Evidence table 6-8. Key Question 3G-I complementary and alternative therapies

Specific Characteristics of PopulationTreatmentMain Outcomes
Study/YearNType of TrialComparisonLength of TrialPopulationInclusion/Exclusion CriteriaMeasures UsedHysterectomy (#/n)Bilateral Oophorectomy (#/n)Premature Ovarian Failure (#/n)Breast Cancer (#/n)Use of SERMS (#/n)Behavior or Lifestyle Factors (#/n)Recent discontinuation of HRT (#/n)High or Low BMI (#/n)Main Drug type; dose; regimenOther Drugs type; dose; regimenHot FlashesVaginal DrynessSleepMoodCognitiveSomaticUrinaryUterine BleedingSexual DysfunctionQuality of LifeOther OutcomesWithdrawalsWithdrawals due to AEsAdverse EffectsNCCAM CategoryComments
Aiello, 2004173RCTHH12 monthsPostmenopausal women recruited from the greater Seattle area (50–75 years of age) through mass mailings and media placements.Inclusion:Adherance to exercise via daily activity logs, food frequency questionnaire, information on menopause symptoms and their severity was collected at 0,3,6,9, and 12 months with a self-administered questionnaire, which was a modified version of a questionnaire used by the Women's Health Initiative, DEXA was conducted at baseline and 12 months for leanness13–18%NRNRNRNRNR35–38% had taken in the remote pastAverage was 30.5 and 30.6 in each group45 minutes of moderate-intensity exercise, 5 days/week for 12 monthsControl was invitation to attend 45 minute weekly stretching session for 12 monthsNo change in frequency over the yearNRNo change in either group over the yearNo change in depressive feelings in either group over the year (only 13% had a baseline)No change in either group over the year; when analyzed by time since menopause those within 5 years of menopause had a significant decrease in memory problems in the exercise group compared to the controls (OR at 6 mo=0.2; 95% CI, 0.08–0.6). This was sustained at 9 and 12 months.NRNRNRNRNRWhen analyzing the subset of moderate/severe menopausal symptoms (n=11 exercisers, 10 controls), a significant decrease in hot flashes was seen over the year in the control group (p=0.02 but not in the exercisers)6/87 in the exercise group; 2/86 controlsNoneNoneMind-bodyOnly RCT looking at exercise
Average age 60.7 and 60.6 SD (6.6 and 6.7years). Approximately 60% had some menopausal symptoms.1. Sedentary at baseline (<60 min/week of moderate-to vigorous exercise)
2. BMI>25.0 or over 24.0 with body fat>33%
Exclusion:
1. Taking HRT
2. Smoker
Albertazzi, 1998 &1999104RCTP12 weeksMean age 53, range of 48–61.Inclusion:Daily diary; Kupperman IndexNRNRNRNRAllowedNRHad to be off at least 6 weeksMean was 25.9 for both groups with range from 18–36Casein 60 grams daily for 12 weeksSoy powder (Supro Brand Protein Technologies, St. Louis, MO) 60 grams/day; this contained 76 mg of isoflavones (aglycone units)Hot flash reduction was seen in both group (43.6 % reduction in soy group compared with 31.3% reduction in placebo group). Soy group had greater reduction than casein group at 12 weeks (p<0.01)Vaginal maturation indices did not increase in the soy group, but did significantly increase in the casein groupNRNRNRNRNRNRNRNRKupperman index values as a whole did ‘not change’25/51; 11 in the soy group and 14 in the casein group14 patients, 7 in each group dropped due to gastrointestinal side effects; lack of efficacy caused 3 patients in the casein group and 1 person in the soy group to withdrawGastrointestinal - constipation 48%Biologically based therapies
Women postmenopausal requesting treatment for severe hot flushes.1. ≥ 6 months since the last menstrual period or ≥ 6 weeks since bilateral oophorectomy was performed
2. Seven moderate to severe hot flushes, including night sweats/24 hours during at least the last 2 weeks of the 4 week prestudy period
3. FSH>50 and estradiol <35
Exclusion:
1. HRT or any other drug for the treatment of climacteric symptoms, such as Vitamin E, clonidine, veralipride.
Anarte, 199873RCTHH6 months45–55 year old postmenopausal women with less than 3 years evolution, no previous treatment; all attending a Menopause Unit in Southern SpainNone reported other than population definition except that patients in whom hormonal treatment was contraindicated were excludedKupperman Index, plus the emotional alternation, anxiety and depression scales of the Granada Gynecological Questionnair of Salvatierra et al.NRNRNRThose with contraindication to HRT excludedNRNRNo previousNRTransdermal estrogen with cyclical progesteroneHRT plus Psychological counseling (Education, counseling and behavioral element)In both groups there was significant improvement in vasomotor symptoms (p<0.0001NRInsomnia significantly improved in the combined group (HRT + counseling) p=0.0001 from baseline and 0.0022 between groups. Insomnia was not significantly improved in HRT group.Combined treatment group has significant benefit in nervousness (p=0.0001), anxiety, depression, emotional alteration, melancholia (p=0.0001) over HRT only group, however, both groups had significant improvement in these parameters from baseline. HRT only nervousness (p=0.0001) and anxiety (p=0.0002); combined group both had p = 0.0001.NRNRNRNRNRNRWeakness and fatigue improved in combined group over HRT alone group (p=0.0001); same with palpitations. Neither group had improvement in joint and muscle pain or headache symptoms.NRNRNRMind-body
Atkinson, 2004205DB RCTP1 yearWomen recruited from a breast clinic in Cambridge, UKExclusion:28 day menopausal symptom diary at baseline and 12 months; severity and frequency of 21 symptoms associated with menopauseNRNRNRExcludedNRNRNRMeasured but not reportedPromensil 1/day; 26 mg biochanin, 16 mg formononetin, 1 mg genistein, 0.5mg diadzein derived from red cloverPlaceboInteraction between treatment group and menopausal status for changes in menopausal symptom score and number of hot flashes was not statistically significant p<0.05NRNRNRNRNRNRNRNRNRNR16/102 withdrew from Promensil group and 12 /103 from placebo withdrewNone reported; most withdrew to go on HRTNoneBiologically based therapies
1. History of breast cancer, major breast surgery
2. Use of HRT
Baber, 199951DB RCTP7 monthsUnpaid female volunteersInclusion:Greene Climacteric ScaleExcludedNRNRNRNRVegetarian > 10g legumes/ day excludedNone for 3 monthsWeight reported in kg with mean 67–71 kg +/−-11.0–12.8Promensil (Novogen Ltd, Sydney); Promensil is a standardized isoflavone supplement prepared from red clover extract in 500mg tablet form containing 40 mg/tablet; contains genistein, daidzein, biochanin, and formononetinPlaceboGreene score and flush frequency decreased in both placebo and active groups during the 3 months of treatment (p=0.003); no difference between groupsNRNRNRNRNRNRNRNRNRSignificantly different (p=<0.001) in urinary isoflavones between baseline and 3 months in the supplemented group; not the case in the placebo group8/51 withdrew7 withdrew for personal reasons; 1 withdrew for medical reasons not related to the studyNRBiologically based therapiesAfter urine isoflavone analysis was performed, it became apparent that many subjects in the placebo group displayed high urinary isoflavone excretion
1. Aged 45–65
2. > 3 hot flushes/day
Exclusion:
1. Intercurrent medical problems
2. HRT or antibiotics in previous 3 months
3. FSH<30
4. Menstruation in previous 6 months
5. Hysterectomy
6. Vegetarian (>10g legumes per day)
Baird, 199597RCTControl Usual care4 weeksVolunteers recruited through newspaper ads, flyers, and radioInclusion:Health habits and history questionnaire, Luteinizing hormone, follicle stimulating hormone, vaginal cytology, urinary phytoestrogenNRNRNRNRNRNRNone for 6 monthsNR1/3 of calories to come from soy flourControl was usual care dietNRNo change in vaginal maturation indexNRNRNRNRNRNRNRNRNo change in FSH, LH,6/97 withdrew, 3 were found ineligible after screening, 2 from other family emergencies and 1 could not tolerate soy foodsNoneNoneBiologically based therapies
