The effect of sirolimus on sex hormone levels of male renal transplant recipients

BACKGROUND: It is unclear whether sirolimus, a newer immunosuppressive agent, widely used in renal transplantation, affects male sex hormone levels or sexual function. METHODS: Sex hormone profiles in male renal transplant recipients were obtained and compared between a sirolimus-treated group and a group not on sirolimus in a cross-sectional study. Both groups also completed a sexual dysfunction questionnaire. RESULTS: Sixty-six subjects were evaluated, 32 in the sirolimus group and 34 in the control group. Total testosterone level was significantly lower in the sirolimus group than the control group (393.3 +/- 188 vs. 537.4 +/-232 pg/mL; p = 0.08) while follicle stimulating hormone and luteinizing hormone levels were significantly higher in the sirolimus group (12.8 +/- 14 vs. 6.0 +/- 5, p = 0.013; 10.9 +/- 14 vs. 4.7 +/- 4, p = 0.018, respectively). There was a significant negative correlation between 24-h sirolimus trough and total testosterone levels (p < 0.03). By multiple regression analysis, use of sirolimus was independently associated with decreased total testosterone level. There was no significant difference in subjective sexual dysfunction as assessed by questionnaire scores between the two groups. There was no correlation between questionnaire scores and total testosterone level. CONCLUSION: Sirolimus is associated with decreased total testosterone levels in male renal transplant recipients. It is unclear whether sirolimus may affect other aspects of sexual function.     

Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria

There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.     

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.     

Function of the ovaries in female kidney transplant recipients

OBJECTIVES: One of the effects of an improved general health state after successful kidney transplantation in women of reproductive age is recurrence of regular menstrual function. MATERIALS AND METHODS: Sixty-three ovarian cycles in female kidney transplant recipient, aged from 18 to 44 years, at 1.5 to 15 years after transplantation, were compared with 50 cycles of healthy women. We monitored the menstrual cycle duration as well as follicle stimulation hormone (FSH), leutinizing hormone (LH), estradiol, progesterone, prolactin, creatinine, and testosterone serum concentrations as well as hematocrit and obtained sonographic observations of ovarian follicle growth and ovulation. RESULTS: Of the recipients, 68.1% had regular menstrual cycles. Ovulatory cycles were observed in 45% of patients. Estradiol concentration established in the first phase of the cycle was significantly higher among the transplanted group (mean value 226.86 +/- 97.45 pg/mL vs 140.00 +/- 61.00 in the controls). A significantly lower level of progesterone (15.05 +/- 17.34 ng/mL vs 30.79 +/- 18.48 ng/mL in the controls) and of testosterone were observed in kidney recipients. Other hormonal parameters did not differ significantly between the groups. CONCLUSIONS: Similar serum FSH, LH, and prolactin concentrations as well as increased levels of estrogens were observed in kidney transplant recipients compared with healthy nonrecipients. The rate of ovulatory cycles in regularly menstruated kidney graft recipients was similar to that of healthy women. Stabilization of graft function resulted in restoration of normal ovarian hormone metabolism and ovulatory cycles in female kidney transplanted recipients.     

Effect of hyperprolactinemia and age on the hypogonadism of uremic men on hemodialysis

Primary hypogonadism has been commonly reported among uremic men on hemodialysis, characterized by low testosterone levels, increased luteinizing hormone and sometimes follicle-stimulating hormone levels. Little is known about the influence of hyperprolactinemia and age on this hypogonadism. In 149 hemodialysis patients and in 60 healthy subjects the serum levels of testosterone (T), gonadotropins (LH and FSH) and prolactin (PRL) were assessed through radioimmunoassay. Mean +/- SD hormone levels were: T 274 +/- 125 ng/100 ml, lower than controls; LH 44.7 +/- 46.1 mlU/ml and FSH 17.6 +/- 18.4 mIU/ml, both higher than controls. PRL 31.3 +/- 49.4 ng/ml, higher than controls. A positive correlation between LH and FSH, a negative correlation between PRL and both T and LH was found. Moreover T and FSH were correlated with age only in the normoprolactinemic patients. These data suggest: a common damaging mechanism by uremia on both interstitial and tubular structures of the testis; a central antigonadal influence of hyperprolactinemia even if a direct action on the testis cannot be excluded; a worsening action of age on the gonadal function of these patients.     

