Antifertility Effects of LHRH Agonists in the Male

Labrie, Fernand; Bélanger, Alain; Cusan, Lionel; Séguin, Carl; Pelletier, Georges; Kelly, Paul A.; Reeves, Jerry J.; Lefebvre, Fleur-Ange; Lemay, André; Gourdeau, Y; Raynaud, Jean‐Pierre

doi:10.1002/j.1939-4640.1980.tb00034.x

Cited by 190 publications

(61 citation statements)

References 46 publications

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“…In addition, GnRH-A do not suppress basal LH levels in intact male rats during chronic treatment. With a variety of regimens (i.e., D-Leu6-GnRH, ng [57]; D-Ala6-GnRH; 100 ng-1 yg [10,58,59]; D-Tryp6-GnRH, 0.001-1 ,g [12]; Bus-erelin, 0.034-34 yg, or GnRH itself, 0.034-340 ug/d [11]), basal LH was unchanged or increased in intact animals, while suppression occurred exclusively in castrates. Only with very high dose GnRH (i.e., 200 ug q.d.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…13 Specifically, the efficacy of a well-tolerated LHRH agonist in CaP treatment and their efficacy in prolonging life in localized CaP has been observed. 14,15 A significant difference in prostate specific antigen (PSA) progression and organ-confined disease progression was shown in the Canadian trial of 3 and 8 months of leuprolide plus flutamide. 16 A highly significant overall survival benefit for external beam radiation therapy (ERBT) and ADT versus EBRT alone has also been reported.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of androgen deprivation therapy in prolonging survival of older men treated for locoregional prostate cancer

Holmes

Chan

Jiang

et al. 2007

Prostate Cancer Prostatic Dis

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Epidemiologic and experimental evidence suggests the effectiveness of androgen deprivation therapy (ADT) in prostate cancer (CaP) management. Although ADT has been increasingly used as mono-therapy in CaP, the survival benefit of ADT remains unclear. We examined the effectiveness of ADT in prolonging survival in a community-based cohort of 64 475 older men diagnosed with locoregional CaP, in 1992-1999 with last follow-up through December 2002, in 11 Surveillance Epidemiology and End Results (SEER) registries. The effect of ADT on survival was assessed using Kaplan-Meier's method, log-rank test and Cox proportional hazards. After adjustment for propensity to receive ADT, the ADT and non-ADT groups were significantly different in the distribution of covariates except for comorbidity score and SEER registries. The crude overall mortality was significantly higher in cases with ADT compared with cases that received no ADT, hazard ratio (HR ¼ 1.54; 95% CI ¼ 1.50-1.58). However, mortality was substantially reduced (1.04, 1.00-1.08) after adjusting for standard care, socio-demographics, tumor characteristics, prognostic factors and chemotherapy. Therefore, ADT was not associated with significantly increased survival benefit for older men with locoregional CaP. Further studies may be needed to explore whether ADT is associated with other health benefits and the cost-effectiveness of these benefits.

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“…In fact, when we first administered a GnRH agonist to a patient with stage B prostate cancer, a 70-85% reduction in the serum levels of testosterone and dihydrotestosterone (DHT), respectively, occurred as early as 2 weeks after the start of therapy (Labrie et al 1980; Fig. 1).…”

Section: Discovery Of Medical Castration With Gnrh Agonists and Its Imentioning

confidence: 99%

“…The drug innovations in the field of prostate cancer have been gonadotropinreleasing hormone (GnRH) agonists (Labrie et al 1980(Labrie et al , 1996(Labrie et al , 2005a used to achieve medical castration and the pure antiandrogens or compounds having exclusive antagonistic activity at the androgen receptor (AR) (Neri et al 1967, El Etreby et al 1987, Furr et al 1987 administered in association with medical or surgical castration , 1985, Crawford et al 1989, Labrie 2007. The combination of castration with a pure antiandrogen has been called combined androgen blockade (CAB).…”

Section: Introductionmentioning

confidence: 99%

GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer

Labrie¹

2014

Endocrine-Related Cancer

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The discovery of medical castration with GnRH agonists in 1979 rapidly replaced surgical castration and high doses of estrogens for the treatment of prostate cancer. Soon afterwards, it was discovered that androgens were made locally in the prostate from the inactive precursor DHEA of adrenal origin, a mechanism called intracrinology. Taking into account these novel facts, combined androgen blockade (CAB) using a pure antiandrogen combined with castration in order to block the two sources of androgens was first published in 1982. CAB was the first treatment shown in randomized and placebo-controlled trials to prolong life in prostate cancer, even at the metastatic stage. Most importantly, the results recently obtained with the novel pure antiandrogen enzalutamide as well as with abiraterone, an inhibitor of 17a-hydroxylase in castration-resistant prostate cancer, has revitalized the CAB concept. The effects of CAB observed on survival of heavily pretreated patients further demonstrates the importance of the androgens made locally in the prostate and are a strong motivation to apply CAB to efficiently block all sources of androgens earlier at start of treatment and, even better, before metastasis occurs. The future of research in this field thus seems to be centered on the development of more potent blockers of androgens formation and action in order to obtain better results at the metastatic stage and, for the localized stage, reduce the duration of treatment required to achieve complete apoptosis and control of prostate cancer proliferation before it reaches the metastatic or noncurable stage.

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Antifertility Effects of LHRH Agonists in the Male

Cited by 190 publications

References 46 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.

Effectiveness of androgen deprivation therapy in prolonging survival of older men treated for locoregional prostate cancer

GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer

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