1. Age less than 65
2. No menses for ≥ 2 years
3. No use of estrogen or antibiotics ≥ 6 months
4. No use of prescription drugs known to effect outcomes, such as corticosteroids.
Balk, 200227RCTP6 monthsPostmenopausal women were recruited from clinics and private gynecology, family practice, and internal medicine offices in Pittsburgh. Advertisements were placed in newspapers, on radio, and on the web site for Magee-Women's Research Institute home page.Inclusion:Endometrial biopsyNRNRNRNRExcludedNROver 1 year to be eligibleMean was average100 mg soy/cereal/dayN/ANo differenceNo differenceSoy had more insomniaNo difference (depression)N/AN/ANo differenceN/ANo difference (decreased libido)N/AHeadache, palpitation, night sweats, no difference2/13 from placebo and 6/14 from the soy groupYesFlatulence, poor taste - no improvementBiologically based therapies
1. Over 40 years, postmenopausal, no vaginal bleeding for 1 year or >30 years old with BSO or POFMenopausal Symptoms Questionnaire by Brzeginski, et alNumber not stated
2. Omnivore
3. Intact uterus
Exclusion:
1. HRT in past year
2. Use of SERMs
Bellipanni, 200179RCTP6 monthsNo relevant pathologies, taking no drugs, hormones or herba preparation and conducting a normal lifestyle with typical Mediterranean diet rich of carbohydrates and fresh vegetablesInclusion:Questionnaire in which life habits, physiological data, data concerning previous pathologies, treatment-related side-effects, treatment-induced alterations, effects on perimenopausal symptoms (neurovegetative, sleep, psychological) werer recorded at time 0 and at 3 and 6 months. Questions concerned duration and character of their menstrual cycle and/or psychosomatic, peri- and menopause related symptoms such as irritability, morning mood and depreession, insomnia, night sweatings, headache, stypsis, amnesia, hot flushes, palpitations, and body weight increase.NRNRNRNRNRAll non-smokers and no alcohol abuseNRNR3 mg melatonin/dayPlaceboNo significant difference between groupsNRNo significant difference between groupsAfter analysis of all answers, the evaluation of different typical perimenopause or menopause-related symptoms or alternations did not disclose a clear-cut difference between the two groups, with the notable exception of a very significant improvement of mood and complete disappearance of morning depression in the melatonin-treated women.NRNRNROnly episodical improvement of regularity and duration of menstrua cycles were reported. Six menopausal women (at 1 and 2 years after total cessation of the menses) reported a re-acquisition of normal (bleeding and duration) menstrual cyclesNRNRInformation on LH, thyroid and FSH resultsNRNRNRBiologically basedPoor study
1. Age 42–62
Blatt, 1953748DB RCT5 arms with controls and placebo3 yearsClimacteric womenNRMenopausal index, a validated scale that represents a numerical conversion of the severity of the 11 most common menopausal symptoms.NRNRNRNRNRNRNRNRVitamin E 50–100mg tid (n=82) vs. ethinyl estradiol 0.05mg (n=107) vs. conjugated equine estrogen 1.25mg (n=173) vs. phenobarbital 15mg tid (n=88).Placebo (n=298)All results reported by menopausal index of which several questions pertain to vasomotor symptoms. No p values are given in paper due to date of publication. However, 66.5% of both estrogen groups had an excellent response to treatment (as compared to 13.4% of Vitamin E, 23.6% of phenobarbital and 15.6% of placebo patient)NRNRNRNRNRNRNRNRNRNRNRNRNRBiologically based
Boblitz, 2003 (Abstract Only)179RCTP6 weeksWomen with menopausal symptomsNRKupperman Menopause Index; CGI scores for anxiety, impaired drive, depressive mood and nervousness/irritabilityNRNRNRNRNRNRNRNRRemifemen Plus; 20 mg black cohosh, 250 mcg of hypericinPlaceboNRNRNRIn all Greene Climacteric Index items referring to psychological symptoms, Remifemin Plus was superior to placebo (p<0.001)NRNRNRNRNRNRA decrease in Kupperman Index total score demonstrated significant superiority of the active to placebo (p<0.001)NR6 withdrew in each group due to adverse events, none seriousNRBiologically based
Brzezinski, 1997145RCTControl Israeli diet (usual care)12 weeksWomen who were peri and postmenopausal (43–65 years) with climacteric complaints from the outpatient menopause clinic at Hadassah Medical Center, Jerusalem, IsraelInclusion:Menopause symptoms questionnaire (MSQ); evaluates hot flashes, night sweats, palpitations, headache, depression, vaginal dryness, urinary discomfort, insomnia, and decreased libido on a four point scale. Serum phytoestrogen concentrationsIncludedIncludedNRNRNRNRCould not be taken at the time of study26.24 ± 0.48 for PE group and 25.82 ± 0.87 in control groupPhytoestrogen rich diet, approximately 1/4 of their calories (PE group)Regular Israeli diet; told to avoid soy products and flax seedSignificantly reduced in PE group over controls (p=0.004)Significantly reduced in PE group over control (p=0.005)NRNRNRNRNRNRNRTotal score of menopausal symptomatology (MSQ score) was reduced greatly in both groups during the study groups, but the difference between the groups was not significantAverage of 100-fold increase in the phytoestrogen serum levels of the PE group; no change in the control group31/1454/95 in the PE group due to intolerance of diet; 2/95 in soy group and 7/50 in control group withdrew due to unbearable menopausal symptoms; other dropouts were due to personal reasonsNRBiologically based therapiesInteresting as came from food, tofu, soy milk, and flax seed largely
1. Natural or surgical menopause (≥ 3 months of amenorrhea)
2. FSH>30, LH>20, and low plasma estradiol level (<200)
3. ≥ 1 of the following symptoms: hot flashes, night sweats, insomnia, depression, vaginal dryness, or dyspareunia
Exclusion:
1. Evidence of acute medical illness
2. Use of gonadal hormones or any medication known to influence menopausal symptoms or endocrine variabels
3. Known or suspected allergic reaction to specific food items.
Burke, 2003241DB RCTHH24 monthsWomen aged 45–55 were recruited from the community and seen at Wake Forest University.Inclusion:Self report in symptom diaries.56/241NRNRExcludedNRNR180/2410/24125g of soy with 42mg a day of isoflavones or 25g of soy with 58mg a day of isoflavones25g of soy, alcohol washed to remove isoflavones (Control)Rapid reduction in all groups, including control. No difference between groups.NRNRNRNRNRNRNRNRNRNRNRNRNRBiologically based therapies170/241 used OC
White: 88%1. Perimenopausal (only 1 period in preceding 3 months)Significant reduction for all groups from baseline (p<0.0001) but no difference between groups (p=0.10).
