Andrew G Herzog1, Cheryl A Frye2. 1. From the Harvard Neuroendocrine Unit (A.G.H.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Psychology (C.A.F.), University of Albany-SUNY, NY. aherzog@bidmc.harvard.edu. 2. From the Harvard Neuroendocrine Unit (A.G.H.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Psychology (C.A.F.), University of Albany-SUNY, NY.
Abstract
OBJECTIVE: To determine whether allopregnanolone (AP) may mediate seizure reduction in progesterone-treated women with epilepsy. METHODS: The NIH Progesterone Trial compared the efficacy of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects, randomized 2:1 to progesterone or placebo, stratified by catamenial vs noncatamenial designation. Treatments were compared on proportions of 50% responders, and changes in seizure frequency from 3 baseline to 3 treatment cycles. Serum AP levels were measured by radioimmunoassay from 155 women with intractable focal-onset seizures who had baseline and treatment-phase midluteal serum samples drawn each cycle for hormone measurements. RESULTS: There was no significant correlation between percentage changes in AP levels and seizure frequencies from baseline to treatment for either the catamenial or noncatamenial stratum. There was a significant correlation for the subset of subjects who showed a significantly greater responder rate in the post hoc analysis of the trial, i.e., subjects who had a 3-fold or greater increase in average daily seizure frequency perimenstrually compared with the midfollicular and midluteal phases (C1 ≥ 3: r = -0.442, p = 0.013, and specifically for C1 ≥ 3 progesterone-treated subjects [r = -0.452, p = 0.035], but not other groups [C1 ≥ 3 placebo: r = -0.367; C1 <3 progesterone: r = 0.099; C1 <3 placebo: r = 0.131; p = not significant]). CONCLUSIONS: The findings support AP as a mediator of seizure reduction in progesterone-treated women who have a substantial level of perimenstrually exacerbated seizures.
RCT Entities:
OBJECTIVE: To determine whether allopregnanolone (AP) may mediate seizure reduction in progesterone-treated women with epilepsy. METHODS: The NIH Progesterone Trial compared the efficacy of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects, randomized 2:1 to progesterone or placebo, stratified by catamenial vs noncatamenial designation. Treatments were compared on proportions of 50% responders, and changes in seizure frequency from 3 baseline to 3 treatment cycles. Serum AP levels were measured by radioimmunoassay from 155 women with intractable focal-onset seizures who had baseline and treatment-phase midluteal serum samples drawn each cycle for hormone measurements. RESULTS: There was no significant correlation between percentage changes in AP levels and seizure frequencies from baseline to treatment for either the catamenial or noncatamenial stratum. There was a significant correlation for the subset of subjects who showed a significantly greater responder rate in the post hoc analysis of the trial, i.e., subjects who had a 3-fold or greater increase in average daily seizure frequency perimenstrually compared with the midfollicular and midluteal phases (C1 ≥ 3: r = -0.442, p = 0.013, and specifically for C1 ≥ 3 progesterone-treated subjects [r = -0.452, p = 0.035], but not other groups [C1 ≥ 3 placebo: r = -0.367; C1 <3 progesterone: r = 0.099; C1 <3 placebo: r = 0.131; p = not significant]). CONCLUSIONS: The findings support AP as a mediator of seizure reduction in progesterone-treated women who have a substantial level of perimenstrually exacerbated seizures.
Authors: A G Herzog; K M Fowler; S D Smithson; L A Kalayjian; C N Heck; M R Sperling; J D Liporace; C L Harden; B A Dworetzky; P B Pennell; J M Massaro Journal: Neurology Date: 2012-05-30 Impact factor: 9.910
Authors: P Porcu; A M Barron; C A Frye; A A Walf; S-Y Yang; X-Y He; A L Morrow; G C Panzica; R C Melcangi Journal: J Neuroendocrinol Date: 2016-02 Impact factor: 3.627
Authors: P Emanuela Voinescu; Kurt D Pennell; Camden P Bay; Zachary N Stowe; Limin Peng; Cheryl A Frye; Kathleen Y Tang; Page B Pennell Journal: Epilepsy Res Date: 2021-09-25 Impact factor: 3.045