The estrogen system can influence anxiety through HPA axis mediation, and it can also regulate DA receptors, influence 5-HT, GABA, OT system [38], etc. Estrogen can activate the MAPK signaling pathway, PI3K-AKT signaling pathway, and adenylate cyclase (cAMP) by binding with estrogen receptors [42,43]. This evidence concerns the gene ESR1 and Anxiety.