Married: 79%2. At least 1 vasomotor symptom a day
High school diploma: 96%3. No use of HRT for 3 months prior to study entry
≥$30,000 annual income: 79%Exclusion:
1. Acute myocardial infarction or stroke within 6 months
2. History of breast or endometrial cancer
3. History of invasive cancer within 5 years
4. Active thromboembolic disease
5. Previous osteoporosis fractures being treated with hormones
6. Low bone density
7. Previous exposure to diethylstilbestrol
8. An endometrial biopsy showing hyperplasia
Bygdeman, 199640RCTHH3 monthsPostmenopausal women complaining of vaginal dryness (aged 43–76, mean 58.28 years)Exclusion:Self diary and vaginal dryness index (Bachmann)NR2/40NRNRNRNRNRNRReplens: 1 vaginal application three times/week for 3 monthsDienoestrol vaginal cream (0.01%) 0.5mg daily for 2 weeks then three times a week for 3 monthsNRBoth groups resulted in a significant increase in the vaginal dryness index with compared to baseline valuesNRNRNRNRNRNRNRNRNR1/40NRNRBiologically based
1. Hormonal-dependent tumors
2. Known or suspected other serious diseases, abnormal genital bleeding, past history of active thromboembolic disorder, vaginal infection
3. HRT in the last 3 months
4. Vaginal use of any douche or lubricant
Cagnacci, 200380RCT, openHH3 monthsWomen (age 47–53) in perimenopause referred to the Menopause Center were enrolled; mean age was 50.2, 51.5 and 51.8Exclusion:State Trait Anxiety Inventory, Self-Evaluations Depression Scale, Greene's Climacteric ScaleNRNRNRNRNRNRNRMean 26.0, 26.9 and 26.7Kava-Kava (KK) 100m/day (15 women) vs. Kava-Kava 200mg/day (19 women)Control was 1000mg Calcium/day (34 women)Both KK groups had significant decline in Greene's score from baseline, but not significantly different from control group.NRNRAnxiety; significant decrease compared to control in both KK groups (p<0.009); Depression scores were significantly decreased from baseline in KK groups, however, not significant from controlsNRNRNRNRNRNRNR12/80; 6 in the control group, and 5 in the 100mg KK group and 1 in the 200mg KK group2 for nausea and gastric painnausea and gastric painBiologically based
1. Organic or neurological pathologies
2. Used hormones, neuroactive or psychotropic drugs in the 3 months preceeding
Carranza-Lira, 200130DB RCTP1 monthPostmenopausal women who attended the Climacteric Clinic of the hospital studiedInclusion:Modified Kupperman IndexNRNRNRNRNRNRNever receivedNo difference between groups (average BMI is 28)Phytoestrogen cream 4mg/day aloe vera; wild yam root extract; almond oil; cartamo oil; jojoba oil; tocopheryl acetate; chamomile extract; sheepshkin root extract oil of ass herb; siberian ginseng extract; to alternating forearms/dayCold cream controlA significant decrease in Kupperman Index Score was found in both groups at the end of treatment (p<0.001), no other significant differences between groupsNRNRNRNRNRNRNRNRNRA significant decrease in KI was found in both groups at the end of the treatment (p<0.001) in both groups from baselineNRNRNRBiologically based therapies
1. No current or previous exposure to HRT
2. FSH >30 and estradiol <30
Chen, 200352RCTHH16 weeksNon-hysterectomized postmenopausal women, aged 45–65 with climacteric complaints were recruited from outpatients attending this Taiwan HospitalInclusion:Greene Climacteric ScaleExcludedExcludedExcludedExcludedNRNRNone within 6 months52–56 kgJWSYS (Sun Ten Pharmaceutical Co., Taipei, Taiwan); 4 grams tid; includes angelica Radix, Atractylodis rhizoma, Paeoniae Radix; Bupleuri Radix; Hoelen; Glycyrrhizae Radix; Moutan Bark; Gardeniae Fructus; Zingiberis Rhizoma, Menthae HerbaPremelle 0.625/2.5 (Wyeth Medica, Newbridge, Co. Kildare, Ireland); one tablet q dJWSYS had significant reduction (p<0.01) in vasomotor symptoms on Greene scale and Premelle did not.NRNRBoth groups had significant improvement in anxiety and depression (p<0.01)NRBoth groups had significant improvement from baseline (p<0.01)NRSee withdrawalsPremelle group had significant improvement (p<0.01), but JWSYS group did notNRBoth JWSYS and Premelle induced a significant reduction of prevalence and severity of menopausal symptoms. (p<0.01)13/37 JWSYS; 11/25 HRT3/37 from Chinese herb group due to vaginal bleeding and abdomenal disturbances; 5/25 from HRT group due to vaginal bleeding and breast tendernessSee withdrawalsBiologically based therapiesNo true control; high drop out rate
1. Last menstruation ≥ 6 months previously
2. No HRT for ≥ 6 months
Exclusion:
1. Severe metabolic, endocrine, or GI disease, concomitant heart disease, uncontrolled hypertension (>160/95), diabetes, endometriosis, undiagnosed vaginal bleeding and psychiatric illness
2. Surgically induced menopause
3. Previous or current estrogen-dependent tumors, other current malignant or life-threatening disease,
4. Previous or concomitant serious or chronic medical conditions.
5. Taking tranquilizers or antidepressants
Chenoy, 199456DB RCTP6 months56 women were recruited from the general gynecology clinic of North Staffordshire Hospital Center, London; from general practitioners' surgeries, and by self referral of volunteers.Inclusion:Self reported symptom diaryExcludedNRNRNRNRNRNone for 2 months priorNRSix months of treatment with either four 500mg evening primrose oil with 10mg natural Vitamin EPlacebo was 500mg liquid paraffin; four capsules twice dailyAll women given placebo showed a significant positive difference between control cycle and last cycle (p<0.05). Women given gamolenic acid, however, did not show a significant improvement between the control cycle and last available treatment cycle except for a reduction in the maximum number of night time flushes (p-0.014).NRNRNRNRNRNRNRNRNRNR11/28 from placebo and 10/28 from gamolenic acid group2/11 from placebo due to nausea; however main reason stated was lack of clinical responseLack of clinical responseBiologically based therapiesSignificant response to placebo but not to gamolenic acid
1. Menopausal women who had hot flushes at least three times/day
2. Elevated FSH and LH or had amenorrhea for at least 6 months, or both.
Exclusion:
1. Received estrogen replacement or essential fatty acid supplements in the previous 2 months.
2. Taking any form of HRT or other drug for menopausal symptoms during the study, or systemic steroids, non-steroidal anti-inflammatory agents, anticonvulsants, clonidine, and phenothiazides.
Chiechi, 2003187RCTUsual care6 monthsHealthy postmenopausal asymptomatic woman aged 39–60, living in Southern Italy; mean age was 52.7 yearsInclusion:Karyopycnotic index and maturation value of the vagina, FSH, estradiol, urinary daidzein, vaginal smearsIncludedNRNRNRNRNRNR27.06–28.9 meanWomen were given soy increased diet, adding a soy food every day, and two meals twice/week based on phytoestrogen rich food; isoflavone intake of 20–30mg/dayUsual care; and HRTThese women were asymptomaticStatistically significant improvement from baseline in vaginal indices in both the HRT (p<0.01) and soy groups (p=0.03), most in the HRT group; not seen in control groupNRNRNRNRNRNRNRNRNR22 out of control group; 44 out of diet group; 31 out of HRT groupNRNRBiologically based therapiesToo high of drop out rate to be reliable
1. Spontaneous menopause of ≥ 6 months
2. FSH>30, or bilateral oophorectomy
Exclusion:
1. Age >60
2. Heavy drinkers
3. Treatment with HRT, cholesterol-lowering, antiosteoporotic or other interfering drugs (i.e. tibolone)
4. Diabetes or history of cancer
5. In vegetarian or macrobiotic diet
6. Presence of menopausal symptoms requiring therapy
Cleary, 199430RCTP15 weeksWomen age 50–60 years with menopausal symptoms recruited through local and national newspapersInclusion:1. Weekly 1–10 scale Symptom questionnaire during studyNRNRNRExcludedNRNRAt least 18 monthsNRThe spine and pelvis of each subject was treated by a low-force osteopathic technique developed by Fox, and the cranium by cranial techniques following mechanical principles weekly for 10 weeks, followed by a 5 week observation period.Placebo: low-force technique delivered to a joint adjacent to a restricted joint, where it will have no effect; force is so low in both groups that they are unaware they have received treatment weekly for ten weeks followed by five week observation periodReduction in study group of hot flashes (p=0.016) at ten weeks and (p=0.007) at 15 weeks; Reduction in study group of night sweats (p=0.021) at ten weeks and (p=0.016) at 15 weeksNRReduction in insomnia vs control group (p=0.098) at ten weeks and (p=0.018) at 15 weeksReduction in depression in study group compared to controls (p = 0.042) at ten weeks and (p=0.290) at 15 weeks; Reduction in irritability is study group compared to controls (p = 0.184) at ten weeks and (p=0.271) at 15 weeksNRNRReduction in urinary frequency in study group over controls (p=0.021) at ten weeks and (p=0.168) at 15 weeksNRNRAverage symptom score decreased in the study group compared to the control group over the study (p=0.005)Of the 11 hormones studied there was a significant difference in testosterone levels (decreased in study group) (p=0.028); Reduction in pain was greater in the study group: (p=0.04) for neck pain, and (p=0.06) for back painNRNRNRManual Medicine
1. < 4 periods in the previous 12 months2. Pre-, Week 5, and Week 15 blood levels of estradiol, FSH, LH, thyroxine, testosterone, sex hormone binding globulin, prolactin, cortisol, IGF/1, TSH, and GH
