The impact of simple orchiectomy on semen quality and endocrine parameters in postpubertal cryptorchid men

Purpose

The main objectives of this retrospective cohort study were to evaluate reproductive endocrine and semen profiles before and after simple orchiectomy in patients with unilateral postpubertal cryptorchidism and to investigate the relationship between hormone levels and histopathology of the removed testis.

Methods

We evaluated 40 adult males who were admitted to our clinic, between 2001 and 2007, with unilateral undescended testis. Right orchiectomy was performed in 27 patients and left orchiectomy in 13. Semen analysis, serum inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were examined in before and 3?months after orchiectomy. Orchiectomy materials were evaluated histopathologically.

Results

Semen parameters, as well as testosterone and LH levels, did not change in any histopathological subgroups in the postoperative follow-up. In patients with maturation arrest, mean serum inhibin B level statistically significantly decreased from 160.9 to 83.5?pg/ml, and mean FSH level significantly increased from 4.8 to 7.6?mIU/ml after orchiectomy (p value, 0.008 and 0.008, respectively). Though, the levels were still within the normal range of the two hormones.

Conclusions

Simple orchiectomy does not have any effect on semen parameters and testosterone level in patients with postpubertal cryptorchidism. The change in inhibin B and FSH levels after orchiectomy in patients with maturation arrest is not clinically significant.     

Serum levels of inhibin B in men with different causes of spermatogenic failure

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.     

Serum levels of dimeric and monomeric inhibins and the degree of seminal alteration in infertile men with varicocele

The aim of the present study was to establish the serum levels of inhibins and their relationship with the degree of seminal alteration in infertile men. Thirty-six patients with varicocele (Va) and seven non-obstructive azoospermic men (Az) were included. The Va group was divided into two subgroups: Va I (sperm concentration: >20 x 106; n = 21) and Va II (sperm concentration: < 20 x 106; n = 15). Twelve fertile men were included as a control group (Co). Semen analysis and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and Pro-alphaC levels were determined. Serum inhibin B and T levels were significantly lower and FSH and LH significantly higher in group Az when compared with the Co. Inhibin B was unable to differentiate Va I from Va II groups. However, in Va II an increase in FSH levels was observed. An inverse correlation between inhibin B and FSH, a direct correlation between inhibin B and testosterone, sperm concentration, motility and morphology were found. No such correlations were seen when only the Va group was analysed. The lack of correlation between serum levels of inhibin B, gonadotrophins, sperm concentration and seminal parameters observed in Va, adds other factor to the complex pathophysiology of varicocele. Finally, further studies are needed to elucidate if oligozoospermic patients with varicocele have also an impaired negative feed-back mechanism that regulates FSH synthesis and secretion.     

Gonadotrophin stimulation in children with abnormal sexual development

Plasma levels of testosterone were measured by radioimmunoassay before and after 3 days' administration of human chorionic gonadotrophin (HCG) 2,000 IU/d in 34 prepubertal boys (6 normal, 3 with anorchia, 5 with micropenis, 8 with cryptorchidism, 6 with hypogonadotrophic hypogonadism and 6 with hypospadias). The increase in plasma testosterone value ranged from 2.4 nmol/l to 10.5 nmol/l in normal boys. There was negligible (P greater than 0.05) response in boys with anorchia compared with normal children. Subjects with micropenis showed subnormal response (P greater than 0.05). Children with cryptorchidism showed a normal increase in testosterone levels (P greater than 0.05), but in those with hypogonadotrophic hypogonadism and hypospadias the increase was variable (1.2 - 8.8 nmol/l) (P greater than 0.05). Although the HCG stimulation test is not diagnostic in the majority of the sexual disorders, it appears to be sensitive for diagnosing anorchia.     