Gonadal function and immunosuppressive therapy after renal transplantation

End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents.

Methods

Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine <2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n = 15), group II, sirolimus without calcineurin inhibitors (SRL; n = 15), group III, sirolimus in combination with calcineurin inhibitors (SRL * CI; n = 29).

Results

Testosterone was significantly lower in group II versus group I (3.12 ± 1.23 versus 4.39 ± 1.53 ng/mL; P < .0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes.

Conclusion

Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect.     

Erythropoietin and sexual dysfunction

BACKGROUND: Erythropoietin (rHuEpo) therapy has been shown to improve sexual function in the male dialysis population, with several studies suggesting a direct effect upon endocrine function, as well as correction of anaemia. Nevertheless many male dialysis patients receiving rHuEpo continue to complain of sexual dysfunction. METHODS: At a dedicated renal impotence clinic, 65 male dialysis patients were screened for endocrine disturbances. Baseline serum sex hormones were compared between those receiving and not receiving rHuEpo, using either the two-sample t test or the Mann-Whitney U test, after assessing for normality. Results from four patients were excluded on account of either medications (antiemetic phenothiazines), hepatic dysfunction, or carcinomatosis. RESULTS: Twenty-five patients (41.0%) were receiving rHuEpo, the recipients and non-recipients being well matched for haemoglobin (10.19 +/- 0.29 vs 10.55 +/- 0.25 g/dl, n.s.), age (51.1 +/- 1.9 vs 53.6 +/- 2.1 years, n.s.) and duration of sexual dysfunction (median, 3.0 vs 3.0 years, n.s.). The rHuEpo recipients had a higher median creatinine (1090 vs 972 micromol/l, P < 0.02), but similar nutritional status to the non-recipients (albumin 41.0 vs 39.0 g/l, n.s.). The total duration of rHuEpo therapy was 0.85 +/- 0.14 years. Prolactin levels were similar in both the rHuEpo recipients and non- recipients (440 vs 541 mu/l, n.s.), as were LH (11.0 vs 10.5 iu/l, n.s.) and FSH (8.0 vs 6.5 iu/l, n.s.). However, there were significant elevations of testosterone (19.8 +/- 1.3 vs 16.1 +/- 1.1 nmol/l, P < 0.05) and sex hormone binding globulin (SHBG) (40.5 vs 26.0 nmol/l, P < 0.01), with a trend toward elevated oestradiol (304 vs 248 pmol/l, P = 0.095) in the rHuEpo-treated group. Forty-eight subjects (78.7%) received peritoneal dialysis (PD), with the 19 rHuEpo recipients (39.6%) demonstrating increased serum testosterone (21.0 +/- 1.5 vs 16.6 +/- 1.3 nmol/l, P < 0.05), SHBG (40.5 vs 26.5 nmol/l, P < 0.01), LH (15.0 vs 10.0 iu/l, P < 0.01) and FSH (12.0 vs 5.3 iu/l, P < 0.05). These differences were not demonstrated in the 13 haemodialysis (HD) subjects. CONCLUSIONS: Male dialysis patients complaining of sexual dysfunction after correction of anaemia with rHuEpo are characterized by higher levels of serum testosterone and SHBG, but not suppression of hyperprolactinaemia or hyperoestrogenism. Male PD subjects receiving rHuEpo also demonstrated increased LH and FSH.      

