Hormonal effects of high dose medroxyprogesterone acetate treatment in males with renal or prostatic adenocarcinoma

In 18 patients, 12 with renal and 6 with prostatic carcinoma, the gonadal, pituitary and adrenal functions were studied by measurements of steroid hormones and gonadotrophins, before and after six weeks treatment with medroxyprogesterone acetate (MPA), injected intramuscularly 500 mg per day for 5 days each week. The testosterone-oestradiol-binding globulin (TeBg) was measured and the amount of albumin and TeBg bound and unbound testosterone was calculated. Treatment with high doses of MPA caused a profound decrease in serum concentrations of testosterone, dehydroepiandrosterone sulphate (DHEAS), cortisol and TeBg. There were significant decreases in serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol-17 beta. The serum concentration of prolactin was significantly elevated. The protein unbound testosterone fraction was lowered by MPA treatment but less than total testosterone. In conclusion, MPA therapy in high dose alters the gonadal, pituitary and adrenal functions suppressing serum concentrations of androgens, gonadotrophins, cortisol and TeBg but elevating prolactin concentration.     

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.     

Effect of orchidectomy performed after cessation of estrogen therapy on serum testosterone concentrations in patients with prostatic carcinoma

Serum concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined before and after orchidectomy performed at different intervals (2-29 months) after withdrawal of estrogen therapy in patients with prostatic carcinoma. Patients previously treated with estrogen for more than 3 years had low testosterone concentrations after estrogen withdrawal and the values were not significantly changed by orchidectomy. In contrast, in patients treated with estrogen for less than 3 years, the testosterone concentrations were below or within the normal values after estrogen cessation and following orchidectomy, the values were significantly decreased. In both groups of patients the LH and FSH values were within or above the normal range both before and after orchidectomy, but FSH was significantly lower in patients previously treated with estrogen for more than 3 years. In conclusion, orchidectomy performed after cessation of long-term estrogen therapy in patients with prostatic carcinoma is without value, since testosterone levels do not change despite cessation of estrogen treatment or after orchidectomy.     

Testicular endocrine function after withdrawal of oestrogen treatment in patients with carcinoma of the prostate

The serum concentration of testosterone, luteinising hormone (LH), follicle stimulating hormone (FSH) and prolactin were determined at different intervals after withdrawal of oestrogen treatment in patients with prostatic carcinoma. Oestrogen therapy had been stopped in all patients because of the side effects of oestrogens. There was a negative correlation (r = -0.64) between serum testosterone concentrations and the duration of oestrogen treatment in patients investigated for more than 6 months after withdrawal of hormones. However, the decrease in testosterone concentration seems to be time-dependent. Thus patients who were treated for less than 3 years had normal testosterone concentrations approximately 6 months after withdrawal of the oestrogen therapy. This group of patients had a positive correlation (r = 0.49) between serum testosterone concentration and time elapsed after cessation of therapy. In contrast, patients treated for more than 3 years retained low testosterone concentrations even after 6 months. The other hormones did not vary between the groups. It is concluded that patients with carcinoma of the prostate treated with oestrogens for more than 3 years have an impaired Leydig cell function which might be irreversible.     

Influence of orchidectomy or oestrogen treatment on serum levels of pregnancy associated alpha 2-glycoprotein and sex hormone binding globulin in patients with prostatic cancer

Peripheral serum levels of testosterone, immnunoreactive oestrogens (E₂), FSH, LH, prolactin and growth hormone (hGH) and two steroid-sensitive proteins, 'pregnancy-associated α₂-glycoprotein' (α₂-PAG) and sex hormone binding globulin (SHBG), were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Following orchidectomy, the serum levels of testosterone and E₂ decreased whilst the levels of FSH and LH increased significantly. No changes were noted in the serum levels of α₂-PAG, SHBG or prolactin. Oestrogen treatment significantly decreased the serum levels of testosterone, FSH and LH whilst levels of α₃-PAG, SHBG and prolactin were increased significantly. Serum levels of hGH during oestrogen treatment were significantly higher than in patients subjected to orchidectomy. These data are at variance with the established dogma of the oestrogen/androgen balance as a physiological regulator or liver protein synthesis, and indicate that factors other than the endogenous steroids may be operative. hGH may play an important role in this respect.     

