An alternative theory for hormone effects on sex differences in PTSD: The role of heightened sex hormones during trauma

Women are at least twice as susceptible to developing post-traumatic stress disorder (PTSD) compared to men. Although most research seeking to explain this discrepancy has focussed on the role of oestradiol during fear extinction learning, the role of progesterone has been overlooked, despite relatively consistent findings being reported concerning the role of progesterone during consolidation of emotional and intrusive memories. In this review article, we outline literature supporting the role of progesterone on memory formation, with particular emphasis on potential memory-enhancing properties of progesterone when subjects are placed under stress. It is possible that progesterone directly and indirectly exerts memory-enhancing effects at the time of trauma, which is an effect that may not be necessarily captured during non-stressful paradigms. We propose a model whereby progesterone's steroidogenic relationship to cortisol and brain-derived neurotrophic factor in combination with elevated oestradiol may enhance emotional memory consolidation during trauma and therefore present a specific vulnerability to PTSD formation in women, particularly during the mid-luteal phase of the menstrual cycle.