Varicocele ligation on free testosterone levels in infertile men with varicocele

We have analyzed the effects of varicocele ligation on free testosterone levels, and investigated the interrelationships between free testosterone and fertility. The records were retrospectively evaluated for 42 infertile patients who underwent varicocele ligation, with serum free testosterone levels, follicle stimulating hormone (FSH), lutenizing hormone (LH), testosterone, estradiol, prolactin, ejaculated volume, sperm concentration and motility before and after surgery. Serum free testosterone levels increased from 12.97+/-4.16 to 13.59+/-3.93 pg/mL, but the difference was insignificant. The differences before and after surgery of patients in sperm concentration and motility were also insignificant. However, in free testosterone increasing group, the sperm concentration and motility increased significantly, from 4.05+/-4.35 to 7.90+/-8.19 million/mL (P=0.01) and from 30.64+/-21.87% to 41.00+/-22.00%, respectively (P=0.03). The increase in serum free testosterone level by varicocele ligation results in a significant improvement in sperm concentration and motility.     

Hypophyseal-Gonadal Dysfunction in Men with Non-Alcoholic Liver Cirrhosis

Seven males with liver cirrhosis associated with hepatitis and one with schistosomal liver fibrosis were studied for hypophyseal gonadal dysfunction and compared to six age matched controls. Cirrhotics as a group had higher serum 17 beta estradiol levels (22.1 +/- 6.3 vs 7.8 +/- 0.8 pg/ml, p less than 0.05) which did not rise after four days of human chorionic gonadotropin (hCG) stimulation. Conversely, there was an adequate rise in serum testosterone level after hCG stimulation (332.8 +/- 99.7 ng/dl baseline to 887.6 +/- 67.1 ng/dl, p less than 0.01). Compared to the controls, cirrhotics had lower baseline serum follicle stimulating hormone (FSH) (3.6 +/- 1.7 vs. 10.2 +/- 1.5 mIu/ml, p less than 0.02) and higher serum prolactin (13.5 +/- 2.5 vs. 6.8 +/- 1.0 ng/ml, p less than 0.05). Pituitary dynamic function testing in cirrhotics revealed blunted response of luteinizing hormone (LH) and FSH, to luteinizing hormone releasing hormone (LHRH) in four out of eight subjects tested. We conclude that the mechanism of hypogonadism in non-alcoholic cirrhosis is mostly hypogonadotropic in origin rather than primary gonadal injury which is common in alcoholic cirrhosis.     

罗格列酮治疗多囊卵巢综合征对改善内分泌、代谢及排卵功能的疗效

目的　探讨罗格列酮 (Rosiglitazone)对多囊卵巢综合征 (PCOS)合并胰岛素抵抗患者内分泌、代谢及排卵功能的影响。　方法　 2 5例PCOS合并胰岛素抵抗患者于自然月经或撤退性出血第 5天服用罗格列酮 12周 ,观察治疗前后血清生殖激素、胰岛素、血糖、血脂水平及排卵功能的变化。　结果　治疗后 ,患者各时相胰岛素 (INS)水平显著下降 (P <0 .0 1)。高密度脂蛋白胆固醇 (HDL C)显著升高 (P <0 .0 1) ,低密度脂蛋白胆固醇 (LDL C)显著降低 (P <0 .0 5 )。患者血清黄体生成素(LH)、黄体生成素 /促卵泡生成素比值 (LH/FSH)、睾酮 (T)和雄烯二酮 (A)水平均显著下降 (P <0 .0 1) ;性激素结合蛋白 (SHBG)水平显著升高 (P <0 .0 1) ;治疗后克罗米酚促排卵成功率为 72 % ,明显高于治疗前 2 0 % (P <0 .0 1)。　结论　罗格列酮通过改善胰岛素抵抗 ,降低胰岛素水平 ,使PCOS患者异常的血激素、血脂及排卵功能得到明显改善。     

Effect of Chronic Aromatase Inhibition by Δ1 -Testolactone on Pituitary-Gonadal Function in Oligozoospermic Men