Some effects of treatment with ethinyl oestradiol with or without polyoestradiol phosphate in patients with prostatic carcinoma

Eleven patients with prostatic carcinoma were treated with ethinyl oestradiol (Etivex) 50 micrograms three times daily with and 10 patients without 80 mg polyoestradiol phosphate (Estradurin) monthly. Both forms of treatment produced a significant decrease in the serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) and a significant increase in the testosterone-oestradiol-binding globuline (TeBg). Serum prolactin was significantly higher at 1, 3 and 6 months after treatment, in all patients studied, but the concentrations found at 12 and 18 months did not differ from those before treatment. One out of 10 patients treated with ethinyl oestradiol had congestive heart failure. Five out of 11 patients treated with ethinyl oestradiol-polyoestradiol phosphate had cardiovascular or liver complications. Three of the 5 had thromboembolic complications. It is concluded that ethinyl oestradiol given in combination with polyoestradiol phosphate, was not superior in decreasing serum testosterone when compared to ethinyl oestradiol given alone. Furthermore, the oestrogens used, elevated prolactin only, during the first 6 months of treatment. There were fewer complications using ethinyl oestradiol alone than when using ethinyl oestradiol combined with polyoestradiol phosphate.     

The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis

OBJECTIVE: To evaluate whether pretreatment serum hormone levels are a prognostic factor for prostatic cancer with bony metastasis under hormonal treatment. PATIENTS AND METHODS: Between 1980 and 1994, 96 patients with prostate cancer and bony metastasis were included for an evaluation by a retrospective review of their charts. All 96 had received hormonal treatment after a diagnosis of metastatic prostatic carcinoma. Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were assessed before treatment. The patients were divided into two groups according to their response during the follow-up. Group 1 (good response) had no change or resolution of metastatic lesion(s) on the bone scan and a declining prostate-specific antigen (PSA) level. Group 2 had increased PSA or progression of metastatic lesion(s) on the bone scan. Tumours were graded as low (2-4), intermediate (5-7) and high (8-10) using the Gleason score. RESULTS: There were 43 patients in group 1 and 53 in group 2; the overall mean (sd) age was 72.5 (6.8) years and the follow-up 29.5 (0.5) months. The respective mean (sd) levels of testosterone, LH, FSH and prolactin before treatment were 4.6 (1.6) ng/mL, 20.2 (13.3) mIU/mL, 19.6 (18.6) mIU/mL and 20.7 (12.1) ng/mL in group 1, and 2.6 (1.0) ng/mL, 27.3 (11.0) mIU/mL, 27.1 (9.8) mIU/mL and 41.3 (28.4) ng/mL in group 2. The level of testosterone was significantly higher in group 1 than in group 2, while LH, FSH and prolactin were significantly lower in group 1 than in group 2. When stratified by tumour grade, patients in group 1 still had significantly higher pretreatment testosterone and lower LH, FSH and prolactin than those in group 2. CONCLUSION: Higher testosterone and lower LH, FSH and prolactin levels were good prognostic factors for patients with metastatic prostatic cancer under hormonal treatment, irrespective of tumour grading.     

Pituitary-testicular function of prostatic cancer patients during treatment with a gonadotropin-releasing hormone agonist analog. I. Circulating hormone levels

Eight patients with advanced prostatic carcinoma (ages 59 to 78 years) were treated with a potent gonadotropin-releasing hormone (GnRH) agonist analog (buserelin, Hoechst; 600 micrograms intranasally, 3 times daily) and orchiectomized after 6 months of treatment. Endocrine responses were followed by serum hormone measurements during agonist treatment and for 3 months after orchiectomy. Six other patients (65 to 86 years) with advanced prostatic cancer had been orchiectomized as the first therapeutic measure and their blood samples were used as controls. In the GnRH agonist-treated patients, serum immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased after initial stimulation by 70 to 80%, within 1 to 3 weeks (P less than 0.01). FSH partly recovered (P less than 0.05) after the first month of treatment. Serum prolactin (PRL) displayed a slight tendency to decline during buserelin treatment (P less than 0.05). Serum total and free testosterone (T) of the buserelin-treated patients decreased to the castrate range within 3 to 4 weeks after an initial 5-day increase (P less than 0.01). Serum progesterone and 17-hydroxyprogesterone (17-OHP-4) decreased to the castrate range (by 50 to 70%) in 1 week. Only minor changes were observed in sex hormone binding globulin (SHBG). Significant, acute elevations of LH, FSH, T, and 17-OHP-4 were observed only on day 1 after an injection of buserelin (500 microgram i.m.) and not when assessed between day 7 and month 6 of treatment. After 6 months of buserelin treatment, orchiectomy did not affect the serum steroids measured. After orchiectomy, immediate increases in serum LH, and somewhat later in FSH, were seen in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clomiphene citrate administration to normogonadotropic subfertile men: blood hormone changes and activation of acid phosphatase in seminal fluid

Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2-10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly unchanged. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn++ and Mg++.     

