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Oestradiol-17beta and testosterone blood plasma concentrations were measured in dogs with Leydig-cell tumours (n=20), Sertoli-cell tumours (n=6), seminomas (n=9), unilateral inguinal cryptorchidism (n=7), abdominal cryptorchidism (n=9, one bilateral), degenerate scrotal testicles (n=6, two bilateral), and animals with normal scrotal testicles (n=20). The testosterone/oestradiol ratio (testosterone concentration [ng/mL]x100/oestradiol concentration [pg/mL]) was calculated.A considerably higher oestradiol concentration was found in dogs with Sertoli-cell tumours (29.0, 14.4-48.3 pg/mL; median, minimum-maximum; P=0.0256, Mann-Whitney test) and lower oestradiol levels were found in animals with seminomas (12.0, 3.4-17.6 pg/mL; P=0.0025) compared to the healthy control group (18.0, 8.6-31.5 pg/mL). Testosterone concentration was decreased in dogs with Sertoli-cell tumours (0.08, 0.03-0.77 ng/mL) when compared to the control group (1.95, 0.05-3.70 ng/mL; P=0.0012). Testosterone/oestradiol ratios differed from the control (9.6, 0.58-35.8) only in dogs with Sertoli-cell tumours (0.32, 0.06-2.80; P=0.0005). Clinical signs of feminization were observed in five dogs with Sertoli-cell tumour and one dog with a Leydig-cell tumour, and were more often associated with decreased testosterone/oestradiol ratios than with an increased oestradiol-17beta concentration.

Aim: To explore the changes of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) expressions in cryptorchid children and their clinical significance., Methods: The level of serum EGF was measured by radioimmunoassay (RIA) and the expression of EGFR by immunohistochemistry., Results: (1) The level of serum EGF was significantly lower in cryptorchid children than in normal subjects at age group of 5-9 years (P<0.01) and 10-14 years (P<0.01), (2) The level of EGF was significantly lower in boys with impalpable testis than in those with extracanalicular and intracanalicular testes (P<0.01), (3) The serum EGF level increased significantly 6 months after orchiopexy (P<0.05), (4) The EGFR expression in testicular Leydig's cells was lower in 2 approximately 4 year-old boys than in those over 5 years (P<0.05) and (5) the EGFR expression was less positive in the impalpable group and the intracanalicular group than that of the extracanalicular group (P<0.01)., Conclusion: The EGF and EGFR expressions may correlate with the age and the position of testes; orchiopexy improves the EGF and EGFR expressions in cryptorchid boys.

Mullerian inhibiting substance (MIS) is a gonadal hormone expressed in a sexually dimorphic pattern. In males, serum MIS reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. We examined the role of MIS determination in the evaluation of boys with microphallus (n = 62) and/or cryptorchidism (n = 156). MIS was normal in 69.2% of boys with isolated microphallus compared with 38.1% of boys with microphallus and coexisting cryptorchidism (P < 0.05). In the cryptorchid group, MIS was normal in 46.8%, low in 24.4%, and absent in 28.8%. Normal values for age were associated with testicular tissue, whereas undetectable values were indicative of anorchia, except for two boys with MIS gene mutations (persistent Mullerian duct syndrome). These data demonstrated that a basal MIS measurement is more specific and has a higher positive predictive value than stimulated testosterone values for ascertaining the absence of testes (anorchia). In summary, a normal serum MIS concentration in the prepubertal child is a reliable determinant of testicular tissue, whereas an undetectable value is a highly sensitive initial screening test for anorchia. We conclude that preoperative measurement of MIS facilitates the management of children with cryptorchidism and intersex disorders and offers a measure of Sertoli cell function.

Background: Several studies have indicated that cryptorchidism is associated with degenerative changes in both Sertoli cells and germ cells. The gonadal peptide hormone inhibin B reflects Sertoli cell function. Low inhibin B levels are found in a large portion of formerly cryptorchid men who show compromised seminiferous tubule function. It is not known if inhibin B can be used to demonstrate early damage of seminiferous tubules in prepubertal boys with cryptorchidism., Methods: We investigated the relationship between serum levels of inhibin B, testosterone, FSH and LH in 62 prepubertal boys with uni- and bilateral cryptorchidism. Furthermore, we investigated the changes in serum levels of inhibin B and the corresponding changes in serum levels of FSH, LH and testosterone during a short course (3 weeks) of human chorionic gonadotropin (hCG) injections in 18 of these cryptorchid boys., Results: In the 62 prepubertal boys with uni- or bilateral cryptorchidism there were no significant differences in baseline levels (median and range) of inhibin B (88 (20-195) pg/ml vs 78 (35-182) pg/ml; not significant), LH (0.08 (<0.05-0.99) IU/l vs 0.06 (<0.05-1.61) IU/l; not significant) and FSH (0.60 (0.08-3.73) IU/l vs 0.85 (0.25-2.55); not significant) compared with 156 healthy prepubertal boys, and there were no differences in hormonal levels between boys with uni- or bilateral cryptorchidism. There was no correlation between baseline levels of inhibin B and FSH. In boys younger than 9 years, we found no correlation between baseline levels of inhibin B and LH whereas, in boys older than 9 years, baseline levels of inhibin B were positively correlated to baseline LH (Spearman rank correlation coefficient ((R(s))=0.58, P=0.03). Treatment with hCG (1500 IU intramuscularly twice weekly for 3 weeks) resulted in descensus of testes in 9 out of 18 patients. In all boys but one, irrespective of age, hCG induced a marked increase in testosterone into the adult range (from undetectable to 21.8 (7.0-35.4) nmol/l; P<0.001) and completely suppressed FSH and LH levels. Serum levels of inhibin B increased significantly from 116 (50-195) pg/ml to 147 (94-248) pg/ml (P<0.05), but not uniformly. The increase in serum levels of inhibin B was inversely correlated to baseline inhibin B (Rs=-0.52, P=0.03) and baseline FSH (R(s)=-0.59, P<0.01)., Conclusions: We therefore suggest that, in the prepubertal testes, inhibin B is secreted from the prepubertal Sertoli cells following hCG, whereas early pubertal testes with more differentiated Sertoli cells are not able to secrete inhibin B in response to hCG stimulation, perhaps due to lack of germ cell-derived betaB-subunits. We found (a) normal inhibin B levels in prepubertal boys with uni- or bilateral cryptorchidism, (b) that hCG stimulated testosterone markedly and suppressed FSH and LH levels and (c) that hCG treatment stimulated inhibin B levels in the youngest cryptorchid boys. In the oldest prepubertal boys no hCG-induced changes in inhibin B were shown.

Purpose: Human chorionic gonadotropin (HCG) has a stimulatory effect on testicular steroidogenesis and has been widely used for evaluating male Leydig cell function. However, considerable variability exists in the protocols for HCG stimulation tests. In the most commonly used protocols HCG is administered daily for several days. We examine the circulating androgen response after 1 and 3-dose HCG regimens., Materials and Methods: We evaluated 77 prepubertal boys diagnosed with hypospadias, cryptorchidism or micropenis. In 60 boys who underwent 1 dose of 100 IU/kg. or 5,000 IU/1.7 m.(2) HCG serum testosterone and dihydrotestosterone were sampled at 72 (28) and 96 (32) hours after injection, while in 17 who underwent 3 daily age adjusted doses hormone levels were determined on day 4. All blood specimens were obtained and injections were performed at 8:00 to 9:00 a.m. and all specimens were evaluated at the same endocrine reference laboratory., Results: Nonstimulated testosterone levels were prepubertal in all groups. In the 1-dose groups post-stimulation testosterone was elevated 22 to 29-fold from baseline after a weight based and 34 to 35-fold after a body surface area based dose. Testosterone increased 20-fold baseline in the multi-dose group. No significant differences were observed in 72 versus 96-hour hormone levels., Conclusions: Evaluating Leydig cell function by HCG stimulation is an important adjunct to the diagnosis of various urological conditions. A single weight or body surface area based HCG dose with androgen measurement after 3 or 4 days is a practical, reliable and cost saving change in testicular evaluation.

Infertility may be a consequence of cryptorchidism. We previously reported, using a large study cohort, that 38% of formerly bilateral cryptorchid men, 10% of unilateral cryptorchid men, and 5% of the control group were infertile. Men from this cohort donated blood and semen samples for inhibin B, FSH, LH, testosterone, free testosterone, and semen analyses. Results are reported comparing the entire group; some comparisons are based on normal or low sperm density. Data are also presented for men who had fathered children or had unsuccessfully attempted paternity. Mean (+/-SD) inhibin B levels were lower for the cryptorchid men (109 +/- 59 pg/mL) than the control men (153 +/- 60; P < 0.001), and FSH levels were higher (7.4 +/- 6.2 and 4.0 +/- 3.2; P < 0.0001). Inhibin B levels correlated with all other parameters for the cryptorchid group; however, correlations for the control group were only found with gonadotropins. Among the cryptorchid men, levels were significantly greater among men with normal sperm counts than men with low sperm counts (124 +/- 47 vs. 75 +/- 48 pg/mL; P < 0.0001). No difference was present for the control group (155 +/- 61 vs. 149 +/- 63 pg/mL). When the fertile group (based on paternity) vs. the infertile group (based on attempted paternity) were compared, significant differences were found for the cryptorchid group (117 +/- 62 vs. 73 +/- 52 pg/mL; P < 0.03), but not the control group (163 +/- 62 vs. 146 +/- 73 pg/mL). These data reveal relationships not apparent among the control group of men, which includes infertile men. Inhibin B data suggest that a larger portion of formerly cryptorchid men have compromised testicular function than indicated by paternity data. Low levels of inhibin B among individuals are an indication of diminished seminiferous tubule function and thus compromised potential for fertility. Low inhibin B levels together with elevated FSH levels and decreased sperm density are indicative of a high risk of infertility.

We have developed a mammalian cell (COS-1) bioassay, which can measure androgen bioactivity directly from a small amount (10 microL) of human serum. The recombinant assay is based on androgen-dependent interaction between the ligand-binding domain and the N-terminal region of the androgen receptor (AR), which were fused to Gal4 DNA-binding domain of Saccharomyces cerevisiae and transcriptional activation domain of herpes simplex VP16 protein, respectively. The interaction is amplified by coexpression of AR-interacting protein 3 in the cells. The reporter plasmid contains 5 Gal4-binding sites upstream of the luciferase gene; luciferase activity in cell lysates is derived from androgen bioactivity in human serum. Saturating concentration of testosterone in FCS induced more than 700-fold induction in relative luciferase activity. The sensitivity was less than 1.0 nmol/L testosterone in FCS. The intra- and interassay coefficients of variation were 8.3% and 21%, respectively. Interaction between the AR termini was blocked by nonsteroidal antiandrogens, and the assay exhibited minimal cross-reactivity with 17 beta-estradiol. Serum androgen bioactivity was studied in 23 boys (13.9--16.8 yr old) with constitutional delay of puberty and in 9 prepubertal boys with cryptorchidism (1.0--6.4 yr old). Androgen bioactivity was detectable in 15 boys with constitutional delay of puberty and in all boys with cryptorchidism during treatment with human CG (range, 1.0-14.5 nmol/L testosterone equivalents). Serum androgen bioactivity measured by the bioassay correlated strongly with serum testosterone concentration (r = 0.93, P < 0.0001, n = 22) but not to 5 alpha-dihydrotestosterone, dehydroepiandrosterone, or androstenedione levels. We conclude that our novel bioassay enables quantitation of mammalian cell response to bioactive androgens in human serum, even in pediatric patients with relatively low androgen levels.

Purpose: We determined differences in paternity and levels of the hormones inhibin B, follicle- stimulating hormone, luteinizing hormone, testosterone and free testosterone based on the preoperative location of the undescended testis in men with previous unilateral cryptorchidism., Materials and Methods: Testicular location was determined by a review of the medical records and paternity or attempted paternity using a detailed questionnaire administered to 320 men with previous unilateral cryptorchidism. In 103 cases we performed semen analysis and measured the levels of the hormones inhibin B, luteinizing hormone, follicle-stimulating hormone, testosterone and free testosterone. Paternity, sperm count and hormonal parameters were compared with cryptorchid testicular location using analysis of variance and chi-square analysis. Logistic regression was done to analyze pretreatment testicular location as a risk factor for infertility., Results: Paternity, duration of attempted conception in men who achieved paternity, sperm count and hormone levels did not differ based on pretreatment abdominal, internal ring, inguinal canal, external ring, upper scrotum or ectopic testicular location. The overall paternity rate was 90% with the lowest rate of 83.3% in the abdominal group. More than 12 months were required to achieve conception in 28.9% of the study group overall and in 39.4% of the abdominal group. Varicocele and a partner with fertility problems were risk factors for infertility, while abdominal testicular location caused borderline significant risk., Conclusions: Preoperative testicular location in men with previous unilateral cryptorchidism is not a major determinant of fertility according to paternity, sperm count or hormone levels.

Twenty-one young men who underwent testicular biopsy and orchidopexy in infancy consulted owing to infertility and had biopsies again. The first and second biopsy specimens from these patients were compared by means of a semiquantitative study of the seminiferous tubules to evaluate the evolution of germ cells and to correlate these data with spermatozoon numbers. The infant testes showing lesions were classified into 3 types according to the mean tubular diameter and tubular fertility index: (1) slight lesions, (2) marked germinal hypoplasia, and (3) severe germinal hypoplasia. In the adult testes, spermatogenesis was evaluated by calculating the average numbers of spermatogonia, primary spermatocytes, young spermatids, and mature spermatids. These testes were classified as (1) normal; (2) having lesions in the adluminal compartment; (3) having lesions in the basal compartment; and (4) mixed atrophy. The number of differentiated spermatids was correlated with the expected number of spermatozoa in the ejaculate by a power regression curve. The observation of certain histologic lesions in the seminiferous tubules was assumed to indicate excretory duct obstruction: ectasia, indented outline of the seminiferous epithelium, intratesticular spermatocele, apical cytoplasmic vacuolation of Sertoli cells, and mosaic distribution of testicular lesions. There was a correlation between the prepubertal lesions and the degree of spermatogenesis in postpubertal biopsy specimens. The evolution of the 40 testes without regard to their location in infancy (cryptorchid or scrotal) was as follows. The 14 infant testes with a normal histologic pattern (5 testes) or minor lesions (9 testes) evolved to testes with lesions of the adluminal compartment (8 testes), mixed atrophy (4 testes), or lesions of the basal and adluminal compartments (2 testes). The 6 testes with marked germinal hypoplasia evolved to testes with mixed atrophy. The 20 testes with severe germinal hypoplasia evolved to testes with mixed atrophy (17 testes), Sertoli-cell-only tubules (2 testes), or lesions in the basal compartment (1 testis). In the 9 patients with a histologic pattern of obstruction bilaterally (6 men) or unilaterally (3 men), the expected number of spermatozoa according to the correlation curve was much higher than the actual number in the spermiogram. This means that the testes of many azoospermic men produce spermatozoa, and this finding corroborates the importance of testicular biopsy in infertility studies.

