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Expert Opinion on Pharmacotherapy Dec 2021Androgen deprivation therapy (ADT) is currently the backbone treatment of metastatic prostate cancer and is also used in combination with external beam radiotherapy...
Androgen deprivation therapy (ADT) is currently the backbone treatment of metastatic prostate cancer and is also used in combination with external beam radiotherapy (EBRT). Castration may be achieved either by bilateral orchiectomy or by administration of LHRH agonists or GnRH antagonists.: In this article, the authors assess the current and emerging role of GnRH antagonists for the treatment of prostate cancer focusing on oncological results and safety (i.e. cardiovascular risk). In addition, updated data regarding the first orally administered GnRH antagonist, relugolix, is presented.: Studies demonstrate that GnRH antagonists are at least equal with LHRH agonists in terms of testosterone suppression and PSA progression free survival with a major advantage being rapid testosterone suppression. Thus, the optimal group of patients included symptomatic metastatic prostate cancer patients especially if cardiovascular comorbidities or LUTS are also present. Emerging data regarding benefit of the use of GnRH antagonists in patients with concomitant cardiovascular disease are of great interest. Relugolix has emerged as the first orally administered GnRH antagonist able to achieve and maintain testosterone castration levels and it is associated with a profound reduction of major cardiovascular events.
Topics: Androgen Antagonists; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Male; Orchiectomy; Prostatic Neoplasms
PubMed: 34187259
DOI: 10.1080/14656566.2021.1948012 -
American Journal of Physiology.... Jul 2020We have previously shown that systemic injection of erythropoietin-producing hepatocellular receptor A7 (EPHA7)-Fc raises serum luteinizing hormone (LH) levels before...
We have previously shown that systemic injection of erythropoietin-producing hepatocellular receptor A7 (EPHA7)-Fc raises serum luteinizing hormone (LH) levels before ovulation in female rats, indicating the induction of EPHA7 in ovulation. In this study, we aimed to identify the mechanism and hypothalamus-pituitary-ovary (HPO) axis level underlying the promotion of LH secretion by EPHA7. Using an ovariectomized (OVX) rat model, in conjunction with low-dose 17β-estradiol (E) treatment, we investigated the association between EPHA7-ephrin (EFN)A5 signaling and E negative feedback. Various rat models (OVX, E-treated OVX, and abarelix treated) were injected with the recombinant EPHA7-Fc protein through the caudal vein to investigate the molecular mechanism underlying the promotion of LH secretion by EPHA7. was observed strongly expressed in the arcuate nucleus of the female rat by using RNAscope in situ hybridization. Our results indicated that E, combined with estrogen receptor (ER)α, but not ERβ, inhibited and gonadotropin-releasing hormone 1 ( expressions in the hypothalamus. In addition, the systemic administration of EPHA7-Fc restrained the inhibition of and by E, resulting in increased and expressions in the hypothalamus as well as increased serum LH levels. Collectively, our findings demonstrated the involvement of EPHA7-EFNA5 signaling in the regulation of LH and the E negative feedback pathway in the hypothalamus, highlighting the functional role of EPHA7 in female reproduction.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Ephrin-A5; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Feedback, Physiological; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hypothalamo-Hypophyseal System; Hypothalamus; Luteinizing Hormone; Oligopeptides; Ovariectomy; Ovary; Protein Precursors; Rats; Receptor, EphA7; Recombinant Proteins
PubMed: 32396496
DOI: 10.1152/ajpendo.00046.2020