Aromatase inhibition by delta 1-testolactone (Teslac, 500 mg twice daily) for 6 months in 9 patients with idiopathic oligozoospermia lowered the levels of serum estradiol (E2) and thereby sex hormone binding globulin (SHBG) (rS = +0.40, p less than 0.025) to values -35 and -25%, respectively, below the pretreatment values (P less than 0.001 and less than 0.005). The E2 decrease was accompanied by a temporary increase (+50%) in the levels of follicle stimulating hormone (FSH), not of luteinizing hormone (LH), and of 17 alpha-hydroxyprogesterone (17 alpha-OHP), but less of testosterone (T) (+30%), which led to a transient rise in the 17 alpha-OHP/T ratio. The T/E2 ratio and "free T" index (T/SHBG) almost doubled until the end of the treatment period. During delta 1-testolactone treatment the mean sperm density gradually rose from 8.1 +/- 1.3 (SEM) before to 21.3 +/- 6.7 X 10(6)/ml after 6 months (P less than 0.01), whereas the total sperm count almost threefold increased (P less than 0.05). Sperm concentrations exceeding 20 X 10(6)/ml were achieved in 4 of the 9 patients. Two of these patients' wives became pregnant. Although the data point to a pivotal role of estrogens in the pathogenesis of the spermatogenic lesion in some patients with idiopathic oligozoospermia, the lack of a beneficial effect of estrogen lowering in others points to a multicausal nature of the disease entity.     

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.     

The relation between bone density, free androgen index, and estradiol in men 60 to 70 years old

The cause of age-related bone loss in men is poorly understood. Previous studies of the relationship between bone density and serum androgens have yielded inconsistent results, perhaps partly because age is a determinant of both. Recent studies suggest that serum estrogen levels influence bone density in adult men. In order to determine whether bone mineral density (BMD) and bone turnover are associated with serum sex steroids, we investigated 37 normal men within a narrow age range (60-70 years). Bone mineral density at the forearm, hip, and spine, testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI:T/SHBG), estradiol (E), free estradiol index (FEI:E/SHBG), and markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type I C-terminal extension peptide) and bone resorption (hydroxyproline/creatinine [OHPr/Cr], deoxypyridinoline/creatinine [Dpd/Cr], pyridinoline/creatinine, collagen type I cross-linked telopeptide) were measured. Bone mineral density was positively related (r > 0.35, p < 0.05 at all sites) to log FAI, whereas there was no significant relationship between BMD and either serum total testosterone, serum E, or FEI. Bone density at the spine and hip were inversely related to both OHPr/Cr (r > -0.41, p < 0.05 for all sites) and Dpd/Cr (r > -0.36, p < 0.05 for all sites). OHPr/Cr (r = -0.41, p < 0.05) and Dpd/Cr (r = -0.41, p < 0.05) were both inversely related to log FAI. We conclude that BMD and bone turnover in adult men are related to plasma free androgens.     

Leydig cell function in adolescent boys with varicoceles

The incidence of varicoceles in adolescent boys ranges from 5% to 19.5%. We studied five adolescent boys aged 17 to 20 years with visible left-sided varicoceles. All of them had public hair and testicular volumes between 20 to 25 mL and had achieved stage V of pubertal development. Serum gonadotropin response to the intravenous administration of 100 micrograms of gonadotropin-releasing hormone (GnRH) and testosterone response to the administration of 2,000 IU human chorionic gonadotropin (hCG) daily for 3 days before and 3 months after varicocelectomy were measured. Basal levels of both gonadotropins were in the pubertal range, and there was no significant difference between serum levels before and after varicocelectomy. Both gonadotropins, however, showed increased responses to the administration of GnRH (luteinizing hormone [LH]: basal, 12.0 +/- 5.1 mIU/mL; peak, 105.0 +/- 36.0 mIU/mL; follicle-stimulating hormone [FSH]: basal, 11.6 +/- 4.2 mIU/mL, peak, 60.0 +/- 18.0 mIU/ml) that decreased after varicocelectomy (LH: basal, 14.3 +/- 6.0 mIU/mL; peak, 58.6 +/- 12.0 mIU/mL; FSH: basal, 6.8 +/- 4.6 mIU/mL; peak, 38.0 +/- 8.1 mIU/mL). Serum testosterone response to hCG was also significantly improved by varicocelectomy (testosterone peak: before, 780 +/- 210 ng/dL; after, 1850 +/- 170 ng/dL). Testicular biopsy specimens showed no histologic abnormalities and normal spermatogenesis. Endocrine evaluation in adolescent boys with varicoceles could detect an early Leydig cell dysfunction that could be corrected by varicocelectomy.     

