Protection of germinal epithelium with luteinizing hormone-releasing hormone analogue

A dog model for chemotherapy and radiation-induced testicular damage was created to study the protective potential of superactive analogue of luteinizing hormone-releasing hormone, buserelin. Buserelin appeared to offer protection of the canine germinal epithelium against cyclophosphamide, cisplatinum and radiation. Clinical trials with buserelin in patients of reproductive age undergoing treatment for cancer should be encouraged.     

Patient self-injection: a new approach to administering luteinizing hormone-releasing hormone analogues

OBJECTIVE: To investigate the feasibility and advantages of self-injection of a depot dose of luteinizing hormone-releasing hormone (LHRH) analogue in patients with prostate cancer. PATIENTS AND METHODS: Twenty patients (mean age 70.9 years, range 53-85) with locally advanced or metastatic prostate cancer were recruited from urology clinics and, using a defined protocol, were taught to perform self-injection of a depot LHRH analogue (Prostap SR or Prostap 3, leuprorelin acetate, Wyeth Laboratories, Berks, UK). Patients were then followed for 1 year. RESULTS: Of the 20 patients, 11 successfully learned to use self-injection and administered injections for the duration of the study. Ten of the patients chose self-injection and continued to self-inject after the end of this study. CONCLUSIONS: This pilot study of 20 patients showed that it is feasible for a selected group of patients to be taught self-injection of an LHRH analogue, and that some patients prefer this mode of drug administration.     

Successful management of vesicouterine fistula by luteinizing hormone-releasing hormone analog

Vesicouterine fistula is a rare complication of cesarean section. Although surgical repair was mandatory for the management of the fistula previously, a recent review showed high efficacy of hormonal manipulation by the induction of amenorrhea. Herein, we report a new case of vesicouterine fistula secondary to cesarean section successfully treated by luteinizing hormone-releasing hormone analog for 6 months. Conservative hormonal treatment for vesicouterine fistula caused by cesarean section should be considered before surgical repair.     

The natural course of growth hormone-secreting pituitary adenomas after surgery alone--clinical significance of the growth hormone response to thyrotropin-releasing hormone and luteinizing hormone-releasing hormone.

The clinical significance of abnormal growth hormone (GH) secretion in response to thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) was studied in 52 patients with acromegaly due to GH secreting pituitary adenomas treated by trans-sphenoidal microsurgery. The mean period of postoperative follow-up was 4.1 years. In 27 of the 36 patients who had abnormal GH responses to TRH or LHRH before surgery, basal GH levels normalized and abnormal GH responses disappeared immediately after surgery. Among the remaining nine patients, four had normal basal GH levels with abnormal GH responses and five showed persistently abnormal basal GH levels as well as abnormal GH responses. Recurrence requiring retreatment was not observed during follow-up in any of the 31 patients with normal postoperative basal GH levels, regardless of the GH response to TRH or LHRH. All five patients with abnormal basal GH and abnormal GH responses required additional treatment. Among the patients who underwent long-term postoperative TRH and LHRH testing, abnormal GH responses reappeared in three of 19 whose abnormal responses had disappeared immediately after surgery. The abnormal response disappeared spontaneously in two of three patients who had abnormal responses immediately after surgery. In four patients with both abnormal GH responses and abnormal basal GH levels immediately after surgery, abnormal GH responses persisted throughout the follow-up period. In addition, the abnormal GH responses appeared in two of 14 patients who had been nonresponsive before surgery. These results indicate that the postoperative GH response to TRH or to LHRH was not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resected atypical meningioma relapsed to anaplastic meningioma during luteinizing hormone-releasing hormone agonist therapy

A 55-year old man with a history of meningioma treated with LHRH-agonist plus radiotherapy for prostate cancer (PCa) experienced a meningioma growth during hormone therapy (HT). Meningioma was radically resected revealing an atypical meningioma and HT was continued due to the high risk of PCa relapse until symptomatic meningioma relapse occurred after further 10 months. Gross lesions were radically removed and histology revealed anaplastic meningioma. This is the first case of rapid meningioma evolution to an anaplastic histology during LHRH-agonist.     

Management of urinary retention due to benign prostatic hyperplasia using luteinizing hormone-releasing hormone agonist

A common affliction of older men is bladder outlet obstruction secondary to benign prostatic hyperplasia for which the standard treatment is surgical prostatectomy. We report on six men with urinary retention from benign prostatic hyperplasia who were not medically able to undergo surgical prostatectomy but were successfully treated with the luteinizing hormone-releasing hormone (LH-RH) agonist, leuprolide acetate. This therapy is exemplified by the case of a sixty-six-year-old man with hemophilia B and urinary retention. The patient was treated with daily subcutaneous injections of 1 mg of leuprolide acetate, and prostatic size decreased from 132 g to 42 g, with initiation of spontaneous micturition while on treatment. For patients with symptomatic benign prostatic hyperplasia who are not candidates for surgery, treatment with an LH-RH agonist, such as leuprolide acetate, should be considered as a possible alternative.     

