Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Biol Psychiatry. 2013 Feb 15;73(4):371-8. doi: 10.1016/j.biopsych.2012.09.018. Epub 2012 Nov 13.
Fear extinction is a laboratory model of fear inhibition and is the basis of exposure therapy for anxiety disorders. Emerging evidence from naturally cycling female rodents and women indicates that estrogens are necessary to the consolidation of fear extinction. Hormonal contraceptives (HCs) inhibit estrogen production; yet, their effects on fear extinction are unknown.
We used a cross-species translational approach to investigate the impact of HCs and estradiol supplementation on fear extinction in healthy women (n=76) and female rats (n = 140).
Women using HCs exhibited significantly poorer extinction recall compared with naturally cycling women. The extinction impairment was also apparent in HC-treated female rats and was associated with reduced serum estradiol levels. The impairment could be rescued in HC-treated rats either by terminating HC treatment after fear learning or by systemic injection of estrogen-receptor agonists before fear extinction, all of which restored serum estradiol levels. Finally, a single administration of estradiol to naturally cycling women significantly enhanced their ability to recall extinction memories.
Together, these findings suggest that HCs may impact women's ability to inhibit fear but that this impairment is not permanent and could potentially be alleviated with estrogen treatment.
恐惧消退是一种恐惧抑制的实验室模型，也是焦虑障碍暴露疗法的基础。来自自然周期雌性啮齿动物和女性的新证据表明，雌激素是恐惧消退巩固所必需的。激素避孕药（HCs）会抑制雌激素的产生；然而，它们对恐惧消退的影响尚不清楚。
我们使用跨物种转化的方法来研究 HCs 和雌二醇补充对健康女性（n=76）和雌性大鼠（n=140）恐惧消退的影响。
使用 HCs 的女性与自然周期女性相比，表现出明显较差的消退记忆回忆。HC 治疗的雌性大鼠也出现了这种消退障碍，并且与血清雌二醇水平降低有关。在恐惧学习后终止 HCs 治疗或在恐惧消退前给 HCs 治疗的雌性大鼠注射雌激素受体激动剂，都可以挽救这种障碍，所有这些都恢复了血清雌二醇水平。最后，给自然周期的女性单次给予雌二醇可以显著提高她们回忆消退记忆的能力。
综上所述，这些发现表明 HCs 可能会影响女性抑制恐惧的能力，但这种障碍不是永久性的，并且可能可以通过雌激素治疗来缓解。
