Efficacy and safety of Pueraria candollei var. mirifica (Airy Shaw & Suvat.) Niyomdham for menopausal women: A systematic review of clinical trials and the way forward.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria candollei var. mirifica (Airy Shaw & Suvat.) Niyomdham (commonly termed P. mirifica, PM) growing in upland Thailand has a long history as a postmenopausal rejuvenant therapy for indigenants. Its amelioration of menopause symptoms in clinical trials was assessed. MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines. RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores. CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.

Improvements of vaginal atrophy without systemic side effects after topical application of Pueraria mirifica, a phytoestrogen-rich herb, in postmenopausal cynomolgus macaques.

The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy, and the presence of any systemic side effects, were investigated in postmenopausal cynomolgus macaques. Twelve postmenopausal cynomolgus macaques, with complete cessation of menstruation for at least 5 years before start of this experiment, were divided into three groups. They received a topical vaginal application daily of 0.1 or 1% (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone, equilin, 17ß-dihydroequilin, 17α-estradiol and 17α-dihydroequilin at 0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma luteinizing hormone (LH) and sex skin coloration levels were determined at the end of each treatment period to evaluate the systemic side effects. PM significantly increased the proportion of superficial cells in a dose-dependent manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as observed in the CEE group. PM induced no detected systemic side effects, whilst CEE decreased the plasma LH level and increased the reddish color of the sex skin during the posttreatment period. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women.

Pueraria lobata (Kudzu root) hangover remedies and acetaldehyde-associated neoplasm risk.

Recent introduction of several commercial Kudzu root (Pueraria lobata) containing hangover remedies has occurred in western countries. The available data is reviewed to assess if there are any potential concerns in relationship to the development of neoplasm if these products are used chronically. The herb Pueraria has two components that are used as traditional therapies; Pueraria lobata, the root based herb and Pueraria flos, the flower based herb. Both of these herbal components have different traditional claims and constituents. Pueraria flos, which enhances acetaldehyde removal, is the traditional hangover remedy. Conversely, Pueraria lobata is a known inhibitor of mitochondrial aldehyde dehydrogenase (ALDH2) and increases acetaldehyde. Pueraria lobata is being investigated for use as an aversion therapy for alcoholics due to these characteristics. Pueraria lobata is not a traditional hangover therapy yet has been accepted as the registered active component in many of these hangover products. The risk of development of acetaldehyde pathology, including neoplasms, is associated with genetic polymorphism with enhanced alcohol dehydrogenase (ADH) or reduced ALDH activity leading to increased acetaldehyde levels in the tissues. The chronic usage of Pueraria lobata at times of high ethanol consumption, such as in hangover remedies, may predispose subjects to an increased risk of acetaldehyde-related neoplasm and pathology. The guidelines for Disulfiram, an ALDH2 inhibitor, provide a set of guidelines for use with the herb Pueraria lobata. Pueraria lobata appears to be an inappropriate herb for use in herbal hangover remedies as it is an inhibitor of ALDH2. The recommendations for its use should be similar to those for the ALDH2 inhibitor, Disulfiram.

Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women.

OBJECTIVE: To evaluate the preliminary efficacy and safety of Pueraria mirifica (Kwao Keur Kao), phytoestrogen, for the alleviation of climacteric symptoms. MATERIAL AND METHOD: Perimenopausal women attending with climacteric symptoms, such as hot flushes and night sweats, were invited to join the present study, conducted at the Menopausal Clinic, Hat Yai Regional Hospital. The patients were voluntarily enrolled and randomly received the raw material of Pueraria mirifica, oral 50 and 100 mg capsule, once daily for six months, as an open-label study. RESULTS: Of the 10 enrolled patients, 8 cases were completely evaluated. The modified Greene climacteric scale (MGCS) was satisfactorily decreased in both groups. The average scale declined from 44.1 at baseline, to be 26, 17, and 11.1 at 1-, 3-, and 6- month follow-up respectively. No other laboratory abnormalities, except one case had transiently increased the creatinine level, and one case of increased blood urea nitrogen. The mean serum estradiol was slightly increased, while the mean serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were nearly stable. CONCLUSION: Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal. women, but the data is insufficient to draw definite conclusions regarding the estrogenic effect.