Molecular neuroimaging of ovarian steroid effects on the female brain: A systematic review of human non-clinical studies.

Molecular neuroimaging is a powerful tool for studying ovarian steroid effects on the brain. We systematically reviewed non-clinical studies of female reproductive transitions, ovarian suppression, or estradiol (E2) and/or progesterone (P4) administration. Most studies used ≤3T [¹H]MRS to study neurometabolites or PET imaging of glucose metabolism and serotoninergic activity. Results suggest ovarian steroids dynamically influence neurometabolic activity and serotonin neurotransmission. Elevated E2, whether during the late follicular phase or with postmenopausal administration, enhanced glucose-related metabolic activity and excitatory serotonin signaling, while low postmenopausal E2 may shift metabolism away from glucose for energy production. Rising P4, whether during the luteal phase or with postmenopausal administration, attenuated regional energy storage potential and glucose metabolism, while amplifying excitatory serotonin signaling. The perinatal transition was less studied, mostly with [¹H]MRS, and showed non-significant or transient effects. Studies examining outcomes related to neuroprotection, neuroinflammation, and hormone receptor density were limited. We highlight the need for further molecular neuroimaging, including multimodal approaches, to systematically characterize ovarian steroid targets and their molecular context. Advances in MRS and PET offer opportunities to study ovarian steroid effects on neuroplasticity, mitochondrial function, neuroprotection, and neuroinflammation, and there is a need for continued robust prospective longitudinal and experimental studies.