Kaltsouni Elisavet, Gu Xuan, Wikström Johan, Hahn Andreas, Lanzenberger Rupert, Sundström-Poromaa Inger, Comasco Erika
Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Sweden.
Department of Surgical Sciences, Neuroradiology, Uppsala University, Uppsala, Sweden.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111179. doi: 10.1016/j.pnpbp.2024.111179. Epub 2024 Oct 23.
Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored.
Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton.
Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts.
The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism.
EUDRA-CT 2016-001719-19; "Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study."; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE.
经前烦躁障碍（PMDD）是一种在月经周期黄体期由孕酮和雌二醇波动引发的抑郁障碍。选择性孕酮受体调节剂（SPRM）在对孕酮发挥拮抗作用并将雌二醇维持在适度水平时，已显示出对PMDD精神症状的有益效果。孕酮还以其神经保护作用而闻名，而合成孕激素则被认为可促进髓鞘形成。然而，SPRM治疗对白质微观结构的影响尚未得到探索。
作为一项双盲随机对照试验的一部分，采用扩散张量成像收集PMDD患者在接受醋酸乌利司他（一种SPRM）或安慰剂治疗前后的白质完整性数据。进行基于体素的空间统计学分析，以研究SPRM治疗与安慰剂对整个白质骨架上的分数各向异性（FA）、平均扩散率（MD）、径向扩散率（RD）和轴向扩散率（AD）的纵向影响。
体素分析表明，接受SPRM治疗的个体与接受安慰剂治疗的个体相比，任何白质微观结构指标随时间均无变化。PMDD症状的改善与白质微观结构的变化无关。在治疗期间的二次探索性横断面比较中，SPRM组在几条纤维束中显示出比安慰剂组更低的FA以及更高的MD、RD和AD。
主要研究结果表明，与安慰剂相比，SPRM治疗对白质微观结构没有影响。然而，二次探索性分析在治疗后产生了组间差异，这需要对可能受孕酮拮抗作用影响的纤维束进行进一步研究。
EUDRA - CT 2016 - 001719 - 19；“用于治疗经前烦躁障碍的选择性孕酮受体调节剂。一项随机、双盲、安慰剂对照研究。”；https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE
