Psychoneuroendocrinology (2006) 31, 1208–1219 Associations of histories of depression and PMDD diagnosis with allopregnanolone concentrations following the oral administration of micronized progesterone Rebecca R. Klatzkin a , A. Leslie Morrow b , Kathleen C. Light a,b , Cort A. Pedersen b , Susan S. Girdler a,b,Ã a Department of Psychology, University of North Carolina at Chapel Hill, CB #7175, Medical Research Bldg A, Chapel Hill, NC 27599-7175, USA b Department of Psychiatry, University of North Carolina at Chapel Hill, CB #7175, Medical Research Bldg A, Chapel Hill, NC 27599-7175, USA Received 22 May 2006; received in revised form 29 August 2006; accepted 5 September 2006 KEYWORDS Allopregnanolone; Progesterone; Depression; PMDD Summary Twenty-three women with premenstrual dysphoric disorder (PMDD) and 29 non-PMDD controls were compared for plasma progesterone (P) and its neuroactive steroid metabolite allopregnanolone (ALLO), as well as the ALLO/P ratio following the double-blind, placebo controlled administration of 300 mg oral micronized progesterone. Approximately half of each group had prior depression (DEP) (13 PMDD, 12 non-PMDD), though all were free of current depression. Progesterone and ALLO were sampled 160, 190, 225, and 255 min after progesterone administration. Changes over time in plasma concentrations and the ALLO/P ratio were assessed using area under the curve analyses. Women with prior DEP had lower ALLO levels (p ¼ 0.05) and marginally lower P levels (po0.07) following progester- one administration compared to never depressed women, and this was especially evident in the non-PMDD women (po0.01). PMDD women with no prior DEP had higher pre-progesterone ALLO/P ratios than all other groups (Pso0.05) and higher ratios than the never depressed, non-PMDD women following oral progesterone (po0.05). Results could not be accounted for by group differences in steroid hormone binding protein concentrations. For all women, progesterone administra- tion was associated with increased confusion, fatigue, and with reduced confidence (Pso0.01), even after controlling for placebo-associated mood change. These results suggest a persistent effect of prior DEP on P and ALLO concentrations ARTICLE IN PRESS www.elsevier.com/locate/psyneuen 0306-4530/$ - see front matter & 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2006.09.002 Ã Corresponding author. CB7175, Medical Research Bldg A, University of North Carolina at Chapel Hill, Chapel Hill, NC 275997175. Tel.: (919) 966 2544; fax: +919) 966 0708. E-mail address: susan_girdler@med.unc.edu (S.S. Girdler).