Objective: To determine the clinical, physical, sperm and hormonal status during adulthood in cryptorchid patients operated on during childhood, and to assess these variables according to the age at surgery and preoperative testicular position., Patients and Methods: A letter was sent to all 890 patients > 18 years old who underwent surgery for cryptorchidism during childhood; 274 responded and were assessed using a sexual history, physical examination, pituitary axis study and sperm analysis. Data were complete for 251 patients (mean age 21 years, range 18-30); 196 had unilateral (25 anorchic) and 55 had bilateral cryptorchidism. Clinical, surgical and anatomopathological records at surgery during childhood were also reviewed., Results: The mean (SD) age at orchidopexy was 6.4 (3.3) years and the mean age at assessment 21.1 (2.7) years. Semen samples generally showed abnormalities; 10 patients (4%) with bilateral and 57 (23%) with unilateral cryptorchidism had semen values within the normal range. There was no correlation between the sperm count and age at surgery for unilateral or bilateral cases (Spearman test). There was a significant correlation (r = - 0.41) between the sperm count and level of follicle-stimulating hormone (FSH). There were no significant differences in the sperm count for patients with different testicular locations (ANOVA) or in those treated or untreated with human chorionic gonadotrophin (Student's t-test). The only significant relationship (P < 0.001) was between the sperm count and unilateral or bilateral cryptorchidism., Conclusions: The sperm quality of adults operated on for cryptorchidism during childhood is independent of the age at surgery or testicular location, but is influenced by whether the cryptorchidism was unilateral or bilateral. FSH levels were negatively correlated with sperm density.

Objective: To report two cases misdiagnosed as bilateral anorchism in midchildhood on the basis of multiple conventional human chorionic gonadotropin (HCG) stimulation tests and sonograms of the abdomen and pelvis., Methods: In two young male patients with cryptorchidism who were considered to have anorchism, we describe the findings on clinical examination, the testosterone levels before and after standard HCG stimulation testing, and sonographic findings during the midchildhood period. In both cases, as the children approached puberty the diagnosis was found to be incorrect., Results: Two boys, 8 and 91/2 years old, were seen in consultation in our Pediatric Endocrine Clinic with a presumed diagnosis of anorchism. In the first case, multiple conventional HCG stimulation tests were done. In the second case, a single stimulation test was performed during routine follow-up assessments. In both cases, testosterone levels before and after HCG stimulation were consistent with the diagnosis of absent functional testicular tissue. Sonograms of the abdomen and pelvis also failed to detect the testicles. Both patients were ultimately noted to be pubertal (at 14 1/2 and >13 1/2 years, respectively) and to have early pubertal testosterone levels. A testicle was detected in one patient by abdominal computed tomographic scan and in the other by palpation of the inguinal canal., Conclusion: Conventional dosing and duration of the HCG stimulation test, as widely recommended in standard textbooks and in articles in the medical literature, may not elicit positive HCG-induced testosterone responses during midchildhood for detection of functional testicular tissue. During the midchildhood period, which is characterized by low gonadotropin, low sex steroid production, and a highly sensitive hypothalamic-pituitary-gonadal axis to feedback inhibition, a prolonged HCG stimulation test-perhaps of 4 to 6 weeks' duration-may be necessary. In addition, other investigational modalities may need to be used to detect the presence of functional testicular tissue during this developmental period.

To investigate the gonadal control of FSH secretion in prepuberty, we studied the relationship between circulating inhibin B and FSH levels in 16 prepubertal boys with cryptorchidism (age range, 1-8 y). The effect of Leydig cell stimulation on the secretion of inhibin B, sex steroids, and FSH was investigated in nine boys who were given human chorionic gonadotropin (hCG) treatment. In these boys, serum inhibin B, testosterone, estradiol, and gonadotropin levels were measured before and on the fourth day of the last (third) hCG injection, given at 1-wk intervals. Except for one boy with both high inhibin B and FSH concentrations, basal serum levels of these hormones correlated negatively (r(s) = -0.79, n = 15, p < 0.005). This inverse relationship remained significant in the subgroup of boys younger than 2 y of age (r(s) = -0.84, n = 11, p = 0.008) who also had greater variance of serum FSH concentrations than 14 control boys of similar age with normally located testes (p < 0.01). hCG stimulation increased serum testosterone and suppressed serum FSH concentrations in each boy (n = 9, p < 0.005). In the four oldest subjects, the serum inhibin B level increased from the mean of 91 to 135 pg/mL (p < 0.05). These findings suggest that inhibin B regulates FSH secretion in early childhood. Moreover, the hCG-induced suppression of FSH secretion was probably mediated by sex steroids rather than by inhibin B. Finally, the increase in serum inhibin B concentration during the hCG treatment was likely to be indirect via Leydig cell-Sertoli cell or Sertoli cell-germ cell interaction(s).

Purpose: We determined whether there are differences in hormone levels, such as inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone and testosterone, and sperm density in men with a history of unilateral cryptorchidism as stratified by age at orchiopexy., Materials and Methods: A total of 84 men with a history of unilateral cryptorchidism presented to our institution for serum hormone measurement and semen analysis. These parameters were compared using Pearson's correlations and analysis of variance among 4 groups stratified according to age at orchiopexy (range 1 month to 11 years)., Results: Comparison by Pearson's correlation analysis showed that age at orchiopexy significantly correlated inversely with inhibin B (r = -0.274, p = 0.012) and positively correlated with FSH (r = 0.229, p = 0.036). Comparison of mean hormone levels and sperm density by analysis of variance for linear trend revealed a significant relationship between age at surgery with inhibin B (p = 0.032) and testosterone (p = 0.029), while sperm density, FSH and luteinizing hormone were not significantly related. Post hoc comparison of individual means at surgery and at the time of this study demonstrated a significantly higher inhibin B level in the youngest age group than in 2 of the 3 older groups., Conclusions: Men who previously had unilateral cryptorchidism and who underwent orchiopexy by age 2 years have higher inhibin B and lower FSH profiles than those who underwent surgery later in life. This finding suggests an overall beneficial effect of early orchiopexy in boys born with unilateral cryptorchidism.

