Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women

Abstract

Raloxifene is a selective estrogen modulator able to exert an estrogen-like action on some target tissues and a specific antiestrogenic action on the uterus and breast. In ovariectomized rats ,it has beenshown to stimulate the β-endorphin and allopregnanolone concentrations of the anterior and neurointermediate pituitary lobes ,the hypothalamus and the hippocampus. The present study aimed to evaluate,in 12 healthy postmenopausal women ,the effect of 60 mg/day raloxifene hydrochloride administration for 6 months on plasma β-endorphin and allopregnanolone levels ,and on the dynamic changes of bothβ-endorphin and allopregnanolone secretion after the administration of: (1) clonidine ,an α2-presynaptic adrenergic agonist; (2) naloxone ,an opioid receptor antagonist; and (3) fluoxetine,a serotonin selective reuptake inhibitor.The administration of raloxifene significantly increased both circulating β-endorphin and allopregnanolone concentrations ,at both the third and sixthmonths of treatment (p < 0.01). Clonidine ,fluoxetine and naloxone administration before therapy was not able to stimulate the release of β-endorphin ,but the response was completely restoredafter raloxifene administration. Before therapy ,clonidine and naloxone tests were accompanied by a significant rise in allopregnanolone secretion; the same changes were observed after raloxifene administration,but with significantly higher allopregnanolone concentrations at each time considered. While the fluoxetine test before therapy failed to increase the release of allopregnanolone ,the same test after 6months of raloxifene administration was characterized by a significant release of allopregnanolone at 60 and 90 minutes. The present data indicate that raloxifene has an estrogen-like effect on neuroendocrinepathways in postmenopausal women.