title: GABAA Receptor-Modulating Steroids in Relation to Women's Behavioral Health.
abstract: In certain women, increased negative mood relates to the progesterone metabolite, allopregnanolone (allo), during the luteal phase of ovulatory menstrual cycles, the premenstrual dysphoric disorder (PMDD). In anovulatory cycles, no symptom or sex steroid increase occurs but symptoms return during progesterone/allo treatment. Allo is a potent GABAA receptor-modulating steroid and as such is expected to be calming and anxiolytic. A relation to negative mood is unexpected. However, this paradoxical effect can be induced by all GABAA receptor modulators in low concentrations whereas higher concentrations are calming. The severity of the mood symptoms relate to allo in an inverted U-shaped curve at endogenous luteal-phase serum concentrations. Allo's effects on the GABAA receptor can be antagonized by isoallopregnanolone (ISO), an antagonist to allo. ISO has also been used in a preliminary clinical trial on PMDD ameliorating symptoms with good effect in PMDD patients.
authors.affiliation: Department of Clinical sciences, Obstetrics and Gynecology, Umeå neurosteroid research center, Umeå University, Building 6M 4th floor, Umeå, Sweden. torbjorn.c.backstrom@umu.se.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bäckström
authors.affiliation: Department of Clinical sciences, Obstetrics and Gynecology, Umeå neurosteroid research center, Umeå University, Building 6M 4th floor, Umeå, Sweden. Marie.Bixo@umu.se.
authors.forename: Marie
authors.initials: M
authors.lastname: Bixo
authors.affiliation: Department of Clinical sciences, Obstetrics and Gynecology, Umeå neurosteroid research center, Umeå University, Building 6M 4th floor, Umeå, Sweden. Jessica.Stromberg@umecrine.se.
authors.forename: Jessica
authors.initials: J
authors.lastname: Strömberg
mesh_terms: D000339:Affect / Q000187:drug effects / Q000502:physiology; D005260:Female; D018757:GABA Modulators / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000378:metabolism*; D065446:Premenstrual Dysphoric Disorder / Q000378:metabolism / Q000523:psychology / Q000628:therapy; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D011280:Pregnanolone
keywords: GABAA receptor-modulating steroids; Mood symptoms; Premenstrual dysphoric disorder