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.     

Endocrinological Studies in Patients with Metastatic Malignant Testicular Germ Cell Tumours

In this study, various serum hormone levels were determined in patients with metastatic testicular germ cell tumours. Raised LH levels, due to a cross reaction with hCG in the radioimmunoassay, were observed in 20 out of 29 patients with active disease and were mainly caused by gonadotrophin production in the tumour tissue. Increased LH levels were frequently observed in the patients with non-seminomatous tumours, but were also found in 4 (out of 6) patients with metastatic seminoma. One should, however, preferably use a specific hCG radioimmunoassay in order to measure tumour hCG as a tumour marker with a high diagnostic accuracy. In patients with active disease despite ongoing combination chemotherapy which included LH suppressing medication, serum testosterone remained above 6 nmol/l in 11 out of 16 patients. These patients remained sexually potent, while testosterone values below 6 nmol/l usually were combined with sexual impotence in patients during combination chemotherapy.
These data strongly suggest that the tumour hCG has a biological activity, stimulating the remaining testis to increased testosterone secretion in these patients. The serum E₂-17β levels were slightly to moderately increased in half of the patients with metastatic disease. Markedly increased serum E₂-17β levels (> 0.30 nmol/l) and very high prolactin values (> 32 μg/l) were observed only in patients with high LH levels (> 9.5 μg/l) and a large tumour burden. These observations indicate that E₂-17β and prolactin determinations are of minor value for early detection of tumour manifestations. Serum FSH cannot serve as a tumour marker in patients with testicular germ cell tumours.     

Clinical studies in an adult male patient with "isolated follicle stimulating hormone (FSH) deficiency"

Previous reports concerning isolated follicle stimulating hormone (FSH) deficiency and its possible pathogenesis have been conflicting. Both "normal" and "abnormal" FSH response to luteinizing hormone releasing hormone (LHRH) infusion have been described. We studied a 22-year-old man with normal basal serum testosterone and luteinizing hormone (LH) levels but undetectable levels of serum FSH. His serum LH titers showed one secretory spike during a 40-hour sampling at 20-minute intervals, whereas his serum FSH titers remained undetectable (less than 0.4 IU/l). Infusion of LHRH, 0.2 microgram/minute for 4 hours, induced the expected rise in the serum LH levels, but serum FSH levels remained low and only at one point reached 0.9 IU/l (normal adult male basal range 0.9-10.3 IU/l). The patient received LHRH, 100 micrograms/day, for three days. A second LHRH infusion, 0.2 microgram/minute for 4 hours, induced a normal rise in both the serum LH and FSH titers. The serum sex steroid binding globulin level was 10.3 ng DHT bound/ml (normal adult male level 8.0 +/- 0.3 ng DHT bound/ml). Presence of circulating auto-antibodies to the serum FSH was excluded by determining the binding of [125I] FSH with the patient's serum and comparing it with sera obtained from two normal male adult volunteers. Pituitary function tests were otherwise intact. Presence of a pituitary tumor was excluded by computerized axial tomography and x-ray studies of the pituitary fossa and normal visual fields. Clinically, the patient demonstrated cryptorchidism, hypospadias, surgically repaired omphalocele, and bilateral hearing loss.(ABSTRACT TRUNCATED AT 250 WORDS)     

PRETREATMENT FOLLICLE-STIMULATING HORMONE: A PROGNOSTIC SERUM MARKER OF SPERMATOGENESIS STATUS IN PATIENTS TREATED FOR GERM CELL CANCER

Purpose

We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio.

Materials and Methods

Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy.

Results

Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation.

Conclusions

Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.     