Cyclosporine-induced alterations in the hypothalamic hypophyseal gonadal axis in transplant patients

We evaluated the response of 20 male patients, 13 cadaveric kidney and 7 heart transplant recipients, to the administration of 100 micrograms GnRH (gonadotropin-releasing hormone) and 500 micrograms TRH (thyrotropic-releasing hormone). All of the heart transplant recipients and 7 of the kidney transplant patients were receiving a combination of cyclosporine, azathioprine and prednisone; while the 6 remaining kidney transplant patients received azathioprine and prednisone. The patients receiving cyclosporine had decreased plasma levels of prolactin, and manifested a blunted response to TRH administration for prolactin and TSH. The heart transplant patients had a blunted response of LH and FSH to the administration of GnRH. The levels of testosterone were found to be low in all patients regardless of the immunosuppressant therapy. Despite the low testosterone levels, no increment in the concentration of LH or FSH was present. Intramuscular administration of HCG (human chorionic gonadotropin) (Ayerst Laboratories, New York, N.Y.) failed to increase the testosterone concentration in 5 of 6 patients with renal transplants, 3 taking cyclosporine and 3 taking azathioprine. This study suggests that cyclosporine has a selective effect on the hypothalamus and/or hypophysis, resulting in lower baseline levels of plasma prolactin and a pituitary insensitivity to TRH administration. In addition, FSH and LH were low or normal in the presence of low testosterone levels, suggesting that the hypothalamic pituitary gonadal axis is impaired. Furthermore, there may be a direct toxic effect of the immunosuppressant medications on the gonads, manifested as lower testosterone levels and inability to respond to the administration of HCG.     

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.     

Influence of erythropoietin treatment on gonadotropic hormone levels and sexual function in male uremic patients.

OBJECTIVE: The purpose of this study was to evaluate whether levels of sex hormones and sexual function differ in renal failure patients with and without uremia and the effect of treatment with recombinant human erythropoietin (rhuEPO). MATERIAL AND METHODS: Fifteen males with chronic renal failure who were not receiving hemodialysis and 25 male renal failure patients with uremia who were undergoing hemodialysis were enrolled before and after rhuEPO therapy. Fifteen male volunteers matched for age and weight were also studied. Levels of various blood biochemicals were measured in all patients before and 1 week after rhuEPO treatment. Sexual function was also studied in all patients before and 6 months after rhuEPO treatment. RESULTS: The control group had significantly higher levels of testosterone (6.21 +/- 1.21 ng/ml) and hematocrit (Hct) (43.2 +/- 2.1%) and significantly lower levels of prolactin (5.27 +/- 1.21 ng/ml), follicular-stimulating hormone (FSH) (7.51 +/- 2.36 mIU/ml) and leutinizing hormone (LH) (4.23 +/- 2.10 mIU/ml) than the two patient groups (p < 0.05 for all comparisons). Patients with renal failure only had significantly lower levels of testosterone and Hct (2.54 +/- 0.53 ng/ml and 21.4 +/- 1.4%, respectively) than those with uremia (3.65 +/- 0.52 ng/ml and 24.3 +/- 2.5%, respectively; p < 0.001 for both comparisons). After rhuEPO therapy, the testosterone and Hct levels of the two patient groups did not reach the level of the control subjects (p < 0.05 for both comparisons). Similarly, the levels of prolactin, FSH and LH were significantly higher in both patient groups than those of control subjects after rhuEPO therapy (p < 0.001 for both comparisons). However, after rhuEPO therapy, significant increases in testosterone and Hct levels were found in both patient groups (p < 0.001 for both comparisons). Sexual function was also markedly improved in the hemodialysis patient group. While 20/25 (80%) male hemodialysis patients reported improved sexual function after rhuEPO treatment, only 3/15 (20%) chronic renal failure patients reported improvement. CONCLUSIONS: In patients with advanced uremia, rhuEPO therapy may result in improved gonadotropic hormone levels and sexual function. Good dialysis quality may contribute to the increase in the incidence of patients with better sexual function.     