Relationships between serum hormone levels and semen quality among men from an infertility clinic

Participation rates in epidemiologic studies on semen quality are generally very low, raising concerns as to the potential for selection bias. Since hormones both initiate and maintain spermatogenesis, they may serve as surrogates of semen quality in epidemiologic studies. For this reason, in the present study, we explored the influence and predictive ability of reproductive and thyroid hormones on semen quality among men who were partners in an infertile couple. Between 1999 and 2003, 388 men were recruited from Massachusetts General Hospital Andrology Laboratory for clinical evaluation of fertility status. Fresh semen samples were assessed for quality (concentration, motility and morphology) and the serum levels of hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, sex hormone-binding globulin (SHBG), testosterone, free androgen index, free T4, total T3, and thyroid-stimulating hormone (TSH), were measured. Multiple logistic regression revealed increased odds for below-reference sperm concentration and morphology in men with increased FSH, and decreased odds for below-reference sperm concentration and motility in men with increased inhibin B. When FSH and inhibin B were divided into quintiles, the relationships with sperm concentration showed evidence of a threshold value. However, the ability of specific FSH (10 IU/L) and/or inhibin B (80 pg/mL) cutoff values to predict semen quality was lower than in previous reports. In multiple linear regression analysis, FSH and LH were inversely associated with sperm concentration, motility, and morphology. Inhibin B and free T4 were positively associated with sperm concentration, while there was a suggestive positive association between testosterone and sperm motility. In conclusion, we have found that FSH, LH, inhibin B, testosterone and free T4 levels are associated with human semen parameters. Additional consideration should be given to the utility of serum hormone levels as a surrogate for semen quality in epidemiologic studies in which the collection of semen is difficult due to logistical and/or volunteer rate constraints.     

Decrease of anti-Mullerian hormone in genetic spermatogenic failure

The aim of this study was to compare anti-Mullerian hormone (AMH) plasma levels in patients with azoospermia according to the physiopathology. In a prospective clinical study from April 2008 to March 2009 in University Hospital, we measured AMH levels in 49 consecutive patients with azoospermia. AMH plasma levels were correlated with FSH, inhibin B, bioavailable testosterone plasma levels and testicular volume and compared between nonobstructive azoospermia (NOA) and obstructive azoospermia (OA) and within four physiopathological subgroups of NOA: genetic, cryptorchidism, cytotoxic and unexplained. AMH, FSH, inhibin B, bioavailable testosterone plasma levels and testicular volumes were all related to each other. AMH plasma levels were lower in NOA relatively to OA. Lowest values were observed in cases of genetic NOA and on the other hand, the values observed in case of cytotoxic NOA were as high as the values observed in OA. FSH, inhibin B, bioavailable testosterone and testicular volume were not different between genetic and cytotoxic NOA. These results suggest that the decrease in AMH plasma levels is related to the origin of NOA, with low values in genetic NOA and values similar to OA in cytotoxic NOA. Further studies will be useful to understand the fine regulation of AMH production.     

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.     

Leptin levels in infertile male patients are correlated with inhibin B, testosterone and SHBG but not with sperm characteristics

In the present study, differences in leptin levels between different groups of male patients presenting with infertility problems and possible correlations between leptin levels and clinical, spermiological, histological and hormonal characteristics were examined. Two hundred and ten male partners from infertile couples were included in the study. Based on clinical examination, spermiogram and testicular histology results, patients were divided into four groups: 42 men with non-obstructive azoospermia, 15 men with obstructive azoospermia, 68 men with oligoasthenoteratozoospermia and 85 men with normozoospermia. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, testosterone, sex hormone binding globulin (SHBG) and leptin were measured. After adjustment for body mass index, there was a negative correlation between serum levels of leptin and inhibin B, total testosterone and SHBG (r = -0.189, p = 0.009, r = -0.250, p = 0.001 and r =-0.221, p = 0.003 respectively) but there was no correlation between leptin and classical sperm characteristics. Our results therefore demonstrate a link between leptin and testicular function, independently of FSH and LH, possibly involving testosterone and SHBG through a regulation of Leydig cell function.     