No association of serum gonadal or pituitary hormones with prognostic parameters in stages T1 to T3 PN0M0 prostate cancer

PURPOSE: Recent reports suggest a possible association of the clinical aggressiveness of prostate cancer with low serum testosterone, and high serum levels of lutenizing hormone (LH) and/or follicle-stimulating hormone (FSH). This hypothesis was tested in the current study. MATERIALS AND METHODS: Serum levels of testosterone, LH, FSH, estradiol and sex hormone-binding globulin were determined as well as the calculated ratio of testosterone-to-sex hormonebinding globulin in 370 patients with newly diagnosed, stages T1 to T3 pN0M0 prostate cancer. The results were related to T category, Gleason score and serum prostate specific antigen (PSA). RESULTS: No statistically significant association was found for the serum levels of testosterone, LH, FSH, estradiol, sex hormone-binding globulin or the testosterone-to-sex hormone-binding globulin ratio with T category, Gleason score or PSA. In contrast to expectations, serum testosterone values within the lowest quartile were not associated with elevated LH. Of the 370 patients 17 (5%) had serum testosterone below the normal range (8 nmol./l. or less) and only 3 of these 17 showed elevated LH levels. CONCLUSIONS: Serum levels reflecting the pituitary-gonadal axis at diagnosis are not associated with clinically used measures of tumor aggressiveness (T category, Gleason score or PSA) in patients with newly diagnosed T1 to T3 pN0M0 prostate cancer.     

Effects of hCG stimulation after withdrawal of long-term oestrogen treatment in patients with prostate carcinoma

Testosterone depletion is the keystone for therapy of patients metastic prostatic carcinoma. Our objective was to investigate Leydig cell function and testosterone levels after withdrawal of long-term endocrine treatment in patients with prostatic carcinoma. Thirteen patients with prostatic carcinoma, previously treated with oestrogens for at least 4 y, were stimulated with 5000 IU human chorionic gonadotrophin (hCG). The stimulation was performed 3-6 y after cessation of the oestrogen therapy. Serum concentrations of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and 24 and 48 h after hCG stimulation. Before hCG stimulation all patients had low serum testosterone concentrations (mean 2.0+/-0.2 nmol/l) and 24 and 48 h after hCG stimulation the values had not significantly increased (mean 2.4+/-0.2 and 2.5+/-1.1 nmol/l, respectively). LH and FSH were within or above the normal range before but after hCG stimulation the values significantly increased. In conclusion, the study shows that the Leydig cells were unable to respond to hCG stimulation more than 3 y after cessation of oestrogen therapy. The Leydig cell function seems to be irreversibly impaired by long-term oestrogen treatment.     

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.     

Leydig cell function in patients with testicular cancer during and after chemotherapy

In two groups of patients with disseminated testicular carcinoma the effect of combination chemotherapy on the pituitary-gonadal axis was evaluated, after unilateral orchiectomy: The two groups comprised 15 patients without hCG-producing metastases (group A), and 14 patients with hCG-producing metastases (group B). Seven patients who had received no chemotherapy were studied one year after unilateral orchiectomy as a control group (group C). In group A, serum levels of testosterone and oestradiol increased during chemotherapy, as did the levels of LH and FSH. The serum LH and FSH response to LHRH was increased following chemotherapy, whereas the serum testosterone increase after hCG stimulation remained unchanged. A rise of 316% in SHBG binding capacity was found after chemotherapy. This presumably accounted for the elevated steroid levels in the presence of high gonadotrophin levels, but unaltered Leydig cell response. The elevated serum levels of testosterone and oestradiol and the suppressed serum FSH levels normalized during disappearance of ectopic hCG production in group B patients. Leydig cell refractoriness to hCG and the FSH response to LHRH also reverted to normal. After chemotherapy, FSH, but not LH levels exceeded those of group C patients, presumably as a result of the azoospermia induced by chemotherapy. The hormonal changes associated with chemotherapy are best explained by an increase in serum binding proteins, notably SHBG.     

Response of circulating gonadotropin levels to GnRH agonist treatment in prostatic cancer

