LOW PLASMA TESTOSTERONE IN VARICOCELE PATIENTS WITH IMPOTENCE AND MALE INFERTILITY

Archives of Andrology Journal of Reproductive Systems ISSN: 0148-5016 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/iaan19 LOW PLASMA TESTOSTERONE IN VARICOCELE PATIENTS WITH IMPOTENCE AND MALE INFERTILITY Abdel Khalek Hassan Younes To cite this article: Abdel Khalek Hassan Younes (2000) LOW PLASMA TESTOSTERONE IN VARICOCELE PATIENTS WITH IMPOTENCE AND MALE INFERTILITY, Archives of Andrology, 45:3, 187-195, DOI: 10.1080/01485010050193968 To link to this article: https://doi.org/10.1080/01485010050193968 Published online: 09 Jul 2009. Submit your article to this journal Article views: 33 View related articles Citing articles: 15 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalinformation?journalcode=iaan19 Download by: [46.3.194.212] Date: 29 December 2017, At: 17:26

ARCHIVES OF ANDROLOGY 45:187 195 (2000) Copyright ã 2000 Taylor & Francis 0148-5016 /00 $12.00 +.00 LOW PLASMA TESTOSTERONE IN VARICOCELE PATIENTS WITH IMPOTENCE AND MALE INFERTILITY ABDEL KHALEK HASSAN YOUNES Department of Andrology, Al Azhar University, Cairo, Egypt To study the affect of bilateral varicocele (grade 3) on impotence and male infertility patients, 29 patients were selected from an outpatient clinic during 15 May 1998 to 15 August 1999 (the mean age was 33.9 ± 6.3), 15 patients complaining of erectile dysfunction and 14 patients complaining of male infertility. The mean duration of impotence was 3 ± 2.3 years and for male infertility was 6 ± 2.5. All organic and psychogenic causes related to impotence and male infertility except bilateral varicocele (grade 3) and low plasma testosterone were excluded by clinical and laboratory investigations. Twenty males with normal erection and fertility were included as controls. Detailed medical history and complete physical examination included measurement of testicular size by orchiometer; semen and hormonal parameters were measured for all patients and control. In impotent patients left and right testicular volume was significantly decreased (p <.05), while in male infertility patients left and right testicular volume was highly significantly and, significantly decreased (p <.005, p <.05) compared to controls. In male infertility patients, left testicular volume was highly significantly decreased compared to impotent patients (p <.005). The sperm count and semen volume in impotent patients was significantly decreased (p <.05, p <.01), but no significant differences were found in sperm motility and abnormal forms, while in male infertility the sperm count was highly significantly decreased (p <.005), the sperm motility was significantly decreased (p <.05), the abnormal form was significantly increased (p <.05), but in the semen volume there was no significant difference compared to controls. In impotent patients the sperm count was significantly increased and abnormal form was significantly decreased compared to male infertility (p <.05). The mean serum testosterone was significantly decreased in impotent patients (p <.01), and highly significantly decreased in male infertility (p <.005) compared to controls. The mean serum FSH was significantly increased in male infertility (p <.05) and nonsignificant in impotent patients compared to controls. The mean serum LH and prolactin levels were nonsignificant in both impotent and male infertility patients compared to controls, but LH was significantly increased in impotence compared to male infertility patients (p <.025). Therefore, bilateral varicocele (grade 3) is associated with significant reduction in testicular function with significant increase in serum levels of FSH and LH, which may cause erectile dysfunction and male infertility. Keywords plasma, testosterone, varicocele, infertility, impotence During the last century much attention has been given to varicocele as a potential cause of testicular dysfunction and subsequent male infertility, but with little information about the possible relationship between varicocele and erectile failure. Few studies reported the correlation between varicocele and sexual dysfunction [4, 19, 28]. In spite of that, it is not less Address correspondence to Dr. Abdel Khalek Hassan Younes, Department of Andrology, Al Thomairy General Hospital, P.O. Box 1666, Al Khobar 31952, Kingdom of Saudi Arabia. 187