Serum hormone levels in patients with malignant testicular germ cell tumours without clinical and/or radiological signs of tumour

In patients treated for malignant testicular tumours without clinical and/or radiological signs of tumour, the following serum hormone levels were found: In 15% of the patients there was a slight to moderate rise in luteinising hormone (LH) levels (up to 6 micrograms/l) due to increased pituitary gonadotrophin production; this was particularly evident soon after radiotherapy/chemotherapy. In 50% of the patients there was a slight to marked increase in follicle stimulating hormone (FSH) levels (up to 11 micrograms/l), especially after radiotherapy/chemotherapy. Serum testosterone levels were in the low range (up to 20 nmol/l) in the majority of the hemicastrated patients regardless of previous treatment. A slight to moderate rise in serum oestradiol-17 beta and serum prolactin levels was noted. During combination chemotherapy with vincristine, Adriamycin D, cyclophosphamide, actinomycin D and medroxyprogesterone acetate the serum testosterone levels were extremely low (below 6 nmol/l) with LH and FSH levels within the normal range. The decrease in testosterone levels was reversible after completion of the combination chemotherapy.     

Hormonal effects of cessation of estrogen treatment for prostatic carcinoma

Serum concentrations of testosterone, luteinizing hormone and follicle-stimulating hormone were measured before, and at 1, 12 and 24 months after cessation of long-term estrogen treatment (mean 8.7 years, range 4.3 to 13.1 years) in 14 patients with prostatic carcinoma but without metastases. In addition, the same hormones were measured before and up to 24 months after orchiectomy in 14 age-matched, previously untreated patients also without metastases. In long-term estrogen-treated patients serum concentrations of testosterone found at 1, 12 and 24 months after cessation of estrogen did not differ significantly either from the value before estrogen withdrawal or from the corresponding values found in age-matched patients after orchiectomy. The concentrations of luteinizing and follicle-stimulating hormones increased significantly in the estrogen-treated patients after cessation of estrogen and in the age-matched patients after orchiectomy. However, luteinizing and follicle-stimulating hormones were significantly lower in the patients after estrogen treatment than in the age-matched patients after orchiectomy. During the study period only 1 patient from the estrogen-treated group had clinical progression and he died of prostatic carcinoma. We conclude that long-term estrogen treatment causes impairment of Leydig cell function in patients with prostatic carcinoma and, as a result, the serum testosterone concentrations do not increase when that treatment is discontinued.     

Hormonal and seminal evaluation of Leydig cell tumour patients before and after orchiectomy

Seven patients (aged 25-38 years) were admitted because of mono- or bilateral gynaecomastia. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, 17-beta-estradiol, delta4-androstenedione, dehydropiandrosterone sulphate (DHEA-S) and 17-OH-progesterone were determined and semen analysis was carried out. FSH and LH levels were also measured after acute LH-RH administration (100 microg intravenously), and testosterone and 17-beta-estradiol were also evaluated after acute human chorionic gonadotrophin (hCG) administration (5000 IU intramuscularly). Testicular echography demonstrated the presence of a solid hypoechoic tumour. Therefore all patients were submitted to hemicastration by orchidofuniculotomy and a benign Leydig cell tumour was diagnosed in the removed testes. Hormonal and semen evaluations were repeated 3, 6, 9 and 12 months after surgery. The data before and after surgery were compared with a control group of 10 age-matched males. Before surgery, patients showed low FSH basal plasma levels; high levels of 17-beta-estradiol and low testosterone levels similar to those after hCG administration. A dyspermia was observed. Unilateral orchidectomy eliminated the autonomous secretion of oestrogen(s) so an increase of LH, FSH and testosterone levels, together with an improvement of spermatogenesis, were obtained.     

Dynamic study of serum gonadotrophin and testosterone levels in gossypol-treated men Long term follow-up study of 60 cases

The endocrine effects of gossypol were studied in 26 men for 52 months before, during and after treatment. A further 34 subjects were studied after cessation of gossypol treatment. A control group of 60 age-matched volunteers were monitored for 1 year. No significant changes in testosterone levels were observed during the course of study. Serum LH levels were, however, significantly higher (P less than 0.001) during earlier phases of gossypol treatment and returned to normal after cessation of treatment except in 14 men with persistent disruption of spermatogenesis. In the latter, serum levels of LH and testosterone were significantly higher (P less than 0.001) than those found in normal subjects and significantly lower (P less than 0.05) than in those subjects in which spermatogenesis had recovered. Serum FSH levels did not rise during the first 8-9 months of treatment with gossypol, although azoospermia generally occurred within 76 days of commencing treatment. After 9 months of treatment, serum FSH levels rose gradually and remained significantly elevated (P less than 0.001) after cessation of treatment in both the azoospermic/oligospermic group and in the group in which spermatogenesis recovered. In the latter group the serum levels of FSH were correlated significantly with the sperm concentration.     

