1.4) 8.37 (8.37)† 2.74 (1.27)Free testosterone (pg/mL) 23.1 (3.19) 32.8 (4.37)‡ 9.7 (3.23)

Patients withFSH>10 mIU/mL (n=36)FSH 24.0 (3.3) 15.1 (3.24)*Sperm count 17.7 (4.35) 30.9 (4.40)Motility 20.8 (4.37) 37.5 (4.34)*FSH∏10 mIU/mL (n=42)FSH 7.37 (1.74) 6.58 (1.54)Sperm count 28.8 (4.83) 29.2 (4.92)Motility 27.5 (4.53) 39.5 (4.53)‡

No increase in serum testosterone (n=18):Sperm count 29.4 (4.59) 24.4 (4.40)*Motility 28.0 (3.63) 27.0 (4.25)

Increase in serum testosterone (n=60):Sperm count 23.9 (4.83) 26.7 (4.69)†Motility 29.6 (4.64) 42.0 (4.27)†

*P<0.05; †P<0.01; ‡P<0.001.

examinations, sperm analyses and Doppler ultrasono- 9.02 (1.89) and 30.7 (2.75), respectively, and thediCerences between normal and infertile men with var-graphy. The endocrinological evaluation included assays

of serum FSH, testosterone and free testosterone. A icocele was significant (P<0.05). In contrast to thesignificant diCerence in sperm motility before and afterminimum of three preoperative semen samples were

submitted; the semen specimens were collected and surgery, the diCerence in respective sperm counts wasinsignificant (Table 1). Thirty-six patients with FSH levelsevaluated according to the WHO criteria [11]. Left and

bilateral varicoceles were detected in 40 and 38 patients, of >10 mIU/mL before surgery had lower levels after-ward, but their sperm motility significantly increasedrespectively. All patients underwent microsurgical ingui-

nal varicocelectomy, using a testicular-artery and lym- (Table 1). Forty-two patients with FSH levels of∏10 mIU/mL before surgery had no significant changephatic-sparing technique described by Goldstein et al.

[12]. Before and 1 year after the operation, sperm in FSH afterward but their sperm motility also increasedsignificantly (Table 1). Patients with no increase invariables, serum FSH, testosterone and free testosterone

levels were assessed from combined serum samples taken testosterone levels after surgery had lower sperm countsafter surgery; 60 patients with higher testosterone levels20 min apart. Sperm quality in patients with serum FSH

values of > or <10 mIU/mL and in those with increased had higher sperm counts and motility (Table 1).testosterone levels after varicocelectomy were evaluatedseparately. In addition, the serum hormonal values of

Discussion10 fertile men (mean age 30.1 years, sd 5.26, range23–41) whose physical examinations and Doppler ultra- Varicocele not only has deleterious eCects on the hor-

monal aspects of spermatogenesis but also decreasessonography revealed no evidence of varicocele wererecorded and used as the control group. Values are function through testicular hyperthermia, reflux of toxic

metabolites and seminiferous tubular hypoxia secondarypresented as the mean (sem), with Student’s t-test andthe Wilcoxon paired test used for statistical evaluation. to venous stasis. Therefore every patient will not benefit

similarly from varicocelectomy [13]. Su et al. [9] detectedno diCerence between serum FSH and LH levels in

Resultspatients who had undergone microsurgical varico-celectomy, although the serum testosterone levels inIn men with varicocele, serum FSH levels decreased after

surgery, and serum testosterone and free testosterone these patients improved significantly. However, therewas no significant diCerence between the grade of varico-levels increased (Table 1). The FSH, testosterone and free

testosterone levels in normal men were 8.62 (2.02), cele and serum testosterone levels, but the levels in

© 1999 BJU International 84, 1046–1049

1048 S. CAYAN et al.

2 Greenberg SH, Lipschultz LI, Weinn AJ. Experience withpatients with one testis aCected responded more favour-425 sub-fertile male patients. J Urol 1978; 119: 507–10ably than patients with bilateral varicoceles.

3 Pryor JL, Howards SS. Varicocele. Urol Clin N Am 1987;In the present study, there was a statistically signifi-14: 499–513cant increase sperm counts and motility, and a sig-

4 Weiss DB, Rodriguez-Rigau LJ, Smith KD, Steinberger E.nificant increase in serum and free testosterone levelsLeydig cell function in oligospermic men with varicocele.

after varicocelectomy, although the increase was moreJ Urol 1978; 120: 427–30

significant for free testosterone levels (P=0.001). In 5 Ando S, Giacchetto C, Colpi G et al. Plasma levels of 17-OH-contrast to the sperm counts, sperm motility improved progesterone and testosterone in patients with varicoceles.significantly. This may be explained by the recovery of Acta Endocrinol 1983; 102: 463–9testosterone synthesis, essential for epididymal function, 6 Sirvent JJ, Bernat R, Navarro MA, Rodriguez TJ, Guspi R,

Bosch R. Leydig cell in idiopathic varicocele. Eur Urolthe removal of the hyperthermic eCects of the varicocele1990; 17: 257–61and the amelioration of epididymal function, resulting

