Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

• Women are more vulnerable to anxiety and fear-related disorders than men.
• Estrogen levels can modulate fear and stress responses in women and female rodents.
• Stress affects the critical nodes of fear circuitry.
• Interactions between sex hormones, stress, and fear should be further examined.
• Treatment for anxiety and fear-based disorders should account for hormone status.

This article is part of a Special Issue “SBN 2014”.Women are more vulnerable to stress- and fear-based disorders, such as anxiety and post-traumatic stress disorder. Despite the growing literature on this topic, the neural basis of these sex differences remains unclear, and the findings appear inconsistent. The neurobiological mechanisms of fear and stress in learning and memory processes have been extensively studied, and the crosstalk between these systems is beginning to explain the disproportionate incidence and differences in symptomatology and remission within these psychopathologies. In this review, we discuss the intersect between stress and fear mechanisms and their modulation by gonadal hormones and discuss the relevance of this information to sex differences in anxiety and fear-based disorders. Understanding these converging influences is imperative to the development of more effective, individualized treatments that take sex and hormones into account.