Treatment of cryptorchidism with pulsatile luteinizing hormone-releasing hormone (LH-RH)

This preliminary report describes a new method of treating bilateral cryptorchidism that may modify the need for surgical intervention. Four of five boys (3 1/2, 3 1/2, 7, 11 and 12 1/2 years of age) given hourly subcutaneous pulses of luteinizing hormone-releasing hormone (LH-RH, 10 to 100 micrograms/day, given in a 3-min pulse every hour) showed evidence of testicular descent after 3 to 19 weeks. The battery-operated, programmable syringe driver was well tolerated by the boys, and the daily insertion of the scalp-vein needles was managed at home by their parents.     

Immunobiology of a synthetic luteinizing hormone receptor peptide 21-41.

Immunization of adult male rabbits with a synthetic luteinizing hormone-receptor peptide (LH-RP; representing amino-acids 21-41 of the extracellular domain of the rat LH receptor) resulted in production of high-titer antibodies capable of interacting with particulate and cell-based LH receptors. The antibody produced was able to inhibit binding of 125I-labeled human chorionic gonadotropin (hCG) to a particulate sheep luteal LH receptor preparation by 40%-50%. Maximal inhibitory activity was correlated with high antibody titer. Immunocytometry revealed that the antibody could directly bind to cells having LH receptors, such as rat granulosa and Leydig cells. The antibodies recognized a 77-kilodalton membrane protein in Western blots of mouse testicular extracts. Interaction of endogenous Leydig cell LH receptor with the LH-RP antibody resulted in both hormone agonist and antagonistic activities. The hormone-mimicking activity (increase in serum testosterone over control) was confined only to the early phase of immunization when the antibody titer was low. Blockade of LH receptor during the later part of immunization resulted in a significant reduction in serum testosterone over controls and inhibition of spermatogenesis. DNA flow cytometry showed that a specific and significant inhibition of meiosis (transformation of primary spermatocytes to round and elongated spermatids P < .01) and spermiogenesis (transformation of round spermatids to elongated spermatids P < .0001) occurred following blockade of LH function.     

Chemohormonal therapy as primary treatment for metastatic prostate cancer: A randomized study of estramustine phosphate plus luteinizing hormone-releasing hormone agonist versus flutamide plus luteinizing hormone-releasing hormone agonist

BACKGROUND: The present study was undertaken mainly to investigate whether chemohormonal therapy with estramustine phosphate plus luteinizing hormone-releasing hormone (LHRH) agonist has a more beneficial effect than the hormonal therapy with flutamide plus LHRH agonist for newly diagnosed patients with metastatic prostate cancer. METHODS: A total of 57 patients with metastatic prostate cancer aged 59-80 years (median 74 years) were entered in the study and were randomized to the treatment of estramustine phosphate (560 mg/day) plus LHRH agonist (estramustine group) or flutamide (375 mg/day) plus LHRH agonist (flutamide group) with stratification for the degree of performance status, histological differentiation and bone metastasis. RESULTS: Both of the treatment regimens were well tolerated with similar incidences of adverse drug reactions. The overall response rates (complete response plus partial response) at 12 weeks after treatment in the estramustine and flutamide groups were 76 and 55%, respectively. The median time to objective progression for the estramustine group (25.4 months) was longer than that of the flutamide group (14.6 months). The serum levels of follicle stimulating hormone and testosterone were significantly lower in the estramustine group. CONCLUSIONS: Chemohormonal therapy with estramustine phosphate plus LHRH agonist showed longer clinical progression-free survival than the hormonal therapy with flutamide plus LHRH agonist (P = 0.03), although there was no significant difference in the overall survival. A larger-scaled trial with more statistical power is required to clarify that the former regimen is more beneficial than the latter for newly diagnosed patients with advanced prostate cancer.     

