<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kokras, N</style></author><author><style face="normal" font="default" size="100%">Hodes, G. E.</style></author><author><style face="normal" font="default" size="100%">Bangasser, D. A.</style></author><author><style face="normal" font="default" size="100%">Dalla, C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Sex differences in the hypothalamic-pituitary-adrenal axis: An obstacle to antidepressant drug development?</style></title><secondary-title><style face="normal" font="default" size="100%">Br J Pharmacol</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">*Hypothalamo-Hypophyseal System</style></keyword><keyword><style  face="normal" font="default" size="100%">*Pituitary-Adrenal System</style></keyword><keyword><style  face="normal" font="default" size="100%">*Sex Characteristics</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antidepressive Agents/*therapeutic use</style></keyword><keyword><style  face="normal" font="default" size="100%">Arginine Vasopressin/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Corticotropin-Releasing Hormone/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Depression/*drug therapy/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Development</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Glucocorticoid/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Mineralocorticoid/metabolism</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Nov</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">21</style></number><edition><style face="normal" font="default" size="100%">20190626</style></edition><volume><style face="normal" font="default" size="100%">176</style></volume><pages><style face="normal" font="default" size="100%">4090-4106</style></pages><isbn><style face="normal" font="default" size="100%">0007-1188 (Print)0007-1188</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been implicated in the pathophysiology of depression, and HPA axis-based compounds have served as potential new therapeutic targets, but with no success. This review details sex differences from animal and human studies in the function of HPA axis elements (glucocorticoids, corticotropin releasing factor, and vasopressin) and related compounds tested as candidate antidepressants. We propose that sex differences contribute to the failure of novel HPA axis-based drugs in clinical trials. Compounds studied preclinically in males were tested in clinical trials that recruited more, if not exclusively, women, and did not control, but rather adjusted, for potential sex differences. Indeed, clinical trials of antidepressants are usually not stratified by sex or other important factors, although preclinical and epidemiological data support such stratification. In conclusion, we suggest that clinical testing of HPA axis-related compounds creates an opportunity for targeted, personalized antidepressant treatments based on sex. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.</style></abstract><accession-num><style face="normal" font="default" size="100%">31093959</style></accession-num><notes><style face="normal" font="default" size="100%">10.1111/bph.14710</style></notes><custom1><style face="normal" font="default" size="100%">N.K. and C.D. have received honoraria and financial support from Janssen‐Cilag and Elpen S.A. None of those is relevant to this study.</style></custom1><custom2><style face="normal" font="default" size="100%">PMC6877794</style></custom2><auth-address><style face="normal" font="default" size="100%">Department of Pharmacology, National and Kapodistrian University of Athens, Athens, Greece.First Department of Psychiatry, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.Department of Psychology, Temple University, Philadelphia, Pennsylvania.</style></auth-address><remote-database-provider><style face="normal" font="default" size="100%">NLM</style></remote-database-provider></record></records></xml>