Purpose: Although the prepubertal immune system cannot recognize postmeiotic germ cell antigens, an overall 21 to 28% incidence of antisperm antibodies directed at these antigens has been reported preoperatively in prepubertal children with cryptorchidism and other inguinoscrotal anomalies. We investigated the prevalence of antisperm antibodies in these prepubertal patients before and after surgery., Materials and Methods: We examined 82 prepubertal boys 0.6 to 13.2 years old, including 33 with unilateral cryptorchidism, 21 with inguinoscrotal anomalies and 28 who were normal. IgG, IgM and IgA antisperm antibodies were determined by the indirect Immunobead test. Serum testing was repeated 1 and 2 years postoperatively and annually for 2 more years in the normal children. Also sera from 183 infertile men 21 to 47 years old with a history of cryptorchidism and/or inguinal hernia operated on in childhood were similarly studied., Results: Of the adults 70 (39%) tested IgG positive, including 12 (7%) who were also IgA positive, and all tested IgM negative. Repeat measurements were negative for all IgG, IgA and IgM isotypes in all children, patients and controls., Conclusions: We conclude that there are no antibodies to sperm surface antigens in prepubertal children with cryptorchidism and inguinoscrotal anomalies before and within 2 years after surgery. Autoimmunity against postmeiotic sperm membrane antigens is apparent in adults only.

Background: Cryptorchidism, testicular ectopia and rectractile testicle are different pathologies with conceivable different prognosis. As a matter of fact spermiogram used in these patients for the prognosis is really worse in bilateral cryptorchid than ectopic patients, because the tubular damage is present in the former than in the latter. It does not mean, anyway, that direct correlation exists between age of the patient at the operation and fertility., Methods: 171 patients operated on for cryptorchidism or testicular ectopia at the Pediatric Surgery Department of the Regional Hospital of Treviso during the years 1974-1983 under-went follow-up at the age of 18 years with clinical evaluation, hormonal dosage (testosterone and gonadotropin after stimulus as GnRH) and spermiogram., Results and Conclusions: The present study does not differ from many other studies about hormonal levels and spermiograms of cryptorchid patients; it underlines long term follow-up utility of patients operated on for cryptorchidism and stresses the need of an eventual psychological evaluation of these patients.

Inhibin B appears to be the physiological feedback signal for FSH. Herein the determination of serum levels of inhibin B, FSH, LH and testosterone in 148 infertile patients and their association with clinical findings and seminal parameters are reported. A significant negative correlation of FSH and inhibin B (r = -0.60) was found. LH levels showed a significant inverse correlation (r = 0.37), but a weak regression (c0 = 0.01). No correlation with testosterone levels occurred. A significantly positive correlation was observed between testis volume and inhibin levels (r = 0.39) as well as between sperm count and inhibin levels (r = 0.39). To evaluate whether the secretion of inhibin B depends on the nature of damage to the Sertoli cells, inhibin levels in 23 patients with varicocele; eight after cryptorchidism, and 16 after hemiorchiectomy were compared to those of other patients without these diseases, but identical sperm count. No significant differences were found. In 20 men undergoing testicular biopsy, inhibin levels were compared to histology. Although the men with Sertoli-cell-only syndrome had significantly lower levels ((15.83 +/- 12.2) pg ml-1) than those with normal spermatogenesis ((183.8 +/- 112.3) pg ml-1), a distinction between patients with hypospermatogenesis from those with normal spermatogenesis was not possible on the basis of inhibin levels. Between these groups, the distinction was better achieved by the FSH levels (sensitivity of 85%). We conclude that inhibin B levels are a serum marker of Sertoli cell function, but the prediction of the quality of spermatogenesis is not superior to that of FSH levels.

It is a common clinical practice to estimate FSH, LH and testosterone levels in patients with unilateral undescended testis (U/L UDT) as a prognostic pointer to fertility potential. Is this practice correct? To ascertain this aspect, new born rats were operated to create experimental U/L UDT by gubernaculectomy and anchoring the gubernaculum to anterior abdominal wall. Fertility and hormone levels were evaluated later in adult life. Though fertility of rats with U/L UDT was significantly less (p < 0.01) than the controls, no significant alterations were found in the levels of serum testosterone, FSH and LH. Even though variations in the hormone levels may be responsible, to a certain extent, for the decrease in fertility potential in U/L UDT, estimation of sex hormone levels in U/L UDT is not a sensitive indicator of fertility potential. U/L UDT may additionally be affecting fertility through non-endocrinological mechanisms.

Objective: Descent of the testes is essential for normal function, with cryptorchidism being associated with defective spermatogenesis. The postpubertal function of cryptorchid testicles seems to be related to the original location of the undescended testis and the age at the moment of treatment. The objective of this study was to evaluate the pubertal development and gonadal function in postpubertal patients treated for cryptorchidism during childhood., Patients and Methods: Twenty postpubertal males with a mean age of 17.35 years (range: 15-21 years) and treated for cryptorchidism during childhood were evaluated for pubertal development and gonadal function. A hormonal study which included basal determinations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), testicular volume assessed by Prader's orchidometer and semen analysis was performed on each patient., Results: Complete virilization was observed in all patients. The start and development of puberty were normal in all cases (except one patient that started puberty at 10 years of age). Basal studies in all patients showed normal levels of LH and testosterone. FSH levels were increased in 3 patients and normal in the other 17 patients. Fourteen patients achieved normal spermatogenesis with more than 20 million spermatozoa/ml. In the other 7 patients (35%), 5 with unilateral cryptorchidism and 2 with bilateral cryptorchidism, the sperm count remained below 20 million with a range of 0.8 to 18.4 x 10(6) spermatozoa/ml. The three males with elevated levels of FSH also presented oligospermia., Conclusions: The results obtained show that pubertal development is normal after cryptorchidism. Impaired spermatogenesis is a major factor in undescended testes. Basal SH levels can be useful in predicting germinal damage secondary to cryptorchidism.

Purpose: We verified the prevalence of serum antisperm antibodies at diagnosis in a large group of cryptorchid boys, and determined whether it may be influenced by orchiopexy., Materials and Methods: We prospectively evaluated serum antisperm antibodies in 186 and 23 boys 0.67 to 14.25 years old with unilateral and bilateral cryptorchidism, respectively, before, and 3, 12 and 24 months after surgery. At diagnosis Tanner stage was 1 and 2 or 3 in 188 and 21 cases, respectively. During the 2-year followup 23 boys entered puberty. A total of 111 normal prepubertal (Tanner stage 1) and 54 pubertal (Tanner stage 2 or 3) boys served as controls. Antisperm antibodies were detected using the tray agglutination and indirect immunobead tests., Results: At diagnosis 29 cryptorchid boys (13.8%) were antisperm antibody positive, including 21 of the 188 prepubertal (11.1%) and 8 of the 21 pubertal (38%) boys (significantly different, chi-square test p <0.001). In 27 cases the tray agglutination test was positive with titers between 1:16 and 1:512, in 18 the indirect immunobead test was positive for IgG with titers between 1:10 and 1:100, and in 16 both tests were positive. There was no statistical difference when antisperm antibody results were analyzed for unilateral and bilateral cryptorchidism or testis location. All normal boys were antisperm antibody negative. During the 2-year followup antisperm antibodies appeared in 1 previously negative case, and the antibody titer increased to 128 to 512 in the tray agglutination and to 1:100 in the indirect immunobead tests in 4 positive cases. In all of these cases pubertal changes were also observed., Conclusions: Our study indicates that cryptorchidism may elicit an autoimmune response against sperm antigen in childhood independent of testis location and orchiopexy. Moreover, patients of pubertal age appear to be at higher risk for antisperm antibody development.