Effects of luteinizing hormone-releasing hormone agonist on bladder carcinogenesis in male rats]

In previous studies, it has been suggested that the suppression of testicular androgen had inhibits bladder carcinogenesis. In this study we investigated which phase of bladder carcinogenesis is inhibited by the hormonal change of the hypothalamus-pituitary-testicular axis induced by the depot form of the LH-RH agonist. All rats were treated with 0.05% BBN in tap water for 8 weeks and were observed for the following 16 weeks. They were divided into five groups. Group 1 (Control group); The LH-RH agonist was not administered. Group 2 (Initiation group); The LH-RH agonist (depot form) was administered subcutaneously two weeks before and after the initiation of the experiment. Group 3 (Promotion group); The LH-RH agonist (depot form) was subcutaneously administered at intervals of 4 weeks starting 6 weeks after the initiation of the experiment. Group 4 (Full term group); The LH-RH agonist (depot form) was administered subcutaneously at intervals of 4 weeks starting from 2 weeks before the initiation of the experiment. Group 5 (Castration group); Bilateral orchiectomy was performed one week before the beginning of the experiment. From our results, the followings were suggested, (1) more intensive inhibition of bladder carcinogenesis was observed in the group which received the LH-RH agonist (depot form), compared with the Castration group, (2) the bladder carcinogenesis was more intensively inhibited when the LH-RH analogue (depot from) was given in the promotion phase and (3) not only testosterone but also the regulatory system of the hypothalamus-pituitary-testicular axis is related to the bladder carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time course of serum testosterone and luteinizing hormone levels after cessation of long-term luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer

INTRODUCTION: In order to elucidate the influence of hormone-releasing hormone (LH-RH) agonist therapy cessation on pituitary/testicular function and its clinical implications, we investigated prospectively hormonal (luteinizing hormone: LH; testosterone: T) responses in patients with prostate cancer who received long-term LH-RH 10 agonist therapy. PATIENTS AND METHODS: A consecutive 32 patients who had received LH-RH agonist therapy over 24 months were enrolled. As a baseline, T and LH were measured at the time of LH-RH agonist therapy cessation, monthly for 3 months, and subsequently, every 3 months. RESULTS: The median duration of LH-RH agonist therapy was 30 months (24-87 months) with median follow-up duration of 24 months following cessation. All patients had castrated T levels and suppressed LH levels at baseline. Median duration of castrated T levels following cessation was 6 months. Median time to normalization of T levels was 24 months. LH levels returned to normal within 3 months in all cases. Patients who received androgen deprivation therapy for 30 months or longer required a longer time for recovery of T levels. Patients over 65 years of age showed a statistically significant longer time for recovery of T levels (P=0.0167). CONCLUSIONS: Long-term LH-RH agonist therapy has remarkable effects on serum T level that last for a significant time after cessation, a fact that should be applied to the interpretation of both PSA and serum T levels after cessation of androgen deprivation therapy.     

Treatment of prostatic cancer with a depot form of a luteinizing hormone-releasing hormone analogue

Chronic administration of a depot form of D-Trp6 luteinizing hormone-releasing hormone (LH-RH), an LH-RH analogue (3 mg i.m. every 28 days for a mean period of 9.1 months), to 14 patients with locally extended or metastatic cancer of the prostate provided a good degree of disease control. After a slight and transient increase in gonadotropin secretion, the peptide induced a sharp and long-lasting inhibition of both gonadotropin and testosterone secretion, contemporaneously with clinical improvement and without any important side effects. These results are comparable to those recorded by others after daily administration of LH-RH analogues.     

Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate

Luteinizing hormone-releasing hormone agonist therapy for prostate cancer is a new method of management for metastatic disease. During the initial 1 to 2-week period of administration an increase in serum testosterone concentration can lead to an exacerbation of clinical symptoms (flare phenomenon). Two patients are summarized who received luteinizing hormone-releasing hormone agonist therapy without flare blockade and died suddenly during month 1 of therapy. A review of 765 patients in 9 series found 10.9% who suffered disease flare and 15 who died during disease flare. Of these 17 patients 12 were similar to our 2. These data suggest that any patient placed on luteinizing hormone-releasing hormone agonist therapy for prostate cancer merits some form of flare blockade during the initial 1 or 2 months of therapy.     

Effects of interleukin-2 on hypothalamic and plasma luteinizing hormone-releasing hormone levels in rats

To investigate the effects of interleukin-2 (IL-2) on the hy-pothalamic and plasma luteinizing hormone-releasing hormone(LHRH) levels and serum testosterone (T) level in rats. The hor-mones were measured by radioimmunoassay. Two different dosesof IL-2 (1000 U and 2000 U) were injected. The results showedthat IL-2 slightly decreased the hypothalamic and plasma LHRHlevels, but the differences with the controls were not significant.The administration of 2000 U IL-2 significantly decreased the serumT level. Results suggest that IL-2 may play an inhibitory role onhypothalamic LHRH secretion and decrease serum T level in Rats.(Chin J Androl 2001; 2: 85-6, 91)     