Involvement of inhibin in the regulation of follicle-stimulating hormone secretion in the young adult male Shiba goat

The roles of inhibin and testosterone in the regulation of gonadotropin secretion were investigated in young adult male Shiba goats (8-12 months of age). Plasma levels of inhibin but not testosterone abruptly decreased after hemicastration (75% of the initial level), concomitant with a progressive rise in plasma levels of FSH. Removal of the remaining testis at 33 days after the hemicastration quickly decreased plasma levels of both inhibin and testosterone and induced a progressive increase in plasma FSH and LH. Implantation of testosterone sheets immediately after castration suppressed the increase in plasma FSH in part only, whereas the increase in LH secretion was almost completely suppressed. An i.v. injection of antiserum against [Tyr30] porcine inhibin alpha(1-30) resulted in a significant increase in plasma FSH in a dose-dependent manner, without altering plasma concentrations of LH. These findings clearly indicate that both inhibin and testosterone physiologically regulate FSH secretion and that testosterone is the principal gonadal factor regulating LH secretion in the adult male goat.     

Inhibin B regulating follicle-stimulating hormone secretion during testicular recrudescence in the male golden hamster

In the present study, to clarify whether inhibin affects follicle-stimulating hormone (FSH) secretion in the recrudescence of the male golden hamster, we used a recently developed specific enzyme-linked immunosorbent assay (ELISA) in order to measure 2 forms of inhibin molecules: inhibin B and inhibin pro-alphaC. In addition, we used the radioimmunoassay (RIA) to measure immunoreactive (ir-)inhibin, FSH, luteinizing hormone (LH), and testosterone. And finally, we used the proliferating cell nuclear antigen (PCNA) and computer-assisted sperm motion analysis (CASA) methods to ascertain how well spermatogenesis and sperm motility recover from the photoinhibition caused by exposure to a short-day (SD; 10-hour light: 14-hour dark) photoperiod. Animals were exposed to SD for 15 weeks, and then their testes were checked carefully and found to be completely regressed. Thereafter, those animals were transported to a long-day (LD; 14-hour light: 10-hour dark) photoperiod. Sampling was carried out at weeks 0 (exposed SD 15 weeks), 1, 2, 4, 6, 8, and 10. Plasma FSH rapidly increased and reached peak levels 2 weeks after transferral to the LD photoperiod and then declined to normal LD levels at week 6. Circulating ir-inhibin, inhibin B, and inhibin pro-alphaC rose to normal LD levels by week 4. A highly significant inverse correlation was observed between plasma FSH and inhibin B but not between FSH and either ir-inhibin or inhibin pro-alphaC. Plasma testosterone recovered to normal LD levels within 1 week. Sperm motility parameters were low until week 2 and recovered to normal LD levels from weeks 4 to 10. PCNA-labeled cells were confined to the spermatogenic cells of the seminiferous tubules, though Leydig and Sertoli cell nuclei were never stained for PCNA during the period studied. The number of pachytene spermatocytes and the diameter of seminiferous tubules increased in a time-dependent manner after transferral from SD to LD. In conclusion, these results suggest that 1) secretion of inhibin B may be stimulated by an early rise in FSH; 2) inhibin B suppresses FSH secretion from weeks 2 to 10, after transferral to the LD photoperiod; and 3) testes recrudescence is based on the increase in the number of sperm cells instead of the increase in the number of Sertoli and Leydig cells of the male golden hamster.     

