Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo

Context Caution about taking estrogen for treating postmenopausal vasomotor symptoms has led to increasing substitution of herbal regimens despite few tests of their effectiveness. Contribution The authors randomly assigned 351 perimenopausal or post... show more

Context Caution about taking estrogen for treating postmenopausal vasomotor symptoms has led to increasing substitution of herbal regimens despite few tests of their effectiveness. Contribution The authors randomly assigned 351 perimenopausal or postmenopausal women to herbal treatments (black cohosh, multibotanicals, or multibotanicals plus counseling about dietary soy), estrogen with or without progesterone, or placebo. At 3, 6, and 12 months, patients receiving the herbal interventions had the same change in vasomotor symptoms as those receiving placebo (except for more severe symptoms at 12 months for patients taking multibotanicals plus dietary soy). Estrogen substantially decreased vasomotor symptoms. Cautions Most participants were white and were well-educated. Implications Herbal regimens did not reduce postmenopausal vasomotor symptoms in this sample of women. The Editors Hormone therapy remains the recommended treatment for vasomotor symptoms, but trials have shown serious risks with even short-term use (1, 2). The use of herbs, particularly black cohosh, multibotanical supplements, and dietary soy for menopausal symptoms has grown dramatically (36). Few of these approaches have been scientifically evaluated. Women and providers are seeking safe, effective alternatives to hormone therapy. We designed the Herbal Alternatives for Menopause Trial (HALT) to provide rigorous evidence on the efficacy and short-term safety of commonly used naturopathic approaches for management of vasomotor symptoms. Methods Design Overview and Setting HALT was a 1-year double-blind, randomized, controlled trial designed to investigate the effects of 3 naturopathic approaches for vasomotor symptom relief and hormone therapy compared with placebo. Study methods have been described elsewhere (7). The Group Health Institutional Review Board approved this study, and a data and safety monitoring committee monitored it. The study was conducted at Group Health, an integrated health plan in Washington State. Participants Eligibility criteria were as follows: age 45 to 55 years; late menopausal transition (1 skipped menses within the preceding 12 months) or postmenopausal (no bleeding within 12 months, or follicle-stimulating hormone level> 20 IU/mL if patient had undergone hysterectomy without bilateral oophorectomy); and 2 or more vasomotor symptoms per day over 2 weeks (6 moderate to severe symptoms). Women in menopausal transition were included because many are highly symptomatic and trial data are lacking for this group. Exclusion criteria were the following: contraindications to hormone therapy; use of hormone therapy or oral contraceptives within 3 months before the trial; use of herbal medicines for menopausal symptoms within 1 month before the trial; soy allergy; bilateral oophorectomy; history of breast cancer; and nonadherence during the run-in period (<80% of capsules taken). From May 2001 through August 2003, women were recruited by using direct mail. Screening calls determined initial eligibility. Women attended an orientation visit at which eligibility was confirmed, physical measurements were collected, and placebo medication and questionnaires for the 2-week run-in period were provided. Randomization and Interventions Participants were randomly assigned by using SAS software (SAS Institute, Inc., Cary, North Carolina), stratified by previous hormone therapy and hysterectomy; block sizes within strata ranged from 5 to 25. Treatment assignments were sent to the University of Washington Research Pharmacy, where medications were bottled and labeled with a sequential identification number without treatment group indication. At the randomization visit, vasomotor symptom diaries and medication counts were examined to confirm eligibility and adherence. The study nurse determined the appropriate stratum, assigned the participant the next study number in that stratum without knowledge of group assignment, and distributed study medications. The publication of results from the Women's Health Initiative (WHI) estrogenprogestin trial (2) raised new concerns about the safety of estrogen therapy. New study participants were given the choice of 5-arm (including hormone therapy) versus 4-arm (no hormone therapy) randomization. Current participants gave consent again, incorporating risk estimates from the WHI, and were given the option of finding out whether they had been assigned to hormone therapy; 16 were unblinded, 1 discontinued use of the study drug, and all remained enrolled. Following publication of the WHI Memory Study (8, 9), we informed participants of those findings and restricted randomization to herbs and placebo. No further women were unblinded or discontinued use of the study drug. Naturopathic medicine provided the model for study interventions. The herbal products, doses, and soy diet were based on approaches used by naturopaths when the study was designed (7). The study groups were as follows: 1) black cohosh (Actaea racemosa or Cimicifuga racemosa, 160 mg daily; 2.5% triterpene glycosides; 70% ethanol extract); 2) multibotanical; 3) multibotanical plus soy diet counseling; 4) conjugated equine estrogen, 0.625 mg daily, with (for women with a uterus) or without (for women without a uterus) medroxyprogesterone acetate, 2.5 mg; and 5) placebo. The multibotanical delivered daily doses of the following: black cohosh, 200 mg; alfalfa (Medicago sativa), 400 mg; boron, 4 mg; chaste tree (Vitex agnus-castus), 200 mg; dong quai (Angelica sinensis), 400 mg; false unicorn (Chamaelirium luteum), 200 mg; licorice (Glycyrrhiza glabra), 200 mg; oats (Avena sativa), 400 mg; pomegranate (Punica granatum), 400 mg; Siberian ginseng (Eleutherococcus senticosus, standardized constituents 0.8% eleutherosides E and B), 400 mg. Black cohosh was provided by Pure World, Inc., (Hackensack, New Jersey). The multibotanical, ProGyne, was purchased from Progena Professional Formulations (Albuquerque, New Mexico) and encapsu show less