升麻在中国和美国的不同命运
升麻“ black cohosh ”用于治疗女性更年期综合征的研究，在中国和美国的结果十分不同。升麻制品（如希明婷片，山东绿叶制药有限公司）在中国的研究中安全有效。总有效率达到81．01% （文1和文2，及山东绿叶制药有限公司对希明婷片的介绍［文3］和新闻［文4］［文5］）。而目前美国的临床实验证实black cohosh制品对hot flashes无效（[［文6］－［文7］）。在美国fda网站查black cohosh，多为对销售商的警告信。
［文1］：
希明婷片治疗女性更年期综合征的临床研究
薛赛琴 1 姜 坤 1 张 琼 2
摘要 目的 观察希明婷片治疗女性更年期综合征的有效性和安全性。 方法 采用多中心、随机、双盲、安慰剂平行对照研究方法，将 492 例女性更年期综合征患者随机分入试验组和安慰剂对照组，观察治疗前后烘热汗出、烦燥易怒等更年期综合征相关症状评分的改变，以及生命体征、血尿便常规、心电图、肝肾功、激素水平（ e 2 、 fsh ）的变化。 结果 治疗后试验组主症烘热汗出、烦躁易怒，次症失眠、胁痛、头晕耳鸣、腰膝酸痛、忧郁寡欢以及症状总积分改善程度均优于安慰剂对照组，差别具有统计学意义（ p<0.01 ）。治疗前后生命体征、血尿便常规、心电图、肝肾功、激素水平（ e 2 、 fsh ）的改变两组间差别无统计学意义（ p>0.05 ）。 结论 希明婷片治疗女性更年期综合征是安全的、有效的。
关键词 希明婷片、升麻、更年期综合征
a clinical study of ximingting tablets in the treatment of women with climacteric syndrome xue sai-qin ， jiang kun ， zhang qiong. et al xi yuan hospital of china academy of traditional chinese medicine ， beijing （ 100091 ）
objective to observe the efficacy and safety of ximingting tablets in the treatment of women with climacteric syndrome. methods this was a multi-centered, randomized, double-blind and placebo controlled trial. four hundred and ninety-two patients with climacteric symptoms were randomly assigned into two parallel groups, the investigated group and the placebo-controlled group. the climacteric symptoms such as hot flushes, sweating, irritation were studied before and after the treatment. the changes of vital life signs, blood routine, urine routine, stool routine, electrocardiogram, liver and kidney functions, and hormones （ e 2 ， fsh ） were also assessed. results the improvement of the primary symptoms after the treatment, such as hot flushes, sweating, irritation and secondary symptoms of insomnia, pain in ribs, tinnitus and vertigo, arthralgia and myalgia, and depression in the investigated group, was superior to those symptoms in the placebo controlled group. the difference was statistically significant （ p<0.01 ） .the changes of vital life signs, blood routine, urine routine, stool routine, electrocardiogram, liver and kidney functions, and hormones （ e 2 ， fsh ） in the two groups showed no statistical difference （ p>0.05 ） . conclusion ximingting tablets was efficacious and safe for the treatment of women with climacteric syndrome.
key words ximingting tablets ； rhizoma cimicifugae ； climacteric syndrome
希明婷片是从西升麻（ c.foetida l. ）中提取的以三萜皂苷为主要成分的植物药，是由中国医学科学院药用植物研究所和山东绿叶制药有限公司联合研制的治疗女性更年期综合征的二类新药，为验证其有效性和安全性，受国家食品药品监督管理局委托， 2003 年 2 月～ 9 月，我院作为负责单位对该药进行了临床研究，现将研究结果报告如下。
作者单位： 1. 中国中医科学院西苑医院妇科； 2. 中国中医科学院临床药理 （北京 100091 ）
通讯作者：薛赛琴 010 － 62875599 － 6452
［文2］：
现代妇产科进展
progress in obstetrics and gynecology
2006 vol.15 no.12 p.934-936
希明婷片治疗妇女围绝经期综合征的临床观察
张丹 徐克惠 段秀蓉
摘 要：目的:探讨希明婷片治疗妇女围绝经期综合征的有效性和安全性.方法:采用多中心、随机、开放、阳性对照研究方法,将60例围绝经期综合征患者随机分为实验组和对照组(倍美力组),应用kupperman index量表,评价治疗前后潮热多汗、烦燥易怒、失眠等围绝经期症状评分值的改变及患者治疗前后血常规、尿常规、肝肾功能、激素水平、b超等变化.结果:治疗后两组患者的潮热多汗、烦燥易怒、失眠等症状总积分均低于治疗前,差异有统计学意义(p＜0.05),两组间差异无统计学意义(p＞0.05);治疗前后血常规、尿常规、肝肾功、血雌激素(e2)、卵泡刺激素(fsh)、子宫内膜厚度等改变两组患者均无统计学意义(p＞0.05).结论:希明婷治疗妇女围绝经期综合征有效安全.