2. Abnormal FSH/LH analysis
Exclusion:
1. Current or past HRT in last 18 months
2. Any debilitating medical condition
3. Any facial or spinal surgery
4. Taking medication likely to affect their hormonal or sympathetic systems, such as thyroxine, or beta-blockers
5. Any past or present patient of the researcher
Cohen, 200318RCTHH12 weeksWomen were recruited by flyers and by advertisements in local newspapers in a New England ; 11/17 women had ceased having menstrual cycles within the past 2 years and the remaining 6 women had not had a period in 3–4 months; Mean age was 47.3 years (43–53)Inclusion:4 scale daily symptom diaryNRNRNRNRNRNRExcluded at least 3 months priorNR9 week acupuncture treatment protocol consisting of 1/week for 3 weeks then once every other week for a total of 6 treatments followed by 3 nontreatment weeks (20–30 minutes/ treatment) (EA group)UB15, 23, 32; GV 20, H7; pericardium 6; SP6, 9; L3 for experimental group; comparison is general tonic (shen mein) L4;K7 and ear points (7)EA group showed a decrease in mean monthly hot flush severity (30%) for site-specific acupuncture from baseline to month 2 (p=0.05), baseline to month 3 (p=0.005) and baseline to posttreatment month 4 (p-0.019). The comparison acupuncture treatment group had no change in severity from baseline over the treatment phase.NRSleep disturbances in the EA group declined over the study and reached a statistically significant difference (0.05) from baseline in posttreatment month. This also accured in the comparison group.Mood changes decreased in both groups between baseline and posttreatment month of the study; EA group p=0.05; comparison acupuncture group (0.056)NRNRNRNRNRNRNR1/18Withdrew prior to randomizationNoneAlternative Health Systems
1. Ability of self-identification of menopausal hot flushes
2. Ceased previous treatment of menopausal symptoms with hormones, other medications, herbs, or acupuncture at least 3 months prior to enrollment in the study to allow for a sufficient cleansing period
Exclusion:
1. Women with hormonal supplementation, other pharmacologic therapies, herbal remedies, or acupuncture (including acupressure).
Crisafulli, 200490RCTP, HH1 yearHealthy, ambulatory women, referred by the Department of Internal Medicine and the Department of OB/GYN at University of Messina, Italy, age 47–57Inclusion:Self-reported diary of the number of hot flushes, 14 days before each assessment; only number used, not severityNot allowedNot allowedNRNRNRNot allowed if smoked > 10 cigarettes/dayNone for 12 monthsAverage for all groups was 23–241mg/day estradiol combined with noresthisterone; genistein (n=30) at 54mg/dayPlaceboEstrogen group, flush score decreased by 53% (p<0.001) compared to placebo at 3 months. This was maintained at 6 and 12 months. Genistein group decreased by 22% (p<0.01) after 3 months; 29% at 6 months (p<0.001) and 24% at 12 months (p<0.01) compared to placebo. The difference between the estrogen group and the genistein group was significant at all measurements (p<0.05)NRNRNRNRNRNRNRNRNRNR7NoneNoneBiologically based therapiesFunding source not reported; important study due to length.
1. No surgical menopause patients
2. No period for 12 months, FSH>50 and estradiol level <100.
Exclusion:
1. Clinical or lab abnormalities suggesting cardiovascular, hepatic, renal disorders, coagulopathy
2. Use of oral or transdermal estrogen, progestin, androgen or other steroids in the preceeding year
3. Smoking >10 cigarettes/day
Dalais, 199852DB RCTHH7 months52 postmenopausal women were recruitedInclusion:Hot flush diaryNRNRNRNRNRNon smokers; non vegetariansNone for 3 months priorNR45 grams of soy (high phytoestrogen), linseed (high phytoestrogen), or wheat diet; dosage of isoflavones (daidzein, genistein) was 52.64 ± 8.68 mg/dayWheat dietIn women consuming linseed and wheat, a significant decrease in hot flush rate was observed following 12 weeks of ingestion (41% decrease, p<0.009; 51% decrease, p<0.001 respectively) compared to baseline. No significant decrease in hot flush rate was detected during soy ingestion.Women ingesting soy showed signicant increase in vaginal cytology maturation index (p-0.03); none for other two groupsNRNRNRNRNRNRNRNRUrinary excretion of daidzein, genistein, enterodiol and enterolactone increased significantly (10–30 fold) during soy and linseed ingestion, respectively (p<0.01). No such changes in wheat group8/52Personal reasonsNRBiologically based therapies
1. Age 45–65
2. FSH > 40
3. > 14 hot flashes/week
4. 12 months of amenorrhea
5. No antibiotic or hormone replacement therapy use for the preceding 3 months
6. Non-smoker and non-vegetarian
Davis, 200155DB RCTP12 weeksWomen, age 45–70 years were recruited through the Jean Hailes Foundation Newsletter, newspapers, radio station interviews and the medical unit of the Jean Hailes FoundaionInclusion:Daily diary of the frequency of hot flushes and night sweats for four weeks before treatment and for the entire 12 weeks of the study period. The Menopause Specific Quality of Life Questionnaire (MENQOL) and urinary phytoestrogen excretionNRNRNRNRNRNR44.4% of placebo group had previously used HRT, and 53.6% of CMH has previously used HRTBody mass index was 26.1 (24.3, 27.9) in placebo group; and 25.7 (23.9, 27.5) in CMH groupBoth placebo and CMH produced by Ningbo Daekang Herbs Co Ltd (Ningbo, China)Placebo was cornstarch with a bitter taste enhancerFrequency of vasomotor symptoms were reduced in both CMH and placebo groups. Difference between groups was not significant (p =0.09) A progressive decline in the frequency of vasomotor symptoms with treatment duration was seen in both groupsNRNRNRNRNRNRNRNRA reduction in score was seen in all four domains of the MENQOL scores. 'This was significant only for the physical, vasomotor, and sexual domains in the CMH group, and the physical domain in the placebo group. The difference between the two treatment groups was not significant for any of the four domainsWomen with more than four years of ammenorrhea had a significantly greater response to placebo than to CMH; significant greater reduction in score was seen with CMH compared with placebo in the vasomotor domain of the MENQOL for age <55, BMI <25, and previous nonusers of natural therapies (p<0.05)14/42 in Chinese herbal group; 9/36 in placebo group.Most withdrew in the first week after randomization due to the taste of both productsIn CMH group, two became asymptomatic before study began and withdrew, and on started HRT; 7 withdrew due to taste intolerance, 2 were lost to follow-up, and 2 withdrew due to other illness; in placebo group, one withdrew before the study commenced due to lack of symptoms, 2 withdrew due to no benefit, one withdrew due to other illness, one was lost to follow-up and 3 withdrew due to taste intoleranceBiologically based therapies (specifically comments in article that this is not assessing TCM)Herbs in CMH = rehmannia glutinosa, Cornus officinalis, Dioscorea opposita, Alisma orientalis, Paeonia suffruticosa, Poria cocos, Citrus reticulata, Lycium chinensis, Albizzia julibrissin, Zizyphus jujuba, Eclipta prostarata, Ligustrum lucidum
1. Non-Asian women who had lived in Australia for at least ten years
2. Postmenopausal (>12 months amenorrhea and FSH >25)
3. Reported at least 14 hot flushes or night sweats/week
Exclusion:
1. Use of HRT, Chinese medicinal herbs (CMH), or other natural therapies during the eight weeks before baseline
2. Preexisting gastrointestinal, renal, or liver disease, diabetes mellitus requiring treatment, uncontrolled hypertension, undiagnosed vaginal bleeding, systemic glucocorticosteroid use
3. Undergoing cancer therapy
4. Women who had consumed a high phytoestrogen diet for the four weeks before baseline
Duffy, 200336DB RCTP12 weeks36 postmenopausal women aged 50–65 were recruited by circular email at King's College London from a database of those who had previously participated in a study on bone mineral density at Guy's Hospital.Inclusion:Hospital Anxiety & Depression Scale; Greene Climmacteric Scale; Stanford Sleepiness Scale; Epworth Sleepiness Scale; paced Auditory Serial Addition test; plus short-term memory test from the Weschler Memory Scale; plus samples from the Cambridge neuropsychological Test Automated Battery ‘list all the animals they could think of in 1 minute’13–22%IncludedNRNRNRAll nonsmokers; caffeine and alcohol assessed, plus diet; alcohol intake significantly less in soy group (p<0.05); high IQ in both groups (118 and 115)None in past 12 monthsNRSoya isoflavone supplement used was Solgen 40 (Solbar Plant Extracts, Ashdod, Israel). Each capsule contained 30 mg total isoflavone equivalents. Dose was two capsules/day for 12 weeksIdentical looking placebo capsules; told to avoid Soya foods and food products containing Soya for the duration of the study, and for the two weeks priorNo significant effects of treatment on any of the menopausal symptoms assessed by the Greene Climacteric ScaleNRNo differenceNo differenceSignificant improvement in memory in Solgen group (delayed recall of pictures (p<0.03); immediate story recall (p<0.06); corrected for practice effect; also learning the reversal of the simple discrimination rule (p=0.05)No differenceNRNRNRNRImproved time to learn complex tasks greater in Solgen group than placebo (p<0.05 and <0.003)3/36NoneNoneBiologically based therapies
1. No menstruation for the previous 12 months
Exclusion:
1. Had used HRT in previous 12 months
2. Use of antibiotics in the previous 3 months
3. Current illness or use of psychoactive medication.
Three subjects were excluded during the course of the treatment, two because they started treatment with amitryptiline and one because she started HRT
Faure, 200275DB RCTP4 monthsPostmenopausal women requesting treatment for hot flushes.Inclusion:Self report by diary.NRNRNRNRNRNRAt least 6 weeksNR70mg/day of Genisten and Diadzin (Phytosoya) 325mg four/day = 70mg of G/DPlaceboThe Intention-to-treat analysis indicated treatment effect on the change in frequency of hot flashes for the intervention group (p=0.01).NRNRNRNRNRNRNRNRNRNR6 soy groupNRNRBiologically based therapies
1. ≥ 6 months out from last menses14 placebo
2. FSH >40
3. ≥ 7 moderate to severe hot flashes per 24 hours
4. ≥ 6 weeks since last HRT use
Freedman, 199233RCTHH4 weeks33 women were recruited from newspaper advertisements; mean age in years was 50.7 ± 8.6 in paced respiration group; 53.1 ± 6.0 in muscle relaxation group; and 53.9 ± in alpha wave feedback groupInclusion:Ambulatory monitoring of sternal skin-conductance level and abdominal and thoracic ventilation; in addition thoracic and abdominal ventilation were recorded on two additional channels of the Medilog using inductance plethysmography (Respitrace); serum epiIncludedIncludedNRNRNRNRNone for 1 yearNR (mean weight with variation recorded in pounds)8 1-hour biweekly treatment sessions of paced respiration training8 1-hour treatment sessions of alpha-EEG biofeedback, or Patients were taught muscle relaxation by a research assistant using previously published methodsHot flash frequency declined significantly (p<0.02) for the paced-respiration group but not for the muscle relaxation (p>0.2) or alpha wave feedback group (p>0.5).NRNRNRNRNRNRNRNRNRAnalysis of vafriance on respiration rate showed a significant (p<0.02) Group x Pretreatment/Posttreatment interaction effect. Simple effects tests showed a significant pretreatment/posttreatment increase in tidal volume for the paced respiration group (p<0.03) but not for the muscle relaxation group (p>0.8) or alpha wave feedback (p>0.5)NRNRNRMind-body interventions
1. Amenorrheic ≥ 1 year
2. ≥ 5 hot flashes/day
Freedman, 199524RCTHH4 weeksWomen recruited from newspaper advertisement; age was 52.5 years ± 1.6 for paced respiration group; 52.7 ± 1.6 years for alpha feedback groupInclusion:Ambulatory monitoring of sternal skin-conductance level and abdominal and thoracic ventilation; in addition thoracic and abdominal ventilation were recorded on two additional channels of the Medilog using inductance plethysmography (Respitrace); serum epinephrine and norepinephrineIncludedIncludedNRNRNRNRNone for 1 yearNR (mean weight with variation recorded in pounds)8 1-hour biweekly treatment sessions of paced respiration training8 1-hour treatment sessions of alpha-EEG biofeedbackHot flash frequency declined significantly (p<0.001) for the paced-respiration group but not for the alpha wave feedback group.NRNRNRNRNRNRNRNRNRThe 24-hour patern of skin-conductance level of significantly altered for the paced respiration group (p<0.001); no significant change in any of the biochemical measuresNRNRNRMind-body interventions
1. Amenorrheic ≥ 1 year
2. ≥ 5 hot flashes/day
Germaine, 198426RCTHH6 monthsMenopausal women, 44–61 years (Mean=50.3 years); 12 premenopausal women, all reporting regular menstrual periods from 22–45 served as controlsInclusion:Heat stress test (HST); this is 2 circulating water pads maintained at 42° C to the subjects torso whild supine on a bed in a 23° C room. Subjects were instructed to signal the earliest perception of a hot flash by pushing a hand-held button; following the HST 1 the 14 menopausal women were randomly assigned to receive 6 weekly sessions of progressive musle relaxation or alpha EEG biofeedback; HSTs were then administered 1 week later and then final test at the end of training.NRNRNRNRNRNRNRNRProgressive muscle relaxation (PMR)Alpha EEG biofeedbackIncrease in heart rate during the heating period, whereas premenopausal women declined in heart rate. Significant reduction in PMR group compared to controls during third HST (Significant test p<0.0003, and Group X Test p<0.002) were found. Also time was significantly longer (p<0.01) for onset of hot flush in the PMR group compared to control group. This change was significant between HST 2 and HST 3 for the PMR group but not the control group (p<0.01).NRNRNRNRNRNRNRNRNRNRNRNRNRMind-body interventionsNovel way of confirming the presence of hot flushes
1. ≥ 2 hot flashes/day
2. No HRT
3. No periods
Han, 200282DB RCTP5 monthsWomen, age 45–55 yearsInclusion:Kupperman Index; height, weight, blood pressure, lipid, and hormone levels, transvaginal sonographyExcludedNRNRExcluded if within past 5 yearsNRAll exercised less than three times/week; 30% smokers in placebo group; 20% smokers in isoflavone group;None allowed for 12 monthsNRSoy isoflavone 83.3 mg/day; soy protein 50.3 mg and isoflavone 33.3mg. Genistein, daizein, and glycitein in aglycone form 23.3.mg, 6.2mg, and 3.8 mg, respectively.Placebo was 83.3 mg composed of purified soy protein 50.3mg without isoflavones and glucose 33.3mgIsoflavone group declined more than placebo group (p<0.01)NRInsomnia score decreased in isoflavone group more than placebo group (p<0.01)Isoflavone group improved score over placebo in melancholia, nervousness (p<0.01)NRNRNRNRNRNRAll measures of Kupperman scale (vasomotor, paresthesia, insomnia, nervousness, melancholia, vertigo, weakness, arthralgia and myalgia, headache, palpitation, formication) showed individual statistical improvement in isoflavone group over placebo (p<0.01)1 out of 41 in each group; 1 for ‘poor response’ and 1 for ‘nausea’NRNRBotanically basedSoy isoflavone obtained from eugenbio Co. Ltda, Seoul, South Korea
1. Intact uterus
2. FSH > 25
3. Estradiol < 20
4. Presence of hot flashes
5. ‘in menopause’ at least 12 months
Exclusion:
1. Using lipid-lowering drugs, antidiabetic medications, soybean-derived products, or herbal supplements
2. History of uncontrolled hypertension, stroke or TIA
3. Cancer diagnosed less than 5 years ago
4. Previous myocardial infarction
Hartley, 200334DB RCTP1 weekPostmenopausal women aged 53–65 were recruited from those responding to articles in national and local pressInclusion:National Adult Reading Test-Revised version; Hospital Anxiety and Depression Scale, Greene Climacteric ScaleStanford Sleepiness Scale, Epworth Sleepiness Scale, Immediate and delayed paragraph recall from the Weschler Memory Scale-Revised, and several other brain function measuresIncludedIncludedNRNRNRSmokers includedNone for 12 months prior to studyMean 66kgGinkyo One-A-Day 120mg tablet/day containing 25% Ginkgo flavonoids and 6% terpenoidsPlaceboNo significant effect of treatment on any of the menopausal symptoms assessed by the Greene Scale, however all improved from baseline (p<0.001)NRNo effectNo difference between groupsNot significant between groupsNRNRNROne parameter of Greene's scale that did not improve over timeNRNR3One in the placebo group because of brief menstrual period and two in the Ginkgo group because testing was too demandingNRBiologically based