高黄体生成素水平与早发黄体生成素峰的概念

<正> 黄体生成素(luteinizing hormone,LH)是由垂体前叶促性腺激素(gonadotropin,Gn)细胞合成分泌的糖蛋白激素。LH的分泌呈脉冲式,受下丘脑促性腺激素释放激素(gonadotropin releasing hormone,GnRH)、卵巢雌激素、孕激素和抑制素的综     

Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer

OBJECTIVE: To investigate the incidence of bone fractures in patients receiving luteinizing hormone-releasing hormone agonists (LHRH-a) for prostate cancer (in whom a continued low testosterone level after the long-term administration of these drugs reduces bone mineral density), and thus determine the risk of secondary osteoporosis. PATIENTS AND METHODS: Between 1994 and 1999, 218 patients (mean age 77.3 years) were treated for >/= 6 months with LHRH-a for prostate cancer; of these, 14 (6%) had a bone fracture during their treatment. Patients with fracture associated with motor vehicle accidents were excluded. The bone density in the third lumbar vertebra was meas-ured using quantitative computed tomography. Osteocalcin, 1,25-(OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone and calcitonin were measured as metabolic markers. RESULTS: The mean age of the patients with fracture was 78 years; the mean (range) interval from the start of treatment to fracture was 28 (11-46) months. There was no case of a bone fracture at the site of a metastasis from prostate cancer. The bone density was significantly lower in the patients with a fracture than in those without. Of the bone metabolic markers, NTx was higher in those with a fracture. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically, and to evaluate secondary osteoporosis in patients receiving long-term LHRH-a for prostate cancer.     

Protecting spermatogonia from apoptosis induced by doxorubicin using the luteinizing hormone-releasing hormone analog leuprorelin

PURPOSE: The present study was performed to investigate the protective effect of leuprorelin (LH-RH analog), on spermatogonia apoptosis induced by doxorubicin (DXR) in the Sprague-Dawley rat model. METHODS: Twenty-four adult male rats were divided into the following four groups: (i) control group; (ii) group given doxorubicin (intravenous injection, 8 mg/kg); (iii) group given leuprorelin (subcutaneous injection, 3 mg/kg); and (iv) group given both doxorubicin (intravenous injection, 8 mg/kg) and leuprorelin (subcutaneous injection, 3 mg/kg). Evaluation for quantification of apoptotic spermatogonia was made by the ratio of TUNEL-labeled spermatogonia versus 100 Sertoli cells in each seminiferous tubule. Two hundred seminiferous tubules of each rat were assessed. RESULTS: The ratio of apoptotic spermatogonia versus 100 Sertoli cells at stages II-IV of the groups given DXR (groups 2 and 4) were significantly higher than those of the other groups. However, the value at stages II-IV of the group given both DXR and leuprorelin (group 4) was significantly lower than that of the group given DXR (group 2). CONCLUSION: The significant prophylactic effect (P < 0.05) of LH-RH analog against doxorubicin-induced spermatogonial apoptosis was observed in a stage specific manner by microscopic evaluation with TUNEL.     

Biological activity of luteinizing hormone in uraemic children: spontaneous nocturnal secretion and changes after administration of exogenous pulsatile luteinizing hormone-releasing hormone — preliminary observations

Normal pubertal progression is associated with quantitative and qualitative changes in gonadotrophin release. Uraemic children show a delayed or disturbed puberty. We have therefore examined nocturnal gonadotrophin and sex steroid secretion in seven males and three females [age 11–15 years, pubertal stage (PS) 1-3] with chronic renal failure on conservative treatment. In addition to immunoreactive luteinizing hormone (i-LH) we have measured the biological activity of LH (b-LH). Nine children aged 12–17 years with PS 1-3 and normal renal function served as a control group. In two uraemic children, i-LH, b-LH, follicle stimulating hormone and sex steroids were evaluated before and 7 days after pulsatile LH-releasing hormone (LHRH) administration (150 ng/kg body weight subcutaneously every 120 min). Mean i-LH levels were higher in uraemic children than in controls. An increase in i-LH during sleep was found in all controls and in eight of ten uraemic subjects. Mean b-LH levels were lower during sleep and the b/i LH ratio was reduced in uraemic children with PS 2-3 whether asleep or awake compared with controls. Pulsatile administration of LHRH provoked a rise of i-LH and b-LH levels with an increased b/i LH ratio, suggesting an intact pituitary responsiveness. These preliminary data indicate that the gonadotrophin control of LH is abnormal in uraemic children, and that biopotency of LH secretion might be improved after shortterm pulsatile LHRH administration.