Chinese Medicine for Menopausal Syndrome： Current Status, Problems and Strategies

The use of Chinese medicine （CM） for the management of menopausal syndrome is considered effective both at home and abroad, and more and more clinical studies are confirming its efficacy. However, many problems still exit in current studies, such as the standard of CM syndrome differentiation, the design methodology and criteria to assess the quality of clinical trials and the efficacy of interventions. In this paper, the authors present the CM research and treatment strategies for menopausal syndrome with concepts explaining the CM understanding of the mechanism of the disorder. It is concluded that CM is effective for menopausal syndrome, but improvement in both study methodology and treatment strategy is needed. In detail, it is firstly necessary to conduct clinical studies to evaluate the difference of various CM treatments for menopausal syndrome manifesting different symptoms, so as to establish a comprehensive treatment protocol of CM. Secondly,an acknowledged evaluation system needs to be founded, which embodies the characteristics of CM, and covers appropriate endpoint indices and parameters to objectively evaluate the effect and study quality of CM. Finally, an epidemiological survey with large sample size should be implemented with robust statistical design and CM expertise to collect data for establishing diagnostic criteria for menopause in different stages and with different symptoms.

Management of genitourinary syndrome of menopause in breast cancer survivors:An update

There is increasing attention about managing the adverse effects of adjuvant therapy(Chemotherapy and anti-estrogen treatment)for breast cancer survivors(BCSs).Vulvovaginal atrophy(VVA),caused by decreased levels of circulating estrogen to urogenital receptors,is commonly experienced by this patients.Women receiving antiestrogen therapy,specifically aromatase inhibitors,often suffer from vaginal dryness,itching,irritation,dyspareunia,and dysuria,collectively known as genitourinary syndrome of menopause(GSM),that it can in turn lead to pain,discomfort,impairment of sexual function and negatively impact on multiple domains of quality of life(QoL).The worsening of QoL in these patients due to GSM symptoms can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly.The diagnosis of VVA is confirmed through patient-reported symptoms and gynecological examination of external structures,introitus,and vaginal mucosa.Systemic estrogen treatment is contraindicated in BCSs.In these patients,GSM may be prevented,reduced and managed in most cases but this requires early recognition and appropriate treatment,but it is normally undertreated by oncologists because of fear of cancer recurrence,specifically when considering treatment with vaginal estrogen therapy(VET)because of unknown levels of systemic absorption of estradiol.Lifestyle modifications and nonhormonal treatments(vaginal moisturizers,lubricants,and gels)are the first-line treatment for GSM both in healthy women as BCSs,but when these are not effective for symptom relief,other options can be considered,such as VET,ospemifene,local androgens,intravaginal dehydroepiandrosterone(prasterone),or laser therapy(erbium or CO2 Laser).The present data suggest that these therapies are effective for VVA in BCSs;however,safety remains controversial and a there is a major concern with all of these treatments.We review current evidence for various nonpharmacologic and pharmacologic therapeutic modalities for GSM in BCSs and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research.We include recommendations for an approach to the management of GSM in women at high risk for breast cancer,women with estrogen-receptor positive breast cancers,women with triplenegative breast cancers,and women with metastatic disease.

Discussion on the mechanism of TCM treatment of climacteric syndrome based on TCM inheritance assistance system and network pharmacology

Background:To explore the law of traditional Chinese medicine in the treatment of climacteric syndrome,and to study the potential mechanism of traditional Chinese medicine therapy.Methods:For the relevant prescriptions collected from Chinese Journal Full-text Database,Wanfang medical network,PubMed and EMBASE were transferred to the traditional Chinese medicine inheritance assistant system(TCMISSV2.5)to conduct the nucleocentric drug group analysis.In this study,we used BATMAN-TCM(http://bionet.ncpsb.org/batman-tcm/)online analysis tool to analyze Therapeutic Target Database disease enrichment and Kyoto Gene and Genome Encyclopedia(KEGG)pathway enrichment,and Cytoscape(3.7.1)software was used to construct disease-target and KEGG pathway-target networks for visualization.Results:Among the 103 prescriptions,3 pairs of core drug combinations and 9 new prescriptions were selected by data mining.In the KEGG pathway of Zhimu(Anemarrhenae rhizoma)and Huangbo(Phellodendri Chinensis cortex),the most potential targets were found in the neural active ligand receptor interaction pathway.Conclusion:The compatibility of Anemarrhenae rhizoma and Phellodendri Chinensis cortex may play a role in the treatment of nervous system symptoms in patients with climacteric syndrome by interfering the neuroactive ligand receptor interaction signaling pathway.