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) responses to 6-month treatments with a gonadotropin-releasing hormone (GnRH) agonist (buserelin) and subsequent orchiectomy were studied in patients with advanced prostate cancer. For treatments, either an intranasal (600 micrograms, 3/day, n = 8) or subcutaneous depot preparation (6.6 mg every other month, n = 5) were used. A third group of patients received intranasal buserelin (400 micrograms, 3/day, n = 12) for 35 months. LH and FSH were measured using radioimmunoassay (RIA) and a sensitive (0.04 IU/L) immunofluorometric assay (IFMA). In addition, selected samples were analyzed for bioactive (bio) LH. The RIA-LH levels decreased 70% with intranasal treatment. In contrast, when monitored by IFMA, the reduction was greater than 90%: 0.2 to 0.3 IU/L with intranasal and 0.044 to 0.052 IU/L with depot treatment (P less than 0.01). Gonadotropin suppression was stable up to 35 months. Bio-LH and IFMA-LH levels decreased in parallel during treatment, with no apparent changes in the bio/immuno ratio. FSH levels were suppressed temporarily during the treatments. After castration and cessation of buserelin treatment, serum LH and FSH increased rapidly in the intranasal treatment group but only marginally during 3 months in the depot group. Serum T reached the castrate range when IFMA-LH decreased below 0.5 IU/L. A further decrease in LH (less than 0.1 IU/L) still suppressed the intratesticular T concentration measured after orchiectomy. In conclusion, IFMA offers an improved method to monitor the antigonadotropic effect of GnRH agonist treatment. The results emphasize the necessity of profound LH suppression to achieve maximal inhibition of testicular androgen production.     

Post-treatment fertility in patients with testicular cancer. III. Influence of radiotherapy in seminoma patients

Sperm analysis and serum hormone measurements (LH, FSH, testosterone) were performed in 29 patients after orchiectomy for seminoma before and after irradiation. Before radiotherapy 14 of 20 orchiectomized patients were azoospermic or had impaired spermatogenesis. A minimum sperm count was found 1 year after radiotherapy with gradual improvement up to 2 years. The recovery of sperm cell production was impaired most in patients with pre-treatment sperm counts less than 3 million/ml. Serum testosterone remained at low normal levels throughout the observation period. The mean serum FSH was increased 1 year after radiotherapy but returned to normal in 50% of patients within 3 years after treatment. This post-treatment increase in FSH was significantly correlated with increased pre-treatment FSH but not with the gonadal dose, which was 1 to 3% of the target dose. Severe disturbances in spermatogenesis, observed 2 to 3 years after radiotherapy for early seminoma, are likely to be the expression of a highly impaired pre-treatment sperm cell production and only to a lesser degree dependent on the irradiation of the remaining testicle.     

Testicular Function after Combined Chemotherapy for Metastatic Testicular Cancer

In 10 patients cured for metastatic testicular cancer by combination chemotherapy serum hormone levels and serum agglutinating antibodies were analysed 12 to 35 months after discontinuation of the treatment. Together with these examinations sperm analysis was done. All patients had increased levels of follicle stimulating hormone (FSH). Serum testosterone was usually in the lower part of the normal range (below 20 nmol/***l). In eight patients the serum agglutinating antibodies were normal, while two patients had increased levels. In all patients azoospermia was observed, indicating long-lasting infertility in patients testicular cancer treated by combination chemotherapy. The possible importance of cryopreservation prior to start of chemotherapy is discussed.     

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.     

Acute hormonal changes following chemotherapy for Hodgkin's disease in man

Eleven men, aged 21 to 60 years, with Hodgkin's disease have been studied before, during, and after chemotherapy. Blood samples were obtained for hormone analyses. In all 11 patients FSH levels rose following chemotherapy, in ten LH and testosterone rose, and in seven estradiol rose above pretreatment values. For each hormone the mean peak post-treatment value was significantly higher than pretreatment values. While there are mechanisms to explain the rise in testosterone and estradiol, the rise in LH in the face of increasing testosterone and estradiol values is unexplained. We propose that feedback regulation of LH by the testis includes a mechanism that is independent of testosterone and estradiol and that this mechanism is damaged during chemotherapy.     