7 Hudson RW, Perez-Marrero RA, Crawford VA, McKay DE.in testicular hypothermia [14]. However, varico-Hormonal parameters of men with varicoceles before andcelectomy does not necessarily improve sperm valuesafter varicocelectomy. Fertil Steril 1985; 43: 905–10proportionally to the amelioration in hormonal and

8 Segenreich E, Shummuely H, Singer R, Servadio C.spermatogenetic function.Andrological parameters in patients with varicocele and

Fujisawa et al. [15] performed high ligation in 25fertility disorders treated by high ligation of the left

adolescents with varicoceles; sperm quality improved in spermatic vein. Int J Fertil 1986; 31: 200–317 patients but the authors detected no significant 9 Su LM, Goldstein M, Schelegel P. The eCect of varico-diCerences in serum testosterone levels before and after celectomy on serum testosterone levels in infertile mensurgery. Podesta et al. [16] carried out varicocelectomy with varicoceles. J Urol 1995; 154: 1752–5

10 Comhaire F, Vermeulen A. Plasma testosterone in patientsin 25 adolescent males with varicoceles and rec-with varicocele and sexual inadequacy. J Clin Endocrinolommended it for adolescent varicocele. In that study,Metab 1975; 40: 824–9serum testosterone levels and testicular volume

11 World Health Organization. Laboratory Manual for theimproved, but they detected no change in serum LH andExamination of Human Semen and Semen–Cervical MucusFSH values. Haans et al. [17] assessed testicular volume,Interaction, 3rd edn. New York: Cambridge Universitysemen quality and hormonal variables in normal individ-Press, 1993

uals and adolescents with varicoceles; they found no12 Goldstein M, Gilbert BR, Dicker AP, Dwosh J, Gnecco C.

diCerence between the groups in hormone levels but Microsurgical inguinal varicocelectomy with delivery ofthere was a prominent decrease in sperm counts in the the testis: an artery and lymphatic sparing technique.adolescents with varicoceles, in accord with the dysfunc- J Urol 1992; 148: 1808–11tion of the testes. In a series of 145 patients, Plymate 13 Nagler HM, Luntz RK, Martinis FG. Varicocele. In Lipshultz

LI, Howards SS, eds. Infertility in the Male, 3rd edn, Stet al. [18] found marked increases in serum FSH levels,Louis, Missouri: Mosby Year Book, 1997: 336–59contrasting with the deterioration in sperm quality. They

14 Schlegel PN, Chang TSK. The testis, epididymis, and ductusreported that serum inhibin, an indicator of seminiferousdeferens. In SwerdloC RS, Wang C, eds. Physiology of Maletubule function, could be used to assess these patients.Reproduction. Campbell’s Urology, 6th edn, Philadelphia: WBIn the present study, there was also a significant decreaseSaunders, 1992: 208in serum FSH levels after surgery that might be explained

15 Fujisawa M, Hayashi A, Imanishi O et al. The significanceby the improvement in Sertoli cell function. of gonadotropin-releasing hormone test for predicting

Varicocelectomy probably has positive eCects on Leydig fertility after varicocelectomy. Fertil Steril 1994; 61:cell function. Defective testosterone synthesis has been 779–82reported to be associated with varicocele [5,19], probably 16 Podesta M, Gottlieb S, Medel R, Ropelato G, Bergada C,through intratesticular hyperthermia, which inhibits Quesada EM. Hormonal parameters and testicular, in

children and adolescents with unilateral varicocele:17a-hydroxyprogesterone aldolase, an enzyme respon-Preoperative and postoperative findings. J Urol 1994;sible for the conversion of 17a-hydroxyprogesterone to152: 794–8testosterone [20,21]. Thus both Leydig cell function and

17 Haans LC, Laven JSE, Mali WPTM, Velde ER, Wensing CJG.serum free testosterone levels should be improved onTestis, semen quality, and hormonal patterns in adolescentsremoving the inhibition of 17a-hydroxyprogesteronewith and without a varicocele. Fertil Steril 1991; 56: 731–6

aldolase by relieving intratesticular hyperthermia18 Plymate SR, Paulsen CA, McLachlan RI. Relationship of

through varicocelectomy. serum inhibin levels to serum follicle stimulating hormoneand sperm production in normal men and men withvaricoceles. J Clin Endocrinol Metab 1992; 74: 859–64

References 19 Takeyama M, Honjoh M, Kodama M et al. Testicularsteroids in spermatic and peripheral veins after single1 Saypol DC. Varicocele. J Androl 1986; 2: 61–71

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injection of HCG in patients with varicocele. Arch Androl Authors1990; 24: 207–13 S. Cayan, MD, Assistant Professor of Urology.

20 Goldstein M, Eid JF. Elevation of intratesticular and scrotal A. Kadioglu, MD, Associate Professor of Urology.skin surface temperature in men with varicocele. J Urol I. Orhan, MD, Specialist of Urology.1989; 142: 743–5 E. Kandirali, MD, Resident of Urology.

21 Wright EJ, Young GP, Goldstein M. Reduction in testicular A. Tefekli, MD, Resident of Urology.temperature after varicocelectomy in infertile men. Urology S. Tellaloglu, MD, Professor of Urology.1997; 5: 257–9 Correspondence: Dr S. Cayan, P.K. 202, Tarsus, 33400 Turkey.

e-mail: selahittincayan@superonline.com

© 1999 BJU International 84, 1046–1049