Newton 2006.
| Methods | Design: randomised, double‐blind, placebo‐controlled, multicentre, parallel group trial Randomisation ratio: not stated Study duration: 25 months (from May 2001 to August 2003) |
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| Participants | Participant characteristics: 351 women were randomised (black cohosh = 80, multi‐botanical = 76, multi‐botanical plus dietary soy = 79, CEO and MPA = 32, placebo = 84), and 45 (12.8%) dropped out. Mean age (black cohosh = 52.0 ± 2.2 years, multi‐botanical = 52.2 ± 2.5 years, multi‐botanical plus dietary soy = 52.5 ± 2.5 years, CEO and MPA = 52.3 ± 2.6 years, placebo = 52.0 ± 2.5 years). Duration of menopause not stated Inclusion criteria: female, late menopausal transition (≥ 1 skipped menses in the last 12 months) or postmenopausal (no bleeding in the last 12 months) or FSH > 20 IU/mL (if participant had undergone hysterectomy without bilateral oophorectomy), aged between 45 and 55 years, and ≥ 2 vasomotor symptoms daily over the past 2 weeks (with ≥ 6 moderate to severe symptoms), negative mammogram in the last 2 years, normal thyroid stimulating hormone level Exclusion criteria: contraindications to HT, use of HT or oral contraceptives within the last 3 months, use of herbal medicines for menopausal symptoms within the last month, allergy to soy, bilateral oophorectomy, history of breast cancer, non‐adherence (< 80% of capsules administered) during the run‐in period Diagnostic criteria: not stated Co‐morbidities: not stated Co‐medications: not stated |
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| Interventions | Number of study centres: not stated Country/location: Washington state, US Setting: group health (an integrated health plan) Intervention (route, total, dose/day, frequency): oral ethanolic extract of Cimicifuga racemosa rhizome and root (CimiPure, 80 mg, standardised to 2.5% triterpene glycosides) 2 capsules daily; oral multi‐botanical (ProGyne, incorporating 50 mg C. racemosa extract) 4 capsules daily; multi‐botanical (ProGyne, incorporating 50 mg C. racemosa extract) 4 capsules daily plus soy diet counselling; oral CEO (0.625 mg) 1 tablet daily, with (for women with a uterus) or without (for women with a uterus) MDP (2.5 mg) 1 tablet daily Control (route, total, dose/day, frequency): oral placebo (dose and constitution is not described) Duration of intervention: 12 months (52 weeks) Duration of follow‐up: not applicable Run‐in period: 2 weeks Treatment before study: not applicable Titration period: not applicable |
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| Outcomes | Primary outcomes: mean Wiklund Vasomotor Symptom subscale score, hot flushes and night sweats (frequency and intensity), vaginal bleeding Secondary outcomes: daytime hot flush rate, night‐time sweat rate, total Wiklund Menopause Symptom Scale Score, vaginal dryness, menstrual cyclicly, vaginal cytology, serum FSH, serum LH, serum oestradiol, serum sex hormone binding globulin Additional outcomes: adverse events |
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| Notes | Newton 2006 and Reed 2008 report the same study, but different outcomes. This study reported change‐from‐baseline scores; final value scores were provided on request. Standard errors had to be converted to standard deviations to be suitable for the pooling of results | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "participants were randomly assigned by using SAS software, stratified by previous HT and hysterectomy; block sizes within strata ranged from 5 to 25" Comment: probably done |
| Allocation concealment (selection bias) | Low risk | Quote: "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" Comment: probably done |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Quote: "double‐blind"; "to facilitate blinding, medications and lactose placebo were encapsulated to provide 2 white and 2 blue capsules to each woman" Comment: probably done |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | "mixed‐model analysis allowed us to use a true intention‐to‐treat approach" Numbers of withdrawals were similar between groups, though reasons for withdrawal differed. 16 women were unblinded; however, numbers were not given for each group separately |
| Selective reporting (reporting bias) | Unclear risk | All primary and secondary outcomes listed were reported, although no study protocol was published or lodged |
| Other bias | Unclear risk | Baseline differences in BMI were observed |