Endocrine profiles and gonadotropin response to Gn-RH of men with testicular cancer

PURPOSE: To investigate the function of the hypothalamic-pituitary-testicular axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (Gn-RH), semen quality, and serum levels of sex steroid hormones in patients with testicular cancer. PATIENTS AND METHODS: Basal serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and human chorionic gonadotropin-beta (hCG-beta) were measured before and after high orchiectomy in 20 patients with germ cell tumors of the testicle (9 with seminoma and 11 with nonseminomatous tumor). Semen quality and basal serum levels of testosterone, free testosterone, and estradiol were measured before orchiectomy. The Gn-RH test was performed before orchiectomy in all patients and after orchiectomy in patients without detectable gonadotropin levels in pre-operative serum samples. Gonadotropin levels were measured at 0, 30, 60, 90, and 120 minutes after intravenous injection of 100 micrograms of luteinizing hormone-releasing hormone (LH-RH). RESULTS: Serum gonadotropin concentrations were not detectable in 6 of 8 (75%) men with hCG positive tumors or in 4 of 12 (33.3%) men with hCG negative tumors before orchiectomy. Before surgery, 10 men without detectable gonadotropin levels showed complete suppression of the LH and FSH responses to LH-RH and 10 men with detectable gonadotropin levels showed significant increases in the LH and FSH responses (p < 0.01) at 30 minutes. After surgery, the Gn-RH test was performed in 9 men without detectable gonadotropin levels prior to surgery. Seven of these 9 men exhibited significant increases in the LH and FSH responses (p < 0.01) at 30 minutes while no response to LH-RH before or after surgery was seen in 2 men with detectable serum hCG-beta. We observed a significantly lower sperm density (median 7.5 x 10(6)/ml, range 0.4 to 17.8) in men with hCG positive tumors than in men with hCG negative tumors (median 33 x 10(6)/ml, range 0 to 103) (p < 0.002). Although testosterone levels did not differ significantly in men with hCG positive tumors and men with hCG negative tumors, free testosterone levels were significantly higher in men with hCG positive tumors (median 28.4 ng/ml, range 8.5 to 39.8) compared with men with hCG negative tumors (median 18.7 ng/ml, range 4.9 to 24.1) (p < 0.002). Estradiol levels were significantly increased in men with hCG positive tumors (median 44 pg/ml, range 26 to 110) compared with men with hCG negative tumors (median 33.5 pg/ml, range 10 to 87) (p = 0.002). CONCLUSION: The present findings indicate that serum hCG producing testicular cancers are associated with a complete suppression of the gonadotropin response to Gn-RH at the pituitary level, resulting in an inhibition of LH and FSH secretion, and also that serum hCG secreted by testicular cancers may suppresses spermatogenesis and may stimulate androgen and estradiol production by the testes. Since suppressed serum gonadotoropin levels are found in men with hCG non-producing testicular cancers, other factors derived from the tumor may cause downregulation of the gonadotropin response to Gn-RH.     

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.     

Testicular endocrine function in patients with prostatic cancer receiving medical castration by long-term administration of LH-RH agonists

Six patients with advanced prostatic cancer who had been treated by long-term administration of LH-RH agonistic preparations (Buserelin or Leupron) were tested for their pituitary-testicular endocrine functions. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2) and dihydrotestosterone (DHT) were measured consecutively. In all medically castrated patients, serum levels of LH, FSH, T, DHT and E2 were suppressed and particularly serum T levels were below the castration level of 1.0 ng/ml. On the other hand, serum PRL levels were unchanged after the long-term treatment with the agonists. Serum LH and FSH levels failed to respond to LH-RH stimulation after the treatment, whereas serum T responded to stimulation by human chorionic gonadotropin (hCG) to various degrees. It was remarkable that, in 4 out of 6 medically castrated patients treated up to more than 3 years, serum T response levels above 1.0 ng/ml were noted. It is suggested that testicular endocrine function to secrete T and DHT in patients under treatment with long-term LH-RH agonist administration are still preserved in response to hCG stimulation.     

