Table 2.
Summary of E2’s Neurobiological Activity During the MT
| Preclinical | Translational | ||||||
|---|---|---|---|---|---|---|---|
| Domain | Mechanism | Summary | E2 Changes | Citation | Summary | E2 Changes | Citation |
| Neurotransmitters | Serotonin | ↑ TPH-2 transcription → ↑ serotonin; ↓ MAOA; SERT regulation | OVX ↓ serotonin; E2 restores | (59–66)2/10/2026 5:10:00 PM | MAO-A ↑ in perimenopause; mixed SERT findings | Limited effect of E2 on receptor binding | (57,67–69,69–71) |
| Dopamine | ↑ TH activity; DAT & D2 receptor modulated by E2 |
OVX ↓ DA markers; E2 restores | (58,72–76) | No D2 change across cycle; HT ↑ DAT | Hormonal contraceptives ↑ DA synthesis | (77–81) | |
| GABA | E2 reduces GABA inhibition; regulates GABA genes | OVX ↑ GABA receptor density; E2 reverses | (82–88) | MRS: ↓ GABA+ in medial PFC during MT | No correlation with circulating E2 | (89–91) | |
| Glutamate | ↑ Glutamatergic transmission; ER-mGluR signaling | OVX ↓ Glu neurons; E2 restores | (58,92–94) | MRS: ↓ Glu in medial PFC during MT | Postmenopause ↓ Glu | (90,95–97) | |
| Neuroimmune | Anti-inflammatory | Suppresses microglia; ↓ cytokines; modulates T cells | OVX ↑ inflammatory mediators; E2 restores | (103–111) | TSPO ↑ with age; E2 mitigates systemic inflammation | Sparse MT-specific data | (112–114) |
| Neurometabolic | Glucose metabolism | ↑ GLUT1/GLUT3; ↑ mitochondrial efficiency | OVX → hypometabolic state; E2 restores | (116–119) | PET: ↓ glucose metabolism postmenopause; HT protective | Greater decline in women vs men | (120–125)2/10/2026 5:10:00 PM |
| Synaptic Plasticity | Spine density | ↑ dendritic spines in hippocampus; cyclic fluctuations |
OVX ↓ spine density; E2 restores | (126–131) | MRI: E2 ↑ hippocampal gray matter volume | PET synaptic density studies lacking | (132) |