188 A. K. H. Younes common to diagnose both conditions associated with each other clinically. Studies in animals [10, 16, 24, 33, 34] and humans [21, 32] suggest that varicocele causes progressive durationdependent testicular damage. Rodriguez et al. [30] and Ghosh and York [11] demonstrated, in animal studies, the low level of serum testosterone biosynthesis in testis associated with varicocele. Nagao et al. [23] and Nieschlag et al. [26] suggested in human studies that varicocele may be associated with poor semen and hormonal parameters, with increased follicle-stimulating hormne (FSH) values, indicating damage to the germinal epithelium and a poor prognosis. Comhaire and Vermeulen [4] found low level of mean serum testosterone in patients with varicocele and sexual dysfunction. Kim and Choi [19] detected possible relationship between varicocele and erectile dysfunction. Gorelick and Goldstein [12] reported lower level of serum testosterone and increased level of FHS in infertile men with varicocele. Varicocele is also associated with decreased testicular size and impaired sex accessory gland secretion with lower semen quality [1, 14, 18]. The aim of this study was to evaluate the local effect of bilateral varicocele on testicular function, especially the mean serum testosterone level as well as testicular volume, semen analysis, and hormonal parameters in erectile dysfunction and male infertility patients. MATERIALS AND METHODS Twenty-nine male patients with bilateral varicocele (grade 3) with mean age 33.9 ± 6.3 (15 patients presented by erectile dysfunction and 14 patients by male infertility) were selected from outpatient clinic during the period of 15 May 1998 to 15 August 1999. The mean duration for impotent patients was 3 ± 2.3 years and for male infertility patients was 6 ± 2.5 years. Detailed medical history was obtained from each of the 29 patients. For the first group, which presented with erectile dysfunction, complete sexual history was taken, including libido, morning erection, duration and percentage of erection, positioning, course, sexual interest, frequency of erection per week, and causes of impotence, including psychogenic and organic (venogenic, arteriogenic, endrocrinogenic, and neurogenic). For the second group, which presented with infertility, reproductive history was obtained, including age of partners, duration of infertility, previous pregnancies, and pregnancy outcome. All organic and psychogenic causes related to impotence male infertility except bilateral varicocele (grade 3) and low plasma testosterone were excluded by clinical and laboratory investigation. Physical examination was performed on all the 29 patients, including general examination, thyroid gland dysfunction, presence of the secondary sexual characters and the presence of gynecomastia, with assessment of span and height to exclude obesity. The diagnosis of varicocele was based on local examination of both testicles and spermatic cords in the erect and supine positions using the Valsalva maneuver. Varicoceles were graded according to Dubin and Amelar [7] into small (grade I), detected only during the Valsalva maneuver; moderate (grade II), easily palpated without the Valsalva maneuver, and grade 3, causing visible bulging of the scrotal skin. Men with subclinical varicocele (diagnosed only by Doppler and by sonagraphy) and those with grade I and II varicocele were excluded from this study. Testis volumes were measured using an orchiometer according to Takihara et al. [37]. The orchiometer was fitted over the stretched anterior scrotal skin with exclusion of the head and body of the epididymis, while the volume was recorded. The local examination also included

Testosterone in Varicocele Infertile Men 189 the penis size, sensation, and the presence of fibrous plaque. Intracorporal injection of prostaglandin E1 (20 IU) was done for all 15 patients with erectile dysfunction; complete full erection occurred within 15 min of injection and detumescenea within 2 h. Semen was obtained by masturbation after 3 days of abstinence and examined within 30 min of ejaculation. Semen volume, sperm concentration, percent progression of motility, and morphology were recorded according to WHO [40]. Testing for antibody coating of sperm was achieved using the mixed antiglobulin reaction test. Hormonal measurements, including serum testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin, were determined by enzyme immune assay from Abbott Diagnostics (USA). Twenty fertile males with mean age 31.2 ± 4.3 were subjected to the previous measurements, including testicular volume and semen and hormonal parameters as for impotent and infertile patients and were included as controls. Student s t test compared mean values of control, impotent, and infertile subjects. The difference was considered statistically significant when p value was <.05. RESULTS Testicular Volume (Table 1, Figure 1) Left and right testicular volumes of impotent patients were statistically significantly decreased compared to normal control (p <.05). Left testicular volume of infertile male was highly significantly decreased compared to normal control and to impotent patients (p <.005). Right testicular volume of male infertility patients was significantly decreased compared to normal control (p <.025). Semen Parameters (Table 2, Figure 2) The semen volume was significantly decreased in impotent patients (p <.01) compared to normal control while it was nonsignificant in male infertility patients compared to both normal control and to impotent patients (p >.10). The sperm count was highly significantly decreased in male infertility patients (p <.005), significantly decreased in impotent patients (p <.05) compared to normal control and significantly increased compared of impotence and male infertility patients (p <.05). Table 1. Mean ± SE of testis volume with bilateral varicocele (grade 3) in impotent and male infertility patients with normal controls P value Male Control Impotence infertility Male Impotence (N = 20) (N = 15) (N = 14) Impotence infertility to male mean ± SD mean ± SD mean ± SD to control to control infertility Left 2.3 ± 2.3 19.2 ± 2.5 18.14 ± 2.1 <.05 <.005 <.005 (S) (HS) (HS) Right 21.3 ± 2.4 2.13 ± 2.6 2.2 ± 2.2 <.05 <.025 >.40 (S) (S)

