Endocrine and exocrine profiles of men with testicular tumors before orchiectomy

In 15 patients with germ cell testicular tumors serum hormone profiles and semen analysis before orchiectomy were evaluated to determine the incidence of defective spermatogenesis associated with testicular tumors. Defective spermatogenesis was noted in 10 patients (66 per cent) on the basis of low sperm concentration, motility or semen volume. Of the 10 patients 7 had sperm concentrations less than 10 million per cc. Endocrine abnormalities occurred in 10 patients, the most common of which were elevations in serum human chorionic gonadotropin and estradiol, and a relative decrease in follicle-stimulating hormone. Three patients who presented with subfertile semen analyses were treated with orchiectomy alone. Repeat semen analyses 4 to 12 months after orchiectomy showed improvement in spermatogenesis and 2 patients achieved a normal semen analysis. Endocrine abnormalities and defective spermatogenesis are common in patients with testicular tumors. These abnormalities precede orchiectomy and imply that a primary germ cell defect exists in these patients.     

The gonadotropin response to synthetic gonadotropin releasing factor in patients with testicular cancer

The response of LH and FSH to synthetic gonadotropin releasing factor (GRF) was investigated in 19 patients with malignant germ cell cancers of the testicle prior to radical orchiectomy. The study showed: 1. Patients with circulating beta-HCG presented with increased plasma levels of oestradiol. Base line FSH and response to GRF were significantly decreased. 2. In patients without detectable beta-HCG plasma concentrations of oestradiol and testosterone were within the normal ranges as compared to healthy age matched controls. Base line levels of FSH and LH were increased and an exaggerated response to GRF was observed. From the results of this study it can be concluded that hypergonadotropic dysfunction of pituitary-gonadal axis exists in patients with testicular cancer of germ cell origin. Beta-HCG production by tumour tissue results in hyperoestrogenism and interferes with the pituitary-gonadal axis in terms of inhibition of pituitary gonadotropin release.     

Endocrine response to a single injection of goserelin 3.6 mg or leuprolide 3.75 mg in men with prostate cancer

Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.     

Subfertility among parents of men diagnosed with testicular cancer

It is well known that men with testicular cancer also have reduced fertility before diagnosis. It is unclear, however, whether their parents also have reduced fertility. We performed a population-based record linkage study comparing parental fertility among 3711 testicular cancer cases and 371 100 control males. The cases were diagnosed from 1961 to 2001, and the data were analysed by logistic regression. Included indicators of parental fertility were number of children, rate of unlike-sex twins as a proxy for dizygotic twinning rate, and proportion of boys. The number of children was reduced across increasing sibship size among both mothers [odds ratio (OR) = 0.95, p(trend) = 0.003] and fathers [OR = 0.97, p(trend) = 0.057] of subjects with testicular cancer. The proportion of unlike-sex twins was also reduced among their mothers [(OR = 0.56, p = 0.049 (adjusted for year of birth)] and fathers [(OR = 0.56, p = 0.049 (adjusted for year of birth)]. The results were only marginally changed when also adjusting for respective parental age. Our study indicates that parents of testicular cancer cases have reduced fertility. This suggests that genetic factors are important in the association between testicular cancer and reduced fertility.     

False positive beta-human chorionic gonadotropin in testicular cancer

Persistent elevations in serum markers after chemotherapy for germ cell testicular carcinoma indicate residual disease. We report on a patient with advanced seminoma with choriocarcinoma who had elevated serum beta-human chorionic gonadotropin (beta-HCG) and residual masses on computerized tomography scan after chemotherapy. Wedge liver resection and retroperitoneal node dissection yielded only necrotic tissue which assayed and immunoperoxidase stained positively for beta-HCG. Serum beta-HCG fell to undetectable levels postoperatively, and the patient remains disease-free after three years. Phagocytosis of necrotic tumor apparently released entrapped beta-HCG resulting in a false positive tumor marker.     

Semen cryopreservation after orchidectomy in men with testicular cancer

OBJECTIVE: To assess the feasibility of semen cryopreservation after orchidectomy in patients with testicular tumour. PATIENTS AND METHODS: The quality of semen samples was investigated in 36 men with testicular tumour (mean age 31.7 years, range 20-49) who were referred to our infertility centre for semen cryopreservation. For each patient, the number of straws, semen volume, number of spermatozoa, and sperm motility before and after freezing were evaluated. RESULTS: Fifteen patients (42%) banked sperm before and 21 (58%) after orchidectomy; the delay was >7 days in 19 patients (53%). The mean age, histological diagnosis and tumour stage did not differ significantly whatever the time of cryopreservation. Semen quality did not differ significantly in patients who cryopreserved sperm before or after orchidectomy and there were no significant differences in sperm values whatever the delay before preservation. Semen quality was the same in patients with seminoma or nonseminoma tumour. CONCLUSION: These findings indicate that spermatogenesis of the contralateral testis is sufficient for successful semen cryopreservation after orchidectomy. Urologists should be encouraged to increase the awareness among oncology teams and patients about the new developments in preserving fertility for patients with cancer.     

Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer

We used an indirect immunoperoxidase technique to localize alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.     

Gonadal dysfunction after testicular torsion: luteinizing hormone and follicle-stimulating hormone response to gonadotropin releasing hormone

We studied 14 postpubertal patients at an average of 33 months after treatment for testicular torsion. Of these patients 11 had been treated by detorsion and 3 by orchiectomy. Five normal male volunteers of the approximate age of the study group served as controls. The patients treated by detorsion were subdivided into 3 groups based on the degree of atrophy of the detorsed testicle: group 1--no testicular atrophy (5), group 2--25 per cent testicular atrophy (2) and group 3--greater than 90 per cent testicular atrophy (4). Mean duration of torsion was greatest in the orchiectomy group (161 hours) compared to 6, 16 and 29 hours for groups 1, 2 and 3, respectively. The serum luteinizing hormone and follicle-stimulating hormone response to an intravenous bolus of 100 mcg. synthetic gonadotropin releasing hormone was measured in all patients. All groups had a greater mean follicle-stimulating hormone response to gonadotropin releasing hormone stimulation than controls (p less than 0.05). Patients who underwent orchiectomy had the greatest follicle-stimulating hormone response to gonadotropin releasing hormone stimulation. Mean luteinizing hormone response to gonadotropin releasing hormone stimulation was normal in patients without atrophy (group 1) but it was greater than controls in patients who had atrophy (groups 2 and 3) or who underwent orchiectomy (p less than 0.05). Several conclusions could be made from our study. All patient groups treated for torsion had evidence of testicular dysfunction. Patients who underwent orchiectomy displayed more testicular dysfunction than patients who had atrophy after detorsion. Testicular dysfunction after torsion is more likely to involve spermatogenic before Leydig cell function.     

Initial gonadotropin levels and sperm parameters differentiate the response to clomiphene citrate in subfertile men

BackgroundEfficacy of clomiphene citrate (CC) in the treatment of male subfertility remains unclear, with inconsistent results in the literature and limited guidance from professional organizations. We sought to stratify the response to clomiphene in men based on their initial gonadotropins and semen parameters.MethodsWe conducted a retrospective analysis of 234 patients from an academic center who took CC for subfertility. Patients with pre-treatment and 3 months follow-up total testosterone (TT) and semen analyses were included. Patients with previous hormone therapy, genitourinary surgery, prior success in conceiving pregnancy, or only one semen analysis were excluded. Primary outcomes were magnitudes of improvement in TT and semen parameters at 3 months. Student’s t-test (alpha =0.05) was used for univariate analyses; multivariable linear regression was used for multivariate analysis.ResultsOne hundred and thirty-seven patients met inclusion criteria. Thirty-four percent of patients experienced improvement in sperm concentration after 3 months of CC treatment, 13% decreased, and 53% showed no change. Using a pre-treatment TT cutoff of 300 ng/dL and gonadotropin thresholds of 7 miU/mL, initial TT did not affect magnitude of improvement in semen parameters, while lower initial gonadotropins showed statistical improvement across all outcomes. Multivariate analysis showed pre-treatment follicle stimulating hormone (FSH) was inversely correlated with improvement in TT [odds ratio (OR): 2.64e-05, 95% confidence interval (CI): 1.32e-09 to 5.28e-01, P=0.04] and sperm concentration (OR: 0.22, 95% CI: 5.70e-02 to 8.48e-01, P=0.03). We also provide initial gonadotropin cutoffs that suggest statistical benefit from CC use.ConclusionsMen with lower gonadotropin levels may expect greater degree of improvement in both hormone and semen parameters with use of CC. Men with azoospermia do not benefit based on semen analyses alone. Degree of non-azoospermia does not affect magnitude of improvement. CC had decreasing efficacy at higher initial gonadotropin levels. These data may provide guidance in stratifying and counseling men for CC treatment.     