We evaluated eleven cryptorchid boys under four years of age to determine the usefulness of serum inhibin as a marker of seminiferous tubule dysfunction. Serum testosterone, inhibin, LH and FSH concentrations were measured by RIA before and after 6 weeks of human chorionic gonadotropin plus human menopausal gonadotropin therapy, and bilateral testicular biopsies were performed at orchiopexy. Hormonal results from the cryptorchid group were compared to those from an age-matched control group. Basal LH and testosterone levels were similar in the two groups. Cryptorchid boys had lower basal inhibin and higher FSH levels than controls. After gonadotropin treatment the inhibin/FSH ratio was lower in cryptorchid than control children, suggesting the presence of seminiferous tubule damage (p = 0.002). Normal numbers of spermatogonia were seen in 6/9 scrotal and in 1/13 cryptorchid testes. The peak of inhibin was positively correlated to the number of spermatogonia (r = 0.68; p = 0.02). We conclude that basal and stimulated inhibin concentrations, as well as basal and stimulated inhibin/FSH ratio, provide additional information on seminiferous tubule function in cryptorchid boys and can be useful to evaluate Sertoli cell function in these patients.

Objective: To assess the value of CBC as a preoperative test in healthy horses undergoing cryptorchidectomy., Design: Retrospective study., Animals: 117 horses., Procedure: Medical records were reviewed to identify horses that had had cryptorchidectomy. Of the 117 horses identified, 102 were found that did not have a known medical condition believed to adversely affect surgery. Preoperative CBC was assessed in terms of abnormalities detected and effects of these abnormalities on development of complications during and after surgery and patient management., Results: Of 102 CBC performed, 55 contained abnormalities. Mild neutrophilia was detected in 40 horses. Of the remaining 15 horses with abnormal CBC, 8 had abnormalities that were considered potentially important. Changes in patient management and development of surgical complications were not associated with these 8 horses. Surgical complications were defined as intraoperative changes in blood pressure, excessive blood loss, development of postanesthetic myopathies, and postoperative wound or respiratory tract infections. Surgical complications developed in 17 horses. Of these, 6 horses had an abnormal CBC that was indicative of mild neutrophilia. Positive and negative predictive values of preoperative CBC on development of perioperative complications were 0.11 and 0.77, respectively., Clinical Implications: On the basis of findings in our study, determination of preoperative CBC does not predict development of complications during or after surgery and does not alter patient management.

Purpose: We characterized follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in boys with surgically documented unilateral absent testes (monorchism) to determine whether measurement of gonadotropin levels could distinguish them from boys with unilateral impalpable cryptorchidism., Materials and Methods: Baseline serum gonadotropin levels were prospectively measured in 43 boys 2 months to 14 years old who presented with a unilateral impalpable testis that was confirmed to be absent at surgery. Control serum specimens were obtained from 63 age matched boys undergoing minor surgery with no evidence of hypospadias, or testicular, hormonal or renal diseases. Serum FSH and LH levels were drawn preoperatively and assayed by double antibody radioimmunoassay. A subgroup of 7 boys with monorchism was also evaluated following gonadotropin-releasing hormone (GnRH) stimulation and compared to age matched boys with a unilaterally impalpable testis discovered surgically., Results: In the monorchism group mean plus or minus standard deviation basal FSH was 4.08 +/- 0.28 mIU/ml. and LH was 4.13 +/- 0.33 mIU/ml. In the control group mean basal FSH was 4.36 +/- 1.52 mIU/ml. and LH was 4.66 +/- 0.75 mIU/ml. No statistical difference existed between the 2 groups for mean basal gonadotropin level. While monorchid boys were more likely to have elevated FSH levels (p = 0.016), this was not true for LH (p = 0.21). Since gonadotropin levels less than 5 mIU/ml. are accepted normal values, this threshold was applied to FSH and carried a sensitivity of 23.8%, specificity 93.8%, positive predictive value 71.4% and negative predictive value 65.6%. Lower cutoff values marginally improved sensitivity but reduced specificity. Peak stimulated levels of FSH and LH following GnRH stimulation failed to distinguish between boys with 1 or 2 testes., Conclusions: Baseline FSH is more likely to be elevated in prepubertal boys with monorchism but it does not appear to be clinically useful when sensitivity and predictive value are poor. Similarly, gonadotropin level following GnRH stimulation is not sufficiently sensitive to advocate the use of hormonal measurements to diagnose prepubertal monorchism.

Background: Müllerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the müllerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of müllerian inhibiting substance., Methods: We measured serum mullerian inhibiting substance in 65 children with virilization at birth and nonpalpable gonads (age at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either after the administration of human chorionic gonadotropin or during the physiologic rise in testosterone that occurs in normal infants., Results: The mean (+/-SD) serum mullerian inhibiting substance concentration in the 17 children with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with 37.5+/-39.6 ng per milliliter in the 48 children with testes (P<0.001). In the latter group, the mean values in the 14 children with abnormal testes and the 34 with normal testes were 11.5+/-11.8 and 48.2+/-42.1 ng per milliliter, respectively (P< 0.001). The sensitivity and specificity of the serum müllerian inhibiting substance assay for detecting the absence of testicular tissue were 92 percent and 98 percent, respectively, as compared with 69 percent and 83 percent for the measurement of serum testosterone. Furthermore, measurement of serum mullerian inhibiting substance was more sensitive than serum testosterone measurement for the identification of children with abnormal testes (67 percent vs. 25 percent), whereas the specificity of the two tests was similar., Conclusions: Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies.

To examine the role of inhibin B in the feedback regulation of FSH secretion in the human male, we determined serial levels in 18 men with idiopathic hypogonadotropic hypogonadism (IHH) during their initial 8 weeks of GnRH replacement. Pulsatile GnRH was administered every 2 h, with the dose increased at 2-week intervals (5-50 ng/kg/bolus). Every 2 weeks, sera were assayed for inhibin B, FSH, LH, and testosterone. Serial comparisons were performed within the IHH group as well as vs. normal men (n = 20). The baseline inhibin B level in IHH patients averaged 68 +/- 11 pg/mL (mean +/- SEM), significantly less than that in normal men (239 +/- 14 pg/mL; P < 0.001). After 8 weeks of pulsatile GnRH, inhibin B levels in the IHH patients increased significantly to 118 +/- 14 pg/mL (P = 0.003). During GnRH replacement, FSH concentrations correlated negatively with inhibin B concentrations at all doses. Patients previously treated with testosterone began with somewhat lower inhibin B levels but demonstrated a significantly greater increase in serum concentrations than patients who had received prior gonadotropin or GnRH therapy. A history of cryptorchidism did not have a significant impact on inhibin B concentrations before or during GnRH replacement. The low inhibin B levels in IHH men at baseline and their prompt increase in response to pulsatile GnRH suggest acute regulation by gonadotropin stimulation of the testis. The variation in inhibin B levels at baseline and in response to GnRH suggest that prior gonadotropin exposure and seminiferous tubular development also modulate inhibin B secretion. The consistent negative correlation between FSH and inhibin B during the induction of sexual maturation with GnRH supports the role of gonadal inhibin B secretion as an important endocrine regulator of FSH in the human male.