190 A. K. H. Younes 22.00 21.50 21.00 20.50 20.00 19.50 19.00 18.50 18.00 17.50 17.00 16.50 20.30 21.30 19.20 20.13 20.20 The sperm motility was significantly decreased in male infertility patients (p <.05) compared to normal control, while no significant difference was found in impotent patients compared to normal control and male infertility patients (p >.10). Nonsignificant difference was found in abnormal forms in impotent patients (p >.10), while it was significantly increased in male infertility (p <.05) compared to normal control and significantly decreased in impotent patients compared to male infertility patients (p <.01). 18.14 Control Impotence Male Infertility Left Right Figure 1. Mean ± SE of testis volume with bilateral varicocele (grade 3) in impotent and male infertility patients with normal controls. Table 2. Mean ± SE of semen parameters with bilateral varicocele (grade 3) in impotent and male infertility patients with normal controls P value Male Control Impotence infertility Male Impotence Semen (N = 20) (N = 15) (N = 14) Impotence infertility to male parameters mean ± SD mean ± SD mean ± SD to control to control infertility Volume 2.8 ± 1.4 1.8 ± 1.3 2.3 ± 1.09 <.01 >.10 >.10 (S) Count 49.2 ± 2.3 48.3 ± 1.3 47.3 ± 2.9 <.05 <.005 <.05 (S) (HS) (S) Motility 4.5 ± 1.3 4.3 ± 1.8 39.6 ± 1.9 >.10 <.05 >.10 (S) Abnormal 21.6 ± 2.7 21.2 ± 2.7 22.8 ± 2.8 >.10 <.05 <.01 form (S) (S)

Testosterone in Varicocele Infertile Men 191 60.00 47.30 48.30 49.20 50.00 40.50 39.60 40.30 Volume 40.00 Count 30.00 21.60 Motility 22.80 21.20 Abnormal Form 20.00 10.00 2.80 2.30 1.80 0.00 Control Impotence Male Infertility Figure 2. Mean ± SE of semen parameters with bilateral varicocele (grade 3) in impotent and male infertility patients with normal controls. Hormonal Parameters (Table 3, Figure 3) Serum testosterone was highly significantly decreased in male infertility patients (p <.005), significantly decreased in impotent patients (p <.01) compared to normal control but no significant difference were found between impotence and male infertility patients (p >.40). Serum FSH was significantly increased in male infertility patients compared to normal control (p <.05), but nonsignificant in impotent patients in comparison to normal control and male infertility patients (p >.10). Table 3. Mean ± SE of hormonal parameters with bilateral varicocele (grade 3) in impotent and male infertility patients with normal controls P value Hormonal parameter Control (N = 20) mean ± SD Impotence (N = 15) mean ± SD Male infertility (N = 14) mean ± SD Testosterone 6.04 ± 1.58 4.97 ± 1.24 4.8± 1.93 FSH 8.27 ± 2.3 8.47 ± 1.53 8.58 ± 1.12 LH 4.68 ± 1.55 4.20 ± 1.46 3.15 ± 1.54 11.59 ± 1.84 11.12 ± 1.66 10.97 ± 1.68 Prolactin Impotence to control Male infertility to control Impotence to male infertility <.01 (S) <.10 <.005 (HS) <.05 (S) >.40 >.10 >.10 <.10 <.025 (S) >.10 >.10 >10

