Clinical Trials And Basic Research On The Treatment Of Oligomenorrhea And Hypomenorrhea With Progesterone And Traditional Chinese Medicine For Replenishing Qi And Bloo

Part ⅠObjective:We aimed to evaluate the effectiveness of Chinese medicine Zhenqi Buxue Koufu Ye,Western medicine progesterone capsules,and a combination of the two in treating oligomenorrhea and hypomenorrhea.Methods:This was a prospective,randomized,multi-center clinical trial conducted between June 2022 to December 2022.Ninety-six oligomenorrhea and hypomenorrhea patients were randomly assigned to receive Zhenqi Buxue KoufuYe(ZQ,29 cases),progesterone capsules(PG,32 cases),or the combined Chinese and Western medicine(COM,31 cases)at a ratio of 1:1:1.Patients in the ZQ or PG group took daily 10 ml bid of Zhenqi Buxue KoufuYe,or 200 mg qd of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively,and patients in the COM group received the same Zhenqi Buxue Koufu Ye combined with progesterone capsules.The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment.Endpoints included the menstrual Traditional Chinese Medicine Syndrome Scale(TCMSS)scores and the total effective rate of TCM syndrome,pictorial blood loss assessment chart(PBAC)scores,clinical efficacy rate,36-item Short Form Health Survey(SF-36)scores,sex hormones and thickness of endometrium.Safety indicators were compared at baseline and after 3 months.Adverse events(AEs)were also recorded.Results:TCMSS scores after 1-and 3-month treatment in all groups were significantly lower than TCMSS scores at baseline(P<0.05).Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with scores after 1-month treatment in the same group(P=0.0013,P<0.001).TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group(P=0.044 and 0.008,respectively).The total effective rate of TCM syndrome of 3-month treatment was significantly improved in three groups compared with that after 1 month of treatment.The total effective rate of the COM group was the highest in the third month of treatment and significantly higher than that of progesterone capsules alone(P<0.0167).Compared with baseline,PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher(P=0.005 and 0.004,respectively).Compared with baseline,only the SF-36 scores of COM group were significantly better after 3 months of treatment(P<0.05).No significant changes in the safety indexes or serious adverse reactions were observed after treatment.Conclusions:The integration of ZQ and PG,or ZQ only had better effects on reducing TCMSS scores compared with PG,and COM showed the higher total effective rate compared with monotherapy.Besides,COM could effectively improve menstrual blood loss and the quality of life.ZQ combined with PG is an effective and safe option for oligomenorrhea and hypomenorrhea patients with Qi-blood and kidney essence deficiency.Part ⅡObjective The results of clinical trial showed that Zhenqi Buxue Koufu Ye combined with progesterone capsule is a safe and effective treatment for oligomenorrhea and hypomenorrhea.This part intends to further explore the mechanisms of the combination of Zhenqi Buxue KoufuYe and progesterone capsules in the treatment of oligomenorrhea and hypomenorrhea through liquid chromatography-tandem mass spectrometry(LC-MS).Methods Serum samples of subjects in three groups were collected before and after 3 months of treatment.LC-MS was used to further analyze the effects of treatment regiments on serum metabolites and metabolic pathways.Results All the three groups regulated the distribution of the VIP metabolites in the same direction,including down-regulating lysine and up-regulating phosphatidylcholine(PC),amino acids,diglycerol(DG)and polyunsaturated fatty acids.In addition,compared with the ZQ and PG groups after 3 months of treatment,the COM group showed more significant improvements in certain PC,phosphatidylcholine(PE),LPC and lysine metabolic derivatives.After 3 months of treatment,the levels of 105 metabolites were changed in the ZQ group,where the important target pathways included choline metabolism,glycerol phospholipid metabolism,insulin resistance.The levels of 102 metabolites were observed in the PG group after treatment,where mainly involved central carbon metabolism,protein digestion and absorption,lysine degradation.Both the ZQ and PG groups were also involved in autophagy,immune regulation,estrogen signaling pathway,adipocyte cytokine signaling pathway,adipocyte lipolysis and other metabolic pathways.The COM group changed the levels of 93 metabolites,which were mainly involved in choline metabolism,glycerol phospholipid metabolism,insulin resistance,central carbon metabolism,protein digestion and absorption,and lysine degradation.Conclusion The combination of Zhenqi Buxue KoufuYe and progesterone capsule can effectively and multi-dimensionally alleviate oligomenorrhea and hypomenorrhea.