Peripheral INSL3 concentrations decline with age in a large population of Australian men

The novel peptide hormone insulin-like peptide 3 (INSL3) is a major secretory product of the Leydig cells of the testis, and in adult men is secreted into the blood, giving rise to circulating concentrations ranging from 0.5 to 2.5 ng/mL. We studied a large randomly recruited cohort of 1183 men from South Australia, comparing serum INSL3 concentrations with age, and a variety of endocrine, cognitive and morphological parameters. While INSL3 concentration declines significantly (p < 0.001) and continuously with age from 1.29 +/- 0.47 ng/mL in young men (age 35-44 years) to 0.79 +/- 0.39 ng/mL in the age group 75-80 years, there is no correlation with testosterone or components of the hypothalamo-pituitary-gonadal (HPG) axis, independent of age, nor with any other parameter measured, including thyroid or prostate status and obesity. For men exhibiting normal follicle stimulating hormone (FSH) and high luteinizing hormone (LH) levels, there was a significant inverse correlation with plasma oestradiol. Unilaterally orchidectomized men had INSL3 values intermediate between intact men and anorchid subjects, and showed inverse correlations (p < 0.001) between INSL3 and FSH or LH concentrations, which were independent of age. Taken together, the data show that INSL3 is an independent measure of Leydig cell function (quality and number), which appears to be independent of acute control via the HPG axis. Its decline with age reflects a decline in the properties of the Leydig cell population only, and emphasizes a gonadal component in the age-related decrease in androgen production.     

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.     

The hypothalamus-pituitary-testis axis in boys during the first six months of life: a comparison of cryptorchidism and hypospadias cases with controls

It is inconclusive whether the feedback mechanisms of the hypothalamus-pituitary-testis (HTP) axis are already established in the first 6 months of life, partly due to the dramatic changes in HPT-axis hormone levels over this period. Moreover, it is unclear whether these hormone levels are aberrant in boys with cryptorchidism or hypospadias, and therefore predictive for future fertility. We studied the regulation mechanisms of the HTP axis, and the effect of age, in boys 1–6 months of age. Secondly, we studied testicular function - as reflected by HPT hormones - in newborns with cryptorchidism or hypospadias. Sera from a population sample of infants with cryptorchidism ( n  = 43), hypospadias ( n  = 41) and controls ( n  = 113) were analyzed for inhibin B, anti-Müllerian hormone (AMH), testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG). LH, testosterone, non-shbg-bound testosterone (NSBT), and AHM levels showed significant age-related trends. After age-correction, a negative correlation between FSH and inhibin B was observed ( r  = −0.43). The only significant group-differences were lower testosterone and NSBT levels in cryptorchidism cases, with a mean testosterone of 1.8 and 2.6 nmol/L and a mean NSBT of 0.48 and 0.70 nmol/L for cryptorchidism cases and controls, respectively. The higher levels of LH, testosterone, and NSBT in boys born pre-term or with a low birthweight indicate that abnormal prenatal development may determine postnatal testis function. Our results support the hypothesis that the inhibin B – FSH feedback loop is already functional before puberty. The lower testosterone and NSBT levels indicate that disturbed Leydig cell function can already be detected early after birth in cryptorchid boys.