192 A. K. H. Younes 14.00 11.59 12.00 10.00 11.12 10.97 8.58 8.47 8.27 8.00 6.00 6.04 4.68 4.97 4.20 4.00 4.80 3.15 Testosterone FSH LH Prolactin 2.00 0.00 Control Impotence Male Infertility Figure 3. Mean ± SE of hormonal parameters with bilateral varicocele (grade 3) in impotent and male infertility patients with normal controls. Serum LH was nonsignificant in impotent and male infertility patients compared to normal control (p >.10) and significantly increased in impotent compared to male infertility patients (p <.025). Serum prolactin, was nonsignificant in impotence and male infertility patients (p >.10) compared to normal control. DISCUSSION Varicocele is a common finding on the physical examination of young men. Although few studies reported the correlation between varicocele and erectile failure [4, 19, 28], the incidence of varicocele in infertile men is increased compared with the incidence in the general population; many men with varicocele have children. The association between varicocele, abnormal semen parameters, and infertility is generally accepted but is not fully elucidated [6, 8, 13, 25, 27, 29, 35, 38, 39]. In a multicentered study on the diagnosis and investigation of the infertile couple through a WHO special program of research in human reproduction, varicocele was present in 11.7% of the total male population and in 25.4% of men with abnormal semen parameters. This study reported deterioration in testicular volume, sperm concentration and motility over time in men with varicocele and direct relation between the size of varicocele and severity of the depression of sperm count [41]. Lipshultz and Corriere [21] compared subfertile patients with varicocele, fertile patients with varicocele, and normal control. They found that the fertile patients with varicocele had a significant diminution in testicular volume compared to normal control as infertile group with varicocele. In the present study left and right testicular volume of infertile males with group III varicocele was significantly decreased compared to normal control (p <.05), this result is in agreement with data obtained by Lipshultz and Corriere [21] and Haans et al. [14]. Also a WHO study of 9034 men showed that varicocele was accompanied by decreased testicular volume [41]. However, Haans et al. [14] reported that although Rt-testicular volume were smaller too in adolescent, the reduction was not significant. Also the left and right testicular volume was significantly decreased in impotent patients with

Testosterone in Varicocele Infertile Men 193 grade 3 varicocele compared to normal controls (p <.05) while left testicular volume in impotence was highly significantly decreased compared to male infertility patients (p <.005). These changes in testicular volume are reflected to changes in growth and length of the seminiferous tubules and concomitantly to the total sperm number [36]. This means that there is a possible association between bilateral varicocele and testicular growth failures in both impotent and male infertility patients. Hafez [15] reported that varicocele is agsociated with decreased testicular volume on the affected side with testicular dysfunction, abnormal semen analysis (including sperm count, motility and morphology), sexual dysfunction, and hormonal changes. The mean semen volume was highly significantly decreased in impotent patients (p <.005) compared to normal controls. This result is in agreement with Comhaire and Vermeulen [4]. They had reported that the secretion products of the secondary sex glands were more often in the lower range in the ejaculates of men combining varicocele with sexual disturbance, proving the decreased testosterone level to induce a deficient function of these glands. But in male infertility there was nonsignificant difference in the mean semen volume compared to normal controls and impotent patients (p >.10). This result is in agreement with Haans et al. [14], Cheval and Purcell [3], and Gorelick and Goldstein [12]. This decrease in the semen volume of impotent patients suggests that varicocele may impair accessory sex gland functions and this may affect the motility of ejaculated sperm in the future. This result is in agreement with Ando et al. [1]. Also in this study the mean sperm count and motility were highly significantly and significantly decreased (p <.005, p <.05), while the abnormal forms were significantly increased (p <.05) in male infertility patients grade 3 varicoceles compared to normal controls. This result is in agreement with Farriss and colleagues [9], Rodriguez et al. [31], Mieusset et al. [22], WHO [41], Gorelick and Goldstein [12]. Haans et al. [14] reported that the relationship between left testis volume and total sperm number in adolescents with a varicocele appeared to be statistically significant while no statistically significant correlation could be found between left testis volume and sperm motility and sperm morphology. Animal and human studies suggest that varicocele causes progressive testicular damage with low level of serum testosterone and increased FHS value, indicating damage to the germinal epithelium [10, 11, 16, 21, 23, 24, 32, 33, 34]. In the present study the mean value of serum testosterone was significantly and highly significantly decreased in impotent and male infertility patients (p <.01, p <.005), respectively, while the mean value of serum FSH was significantly increased in male infertility (p <.05) compared to normal controls. This result is in agreement with Comhaire and Vermeulen [4], Nagao et al. [23], Gorelick and Goldstein [12], and Nieschlag et al. [26]. The mean values of serum LH and prolactin were normal for both groups, but LH value was significantly increased (p <.025) in impotent compared to male infertility patients. This result is in agreement with Nagao et al. [23]. Klyde [20] reported that in most patients with a drop in testosterone, there is a drop in lipido and erectile function, but occasionally there is a loss of only testicular ability to synthesize testosterone, while spermatogenic ability persists with progressive deterioration of testicular function. There is more decrease in synthesis of testosterone with little elevation of LH. The slightly increased in serum LH levels are usually combined with lowered testosterone levels in varicocele patients [5, 17]. Apparently, varicocele-associated testicular growth failure is also associated with a change in Leydig cell responsiveness [14]. Castor-Magana s [2] study showed normal histology on testicular biopsies of adolescents but Leydig cell dysfunction as

