Estradiol surges as dual-purpose mechanisms in evolutionary psychiatry: Neuroendocrine stabilization, stress regulation, and psychosis vulnerability
Background. Estradiol exerts protective effects against psychosis, yet its functional role across the reproductive cycle remains incompletely defined. Prior work demonstrates that estrogen modulates dopaminergic, serotonergic, and immune signaling pathways that influence cognition and psychiatric vulnerability. Central hypothesis. We propose that peri-ovulatory estradiol surges may reflect a selection-shaped neuroendocrine mechanism serving dual functions: enhancing mate-selection-relevant cognition while transiently buffering, defined here as transient stabilization of neural network activity in response to hormonal fluctuations, against psychosis vulnerability during peak fertility. In this framework, “evolutionary” refers to regulatory systems shaped by selection pressures across generations, rather than to reproduction itself. This model extends the estrogen protection hypothesis by situating cyclic estradiol signaling within an evolutionary psychiatry framework. Evidence synthesis and analysis. We further propose a dual-hormone buffering system in which estradiol’s excitatory and plasticity-enhancing effects are balanced by progesterone and its metabolite allopregnanolone, which regulate inhibitory tone and stress responsivity via GABA_A receptor signaling. Dysregulation or rapid withdrawal of either hormone may unmask latent vulnerabilities, contributing to psychiatric instability across reproductive transitions, including perimenstrual, postpartum, and perimenopausal states. Conclusion and translational implications. This coordinated hormonal system may have conferred adaptive advantages by stabilizing cognition and affect during critical reproductive phases. Disruption of this balance in modern contexts may increase vulnerability to psychiatric disorders. This model generates testable predictions and supports receptor-specific therapeutic strategies, including selective estrogen receptor modulators and neurosteroid-based interventions.