Effect of an antiestrogen on the testicular response to acute and chronic administration of hCG in normal and hypogonadotropic hypogonadic men: tamoxifen and testicular response to hCG

The effect of the antiestrogen tamoxifen (Tx) on the acute and chronic hCG administration was evaluated in patients with hypogonadotropic hypogonadism (HH) and in normal men. An hCG test (5000 IU hCG) was performed before, after two months of hCG administration (2000 IU hCG three times weekly) and after two months of hCG + Tx (2000 IU hCG three times weekly plus 20 mg/day of tamoxifen). Blood samples were obtained before and following 24 and 72 h of every test to determine T, E, 17OHP and SHBG. T increased only in HH with both treatments (X +/- SEM: Basal: 97.9 +/- 19.7; hCG: 237.7 +/- 43.2; hCG +/- Tx: 204.7 +/- 10.7 ng/100 ml). 17OHP rose with hCG alone, but not with hCG + Tx in both groups. E, SHBG and 17OHP/T ratio did not change after treatments. hCG tests: E increased 24 h following hCG administration in every test. The ratio 17OHP/T rose at 24 h in the first and second test but in the third test it did not change. These results support the role of E in the acute hCG-induced Leydig cell desensitization. However, the association of Tx does not improve T serum levels, suggesting that E might not be the unique factor involved in the mechanisms for testicular desensitization.     

Inhibin and steroid response to testicular stimulation with pure FSH (Metrodin) in infertile men with unilateral cryptorchidism

Summary. Static measurements of immuno-reactive 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.     

Endocrine and metabolic response to surgery

The neuroendocrine, metabolic and inflammatory aspects of injuryare part of the overall ‘stress response’ (Table 1).This has been studied most commonly in relation to surgery,because the catabolic changes that occur can be observed froma well-defined starting point, but similar features occur intrauma, burns, severe infection and strenuous exercise. Theseresult in substrate mobilization, muscle protein loss and sodiumand water retention, with suppression of anabolic hormone secretion.There is activation of the sympathetic nervous system and immunologicaland haematological changes. Generally, the magnitude of themetabolic response is proportional to the severity of the surgicaltrauma. These changes have probably evolved to aid survivalin a more primitive environment, by mobilizing substrates, limitingtissue damage, destroying infectious organisms and activatingrepair processes. Psychological and behavioural changes accompanythe physiological events. The benefits of the stress responseare not obvious in modern medicine, when physiological changescan be more easily corrected and it may even have a detrimentaleffect. In recent years, research has focused on methods tomodify the response associated with surgery in an attempt toimprove patient outcome. View this table: [in this window] [in a new window]   Table 1 Changes occurring during the stress response       

Endocrine response to masturbation-induced orgasm in healthy men following a 3-week sexual abstinence

This current study examined the effect of a 3-week period of sexual abstinence on the neuroendocrine response to masturbation-induced orgasm. Hormonal and cardiovascular parameters were examined in ten healthy adult men during sexual arousal and masturbation-induced orgasm. Blood was drawn continuously and cardiovascular parameters were constantly monitored. This procedure was conducted for each participant twice, both before and after a 3-week period of sexual abstinence. Plasma was subsequently analysed for concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone and testosterone concentrations. Orgasm increased blood pressure, heart rate, plasma catecholamines and prolactin. These effects were observed both before and after sexual abstinence. In contrast, although plasma testosterone was unaltered by orgasm, higher testosterone concentrations were observed following the period of abstinence. These data demonstrate that acute abstinence does not change the neuroendocrine response to orgasm but does produce elevated levels of testosterone in males.     

Endocrine profiles in pediatric andrology. III. Human chorionic gonadotropin stimulation test in cryptorchid boys

Serum testosterone (T) concentration and urinary 17-ketosteroid (17-KS) excretion were measured under basal conditions and after stimulation with human chorionic gonadotropin (hCG) in 36 prepubertal males (10 normal children and 26 cryptorchid patients). As a function of hCG stimulation, the increase in serum T level was evident in both groups, although the magnitude of the rise was higher in the control group than in cryptorchid boys. No significant differences in serum T or urinary 17-KS were observed between patients with unilateral and bilateral undescended testis, either before or after hCG stimulation. In spite of the wide individual variations in testicular response in all subjects, the test is valuable in assessing Leydig-cell function and in prognosis for virilization at puberty.     

Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis

PURPOSE: We determined the standardized incidence ratio of testicular cancer in infertile men presenting with an abnormal semen analysis compared to the general population. MATERIALS AND METHODS: The charts from more than 3,800 men presenting with infertility and abnormal semen analysis during a 10-year period were retrospectively reviewed. The incidence of testicular tumors diagnosed in this group was compared to that of race and age matched controls during the same period from the general population (as reported by the Surveillance, Epidemiology and End Results [SEER] database). RESULTS: Of 3,847 men 10 (0.3%) with infertility and abnormal semen analysis were diagnosed with testicular tumors. Mean patient age was 32.6 years (range 25 to 52) and all 10 men were diagnosed with a seminomatous germ cell tumor. Two men had a history of cryptorchidism while the remaining 8 had no identifiable risk factors for testicular cancer. The SEER database reported an incidence of 10.6 cases of testicular cancer (95% CI 10.3-10.8) per 100,000 men of similar age group and racial composition during the same period. The standardized incidence ratio of testicular cancer was 22.9 (95% CI 22.4-23.5) when comparing our infertile group to the control population. Exclusion from analysis of the 2 patients with a history of cryptorchidism decreased the standardized incidence ratio to 18.3 (95% CI 18.0-18.8). CONCLUSIONS: Infertile men with abnormal semen analyses have a 20-fold greater incidence of testicular cancer compared to the general population. Patients and physicians should be aware that one of the causes of infertility could be cancer, particularly testicular cancer.     

Effect of estrogen treatment on testicular gonadotropin receptors in prostatic cancer patients

Effects of estrogen treatment on testicular human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) receptors in man were investigated. Ten patients (aged 58 to 75, mean 67 years) with prostatic cancer were treated with diethylstilbestrol diphosphate (DESDP) (300 mg daily, oral administration). They were divided into two groups: 5 of them (aged 58 to 74, mean 67 years) were orchiectomized after 7 days of treatment and the remainder (aged 60-75, mean 67 years) after 6 months of treatment. hCG and FSH receptors in the resected testes of each group were measured and compared with those of age-matched prostatic cancer patients without any treatment (controls). After 7 days and 6 months of DESDP treatment, the number of hCG receptors decreased to approximately 53% and 24%, respectively, of that of the controls. FSH receptors in the testes of the patients treated with DESDP did not differ significantly from those of the controls.     

Semen quality and reproductive hormones before and after orchiectomy in men with testicular cancer

PURPOSE: We clarify the impact of removal of the tumor bearing testis on semen quality and reproductive hormones in men with testicular cancer. MATERIALS AND METHODS: Semen quality and levels of reproductive hormones were investigated in 48 men before and after orchiectomy for testicular cancer. Semen analysis was done in 35 of these men and hormone analyses were done in 47. The hormone data of patients with (14) or without (33) elevated values of human chorionic gonadotropin (HCG) were analyzed separately. RESULTS: Median sperm concentration and total sperm count decreased from 17 x 10(6)/ml. (range 0 to 117) and 39 x 10(6) (0 to 433), respectively, before to 7 x 10(6)/ml. (0 to 69) and 30 x 10(6) (0 to 200), respectively, after orchiectomy. After orchiectomy sperm concentration was decreased in 30 of 35 men (p = 0.001) and azoospermia developed in 3 (9%). In men without detectable HCG median follicle-stimulating hormone levels increased (p <0.001) from 5.7 IU/l. (range 0.01 to 30) before to 10.0 IU/l. (4.6 to 48) after orchiectomy in 33 of 33 patients. Median inhibin B significantly decreased (p = 0.003) from 108 pg./l. (range 60 to 193) before to 95 pg./l. (less than 20 to 141) after orchiectomy. Median luteinizing hormone increased significantly from 3.1 IU/l. (range 1.1 to 9.9) before to 5.2 IU/l. (2.1 to 27) after treatment (p <0.001). Testosterone and sex hormone-binding globulin did not change significantly after orchiectomy. Patients with detectable serum HCG before orchiectomy had a considerable increase in follicle-stimulating hormone after orchiectomy, and a concomitant decrease in testosterone and estradiol. CONCLUSIONS: Semen quality was poor at diagnosis and deteriorated further after orchiectomy compared with pretreatment values. Our findings indicate that in some patients the most appropriate time for cryopreservation of semen is before orchiectomy. Androgen production was maintained by increased luteinizing hormone stimulation after orchiectomy.     

Discordant human chorionic gonadotropin results giving rise to inappropriate therapy in a case of testicular cancer

The most widely cited cause of a falsely elevated human chorionic gonadotropin level in patients with germ cell tumors is an elevated level of partially cross-reacting luteinizing hormone. Other causes of discordant human chorionic gonadotropin results (human chorionic gonadotropin elevated in 1 assay but normal in others) in testicular cancer have received scant attention. A patient with pure seminoma was given inappropriate chemotherapy on the basis of an elevated human chorionic gonadotropin level, later shown to be due to a nonspecific serum interfering substance. A discordant human chorionic gonadotropin result should be suspected when the human chorionic gonadotropin is only modestly elevated, there is no serial increase in the human chorionic gonadotropin level and no other evidence of tumor can be found.