A randomized, double-blind, placebo-controlled trial of Chinese herbal medicine granules for the treatment of menopausal symptoms by stages

Objective:The study aims to evaluate the effectiveness and safety of Chinese herbal medicine granules Danzhi Qing'e formula (DZQE), Erzhi formula (EZ), and their combination (Combined formula) in the treatment of menopausal symptoms at different stages of menopause.Methods:Women between the ages of 40 to 60 years, who met menopausal symptoms diagnostic criteria and experienced hot flushes at least 14 times/week in the last 4 weeks, were recruited to participate in a stratified randomized, double-blind, placebo-controlled clinical trial (n=389). They received a treatment period of 8 weeks and were followed up for 4 weeks. Participants were categorized into two subgroups: 197 in the perimenopausal subgroup (menstrual disorder to 1y after amenorrhea) and 192 in the early postmenopausal subgroup (1-5y after amenorrhea). Participants were randomly assigned to placebo or one of the three herbal formula treatments. The primary outcome instrument was the Menopause-Specific Quality of Life (MENQOL) questionnaire.Results:When analyzing the two subgroups together, DZQE markedly decreased the MENQOL total score at the end of 12th week with statistical significance (P=0.02) and improved vasomotor symptoms after 8 weeks treatment and 4 weeks follow-up (P<0.05). What is more, the combined formula also greatly improved the participants' vasomotor symptoms compared with placebo after the 4 weeks follow-up. No statistically meaningful difference was observed in any other outcomes among the groups. The results of subgroup analysis showed that DZQE and Combined formula were more effective than placebo in improving MENQOL total score for perimenopausal women at the end of week 12. For typical menopausal symptoms such as hot flushes and night sweats, DZQE displayed more favorable effects on early postmenopausal participants. Compared to placebo, the DZQE both showed statistically significant differences after 8 weeks treatment and 4 weeks follow-up. Although at the end of 12th week, DZQE also had better effects than placebo in the perimenopausal subgroup on vasomotor symptoms. Participants in the EZ group did not show a significant difference of any domains in MENQOL compared with participants in the placebo group.Conclusions:The DZQE formula improves the quality of life for menopausal women, especially for those with vasomotor symptoms during the whole menopausal period. The DZQE and EZ combination formula is effective only on perimenopausal symptoms.