The aim of this analysis is to evaluate the gonadal function in children with true undescended testes and in those with retractile testes, in order to verify a possible impairment of the testicular steroidogenesis due to the permanent or transitory anomalous position of the gonad outside the scrotum. The authors carried out a prospective study on 29 prepubertal children affected by true undescended testes (monolateral in 20 cases and bilateral in 9), as well as on 25 prepubertal children with retractile testes (monolateral in 10 cases and bilateral in 15), assaying the testosterone (T) levels, basal and 72 hours after stimulus with human chorionic gonadotrophin (HCG) administered in a single dose of 100 U/kg i.m. Further-more, to verify the hypothesis of a possible progressive reduction of the Leydig cells function, particularly in the gonads bilaterally affected, the authors also evaluated the testosterone response to gonadotrophic stimulus compared to age (> 0 < 4 years). This study in agreement with data already published, confirms the normality of gonadal function both in children with mono or bilateral true undescended testes and in those with retractile testes. The lower the age of the subject the higher is the peak of testosterone after stimulus, confirming the active steroidogenesis of the gonads in infants and small children and sustaining the "non quiescence" of this organ during infancy, even in cases of true undescended testes.

Static measurements of immunoreactive inhibin have proven of little relevance in the diagnosis of testicular disorders. Dynamic evaluation of the inhibin secretory reserve might detect a specific Sertoli cell defect in a subgroup of infertile men. We compared the response of inhibin and steroids to an intravenous injection of pure FSH (Metrodin, Serono, 300 IU) in 13 infertile men with unilateral cryptorchidism to that in eight normal fertile men. Blood was aspirated before, 24, 48, and 72 h after the FSH injection. Two subgroups of patients with unilateral cryptorchidism were detected: those who responded by secreting inhibin in a pattern similar to normal men (seven patients), and those who responded poorly or not at all (six patients). The presumed cause of this difference is a defect of Sertoli cell reserve function due to a combination of insults to the testes, and not to cryptorchidism itself. The difference in response to FSH cannot be predicted from semen analysis nor from static hormone measurements. Overall, inhibin levels correlated significantly with the serum concentrations of FSH (r = -0.36, P < 0.05), testosterone (r = 0.37, P < 0.05), and 17-hydroxyprogesterone (r = 0.66, P < 0.001). It is concluded that, in infertile men with unilateral cryptorchidism, Stimulation of Sertoli cells by FSH can identify a subgroup of patients with Sertoli cell malfunction involving inhibin synthesis.

Objective: To review retrospectively the value of the human chorionic gonadotrophin (hCG) test in the evaluation of prepubertal boys with bilateral impalpable testes., Subjects and Methods: The study comprised 31 boys investigated between 1974 and 1990 at the Hospital for Sick Children, London. All boys had an hCG test consisting of three intramuscular injections of hCG on successive days at a daily dose dependent on their age (< 1 year old, 500 units; 1-10 years, 1000 units; > 10 years, 1500 units). Blood samples were taken before the first dose and 24 h after the last dose and the level of plasma testosterone assessed and expressed as a pre/post ratio., Results: Eight boys had no response to hCG, due to anorchia. One boy had no response to hCG but had bilateral atrophic intra-abdominal testes. Twenty-two boys responded to hCG and had testes whose size was related to the degree of testosterone elevation after this stimulatory test. The hCG test therefore had a positive predictive value of 89% and a negative predictive value of 100%. There was a quantitative difference in testosterone response between 14 boys who had bilateral intra-abdominal testes of 'normal' volume (median pre/post ratio, 11.4) and nine boys who had an otherwise reduced volume of testes (dysplastic or unilateral intra-abdominal) (median pre/post ratio of 4; P = 0.02)., Conclusion: The hCG test is a valid indicator of the presence of functioning testicular tissue. It is predictive of anorchia and a good response to hCG suggests the presence of testes sufficiently large for orchidopexy.

The blood FSH level is often high in patients with severe testicular disorders including cryptorchids. To examine whether inhibin is involved in the increase in FSH we measured immunoreactive inhibin, FSH, LH, and testosterone in 17 patients after orchidopexy. FSH was extremely high (20 mIU/ml or above) in 3 patients. The inhibin level was significantly lower (P < 0.01) in these 3 patients (6.47 +/- 2.19 IU/ml; mean +/- SEM) than in the other 14 patients (14.31 +/- 3.96 IU/ml). All 3 high-FSH patients had azoospermia. Testosterone and LH were normal in one of them. Even considering problems involved in the inhibin assay, the high FSH levels are considered to reflect reductions in the blood inhibin level due to Sertoli cell dysfunction. These findings suggest that inhibin plays an important role in the suppression of FSH at least in some patients after orchidopexy.

In order to elucidate the respective effects of depletion of germ cells and of increase in testicular temperature, rats of the same Wistar strain were rendered experimentally bicryptorchid or sterilized by a busulfan injection in utero and compared to control animals. In both models, germ cells were depleted but numeric evolution and functions of somatic cells differed. The aim of that work was to compare the numeric evolutions of testicular somatic and germ cells to their respective functions in each model before puberty and in adult rats of the same strain. Serum concentrations of FSH, LH and testosterone were compared at 20, 40 and 110 days of age. Histological analyses of Sertoli and germ cells in the seminiferous tubules and of Leydig cells in the intertubular tissue were performed before puberty and at adulthood. Testosterone serum concentrations were depleted in both models starting at 40 days of age and more in busulfan-treated rats. Both FSH and LH levels were increased from 20 days onwards in experimental rats. Additional cryptorchidism in busulfan-treated rats depressed the serum testosterone concentration. At 17 days of age, the cryptorchidism do not modify somatic or germ cell populations while busulfan treatment has induced a decrease of both these populations. Conversely, the cross sectional area of the somatic testicular cells was not affected whatever the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in peripheral plasma luteinizing hormone (LH) and testosterone (T) concentrations and semen quality were investigated in four unilaterally cryptorchid (UC), three bilaterally cryptorchid (BC), and five normal beagles, from 4 to 48 weeks of age. Blood samples were collected at 2- or 4-week intervals, and the LH and T concentrations were determined by radioimmunoassay. Semen samples were collected weekly by digital manipulation. The mean LH and T concentrations in the normal dogs increased after 20 and 22 weeks of age and reached approximately 4 ng/ml and 3 ng/ml respectively at 36 weeks of age. Semen volume and total spermatozoa count increased apparently at 34 and 35 weeks of age respectively. Spermatozoa motility and percentage of abnormal spermatozoa varied less after 38 weeks of age. Plasma LH and T concentrations in the UC and BC dogs had a tendency to remain lower than values in the normal dogs after 26 weeks of age. The semen volume and spermatozoa count in the UC dogs did not increase markedly. The spermatozoa count was less than half that in normal dogs, and the percentage of abnormal spermatozoa was higher throughout the experimental period. All BC dogs had azoospermia. Thus it was evident that development of spermatogenic function during sexual maturation in the UC and BC dogs was insufficient compared with that in normal dogs.

