Editing Valproate (section)

====Endocrine actions====
Valproic acid has been found to be an [[receptor antagonist|antagonist]] of the [[androgen receptor|androgen]] and [[progesterone receptor]]s, and hence as a [[nonsteroidal]] [[antiandrogen]] and [[antiprogestogen]], at concentrations much lower than therapeutic serum levels.<ref name="pmid16165177">{{cite journal | vauthors = Death AK, McGrath KC, Handelsman DJ | title = Valproate is an anti-androgen and anti-progestin | journal = Steroids | volume = 70 | issue = 14 | pages = 946–953 | date = December 2005 | pmid = 16165177 | doi = 10.1016/j.steroids.2005.07.003 | s2cid = 25958985 | hdl = 10453/16875 | hdl-access = free }}</ref> In addition, the drug has been identified as a potent [[aromatase inhibitor]], and suppresses [[estrogen]] concentrations.<ref name="WyllieCascino2012">{{cite book|vauthors=Wyllie E, Cascino GD, Gidal BE, Goodkin HP|title=Wyllie's Treatment of Epilepsy: Principles and Practice|url=https://books.google.com/books?id=j9t6Qg0kkuUC&pg=PA288-IA37|date=17 February 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-5348-4|pages=288–|url-status=live|archive-url=https://web.archive.org/web/20140606200832/http://books.google.com/books?id=j9t6Qg0kkuUC|archive-date=6 June 2014}}</ref> These actions are likely to be involved in the reproductive endocrine disturbances seen with valproic acid treatment.<ref name="pmid16165177" /><ref name="WyllieCascino2012" />

Valproic acid has been found to directly stimulate androgen biosynthesis in the [[gonad]]s via inhibition of histone deacetylases and has been associated with [[hyperandrogenism]] in women and increased [[4-androstenedione]] levels in men.<ref name="UchidaMaruyama2005">{{cite journal | vauthors = Uchida H, Maruyama T, Arase T, Ono M, Nagashima T, Masuda H, Asada H, Yoshimura Y | title = Histone acetylation in reproductive organs: Significance of histone deacetylase inhibitors in gene transcription | journal = Reproductive Medicine and Biology | volume = 4 | issue = 2 | pages = 115–122 | date = June 2005 | pmid = 29662388 | pmc = 5891791 | doi = 10.1111/j.1447-0578.2005.00101.x }}</ref><ref name="IsojärviTaubøll2005">{{cite journal | vauthors = Isojärvi JI, Taubøll E, Herzog AG | title = Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy | journal = CNS Drugs | volume = 19 | issue = 3 | pages = 207–223 | year = 2005 | pmid = 15740176 | doi = 10.2165/00023210-200519030-00003 | s2cid = 9893959 }}</ref> High rates of [[polycystic ovary syndrome]] and [[menstrual disorder]]s have also been observed in women treated with valproic acid.<ref name="IsojärviTaubøll2005" />