关键词：希明婷片;升麻类药;围绝经期综合征
分类号：r711.51 文献标识码：a
文章编号：1004-7379(2006)12-0934-03
the efficacy and safety of ximingting tablets in the treatment of women with menopausal syndrome
zhang dan xu kehui duan xiurong
作者简介：张丹(1965-),男,四川大学华西第二医院妇产科,副教授.主要研究方向:妇科肿瘤及妇科内分泌.
作者单位：张丹（四川大学华西第二医院,成都,610041）
徐克惠（四川大学华西第二医院,成都,610041）
段秀蓉（四川大学华西第二医院,成都,610041）
［文3］：
山东绿叶制药有限公司
希明婷片
产品特点
希明婷片是由山东绿叶制药有限公司生产的国家二类新药，经先进生产工艺从升麻中提取而成，是以三萜皂苷为主要成份的纯天然植物制剂，与本品成分相同的制剂早在 20 世纪 60 年代就已经在欧洲上市，目前德国市场上的产品如“ remifemin ”、美国的“ black cohosh ”均为升麻制品，广泛受到医学界人士的欢迎。
纯天然植物制剂，不含有雌激素： 升麻是一种多年生草本植物，升麻提取药物主要来源于它的根茎部分，三萜皂甙是升麻中最主要的生物活性成份，不含有雌激素成份，在治疗围绝经期症状中具有相当的安全性，避免了 hrt 对乳腺和子宫内膜诱发癌变的风险，是一类安全且有效的 hrt 的替代用药。
疗效确切可靠： 升麻提取药物在国内外临床研究资料十分丰富，大量临床研究表明，该产品能有效治疗女性围绝经期综合征，连续使用 3-6 个月，对缓解围绝经期妇女睡眠障碍、情绪障碍和潮热等方面疗效显著。
安全性好： 服用升麻提取升级物妇女中，仅约 7% 出现轻微的胃肠道不适、头晕、头痛的副反应，减量后症状消失，没有严重的不良反应，也没有与其他药物之间相互作用产生毒性反应的报道。
http://www.luye-pharm.com/
［文4］
围绝经期研究进展研讨会暨希明婷片上市会在重庆举行
阚士雪
2007年4月20日，绿叶制药在重庆隆重召开了围绝经期综合症治疗新药希明婷片上市会，重庆地区妇产科专家90余人参加了本次会议。
重庆市医学会妇产科专委会主任委员、我国著名妇产科专家姚珍薇教授主持会议。中华妇科内分泌专业组组长、北京协和医院妇产科知名专家林守清教授及复旦大学妇产科医院的程从娟教授也分别向大家介绍了希明婷片的临床研究结果。结果显示，希明婷片用于围绝经期综合症的治疗，不仅具有良好的疗效，而且拥有较高的安全性，得到了与会专家的一致认可和好评。
2007年5月8日 http://www.luye-pharm.com/htm/newbrown.asp?newcode=880
［文5］
希明婷片卫星会在昆明成功召开
赵恺
2006年12月2日-5日，我公司在昆明参加了由中华医学会举办的第二次全国绝经相关问题高级学术研讨会。会议期间，公司专门组织了希明婷片的大型卫星会，这次卫星会是希明婷片在全国妇科界专家面前的首次正式亮相。
希明婷片卫星会由北京协和医院著名教授张以文主持，张以文教授和林守清教授是国内非常知名的妇科专家，在妇科内分泌和妇科保健领域都有很高的国际地位。 会上，林守清教授和上海复旦大学附属妇产科医院的程从娟教授分别向大家介绍了希明婷片的医学临床研究情况，并对希明婷片严谨的临床研究方案及良好的疗效给予了高度评价。主讲专家认为，希明婷片既安全又有效，其上市将极大满足更年期综合征患者治疗的需求。与会嘉宾和专家对希明婷片表现出了浓厚的兴趣和信心，整个会议过程紧凑，气氛热烈。本次研讨会的成功举办，为希明婷片的进一步推广打下了良好的基础。http://www.luye-pharm.com/htm/newbrown.asp?newcode=861
［文6］
J Clin Oncol. 2006 Jun 20;24(18):2836-41. Links
Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1.
Pockaj BA, Gallagher JG, Loprinzi CL, Stella PJ, Barton DL, Sloan JA, Lavasseur BI, Rao RM, Fitch TR, Rowland KM, Novotny PJ, Flynn PJ, Richelson E, Fauq AH.
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
PURPOSE: Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. METHODS: A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. RESULTS: Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. CONCLUSION: This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.
PMID: 16782922 [PubMed - indexed for MEDLINE]
［文7］
BMJ 2005;331:924 (22 October), doi:10.1136/bmj.331.7522.924-b
News roundup
Popular herbal remedy for hot flushes is no better than placebo
Abergavenny Roger Dobson
The widely used herbal remedy black cohosh offers little relief from menopausal hot flushes, a new US study shows.
