Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD

Abstract

Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.

Figure 1.

Differential SCR response across phases of the experiment. Mean skin conductance response scores to CS+ and CS− for each trial during each phase of the experiment (acquisition, extinction, and retention).

Figure 2.

Differential SCR by sex and hormonal contraceptive status during acquisition and extinction. The standardized regression coefficient, representing the change in differential SCR over trials, is presented for each sex and hormonal contraceptive group for acquisition and extinction phases. Error bars represent 95% confidence intervals.