Sustained Suppression of Testosterone Production by the Luteinising-Hormone Releasing-Hormone Agonist Buserelin in Patients With Advanced Prostate Carcinoma

Borgmann, V.; Hardt, Wolfgang; Schmidt-Gollwitzer, M.; Adenauer, Hannah; Nagel, R.

doi:10.1016/s0140-6736(82)92279-6

Cited by 109 publications

(29 citation statements)

References 8 publications

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“…Thus, for the patient trials, we chose GnRH-A doses (i.e., 1,000-10,000 ug/d) equivalent to the amounts used in rats when corrected for square meter differences (16). These doses are in striking contrast with the much lower amounts used chronically in three recently published preliminary studies of GnRH-A administration in prostate cancer patients (46)(47)(48). It is pertinent, then, to consider whether LH and androgen suppression were greater in the present study than in those using lower GnRH-A doses.…”

Section: Discussionmentioning

confidence: 72%

“…Our data indicate a 75-90% suppression of plasma LH and FSH to the limit of detectability of the respective RIA. By comparison, Faure et al (48) found no inhibition and Borgmann et al (47) a 60% reduction in three patients. LH levels were not reported in the study of Tolis et al (46).…”

Section: Discussionmentioning

confidence: 90%

“…Reports of these paradoxical actions stimulated several ongoing studies of GnRH-A as potential treatment strategies for androgen-dependent prostatic carcinoma in man (46)(47)(48). We first questioned what doses of analog should be chosen for initial studies in patients.…”

Section: Discussionmentioning

confidence: 99%

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Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

Warner¹,

Worgul²,

Drago³

et al. 1983

J. Clin. Invest.

101

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A B S T R A C T Potent synthetic analogs of gonadotropin-releasing hormone produce parodoxical antireproductive effects when administered chronically. These compounds are minimally toxic and may exhibit no plateau of the dose-response curve even at very high doses. These considerations served as the basis for our systematic evaluation of [D-leucine6-desarginine-glycine-NH210]gonadotropin-releasing hormone (GnRH-A) proethylamide in the very high dose range (i.e., 10-fold larger amounts than previously used). In rats given the analog for 12

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 90%

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Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

Warner¹,

Worgul²,

Drago³

et al. 1983

J. Clin. Invest.

101

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“…These factors notwithstanding, it appears that a remarkably diverse group of hypothalamic replacement regimens of LHRH have proven capable of inducing ovulation and certain generalizations regarding this mode of therapy appear justified. I t appears that intravenous LHRH administration is more effective than the subcutaneous route in these women and that a dosage of LHRH of [1][2][3][4][5] pg intravenuously or 5-10 pg subcutaneously represents the most "physiologic" replacement dosages. Similarly, the various frequencies of LHRH administration to be reported herein demonstrate a convergence upon the 60-90 minute frequency and the results of these studies confirm virtually uniform success rates in hypothalamic amenorrhea when all of these factors are taken into consideration.…”

Section: Hypogonadotropic Malesmentioning

confidence: 99%

An Overview of LHRH and Its Analogues: Clinical Uses

Wf¹

1984

Upsala Journal of Medical Sciences

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BACKGROUNDTwo experimental observations underlie all of the apparently diverse clinical applications of LHRH and its analogues. The first of these experiments is the now classic studies of Knobil's group in which arcuate nucleus-lesioned and pre-pubertal (1 '20) Rhesus monkeys (both LHRH deficient) were replaced with exogenous LHRH. In this ablation and replacement model, continous administration of natural sequence LHRH was unable to restore physiologic levels of gonadotropin secretion. Episodic delivery of 1 pg/kg of LHRH, however, a t a frequency designed to mimic the endogenous gonadotropin pulsations observed in castrate animals, was capable of restoring appropriate gonadotropin secretion to these animals. Moreover, increasing the duration of exposure of the gonadotroph to LHRH resulted in decreasing levels of gonadotropin secretion (14) and thus f i t the general criteria of pharmacologic desensitization of pituitary gonadotropin secretion, i . e . decreasing responsiveness with increasing doses of stimulation.The second experimental observation was made by our group in LHRH deficient adult males with hypogonadotropic hypogonadism employing a longacting LHRH analogue, D-Trp6-Pro9-Net-LHRH (LHRHa) (9). Alternate day administration of 50 mcg of this potent LHRH agonist was capable of producing a stable pulse of gonadotropin elevation for 8 hours, whereas daily administration of the same dose totally ablated pituitary responsiveness to LHRHa administration only to have it restored by either returning the frequency of LHRHa administration to alternate days or lowering the daily dosage. By coupling these two observations, it thus became clear that intermittency of pituitary gonadotroph stimulation by LHRH was absolutely essential for physiologic secretion whereas continuous receptor occupancy by either LHRH or its long-acting analogues could produce an effective and selective blockade of gonadotropin secretion. The selectivity of this blockade is imparted to the system by the specificity of the releasing factor and occurs independently of alterations of any other anterior pituitary function.

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“…2 Suppression of androgens has been achieved by surgical castration (orchiectomy), estrogens, and more recently by chemical castration by the administration of luteinising hormone releasing hormone (LHRH) agonists. 3 Androgens of adrenal origin, may play a signi®cant role in disease progression. In 1945 Huggins and Scott had already reported a secondary response to surgical adrenalectomy in patients who had relapsed following orchidectomy.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide

Schasfoort¹,

Beek

Newling

2001

Prostate Cancer Prostatic Dis

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The use, tolerability and ef®cacy of the non-steroidal anti-androgen nilutamide (Anandron 1 ) in daily clinical practice was investigated in this 5-y project. In total 725 patients were recruited from 27 Dutch centres. The investigated population was very heterogeneous and different therapeutic options were reported. We may conclude that in general good results have been obtained, especially in ®rst line combination therapy combined with luteinising hormone releasing hormone (LHRH) agonists. Patients with a good performance status at inclusion seem to bene®t more from nilutamide combination therapy. Prostate Cancer and Prostatic Diseases (2001) 4, 112±117.

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Sustained Suppression of Testosterone Production by the Luteinising-Hormone Releasing-Hormone Agonist Buserelin in Patients With Advanced Prostate Carcinoma

Cited by 109 publications

References 8 publications

Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

An Overview of LHRH and Its Analogues: Clinical Uses

Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide

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