1. No period for 12 months and healthy.
Exclusion:
1. Use of HRT within the previous 12 months
2. Smoking more than 20 cigarettes/day
3. Current illness or use of psychoactive medication, including soya supplements, Ginkgo or ginseng (herbs were allowed)
Hirata, 199771DB RCTP24 weeksWomen (mean age 52.4 ± 6 years) were solicited through radio, television, and newspaper and magazine information; age range was from 44.7–69.3 years in the placebo group and from 44.5 to 59.6 years in the dong quai group.Inclusion:Kupperman Index; symptom diary; serum estradiol, estrone, and sex hormone-binding globulin levels; vaginal cells, endometrial ultrasounographyExcludedNRNRExcludedNRSmokers excluded; more than 2 alcohol drinks/day excluded; 57% were regular exercisersNo HRT allowed for previous 3 monthsExcluded for weight >30% or < 15% of ideal weight4.5 grams/day of dong quai from root materialMaltodextrin placebo29.4% of the placebo group and 33.3% of the dong quai group reported good or excellent control of their vasomotor symptoms40% of subjects complained of moderate to severe vaginal dryness at baseline; 12 weeks later, about 30% still had this symptomNRNRNRNRNRNRNRNRBoth groups has significant decrease in Kupperman scale from baseline at 6, 12, and 24 months (p<0.0001); No significant changes were seen in serum estradiol level, estrone level, SHBG level, blood pressure, or weight were seen during the study6/36 in the placebo group; 4/35 in dong quai groupPlacebo: 2 dropped due to lack of efficacy; 2 developed ‘minor side effects’; 1 lost interest; 1 developed ‘other health problems’; dong quai; 2 due to lack of efficacy; 1 due to minor side effects and 1 due to other health problemsSide effects: burping, gas, and headache in both groups, with no statistically significant difference between groupsBotanically basedDong quai was extracted from the crushed root of Angelica sinensis by East Earth Herbs, Inc (Eugene, OR). Potency of the study drug material was standardized to 0.5mg/kg of ferulic acid. Oil of orange was added to all study drug material to disguise the aroma of the dong quai.
1. FSH > 30
2. ‘troublesome’ hot flushes >14/week
3. ‘post menopausal’ for ≥ 6 months
4. No HRT for 3 months
Exclusion:
1. Weight >30% or < 15% of ideal weight
2. Previous hysterectomy, serious illness
3. Use of herbal therapy during the previous 3 months
4. Gastrointestinal disorders that resulted in chronic diarrhea or malabsorption
5. History of breast cancer, pelvic irradiation,
6. Tobacco use, or consumption of > 2 alcoholic drinks per day
7. Active liver disease
8. Chronic use of antibiotics
9. Use of vaginal creams or corticosteroids
Hochanadel, 199911DB RCTP12 weeksNaturally postmenopausal women over age 45NRSomatic symptoms, mood and verbal learning performance of naturally post-menopausal women were measuredExcludedNRNRNRNRNRNRNR100 mg/day of encapsulated soy isoflavonePlaceboNo improvementNo improvementNRNo significant difference between groupsNo significant differences between groupsNo significant differences between groupsNo improvementNRNo improvementNRNone of the statistical comparisons between the active and placebo conditions yielded findings in support of the hypothesis that soy isoflavones may be useful fo the treatment of these post-menopausal cognitive or somatic changesNRNRNRBotanically basedPoster. Don't have actual paper
Hudson, 199813DB RCTP3 monthsWomen recruited from a one sentence article in The Oregonian (local newspaper)Inclusion:Self-reported symptom diary (frequency and severity)NRExcludedNRNRNRNRNo HRT for 3 months previouslyNRBotanical formula that contained 500mg combined dry herb: burdock root (2 part), licorice root (2 part), motherwort (1 part), Dong Quai root (2 part) and Mexican wild yam root (1 part) 2 capsules tidRice bran placebo with similar smell and appearance also 2 tid.100% improvement in severity symptom score in verum group (n=7) and 67% improvement in placebo group (n=6). 71% in verum group had improvement in number of symptoms and 17% had improvement in number of symptoms in placebo group. One sided Z-test showed p<0.03, but two-sided Z test did not reveal this to be statistically significantNRNRNRNRNRNRNRNRNRNRNoneNoneNRBotanically basedSize of study was too small
1. Hhot flashes and one additional menopause symptom
2. No HRT for the previous 3 months
3. Natural physiologic menopause with no menses for > 3 months
4. No serious acute or chronic disease
5. No cariovascular disease and normotensive
Hunter, 199986RCTP5 yearsAll women were over 50 years who had been randomized to two 90 minute education groups or no intervention at age 45;Inclusion:1. Sociodemographic and health information surveyNRNRNRNRNRSmokers & exercisers29% taking HRTNREducationN/AHRT users reported fewer hot flashes (p<0.04).No differenceNo differenceNo difference in depression or anxietySignificant difference in knowledge of menopause (p<0.01)Control group more likely than intervention group to believe aches & pains (p<0.01) & skin problems (p<0.05) are due to menopause, no difference as a categoryNRNo differenceImproved sexual function in intervention group (p<0.06)HRT users in comparison to non-users reported that menopause had a greater impact on their lives (p<0.04).Women in intervention group maintained better knowledge & did not attribute so many things to menopause.NRN/AN/AMind-body interventions
1. Premenopausal at age 45, from the age/sex registers of five general practices in south London2. Knowledge about menopause questionnaireControls had lost interest in sex more (p<0.02)Women in prepared group took more exercise (p<0.01) and had lower prevalence of HRT (p<0.01)
Detailed exclusion/inclusion criteria outlined in Maturitas 1998:29:215–243. Menopause Representation Questionnaire (MRQ)
4. Women's Health Questionnaire (WHQ)
Hyde, 1983 (Abstract Only)30RCTHHNRMenopausal womenNRMenopausal symptoms checklist for frequency, intensity and duration of menopausal symptoms; Galvanic skin responsesNRNRNRNRNRNRNRNR12 contingent Galvanic Skin Response feedback conditioning sessions and progressive relaxation training12 non-contingent feedback sessions and were told simply to relaxBoth groups improved; No significant difference between groups was observedNRNRNRNRNRNRNRNRNRNRNRNRNRMind-body interventions
Irvin, 199645RCTHH, P10 weeksPostmenopausal women from the greater Boston area recruited through media sources of public service announcements and newspaper advertisements, and through posted notices at appropriate medical sites, age 44–66Inclusioin:Spielberger State-trait Anxiety Inventory; Profile of Mood States; daily hot flash diaryNRNRNRNRNRNRNRNRRelaxation group (RR); reading group (R) which served as the placebo intervention group, or the charting group which was the control groupReading group was instructed to read leisure material; relaxation group instructed in diaphragmatic breathing and breath awareness; both 20 minutes/dayAll three groups had a change in flash frequency, but these did not reach statistical significance. The RR group did have a significant decrease (p<0.046) in intensity of hot flashes from baseline.NRNROn the POMS the RR group demonstrated a significant decrease in tension-anxiety (p<0.044) and depression-dejection (p<0.013)The reading group showed significant decrease in confusion-bewilderment (p<0.013) on the POMSNRNRNRNRNRNR12/454 left because they found charting to be too intrusive in their lives, 3 dropped out due to snow; 2 because they started their menses again, 2 lack of interest, and 1 who went on estrogen treatmentSee withdrawalsMind-body interventionsInclusion:
