Study On The Treatment On Decreased Ovarian Reserve(Deficiency Of Kidney And Spleen,insuff Iciency Of Blood)with Qilin Pills

BackgroundDecreased ovarian reserve affect increasing number of women nowadays and often impact physical,psychological,sexual,and overall wellbeing.However,modern medicine has not offer accepted effective therapies and chronical application of hormone therapies has potential risks.It has been reported that“invigorating kidney and spleen”is effective in remedying menstrual disorder and benefit to ovarian reserve.Kirin Pill which is composed of 15 herbs is widely used in clinic to regulate menstruation,improve ovarian reserve,and its achieves excellent curative effect,but there is still no definite data to back up its effectiveness.MethodThis randomized,single-blinded,positive drug controlled,multiple-centers trial assessed the effectiveness of“invigorating kidney and spleen”therapies on decreased ovarian reserve.Eligible participants were women aged 18-39 years,conforming to criterion of Chinese and modern medical diagnosis,who was willing to participate in this trial and accept following-up.Participants received 3 menstrual cycles of Qilin pills(6g,orally,twice daily)or Tiaojingcuyun pills(6g,orally,twice daily)in random order.Randomization was completed by a central computer,and participants were allocated in the light of number in numerical order.The outcomes were the ovarian reserve testing,menstrual condition,and other symptoms concerning to asthenia of both the spleen and kidney.Analysis adopting full analysis set,per protocol set were completed by SAS9.2 software.The trial is registered at Chinese Clinical Trial Registry Center,numbered ChiCTR-IPR-17012824.Result1.Basic information of the study A total of 10 hospitals participated in this study.From April 10,2018 to December 21,2018,there were 120 participants involved but 18 of them were lost.The total number of FAS,PPS and SS data sets was 92,92 and 115,respectively.Based on FAS and PPS data sets,demographic data and safety indicators were analyzed respectively finding out comparability between groups.The results showed that other indicators were comparable except for age.There was no significant difference in the total dose of drugs taken by patients between the two groups.2.Ovarian reserve evaluationIn the FAS and PPS data set,under the condition of baseline AMH<1.4ng/ml,AMH value after treatment was significantly higher than that before treatment(p<0.05).Taking the change rate(Hormone value in visiting 4-basic value)/basic value X 100%)as dependent variable,considering the hormone baseline value,age and center effect,the covariance analysis is carried out.The change rate of AMH value of the group of Tiaojingcuyunpills was 78.49%(95%confidence interval:-156.72%?-0.26%)lower than that of Qilin pill.After treatment,the level of FSH in Qilin pill group lower than those before treatment,while E2 value rise.Also there was no significant difference between the two groups before and after treatment.3.Evaluation of TCM Syndrome scoreIn FAS and PPS data set,using LOCF method,the scores of TCM syndromes in both groups were significantly improved compared with those before treatment(p<0.05).Logistic regression analysis showed that after taking medicine for 1 month,removing the effect of age,the effective rate of TCM syndromes in Qinlin pill group was 1.88 times(95%confidence interval:1.181?7.022)higher than that of Tiaojingcuyun pill group.That rate in Visit3,Visit4 and Visits were no statistical different.4.Analysis of regulative effect of menstruationIn the FAS and PPS data set,using LOCF method,the analysis showed that the total effective rate was 47.83%in the group of Tiaojingcuyunwan pill group after taking drugs of 3 menstrual cycles.The total effective rate of Qilin pill group was 43.48%.Logistic regression analysis showed that the effective rate of regulating meridian between the two groups was the same after excluding the influence of age factor.5.Evaluation of safety analysisThe safety analysis was based on SS data set(58 cases in Tiaojingcuyun pill group and 57 cases in Qilin pill group).In this study,66 adverse events occurred in 46 subjects,of which 25 cases occurred 35 times in Tiaojingcuyun pill group and 31 cases in Qilin pill group.There was no significant difference between the two groups.In terms of serious adverse events,there were 2 cases of severe adverse events in 2 subjects,including 1 case in Tiaojing and 1 case in Qilin pill group.There was no significant difference between the two groups.There are no serious adverse reactions in the serious adverse events that occur.Conclusion1.This study was successfully completed the admission and follow-up of participants involved.There was comparability between the experimental group and the control group,and the total dosage taken by participants in different groups was similar.2.Under the condition of baseline AMH<1.4ng/ml,taking Qilin pills for 3 months effectively increased the level of AMH.After taking the drug for 3 months,Qilin pills were superior to Tiaojingcuyun pills in improving AMH.3.Taking Qilin pills for 3 months can effectively improve TCM syndromes.After 1 month menstrual cycle,the effective rate of TCM syndromeimprovement in Qilin pill group was better than that in Tiaojingcuyun pill group.4.Taking Kirin pills for 3 months can effectively improve menstruation,and the effect is the same as that of Tiaojingcuyun pregnancy.5.In this study,there were no definite toxic reactions and side effects of Qilin pills and Tiaojingcuyun pills.6.Qilin pill is effective in improving ovarian reserve,menstruation and TCM syndromes,and this kind of treatment has high safety and few side effects.So,it should be further popularized in clinic.