194 A. K. H. Younes evidenced by abnormal serum response to gonadotropin-releasing hormone and human chorionic gonadotropin administration. It is evident that testicular damage can occur not only early in children but also in some cases before detectable changes in the process of spermatogenesis. Our current observation as well as prior studies in animals and humans suggests that varicocele may cause a progressive decline in testicular function and this may affect erectile and fertility function in the future. In the present study bilateral varicocele (grade 3), which is associated with impotence and male infertility, is usually associated with testicular dysfunction reflected by decreased testicular volume, semen parameters, and testosterone with slightly increased of both FSH and LH. Prophylactic varicocele repair may prevent impotence and infertility in men with varicocele. In conclusion, the testicular dysfunction with bilateral varicocele (grade 3) is associated with erectile dysfunction and male infertility, so early correction of varicocele may improve the erectile potency and fertility rates. REFERENCES 1. Ando S, Carpino A, Buffone M, Maggiolini M, Giacchettto C, Seidita F (1990): Fructose, prostatic acid phosphatase and zinc levels in the seminal plasma of varicoceles. Int J Fertil 35:249 252. 2. Castor-Magana M, Angulo M, Canas J, Uy J (1980): Improvement of Leydig cell function in male adolescents after varicocelectomy. J Pediatr 115:809. 3. Cheval MJ, Purcell MH (1992): Deterioration of semen parameters over time in men with untreated varicocele: evidence of progressive testicular damage. Fertil Steril 57:174 177. 4. Comhaire F, Vermeulen A (1975): Plasma testosterone in patients with varicocele and sexual inadequacy. J Clinic Endocrinol Metab 40:824 829. 5. Comhaire F (1976): Study of the hypothalamo-pituitary-testicular function in patients with varicocele before and after operation. In: Progress in Reproductive Biology: Sperm Action, Hubinont PO, L Hermite M (Eds). Basel, Karger, p 187. 6. Comhaire FH (1986): Varicocele and its role in male infertility. In: Oxford reviews of reproductive biology. Clarke JR (Ed). Oxford, UK: Clarendon, pp 165 213. 7. Dubin L, Amelar RD (1970): Varicocele size and results of varicocelectonomy in selected sub-fertile men with a varicocele. Fertil Steril 21:606. 8. Dubin L, Amelar RD (1971): Etiologic factors in 1294 consecutive cases of male infertility. Fertil Steril 22:469 474. 9. Fariss BL, Fenner DK, Pylmate SR, Brannen GE, Jacob WH, Thomason AM (1981): Seminal characteristics in the presence of a varicocele as compared with those of expectant fathers and prevasectomy men. Fertil Steril 35:325 327. 10. Fussell E, Lewis R, Roberts, Harrison R (1981): Early ultrastructural findings in experimentally induced varicocele in the monkey testis. J Androl 2:111. 11. Ghosh PK, York JP (1994): Changes in testicular testosterone and acid and alkaline phosphatase activity in testis and accessory sex organs after induction of varicocele in noble rats. J Surg Res 56:271 276. 12. Gorelick J, Goldstein M (1993): Loss of fertility in men with varicocele. Fertil Steril 59(3): 613 616. 13. Greenberg SH: Varicocele and male fertility. Fertil. Steril 28:699 706. 14. Haans LC, Laven JS, Mali WP, Velde ER, Wensing CJ (1991): Testis volumes, semen quality and hormonal patterns in adolescents with and without a varicocele. Fertil Steril 56: 731 736. 15. Hafez B (1998): Recent advances in clinical/molecular andrology. Arch Androl 40:187 210. 16. Harrison RM, Lewis RW, Roberts JA (1986): Pathophysiology of varicocele in nonhuman primates: long term seminal and testicular changes. Fertil Steril 46:500 510. 17. Hudson RW, McKay DE (1980): The gonadotropin response of men with varicoceles to goandotropinreleasing-hormone. Fertil Steril 33:427.

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