Cryptorchidism is the most common male sexual disorder. In the case of an abdominal testis there is no objective criterion to choose between autotransplantation or orchiopexy after ligation of the spermatic vessels with subsequent development of collateral blood supply. By combining near infrared spectroscopy (NIRS) with pulse oximetry the active testicular blood volume (ATBV) before and after occlusion of the spermatic vessels can be calculated in an animal model. NIRS is a noninvasive continuous optical technique that measures tissue oxygenation and hemodynamics. Ten boars with one non-palpable testis each were selected. The spermatic vessels and vas deferens were separately prepared and atraumatic occluders were placed around the vessels. ATBV was measured before and after occlusion of the spermatic vessels. The calculated ATBV was 18.3 +/- 2.3 ml/100 g of testicular tissue, not corrected by division by the path length factor, accounting for light scattering in the tissue. In 5 of 10 boars no significant ATBV was found after occlusion of the spermatic vessels, suggesting subsequent atrophy. NIRS combined with pulse oximetry provides us with reproducible quantification of ATBV. The method can be used to investigate the viability of a testis after (temporary) occlusion of the spermatic vessels.

Anti-Müllerian hormone (AMH) is synthesized by immature Sertoli cells and by postnatal granulosa cells. Assay of serum AMH is useful in clinical situations to search for the presence of testicular tissue or to assess its functional value before puberty. At the time of puberty, serum levels of AMH decrease dramatically, a negative correlation has been demonstrated between AMH and testosterone serum levels. AMH assay is also useful in a rare form of male pseudohermaphroditism, characterized by the persistence of uterus and tubes in an otherwise normally virilized patient. AMH levels are undetectable or severely decreased in the case of a mutation of the AMH gene itself. In contrast, the concentration of serum AMH is normal if the syndrome is due to an insensitivity of AMH target organs.

The testis is a common site of relapse in childhood acute lymphoblastic leukaemia (ALL). In adults, testicular relapses of ALL are very rare. A similar age-difference in the frequency of the testicular infiltration exists also in the rat T-cell leukaemia. In the present investigation, the effect of various hormonal treatments and unilateral cryptorchidism on the form of testicular infiltrates by the rat T-cell leukaemia was studied. Inhibition of testicular activity by estradiol treatment (E2) of early pubertal rats injected i.p. with rat T-leukaemic lymphoblasts significantly decreased the proportion of the testis occupied by leukaemic infiltrates. The proportion of the testis occupied by leukaemic infiltrates was significantly higher in the abdominal testes of both early and late pubertal unilaterally cryptorchid rats, than in the scrotal testes of leukaemic control rats. Daily treatment of early pubertal rats with human chorionic gonadotrophin (hCG), or human menopausal gonadotrophin (hMG), did not have an effect on testicular leukaemic infiltration. These studies demonstrate that the leukaemic infiltration of the testis is influenced by the changes in the physiological activity of the testes.

Infertility is common in patients with a history of bilateral cryptorchidism, even after successful prepubertal orchidopexy. Recent data suggest that this defect may be partially due to the existence of hormonal abnormalities in some forms of cryptorchidism. To analyze any potential benefit of hormonal therapy, we have evaluated the immediate and long-term effects of chronic hormonal therapy administered following surgical correction of cryptorchidism. First, using young male rats, we examined the effects of chronic human chorionic gonadotropin (HCG) and a luteinizing hormone-releasing hormone agonist (LHRH-A), alone or combined, on acute pituitary-gonadal axis responsiveness to LHRH administration. High doses of HCG and/or LHRH-A induced deleterious effects on the pituitary-testicular axis in terms of suppression of response to LHRH. Therefore, treatment with a low dose of HCG (50 U/kg/day) for 14 days was used, since it produced a significant increase in intratesticular testosterone (ITT). Second, we tested this hormonal regimen in a cryptorchid rat model. Bilateral cryptorchidism was produced by gubernaculum resection at 14 days of age. Early orchidopexy was performed at age 30 days, and HCG therapy was given from 31 to 44 days of age. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels were determined before and immediately after hormonal therapy, and at sacrifice. Animals were sacrificed at 61 days of age for determination of serum and testicular hormone levels, accessory sex organ weights and testis histology. Five or six animals from each group were retained for breeding studies at the age of 90 days. Hormonal alterations noted immediately following treatment of cryptorchid animals with HCG are not lasting. The data reveal that the fertility defect in bilateral cryptorchidism is partially prevented by early orchidopexy and that adjunctive hormonal therapy is probably of little additional benefit.

Four patients at the age of 20-55 years treated for cryptorchism by means of microvascular anastomosis were presented. Considerable usefulness of autotransplantation was revealed on the basis of 5 procedures performed, especially in the case of intra-abdominal location of the testes.

The development of testes and genital accessory organs, the plasma testosterone concentration and the reactivity of seminal vesicles to catecholamines were studied in rats rendered cryptorchid at the time of prepubertal growth. The wet weights of the accessory organs and the testosterone concentrations were reduced and corresponded to those observed after castration. The response of the seminal vesicle to adrenaline and noradrenaline, but not to methoxamine, showed a reduction in sensitivity. It is suggested that an enhancement of neuronal catecholamine uptake may have occurred. The results also reinforce the idea that development, plasma testosterone concentration and reactivity of seminal vesicles are independent phenomena. In cryptorchidism, despite the consequences arising from the maintenance of the testes at body temperature rather than at the lower temperature of the scrotum, the age that the rat is rendered cryptorchid is also of fundamental importance.

An LH-RH-analogue (LH-RH-A) was administered to 5 cryptorchid (CR) and 6 normal beagles before and after sexual maturation and peripheral plasma LH and testosterone levels were measured. The response patterns of plasma LH levels for LH-RH-A in the CR dogs were similar to those in the normal dogs before and after sexual maturation. It was therefore demonstrated there is little difference in pituitary response to LH-RH-A in the CR and normal dogs. However, the maximum levels of testosterone in the CR dogs were generally lower than those in the normal dogs.

The persistent Müllerian duct syndrome is characterized by the retention of Müllerian derivatives in patients otherwise normally virilized. Clinically, the persistence of uterus and tubes leads either to cryptorchidism or inguinal hernia, depending on whether or not the Müllerian derivatives can be mobilized during testicular descent. The condition is usually discovered at surgery, however preoperative sonography could allow the diagnosis to be made preoperatively. The molecular basis of the persistent Müllerian duct syndrome is heterogeneous, and is reflected by wide variations in the serum concentration of anti-Müllerian hormone. Some cases are apparently due to end-organ resistance, and are associated with normal serum levels of the hormone. Others, characterized by absent or low hormone concentrations, can be explained by mutations of the gene coding for anti-Müllerian hormone, which are distributed along the whole length of the coding region.