Aminoglutethimide in advanced prostatic carcinoma

We have treated 34 patients with advanced prostate cancer, resistant to orchiectomy or oestrogen therapy, with aminoglutethimide. Seven patients (21%) showed improvement in pain and performance status for prolonged periods. By NPCP criteria six patients had stable disease and one had partial tumour response. Six of these patients remained on oestrogen therapy. Suppressed gonadotrophin levels (FSH and LH), despite orchiectomy, correlated strongly with benefit from aminoglutethimide. No relationships between response to treatment and changes in serum testosterone, dehydroepiandrosterone, oestradiol or prolactin were found. Six patients had side effects requiring cessation of therapy. A further 27 patients developed less severe toxicity. Despite its toxicity, these results show that aminoglutethimide has a role in the management of advanced prostatic cancer resistant to primary hormonal manipulation.     

Clomiphene citrate administration to normogonadotropic subfertile men: Blood hormone changes and activation of acid phosphatase in seminal fluid

Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2–10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly significantly during the treatment. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn⁺⁺ and Mg⁺⁺.     

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.     

Combination of a GnRH agonist with an antiandrogen or bromocriptine in the treatment of prostatic cancer; slight potentiation of antigonadal effects

The effect of combined treatment with a GnRH agonist (buserelin depot, BUS, 6.6 mg every 2 months) with an antiandrogen (cyproterone acetate, CPA, 300 mg day-1) or a prolactin-suppressing agent (bromocriptine, BR, 20 mg day-1) on pituitary-testicular function were studied in patients with advanced prostatic carcinoma. The patients (n = 5-6 per group) were treated in this fashion for 6 months and thereafter orchidectomized. Serum testosterone and gonadotrophin responses were followed during treatment, and histology and certain endocrine parameters were studied using testicular tissue obtained at orchidectomy. Serum LH was suppressed in all treatment groups from mean levels of 4-6 IU l-1 to less than 0.1 IU l-1, whilst serum FSH levels decreased in all groups during the first month of therapy from 4.5-7 to 1-2 IU l-1, but recovered thereafter. Only minor increases in serum gonadotrophin levels were evident 3 months after castration. No differences in gonadotrophin responses were seen between the different treatment groups. Serum levels of testosterone were suppressed from 15-20 nmol l-1 to the castrate range (approximately 1 nmol l-1), in each of the treatment groups. Testicular weight decreased significantly more (P less than 0.05) in the BUS + CPA group, compared to the other treatments. No differences were found in the testicular concentration of testosterone, or LH and FSH receptors between the three treatment groups. On histological examination, spermatogenesis was found to be impaired severely in all groups, with the lowest Johnsen score in the BUS + BR group (2.16 +/- 0.13, vs. 2.73 +/- 0.25 with BUS alone, P less than 0.05). Seminiferous tubular diameters were reduced similarly in all treatment groups. In conclusion, the combination of CPA or BR with BUS in the treatment of prostatic carcinoma does not potentiate the suppression of gonadotrophin or testosterone secretion, evidently because the GnRH agonist exerts a maximal suppressing effect. However, other antigonadal effects were enhanced slightly, including suppressed testicular weights by CPA and further suppression of spermatogenesis by BR.     

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.     

Individual variation of hormonal recovery after cessation of luteinizing hormone-releasing hormone agonist therapy in men receiving long-term medical castration therapy for prostate cancer

OBJECTIVE: To evaluate the process of hormonal recovery after cessation of luteinizing hormone-releasing hormone (LHRH) agonist treatment in patients who had received long-term LHRH agonist therapy for prostate cancer. MATERIAL AND METHODS: Men who had successfully undergone androgen deprivation therapy with only monthly LHRH agonist therapy for > 30 months were enrolled and the administration of LHRH agonist was discontinued. Serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prostate-specific antigen (PSA) were measured before the cessation of LHRH agonist therapy and every 4 weeks thereafter, and the administration of LHRH agonist remained suspended until the total testosterone level recovered to > 50 ng/dl. RESULTS: Ten patients were enrolled in the study. The median (range) castration period and the levels of serum LH, FSH, total testosterone and PSA at cessation of therapy were 39 (30-56) months,<0.5 (<0.5-1.8) mIU/ml, 6.4 (3.0-15.9) mIU/ml, 15.3 (5.8-34.7) ng/dl and 0.13 (0.02-0.89) ng/ml, respectively. Testosterone recovered to > 50 ng/dl in all cases. There were large variations in the times required for recovery of LH and FSH (30-100 days) and serum testosterone (30-330 days). PSA began to increase at various testosterone levels, and there was a large variation (0-83%; median 41%) in the ratio of the androgen suppression (testosterone < 50 ng/dl) time to the period of LHRH agonist cessation. CONCLUSIONS: There was considerable variation in the hypothalamus-pituitary-testicular hormone profiles during recovery from long-term medical castration. These findings are noteworthy when interruption of androgen deprivation therapy is applied with the intention of delaying the progression of hormone-refractory cancer or improving the patient's quality of life.     

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.