Xiangshao granules regulate the dopaminergic synapse pathway and improve menopausal anxiety in peri- and postmenopausal Chinese women: A multi-center, double-blind, randomized controlled trial.

Anxiety is common among peri- and postmenopausal women, and many conventional treatments cause side effects. This multicenter, double-blind, randomized, placebo-controlled trial was conducted from December 2021 to June 2023 at 18 centers in China, enrolling 360 women aged 40‒65 years with menopausal anxiety. Participants were randomly assigned to receive Xiangshao granules (high-dose group, n = 180) or a placebo (very-low-dose group, n = 180) for 8 weeks. The primary outcome was the reductive ratio in self-rating anxiety scale (SAS) scores after 8 weeks, while secondary outcomes included the self-rating depression scale (SDS), Kupperman Index, and gastrointestinal symptom score (GIS). After eight weeks, the mean SAS reductive ratio was greater in the high-dose group than in the very-low-dose group (37.7% vs. 28.9%, P = 0.0052), and scores declined more in the high-dose than in the very-low-dose group, with a higher clinical improvement rate (69.8% vs. 56.9%, P = 0.0151). Although no significant between-group differences were observed for SDS, Kupperman Index, or GIS, all showed improvements from baseline. Adverse event rates were comparable. Transcriptomic analysis revealed modifications in the dopaminergic synapse pathway following Xiangshao treatment, while network pharmacology identified FOS, ATF2, and CREB1 as key dopaminergic pathway-related targets. Metabolomic data corroborated these findings. Collectively, Xiangshao granules safely and effectively alleviate menopausal anxiety, potentially by modulating dopaminergic signaling.