This paper is a historic review of two studies of the treatment of cryptorchidism. One was concluded 20 years ago with native LHRH, while the other took place 14 years ago and involved one of the potent LHRH analogues. The first study was initiated at the end of 1971-at a time when the different modes of action of the decapeptide were by far not evaluated to the full extent they are now-and included ten prepubertal boys with undescended testes aged five to ten years. The treatment consisted of intramuscular application of 20 micrograms LHRH once daily for three weeks. Additionally, three boys, five, seven and nine years of age, also presenting undescended testes underwent an LHRH test with intravenous bolus application of 200 micrograms. In all three subjects, a 2.5-fold increase in plasma testosterone was observed 20 min after the bolus. The treatment group showed neither a rise in LH nor in testosterone at the end of therapy. Testicular descent was achieved in six out of six boys with bilateral and in 2/4 with unilateral undescended testes. These good results might be based on the fact that six boys had retractile rather than actually undescended testes. In the second study started in 1978, 18 boys, three to 12 years of age with either unilateral or bilateral cryptorchidism, were treated with a synthetic LHRH analogue ("D-Leu 6, Des-Gly-10 LHRH ethylamide") applied intranasally. The peptide prepared in an aqueous solution was administered in the form of nose drops.(ABSTRACT TRUNCATED AT 250 WORDS)

To obtain more information about testicular inhibin secretion in the prepubertal and pubertal human male, we measured the concentrations of immunoreactive inhibin with a heterologous radioimmunoassay in the spermatic and peripheral venous plasma of 5 prepubertal boys with unilateral undescended testis (Group I, P1), 3 prepubertal boys with inguinal hernia (Group II, P1), and 12 pubertal boys with left idiopathic varicocele. The latter subjects were divided, according to the degree of their pubertal development, in early pubertal (Group III, N = 5, P2) and mid-pubertal groups (Group IV, N = 7, P3-4). In Group I, the mean (+/- SD) spermatic venous concentrations of inhibin (289.4 +/- 120.4 ml eq/l) were significantly higher than the corresponding mean peripheral venous concentrations (162.6 +/- 47.2; p < 0.02) suggesting active testicular secretion of inhibin. In Group II, the spermatic-peripheral inhibin gradient was not significant. In pubertal boys with idiopathic varicocele, the mean concentrations of spermatic inhibin were 1076.6 +/- 532.0 and 1023.4 +/- 274.5 in Groups III and IV, respectively. These levels were about five times higher than the corresponding peripheral concentrations (204.8 +/- 41.9 and 238.9 +/- 38.9; p < 0.005 and p < 0.001, respectively). When the data of all the boys were considered together the spermatic venous concentrations of inhibin were significantly correlated with those of peripheral venous FSH (r = 0.4749, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The objectives of the study were to determine whether a low dose of a luteinizing hormone-releasing hormone analogue (buserelin) has an effect on testicular descent, if buserelin affects germ cell maturation and epididymal development, the incidence of retractile testes in the controlled trials, and if the subsequent administration of human chorionic gonadotropin has any effect on the groups treated. The study was double blind, placebo controlled in which patients with cryptorchidism were assigned randomly into 3 groups: buserelin treatment (22), surgical treatment (18) or placebo control group (19). The 3 groups of patients were similar before treatment in regard to testicular position, chronological and bone age, height and weight, luteinizing hormone, follicle-stimulating hormone, testosterone, penile size and the volume of the contralateral testis. Buserelin (20 micrograms). administered daily in a nasal spray significantly induced testicular descent compared to the group treated with a placebo (p less than 0.01). A normal epididymis was found more often in boys with successful descent (p less than 0.003). Boys treated with buserelin had the highest number and the best maturation index of the germ cells; human chorionic gonadotropin influenced the descent in both groups but it was more efficacious when it was administered after treatment with buserelin, although it had no additional effect on germ cell maturation. None of the boys had retractile testes. Buserelin was capable of inducing testicular descent in addition to increasing simultaneously the number of germ cells and provoking further development of the epididymis.

Seven patients with bilateral undescended testes (9 intraabdominal testes and 5 inguinal testes), aged 7 to 29 years, were treated surgically. Testis autotransplantation was done for 9 intra-abdominal testes, and cryptorchidopexy was done for 5 inguinal testes. Follow-up for 5 to 9 years showed that the transplanted testes survived except 1 atrophied helf a year after operation. The size of the transplanted was as big as that of international testis model 15, and their hardness was moderate. Obvious improvement of secondary sex character and sexual function were observed in 6 of the 7 patients. The value of serum testosterone was norma (1450-600ng/dl) in 4 patients. In 4 patients, sperms were found in semen. The wives of 2 of those patients bore a boy and a girl respectively in 2-3 years after operation. Operative treatment and optimal age for testis autotransplantation are discussed.

A total of 91 boys underwent bilateral orchiopexy with testicular biopsy. The percentage of tubular transverse sections containing spermatogonia, the fertility index (FI) and the number of spermatogonia per tubular transverse section (S/T) were measured and expressed as a percentage of the minimum normal value (FI% and S/T%, respectively). The maximum and mean of the 2 FI% and S/T% values were noted for each patient. At follow-up, testicular volume was measured in 73 men; 71 of these gave a blood sample for FSH and 67 provided specimens of semen for analysis. The maximum and the mean FI% and S/T% values of the patients were positively correlated to maximal sperm density and to volume of pair of testes and negatively correlated to serum FSH. It seems reasonable to use these histological parameters as prognostic indices of fertility potential. In adulthood only 11 patients had sperm density greater than or equal to 20 million/ml, 37 had normal serum FSH and 29 had bilateral testicular volume greater than or equal to 15 ml. Patients with both testes originally placed in the superficial inguinal pouch at surgical exploration had a higher maximal sperm density than the rest of the study group.

Serum levels of Mullerian inhibiting substance (MIS) were measured in boys with cryptorchidism (n = 104) and paired, age-matched controls (n = 104) using an enzyme immunoassay. Control MIS levels were high during the first year of life with a peak level at 4 to 12 months, subsequently diminishing with age. MIS levels in patients with undescended testes also declined with age, although a surge was not found in the first year. Mean MIS concentration of cryptorchid boys was significantly lower than controls (P less than .001). There was a significant reduction of the mean MIS level in children with bilateral cryptorchidism compared with those with unilateral undescended testis (P less than .05). These differences might support the hypothesis that MIS initiates transabdominal testicular descent. However, because most undescended testes are probably the result of anatomical or functional abnormalities during transinguinal testicular descent, differences in MIS levels more likely result from secondary testicular degeneration. In the future, MIS immunoassay should play an important role in the investigation of gonadal function in boys with various genital disorders, including cryptorchidism.

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels and secretory capacity of the in vitro stimulated testis were determined in control and bilateral cryptorchid mice after 7, 14, 21, and 28 days. In a separate study, serum FSH, LH, and testosterone levels were measured in unilateral and bilateral cryptorchid, hemicastrate, and bilaterally castrate adult mice after 28 days of treatment. Serum FSH levels were significantly increased in bilaterally cryptorchid mice compared to controls (0 days) at 7, 14, 21, and 28 days, but serum LH and testosterone levels did not change. At 28 days, the elevated serum FSH levels in the unilateral and bilateral cryptorchid mice were not different than those in hemicastrate mice. However, the FSH levels in bilaterally castrate mice after 28 days were significantly higher than all other groups. Serum LH and testosterone levels were significantly different only in the bilaterally castrate group, compared to control levels. Both the normal and cryptorchid testes of all ages studied were capable of producing equal levels of testosterone in vitro, both basally and with a human chorionic gonadotropin (hCG) dose of 700 mIU/ml (maximum stimulatory dose for both the normal and the 28 day cryptorchid testes). Changes that occur in mice with experimentally induced cryptorchidism are not identical to those seen in the rat. Serum FSH levels increase, but no changes occur in serum LH and testosterone levels. Additionally, a cryptorchid mouse testis is not hyperresponsive to hCG stimulation in vitro.