Long-term effects of a short course of neoadjuvant luteinizing hormone-releasing hormone analogue and radical radiotherapy on the hormonal profile in patients with localized prostate cancer

OBJECTIVE: To assess whether a long-term follow-up shows any reduction in the level of luteinizing hormone (LH) secretion, which could result in declining testosterone levels in men with localized prostate cancer, as most (96%) men have testosterone levels within the normal range by 1 year after treatment with a short course of LH-releasing hormone analogue (LHRHa) and radiotherapy, and LH and follicle stimulating hormone (FSH) remain high at 1 year after treatment, maintaining the testosterone levels. PATIENTS AND METHODS: We prospectively evaluated 55 patients who previously had a short course of LHRHa (median 97 days, range 28-167) and radiotherapy for localized prostate cancer. Eligible patients had documented normal testosterone, LH and FSH levels at baseline and at 1-3 years after radiotherapy. LH, FSH and testosterone were then measured at 5 years after treatment. RESULTS: The mean hormone levels before, at 1-3 years and at 5 years after treatment, respectively, were: testosterone (nmol/L), 15.33, 13.98, 12.97; LH (U/L), 5.51, 9.95, 6.95; and FSH (U/L), 7.95, 22.40, 17.00. The decrease in testosterone level at 5 years vs 1-3 years was not statistically significant and was of little clinical relevance (P = 0.057). LH and FSH levels were higher at 1-3 years than at baseline and decreased significantly (P < 0.001) at 5 years towards the baseline value. The decrease in FSH level was less marked than for LH. CONCLUSION: After a short course of LHRHa and radiotherapy, the testosterone level was maintained at 5 years. LH levels decreased towards the baseline value, suggesting recovery of Leydig cell function. FSH levels remained high, suggesting persistent Sertoli cell damage from treatment.     

Effect of immobilization stress on testosterone and inhibin in male rats

Adult male Wistar rats were subjected to acute and chronic immobilization stress. Changes in plasma levels of LH, FSH and testosterone and in the content of testicular inhibin and testosterone were studied. Plasma LH levels decreased significantly in response to both acute and chronic stress. Significant decreases in plasma testosterone content were also observed after chronic stress. In contrast, plasma FSH and testicular bioassayable inhibin content did not change after acute or chronic stress. These findings indicate that in male rats immobilization stress induced a dissociation in LH and FSH responses, and decreased testosterone while inhibin remained unaffected.     

Differential patterns of inhibin secretion in response to gonadotrophin stimulation in normal men

Inhibin B is produced by the testis, and its constituent alpha and beta B subunits have been localized immunohistochemically to Leydig as well as Sertoli cells in both rodent and human testes. Whether Leydig cells contribute to circulating inhibin B concentrations, however, is uncertain. We have investigated this by selectively stimulating Leydig and Sertoli cells with hCG and FSH, respectively. The study was a randomized crossover trial, investigating responses to 225 IU recombinant FSH or 3000 IU hCG administered s/c 4-6 weeks apart. Ten normal men were recruited to participate. Blood was taken twice before treatment and after 8, 24, 48, 72 and 96 h. Serum was assayed for FSH, LH and testosterone by radioimmunoassay (RIA); inhibin B and pro-alpha C inhibin forms by ELISA. Administration of hCG, but not FSH, caused a rapid increase in blood testosterone levels, which reached a maximum after 72 h (22.2 +/- 2.7-50.1 +/- 4.5 nmol/L, p < 0.001). Inhibin B concentrations in blood were unchanged following either treatment. Conversely, pro-alpha C concentrations increased following both treatments. FSH administration resulted in a gradual increase in pro-alpha C concentrations (369 +/- 18 pg/mL pre-treatment to 453 +/- 33 pg/mL after 96 h, p=0.013). Administration of hCG resulted in a more rapid response, with pro-alpha C concentrations rising from 384 +/- 23 pg/mL pre-treatment to a peak at 48 h of 535 +/- 45 pg/mL (p=0.007). This response was more rapid than that of testosterone. These results demonstrate that adult human Leydig, as well as Sertoli, cells secrete inhibin alpha subunit in response to gonadotrophin stimulation but provide no evidence for the secretion of inhibin B from Leydig cells. The lack of change in inhibin B secretion in response to FSH suggests that more prolonged or intense stimulation of Sertoli cells may be required for secretion of the dimeric form.     