The effect of Wujiadan Recipe on the role of PLC-β/IP3/CaM signaling pathway of hypothalamus in ovariectomized rats

Objective:To investigate the effect of Wujiadan Recipe on PLC-β1,IP3,IP3R,Cam,PLC-β1,IP3R1 mRNA and GnRH,Cam protein from hypothalamus tissue of ovariectomized female rats,and to further clarify whether Wujiadan Recipe plays a role through PLC-β/IP3/CaM signal pathway.Methods:We randomly divided 64 SD adult female rats into NG group(normal group),MG group(the model group),TMC group(the control group with traditional Chinese medicine),WMC group(the control group with western medicine)with 10 rats in each,and Wujiadan Recipe high(WH),Wujiadan Recipe medium(WM)and Wujiadan Recipe low dose group(WL)with 8 rats in each.Except the NG group,we removed the ovarian tissues of other six groups to establish the ovariectomized model.When the model is successfully replicated,we give the medicine to the rats in each group once a day.The TMC and WMC group were given the corresponding dose of Gengnian'an tablet suspension and Bujiale suspension by gavage respectively.The NG and MG group were given equal measure of normal saline.After 4 weeks,the rats were killed.We use ELISA to detecte the levels of PLC-β1,IP3,IP3R and Cam;and we use PCR to detecte the mRNA expression levels of PLC-βand IP3R1;and use WesternBlot to detecte the protein expression levels of Cam and GnRH in rat hypothalamus tissue.Results:The test results of PLC-β1,IP3,IP3R and Cam in the hypothalamus homogenate of the model group were significantly increased than the NG group(P<0.01).The results of PLC-β1 and IP3R1 and GnRHmRNA were significantly increased(P<0.01),and the expressions of GnRH and Cam protein were higher than NG(P<0.01).Wujiadan Recipe could reduce the results of PLC-β1,IP3,IP3R and Cam in hypothalamus of ovariectomized rats,and reduce the expression of PLC-β1 and IP3R1 and GnRH mRNA.Conclusion:Wujiadan Recipe down-regulates GnRH expression,which may be caused by acting on PLC-β1,IP3,IP3R,CaM in hypothalamus of ovariectomized rats,so as to coordinate the function of reproductive axis and improve the reproductive endocrine level of patients with menopausal syndrome.

The effect of Wujiadan Recipe on serum sex hormone and expression of Kiss-1, GPR54 and GnRH in arcuate nucleus of hypothalamus in ovariectomized rats

Objective:To explore the effect of wujiadan Recipe on the expression of FSH,E2 in serum and KiSS-1,GPR54,GnRH mRNA in hypothalamic arcuate nucleus tissue homogenate of ovariectomized rats,and to further explore the mechanism of wujiadan Recipe on menopausal syndrome.Methods:Sixty-four adult female rats were randomly divided into three groups:blank group,model group,Chinese medicine control group,western medicine control group,and wujiadan high,medium and low dose groups.Except for the blank group,all the other groups were ovariectomized.The rats in the normal group and the model group were given the same dose of saline once a day.One rat in the blank group died during the experiment.After 4 weeks of continuous administration,blood was collected from abdominal aorta and brain stereotaxic localization was performed to preserve the arcuate nucleus of hypothalamus.The levels of FSH and E2 in serum were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of Kiss-1,GPR54 and GnRH mRNA in arcuate nucleus of hypothalamus were detected by PCR.Results:1.Compared with the blank group,FSH level in the model group was significantly higher(P<0.01),and E2 level was significantly lower(P<0.01).Compared with the model group,the level of serum E2 in the western medicine control group increased significantly(P.The serum FSH content in each group decreased,especially in the high dose group and the western medicine control group(P<0.01),and in the Chinese medicine control group,the middle dose group and the low dose group(P<0.05).Compared with the blank group,the expression of KiSS-1 mRNA,GPR54 mRNA and GnRH mRNA in the model group increased significantly(P<0.01);compared with the model group,the expression of KiSS-1 mRNA and GPR54 mRNA in the high dose group,middle dose group and Western medicine control group of wujiadan prescription decreased significantly(P<0.05).Compared with the model group,the expression of GnRH mRNA in the high dose group and the western medicine control group decreased significantly(P<0.01);the middle dose group of wujiadan decreased significantly(P<0.05).Conclusion:Wujiadan recipe can improve the serum sex hormone level of castrated rats,and reduce the over expression of KiSS-1,GPR54 and GnRH mRNA in hypothalamic arcuate nucleus of castrated rats,which may be the reproductive endocrine mechanism of wujiadan recipe in the treatment of menopausal syndrome.

Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells

Menopausal metabolic syndrome(MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases(CVD) and type II diabetes mellitus(T2DM). Erzhiwan(EZW),composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan(JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized(OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet βcells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion(GSIS), which was abolished by estrogen receptor(ER)antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.

Hemorrhagic ovarian cyst without peritoneal bleeding in a patient with ovarian hyperstimulation syndrome: case report

Gynecologic and obstetric disorders presenting with abdominal pain are ectopic pregnancy,rupture of endometrial cysts, mature cystic teratoma and torsion of the adnexae. Hemorrhagic ovarian cysts, which included among the functional cysts, are often involved in acute abdomen leading to laparotomy intervention.

Erxian Tang (二仙汤)——Introduction of a Chinese Herbal Formula, Clinical Practice, and Experimental Studies

Erxian Tang （二仙汤, EXT） is a Chinese herbal formula developed for the treatment of menopausal syndrome in women. In the past 50 years, EXT has shown positive efficacy in the treatment of many chronic diseases in TCM, involving syndrome types of Shen （肾） yin-yang deficiency, yin-deficiency caused yang-flourishing, and disharmony of Chong-Ren meridian. Experimental studies have revealed that EXT has multiple pharmacological actions on such multiple targets as hypothalamus-pituitary-target gland axis, immune function and free radical metabolism, etc.