Translational studies of estradiol and progesterone in fear and PTSD

Translational models of fear have greatly informed our understanding of PTSD and its underlying fear circuitry. One of the most replicated findings in the field is the two-fold higher PTSD incidence in females compared to males. While sociocultural factors play a role, the most robust biological influencers to date are gonadal hormones, such as estradiol and progesterone, which fluctuate across the menstrual cycle. Among studies that account for these hormones, most do so in isolation or collect both and only report one. Variation in study findings suggests that the ratio between these two hormones (the P/E ratio) may be an important and missing variable to further understand gonadal hormone influences on fear. Here we review cross-species examinations of fear and PTSD, within the contexts of estradiol and progesterone as well as P/E ratios that were calculated based on extant literature. We then provide recommendations for best practices in assay methods and reporting to improve research on the P/E ratio in fear and PTSD. Ultimately, greater understanding of this important variable will advance efforts to characterize gonadal hormone influences on fear learning processes in humans and animals.