1.General good health1. Postmenopausal women symptomatic, having ≥ 3 flushes/day
2. ≥ 6 months without a menstrual period2. ≥ 6 months of amenorrhea or bilateral oophorectomy, FSH >40
3. Experiencing ≥ 5 hot flashes per 24 hoursExclusion:
4. Willingness to monitor flashes and abide by the protocol1. HRT within the previous 6 weeks
2. Allergy to foodstuffs known to contain isoflavones
3. Current history of active bowel, liver or gall bladder disease
4. Diabetes requiring drug therapy
5. Malignancy (excluding skin cancers)
6. Contraindications to HRT use, vegetarians and/or regular soy product users,
7. Receiving medications that result in liver enzyme induction
Jeri, 200230DB RCTP16 weeksNonvegetarian Peruvian women who had been postmenopausal for more than 1 year; median age was 52 ± 0.7 years for treatment group and 51 ± 0.8 years for control groupInclusion:Self reported diary of frequency and severity of hot flushesNRNRNRNRNRNRExcludedNRPromensil (40 mg standardized isoflavones (genistein, daidzein, formononetin and biochanin))/dayPlaceboReduction in both frequency and severity of hot flushes was reported by women in the treatment group; 14 Promensil women had a 48% reduction from baseline in frequency of hot flashes (p<0.001), controls had a 10.5% reduction. P value not given between groups or for control group; Regarding severity index, 47% reduction in Promensil group from baseline (p<0.001) and no change in placebo form baseline.NRNRNRNRNRNRNRNRNRSignificant reduction in FSH in Promensil group from baseline (59.27 to 48.60) P<0.001)1/15 Promensil groupNRNRBiologically based
1. < 60 with FSH>30, having ≥ 5 hot flushes/ day averaged for more than 1 week
2. Not using HRT, antidepressants, or other medication or soy or other estrogen-active plan products
Knight, 199937DB RCTHH, P12 weeksWomen, age 40–65, were recruited through the University Department of OB/GYN at St. George Hospital, Sydney, AustraliaInclusion:Greene Menopause Scale;self-reported diary of hot flushesNRIncludedNRExcludedNRNRNone within 6 weeksNRPlacebo vs. 40mg of Promensil vs. 160mg of PromensilPromensil is a standardized isoflavone supplement prepared from red clover extract, in tablet form; each tablet contains 40 mg of total isoflavones; genistein (4.0), daidzein (3.5mg) and their methylated precursors biochanin (24.5mgg) and formononetin (8.0mg)Flushing frequency decreased in all groups over the 12 week trial period. There was not difference in flushing frequency between the active and placebo groups. (average 29–34% reduction)NRNRNRNRNRNRNRNRNRNone of the biological parameters of estrogen activity measured, including FSH, SHBG and climacteric symptom scores, showed any change with time, compared to placebo. (average 26% -160mg group to 46% - placebo group reduction in Greene Score over the twelve weeks)2/37Intervention by their general practitionerNRBiologically based
1. Postmenopausal women symptomatic, having ≥ 3 flushes/day
2. ≥ 6 months of amenorrhea or bilateral oophorectomy, FSH >40
Exclusion:
1. HRT within the previous 6 weeks
2. Allergy to foodstuffs known to contain isoflavones
3. Current history of active bowel, liver or gall bladder disease
4. Diabetes requiring drug therapy
5. Malignancy (excluding skin cancers)
6. Contraindications to HRT use, vegetarians and/or regular soy product users,
7. Receiving medications that result in liver enzyme induction
Knight, 200124DB RCTP12 weeks24 subjects were recruited through the University Departments of Obstetrics and Gynecology , Sydney AustraliaInclusion:Daily flush diary; Green Menopause ScaleIncludedIncludedNRExcludedNRNRNone within 6 weeksMean of 66.1–70.2 kgIsoflavone powder, TakeCare, 60g/day; isoflavones 134.4mg/day; (aglycone formulations 77.4mg/day)Casein based powdered drinkFlushing frequency decreased in both groups, but there was not difference in flushing frequency between the active and placebo groups; no difference in Greene Menopause Symptom ScoresNRNRNRNRNRNRNRNRNRNR4/243/12 in the isoflavone group..could not tolerate tasteNoneBiologically based
1. Postmenopausal women, having ≥ 3 hot flushes/day; amenorrhea for 6 months, FSH >40 or bilateral oophorectomy
2. Aged 40–65
Exclusion:
1. HRT within the previous 6 weeks
2. Current history of active bowel, liver or gall-bladder disease; diabetes requiring drug therapy; malignancy; contraindications to HRT use
3. Vegetarians and regular soy-product users.
Komesaroff, 200150DB RCTP3 monthsHealthy menopausal women 45–60 years, currently experiencing symptoms of the menopause, recruited from the Baker Institute Menopause Clinic, and from the local community by advertisements placed in local newspapers and discussion in the electronic media. Mean age was 53.3 ± 1.1 yearsInclusion:Symptom diary self reported including number of episodes of flushing and scores for specific symptoms. Symptom scores were combined to produce values for ‘total’, flushing', and total non-flushing' scores. This approach made possible analysis of specific scores relating to mood, breast symptoms, libido and energy levels.3/50NRNRNRNRNRNone within 6 weeksMean of 27.3 ± 0.8Wild yam preparation (Biogest) supplied in 100gram tubs. Participants were asked to apply one teaspoonful twice daily to the arms, legs or abdomen (manuractures claim that each 1 gram of bioGest contains Dioscorea villosa extract 100mg, Linum usitatissmum oil 2 grams, Perlargonium graveolens oil 100mg, Salvia officinalis oil 100mg and alpha tocopheryl acetate 10mg in a vegetable cream base).PlaceboNo significant difference between the yam cream and placebo in any of the three casesNRNRNRNRNRNRNRNRNRNR19/25 in the Biogest group attributed to unrelieved symptoms and unspecified personal circumstances. 8/25 in the placebo group for same reasonsNo adverse effectsNRBiologically based
1. No HRT for ≥ 6 weeks
2. Last period > 12 months before, FSH>30 or estradiol <130
Exclusion:
1. Significant cardiac, renal or hepatic disease, psychiatric disease, inflammatory conditions or active thyroid disease, diabetes, or a history of breast cancer
Kotsopoulos, 200394DB RCTP3 monthsWomen were recruited from a larger trial.Inclusion:Validated questionnaire of menopause-associated symptoms (measure not stated by name).NRNRNRNRNR0/940/940/94118mg IsoflavonesPlaceboNo change between groups.No change between groups. Intervention group had a significant improvement (p=0.01).NRNo change within groups for psychological outcomesNRNo change between groupsNo change within groups.NRNo change between groups, both intervention and placebo groups improved (p=0.009 and p=0.015, respectively).NRBoth intervention and placebo groups had a significant improvement in facial hair (p=0.04 and p=0.014, respectively) and dry skin (p=0.0027 and p=0.011, respectively).19/94Gastrointestinal side effectsNone seriousBiologically based
Average age: 59–60 years1. Aged 50–75 years10 in treatment groupAll were due to AEs (19)Treatment group: 7 - intolerable; 1 - weight gain; 1 - menopausal symptoms; 1 - unrelated
2. Non smokers9 in placebo groupPlacebo group: 6 - intolerable; 2 - constipation; 1 - allergies
3. Non vegetarians
4. ≥ 12 months amenorrheic
5. FSH >20
Exclusion:
1. On HRT in previous 12 months
2. On phytoestrogens or soy based proteins
3. On antibiotics in previous 3 months
