Estrogen, progesterone, and the menstrual cycle: A systematic review of fear learning, intrusive memories, and PTSD

Women are disproportionately affected by posttraumatic stress disorder (PTSD), and gonadal hormones are implicated in fear learning processes associated with PTSD. In rodents, lower estradiol, particularly during metestrus when progesterone is also low, is associated with impaired extinction. Based on theories that extinction deficits underlie PTSD, individuals with lower estradiol and progesterone may exhibit fear learning deficits and higher PTSD symptomatology. A systematic review was conducted in Psycinfo, PubMed, and Medline databases for studies examining estradiol, progesterone, or menstrual phase in relation to fear learning or PTSD symptoms. Twenty-three studies are organized into fear learning (k = 17) and PTSD symptom (k = 12) studies. Across fear learning studies, higher estradiol was consistently associated with enhanced fear extinction recall and inconsistently and weakly associated with better extinction learning and fear acquisition, respectively. Extending to PTSD symptoms, the association with hormonal status was reversed, such that luteal phase, associated with higher estradiol and progesterone, was generally associated with higher re-experiencing symptoms. Overall, human fear learning studies were consistent with rodent studies. Despite strong experimental links between fear learning processes and PTSD, the clinical translation was inconsistent and may reflect varying methods, imprecise measurement, and greater complexity of hormonal effects on symptomatology.