精液中性激素水平与生殖细胞凋亡的关系

目的:探讨人精液中性激素水平与生殖细胞凋亡的关系。方法:随机选择66例不育患者及30例生育男性,采用ELISA法进行卵泡刺激素(FSH)、黄体生成素(LH)、泌乳素(PRL)和睾酮(T)水平分析,并用脱氧核苷酸末端转移酶(TdT)介导的缺口末端标记(TUNEL)法检测生殖细胞的凋亡。结果:精液中FSH、LH、PRL和T水平30例生育者分别为(1.63±0.15)U/L、(2.18±0.21)U/L、(6.34±0.30)nmol/L、(1.85±0.11)nmol/L,生殖细胞凋亡率为(4.61±1.23)%,而66例不育者4种性激素水平分别为(1.25±0.18)U/L、(1.76±0.32)U/L、(5.86±0.31)nmol/L、(1.45±0.13)nmol/L,生殖细胞凋亡率为(18.36±2.04)%。两者相比各参数差异均有显著性(P<0.01)。不育组FSH、LH、PRL、T水平与生殖细胞的凋亡率呈负相关(r分别为-0.88、-0.93、-0.90、-0.98,P均<0.01)。凋亡的生殖细胞体积缩小,核染色质致密,凝聚在核周形成新月形,或核裂解形成凋亡小体。结论:精液性激素水平与生殖细胞的凋亡有着密切关系,低水平的性激素可能导致睾丸生殖细胞凋亡率增加。     

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.      

Endocrine effects of oestrogen withdrawal in long-term treated patients with prostatic adenocarcinoma

Eighteen patients with prostatic adenocarcinoma, treated with oestrogen for 45 months or more, were followed-up after withdrawal of oestrogen treatment. Serum concentrations of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, testosterone-oestradiol-binding globulin (TeBg) and prolactin were measured at different intervals between 3 and 42 months after cessation of treatment. Serum testosterone concentrations after cessation of oestrogen treatment were low (range 71.4 +/- 6.3 to 120.8 +/- 23.7 nmol/100ml), whereas the concentrations of LH (range 21.8 +/- 3.6 to 32.6 +/- 9.1 U/1) and FSH (range 31.2 +/- 5.5 to 54.7 +/- 9.5 U/1) were within or higher than the reference range. Prolactin (range 6.0 +/- 85.3 to 7.9 +/- 68.2 micrograms/1) was within the reference range. No significant changes in serum concentrations of testosterone, LH, FSH and prolactin occurred during the follow-up period. The serum concentrations of both oestradiol-17 beta and TeBg, found between 13 and 36 months after oestrogen cessation (range 43.8 +/- 4.6 to 46.2 +/- 5.9 and 64.0 +/- 2.5 to 86.0 +/- 10.0, respectively) were significantly lower than the concentrations found between 3 and 12 months (range 71.9 +/- 10.4 to 99.8 +/- 12.9 and 124.1 +/- 15.5 to 140.2 +/- 13.7, respectively). It is concluded that in patients with prostatic adenocarcinoma, long-term oestrogen treatment causes an irreversible impairment of Leydig cell function and consequently a reduced testosterone secretion after cessation of oestrogen treatment.     

Recovery of serum testosterone after neoadjuvant androgen deprivation therapy and radical radiotherapy in localized prostate cancer

OBJECTIVE: To prospectively evaluate the time-course of recovery of serum testosterone levels after a short course of luteinizing hormone-releasing hormone analogue (LHRHa) and radical radiotherapy to the prostate. PATIENTS AND METHODS: Testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were sequentially measured prospectively in 59 men who received short-course LHRHa treatment and radiotherapy for localized prostate cancer. Measurements were made before treatment (baseline), during LHRHa treatment, and at 6, 12, 18, 24 and >40 weeks after the last LHRHa injection. RESULTS: The median (range) time from the first to last LHRHa injection was 116 (54-194) days. The mean (95% confidence interval) testosterone levels (in nmol/L) at baseline, during treatment and at 6, 12, 18, 24 and >40 weeks afterward were 12.0 (10.8-13.1), 0.6 (0.5-0.7), 1.4 (0.6-2.2), 11.4 (9.7-13), 12.2 (10.5-14), 10.4 (8.9-12) and 11.7 (10.5-13). Four men had low baseline testosterone levels (<6.1 nmol/L). At 6 weeks after the last LHRHa injection, no men had testosterone levels in the 'normal' range; 35% were in the normal range at 12 weeks, 85% at 18 weeks, 89% at 24 weeks, and 96% at 1 year. CONCLUSION: After LHRHa treatment and radiotherapy, the testosterone levels of most men had recovered to normal by 18-24 weeks after the last LHRHa injection.