The researchers found no significant differences between women using herbal products and those using placebo in the frequency or intensity of hot flushes (Maturitas 2005;16:134–46).
"Given the serious health risks associated with hormone therapy, we were disappointed to discover that a popular herbal alternative appears to be no more effective than the placebo," said Katherine Newton, lead researcher on the herbal alternatives for menopause study. "Regrettably, we found that black cohosh has little potential to play an important role in the relief of vasomotor symptoms."
The authors of the study, who point to recent studies showing that hormone therapy can cause serious health risks, say the use of herbs, supplements, and dietary soyabean products for menopausal symptoms has grown dramatically but that little evaluation of the products has taken place.
In the study to compare herbal products for menopausal symptoms with placebo and hormone therapy the authors enrolled 351 women aged 45 to 55 whose periods had become irregular or had ceased and who were experiencing moderate to severe hot flushes.
The researchers, from four institutions in Seattle—the Group Health Cooperative, the University of Washington, the Fred Hutchinson Cancer Research Center, and Bastyr University—compared black cohosh, placebo, and hormone therapy.
The women, who were enrolled between 2001 and 2004, were randomly assigned to one of five regimens for a period of one year: black cohosh; a multiple botanical supplement containing 10 different herbs, including black cohosh; the same multibotanical supplement together with counselling to increase dietary soya; hormone therapy (Premarin or Prempro); and placebo.
The participants kept diaries, recording the frequency and intensity of their hot flushes at the start of the trial and at three, six, and 12 months.
The results, presented at a meeting of the North American Menopause Association, show that at three months the diary records were showing that frequency of hot flush decreased by 35% with black cohosh, 15% with the multibotanical, 30% with the multibotanical plus dietary counselling, 21% with the placebo, and 88% with hormone therapy. The findings were similar at six and 12 months.
The same pattern was found when the researchers used a menopause symptom score. At three months, the frequency of hot flushes decreased 27% with black cohosh, 14% with the multibotanical, 23% with the multibotanical plus soy, 15% with the placebo, and 76% with hormone therapy. The findings were also similar at six and 12 months.
The authors, whose study was funded by a grant from the National Institute on Aging and the National Center for Complementary and Alternative Medicine, say that the differences between the herbal regimens and the placebo were not significant but that the difference between the hormone therapy group and the other groups was considered important.
［文8］
Harv Womens Health Watch. 2007 Mar;14(7):5.Links
Hot flash herb no better than placebo in large trial.
[no authors listed]
PMID: 17393591 [pubmed - indexed for medline]
［文9］
Ann Intern Med. 2006 Dec 19;145(12):869-79. Links
Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.
Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J.
Group Health Center for Health Studies, the University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, Washington 98101, USA. newton.k@ghc.org
BACKGROUND: Herbal supplements are widely used for vasomotor symptoms. OBJECTIVE: To test the efficacy of 3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo. DESIGN: 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004. SETTING: Group Health, Washington State. PARTICIPANTS: 351 women age 45 to 55 years with 2 or more vasomotor symptoms per day; 52% of the women were in menopausal transition and 48% were postmenopausal. MEASUREMENTS: Rate and intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor Symptom Subscale. INTERVENTIONS: 1) Black cohosh, 160 mg daily; 2) multibotanical with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo. RESULTS: Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale score did not differ between the herbal interventions and placebo at 3, 6, or 12 months or for the average over all the follow-up time points (P > 0.05 for all comparisons) with 1 exception: At 12 months, symptom intensity was significantly worse with the multibotanical plus soy intervention than with placebo (P = 0.016). The difference in vasomotor symptoms per day between placebo and any of the herbal treatments at any time point was less than 1 symptom per day; for the average over all the follow-up time points, the difference was less than 0.55 symptom per day. The difference for hormone therapy versus placebo was -4.06 vasomotor symptoms per day for the average over all the follow-up time points (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001). LIMITATIONS: The trial did not simulate the whole-person approach used by naturopathic physicians. Differences between treatment groups smaller than 1.5 Vasomotor symptoms per day cannot be ruled out. CONCLUSION: Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms. Clinical Trials Registration number: NCT00169299.
［文10］
Menopause. 2007 Jul 6;Publish Ahead of Print [epub ahead of print] Links
Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study.
Reed SD, Newton KM, Lacroix AZ, Grothaus LC, Grieco VS, Ehrlich K.
From the 1Group Health Center for Health Studies, Seattle, WA; Departments of 2Obstetrics and Gynecology and 3Pathology, University of Washington School of Medicine, Seattle, WA; and 4Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA.
OBJECTIVE:: To evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT). DESIGN:: This was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared. RESULTS:: The five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point. CONCLUSION:: Black cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.