Evaluation of the relative importance of endocrine and paracrine factors in control of the levels of inhibin in testicular interstitial fluid

This study aimed to identify the role of endocrine (FSH, LH, testosterone) or paracrine (Leydig or germ cell) factors in control of the secretion of inhibin into testicular interstitial fluid (IF). This was done by measuring inhibin and testosterone levels in IF, and serum gonadotrophin and testosterone levels in adult rats following the destruction of Leydig cells with ethane dimethane sulphonate (EDS), alone or in combination with testosterone ester (TE) supplementation at various doses initiated at various times after EDS treatment. The effect of germ cell loss (induced by local testicular heating) on its own or in combination with the above treatments was also assessed. Treatment with EDS led to major increases in the levels of inhibin in IF and of FSH and LH in serum whilst testosterone levels in IF and serum fell to undetectable levels. Supplementation with TE (1-25 mg) for 21 days from the time of EDS treatment failed to prevent the initial (+3 days) increase in IF levels of inhibin but thereafter suppressed inhibin to control levels or lower and grossly suppressed FSH and LH levels, irrespective of whether the dose of TE administered did (25 or 5 mg) or did not (1 mg) prevent major seminiferous tubule damage. Partial regeneration of Leydig cells and normalization of testosterone levels occurred in rats 21 days after treatment with EDS alone but this failed to normalize inhibin and gonadotrophin levels. When supplementation with TE (25 mg) was initiated at 3, 6 or 9 days after EDS treatment, IF levels of inhibin were normalized within 3 days and maintained thereafter in parallel with suppression of serum FSH and LH to below control levels. Seminiferous tubule damage induced by local testicular heating (43 degrees C for 30 min) led to increased IF levels of inhibin 3 and 14 days later, in parallel with increased serum levels of FSH (but not LH). Suppression of FSH to subnormal levels in heat-exposed rats by TE treatment (25 mg) restored IF inhibin to control levels or below, a change which still occurred when Leydig cells were destroyed by EDS treatment. It is concluded that secretion of inhibin via the base of the Sertoli cell into testicular IF is controlled primarily by FSH, although local factors may play a minor role. These findings have important implications regarding the possible paracrine role(s) of inhibin in IF during puberty and in the normal adult testis.     

Experimental cryptorchidism in the adult mouse: II. A hormonal study

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.     

Effects of long-term testosterone administration on pituitary-testicular axis in end-stage renal failure

The endocrine effects of long-term testosterone administration were studied in 6 end-stage renal failure patients. During a 3-month control period where no androgens were administered the mean plasma testosterone level (7.3 nmol/l) was depressed while mean plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were elevated at 41.2 mU/ml, 105.5 mU/ml, and 63 ng/ml, respectively. These values were repeated during a 6-month study period where each subject was administered testosterone enanthate (400 mg) intramuscularly once a week. Plasma testosterone levels markedly increased in all subjects with a mean elevation of 72.4 nmol/l, while reductions were observed in FSH and LH levels with values of 2.7 and 16.3 mU/ml, respectively. When compared with control period values, these changes were statistically significant (p less than 0.05). Although the mean plasma PRL level of 49.0 ng/ml was reduced when compared with the control period values, this reduction was not statistically significant. Our control period findings of low plasma testosterone levels coupled with high plasma LH and FSH are consistent with Leydig cell dysfunction. The significant reductions in plasma FSH and LH noted during the study period indicate a negative feedback effect produced by the pharmacologic doses of testosterone. Long-term testosterone administration, however, did not significantly affect the elevated mean PRL levels observed in these subjects.     

