Efficacy of HongHuaXiaoYao Pill, a Chinese patent medicine, for treating perimenopausal syndrome: A multicenter randomized clinical trial

Background and purpose: HongHuaXiaoYao Pill (HHXYP) is a Chinese patent medicine used for the treatment of perimenopausal syndrome. However, its efficacy, safety, and mechanisms of action have not been comprehensively evaluated. This trial aimed to assess the efficacy, safety and possible mechanism of HHXYP in alleviating symptoms and quality of life of women with perimenopausal syndrome (PMPS). Materials and methods: This multicenter randomized controlled trial recruited PMPS participants between January 2022 and December 2023. Sixty participants were randomized 1:1 to receive HHXYP or oryzanol control (OC) for 12 weeks, followed by a 4-week post-treatment follow-up. The primary outcome was the modified Kupperman Index (KI) scores. Secondary outcomes included Hot Flash Scale (HFS), Menopause-Specific Quality of Life (MENQOL), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) scores, serum sex hormones, monoamine neurotransmitters and adverse events. Results: For primary outcome, HHXYP significantly reduced the KI scores for depression and dizziness compared with the OC group. Both groups of patients showed an improvement in HFS scores after treatment, but the difference between the groups was not statistically significant. For the MENQOL scores, both groups exhibited significant improvements in physical symptoms and overall scores. Compared with the OC group, HHXYP significantly reduced HAMD and HAMA scores, and HHXYP showed a greater increase in serum serotonin (5-HT) levels. Both HHXYP and OC significantly reduced follicle-stimulating hormone (FSH) levels, but there was no significant difference between the two groups. No serious adverse events were reported in either group. Conclusion: HHXYP may alleviate anxiety and depressive symptoms and improve quality of life in patients with PMPS. However, larger, adequately powered trials and further mechanistic research are needed to confirm its efficacy and elucidate the underlying mechanisms.