Effect of testosterone, estradiol-17 beta, and 5 alpha-dihydrotestosterone on inhibin production by sertoli cells in culture

Inhibin activity in charcoal-extracted spent culture medium of Sertoli cells in Primary culture (CSCCM) was monitored by following the temporal inhibition of serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in normal adult male rats. Subcutaneous injection of CSCCM reduced LH and FSH levels within 15 min and maintained the inhibition up to 10 hr. No selective suppression of FSH was observed. The model was used to assess inhibin activity in CSCCM from Sertoli cell cultures incubated with 5 alpha-dihydrotestosterone (DHT), testosterone (T), and estradiol -17 beta (E2) (5 micrograms/ml) for 24 hr. CSCCM from T and E2 treated groups suppressed gonadotropins while the group exposed to DHT failed to elicit any inhibition. DHT seems to inhibit the release of inhibin by Sertoli Cells.     

Inhibin secretion is influenced by Ley dig cells: evidence from studies using the cytotoxin ethane dimethane sulphonate (EDS)

Adult male rats given a single intraperitoneal injection of the Leydig cell cytotoxin ethane dimethane sulphonate (EDS) show a significant decrease in testosterone from 7 to 14 days, and elevation of serum FSH and LH levels commencing 7 days after treatment, returning to normal at 28 days for LH and 49 days for FSH. A significant rise in serum inhibin levels was seen at day 14 after EDS treatment with levels returning to normal at day 49. In a second series of experiments, silastic implants of testosterone, either 2.5 cm or 22.5 cm in length, were introduced subcutaneously into adult male rats which were treated with EDS 10 days later. Both doses of testosterone suppressed basal LH levels but did not significantly change FSH levels. The rise in FSH and LH levels seen in normal rats after EDS treatment did not occur in either group of testosterone-implanted rats. However, serum inhibin levels rose significantly in both groups after EDS treatment, suggesting that the rise in serum inhibin levels was not due to stimulation arising from the increase in FSH levels after EDS treatment. The data suggest that the rise in serum inhibin levels after EDS treatment is linked to destruction of the Leydig cells through mechanisms that require further investigation.     

Testosterone Concentrations and Sirolimus in Male Renal Transplant Patients

Sirolimus damages the testes in animals; however, human data are sparse. We conducted a case-control study to obtain further insight into this issue and compared testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin concentrations in matched renal transplant patients who did or did not receive sirolimus. We found that testosterone values were lower (11.2 +/- 6.3 nmol/L vs. 15.5 +/- 7.7 nmol/L, p < 0.05), in 28 sirolimus-treated patients, compared to 28 non-sirolimus-treated controls. Furthermore, these patients more commonly had testosterone concentrations that were below our reference value for normal men. In contrast, FSH and LH concentrations were higher while prolactin levels were not different. These data are consistent with sirolimus-related testosterone suppression and suggest a need for further studies.     

Effect of cryptorchidism and orchidopexy on inhibin secretion by rat Sertoli cells

The present study explored the effects of experimental bilateral cryptorchidism (of 21-, 28-, and 35-days duration) and orchidopexy (14 and 42 days) in the adult rat on the secretion of inhibin by cultures of isolated Sertoli cells. Changes in serum levels of gonadotropins, testis weight, and spermatogenesis also were assessed to verify the effectiveness of the surgical procedures. Cryptorchidy resulted in a progressive decline in testicular weight and a loss of germ cells, associated with increasing serum levels of FSH and LH. Inhibin secretion in vitro became nondetectable by 28 days after surgery. At 42 days after orchidopexy, spermatogenesis showed qualitative recovery, with a small increase in testes weight. Levels of LH in the circulation declined, but only to twice the intact control levels. However, inhibin secretion and serum FSH levels returned to nearly normal values. These results indicate that bilateral cryptorchidism severely impairs the secretion of inhibin and possibly other Sertoli cell functions which may account, at least partly, for the increase in circulating FSH levels and the arrest of spermatogenesis. The effects of cryptorchidism on these parameters can be reversed to a large degree by orchidopexy.