Kritz-Silverstein, 200356DB RCTP6 monthsWomen were recruited through mass mailings based on voter registration lists, newspaper ads, and presentations at local organizations.Inclusion:Beck Depression Inventory (BDI)NRNRYesNRNR2/56 drink soy beverages every dayYesNR110mg/day of IsoflavonesPlaceboNRNRNRNRWomen in the treatment group showed improvement on four of five tests compared to controls (p=0.03)NRNRNRNRNRNRNRNRNRBiologically based therapiesOutcome was significant improved performance on category fluency
Average age: 61 years1. Postmenopausal women aged 55–74 yearsThe Mini-mental Status Examination (MMSE)exact number not statedexact number not stated
Average age at menopause: 49 yearsTrials A & B of the Halstead-Reitan Neuropsychological Test Battery
Category Fluency
Logical Memory and Recall
Leonetti, World Congress on Fertility, 1998 (Abstract Only)90RCTP1 year5 years of menopause, surgical or naturalNRNRNRNRNRNRNRNRNRNR20mg/day of natural progesterone creamPlacebo83% of natural progesterone cream patients had improvement or resolution of vasomotor symptoms compared with 14% of placebo group (p<0.001)NRNRNRNRNRNRNRNRNRNRNRNRNRBiologically based
Lewis, 2002 (Abstract Only)99DB RCTHH, P16 weeksPostmenopausal womenNRMenopause Specific Quality of Life (MENQOL), plus daily diary of frequency and severity of hot flashesNRNRNRNRNRNRNRNRFlaxseed muffin vs. soy flour muffinWheat flour muffinNRNRNRNRNRNRNRNRNRNRANOVA on 4 domains showed no significant time by dietary group interaction in quality of life: vasomotor, psychosocial, sexual, physical or in combined score, hot flash frequency of hot flash severity. No MENQOL domains or hot flash symptoms showed significant group differences: however, all groups showed improvement with time7/33 from flax, 3/33 from soy;3/33 from wheatNRNRBiologically based therapies
Lindh-Astrand, 200475RCTHH12 weeks75 postmenopausal sedentary women with vasomotor symptoms, 48–63 years of age, recruited by advertisement in the local papers and at the gynecological outpatient clinic of a hospital in Sweden; mean age of exercise group was 54 years with BMI of 24.6; estrogen treated women had mean age of 50.9 years and BMI of 25.6Inclusion:Number of flushes during the last day and night in a log-book which was filled in at bedtime for two weeks before and during the 12 week treatment. Also measured the severity of flushes (0–10); also completed questionnaires on aspects of quality of life at baseline, 4,8,12, and 24 weeks, Kupperman Index, VAS to general summary of the total climacteric symptom intensity and distress, MOOD Scale, SCL-904NoneNRNRNRNRNone previousSee population3 times weekly exercise (15 women); also compared to 8 wait listed women and 4 women being observed in a parallel study on hot flushes in women with breast cancerOral estrogen (15 women); 45 other women randomized to three additional arms (2mg/day)The severity of flushes decreased significnatly p=0.041 in the 5 exercising women, who continued the complete follup-up time of 36 weeks (exercising the entire time period). In the estrogen group the mean number of flushes decreased (p<0.001) after 12 weeks and remained at this level; in the waiting list group of 12 untreated women the number of flushes did not change during a period of 8 weeks.NRNRNRNRNRNRNRNRKupperman's Index and Mood Scale only changed significantly in the estrogen group (p<0.01), although SCL-90 improved in both exercise and estrogen group (p<0.01)SCL-90, Kupperman's and VAS all changed significantly p<0.01) at 36 weeks, and mood scale only in the estrogen group5/15 in the first 12 weeks, 5/15 additional in the second 12 weeks in the exercise group; 6/15 in the first 12 weeks from the estrogen group; 0/15 in the second 12 weeks1 from estrogen groupVaginal bleedingMind-body interventions
1. Spontaneous menopause ≥ 6 months previously
Exclusion:
1. Severe endocrine, metabolic or thrombo-embolic disease, uncontrolled hypertension, or daily use of sedatives, anxiolytic or antidepressant medication
2. Exercising regularly more than 1 hour/week
Makkonen, 199330DB RCTP6 monthsWomen, mean age of 52.3 ± 2.7 years for guar gum group; mean age of 53.6 ± 4.0 in placebo groupExclusion:Kupperman Index, weight, height, blood presuure, serum estrone, estradiol, testoserone, androstenedione, FSH, LH, SHBG, TSH, total cholesterol, HDL cholesterol, triglycerides and fasting blood glucoseNRNRNRNRNR3 were smokers in guar gum group; none in placeboAt least 3 months offWeight recorded in kilogramsGuar gum (Guarem, Orion Pharmaceutica, Espoo, Finland) 5 grams 3 times daily for 6 monthsPlacebo was wheat flour granulesBoth groups improved significantly on the Kupperman scale (p<0.001) at 3 and 6 months from baseline. No difference between groupsNRNRNRNRNRNRNRNRNRSee note under hot flashes regarding Kupperman Index scores3 withdrawals from the placebo group, one due to depression and exhaustion, and two due to travelling. No withdrawals from the guar gum groupNANABiologically based therapies
1. Uncontrolled hypertension, diabetes mellitus, liver disease or thromboembolic disease
2. Hormone therapy taken during previous three months
Murkies, 199558DB RCTHH14 weeksWomen were recruited from interested patients in a general practice in Melbourne, Australia and newspaper advertisementsInclusion:Diet diary; flush diary to record daily number of flushes; subjective four point scale of ‘general menopause symptoms’ (flushes, sweats, palpitations, headache, sleep disturbance, depression, tiredness, irritability/nervousenss, frequency/urge to urinate, vagninitis, loss of libido, dyspareunia; vaginal smearsNRNRNRNRNRNon smokersNone for 3 months26.5 ± 0.76 for soy group;45 grams of ‘soy flour’45 grams of refined wheat flourAt 6-weeks there was a significant decrease in hot flashes and general symptom score from baseline in the soy treated group (p<0.05). At 12-weeks there was a significant decrease in hot flashes and general symptom group in both groups (p<0.05) and no significant difference between the 2 flour groups.Vaginal maturation score did not change within or between flour groupsNRNRNRNRUrinary daidzein excretion increased signifiantly over 12 weeks in the majority of women in the soy group with signicant difference between groups (p<0.001)NRNRNRNo change in lipid panels between groups5/28 withdrew from soy group; 6/30 withdrew from wheat groupNRNRBiologically based therapiesSoy Products of Australia donated debittered soy and unbleached refined wheat flour
1. ≥ 12 months of amenorrhea, and FSH>25,25.6 ± 0.68 for wheat group
2. Hot flushes > 14/week
3. Non-smokers
4. Stopped antibiotics or hormonal replacement ≥ 3 months prior
Nachtigall, 199430RCTHH12 weeksPost menopausal womenInclusion:Pap smear done every 4 weeks with specific criteria for atrophy; Vaginal fluid pH; Vaginal health indexNRNRNRNRNRNRNot allowedNRReplens (a nonhormonal bioadhesive local vaginal mosturizer) 3 times/week for 12 weeks2 grams of Premarin Vaginal cream daily for 12 weeksNRVaginal moisture showed significant improvement in both groups at 12 weeks (p<0.005)NRNRNRNRNRNRNRNRVaginal elasticity improved in both groups (p <0.02) from baseline; vaginal pH and vaginal fluid volume improved from baseline (p<0.05)NoneNoneNoneBiologically based
1. > 1 year past their last menstrual period
2. Not on any other HRT
3. Cancer free
4. Experiencing vaginal discomfort or dyspareunia.
Nassef, The 10th World Congress on the Menopause. 2002 (Abstract Only)37RCTP3 monthsPostmenopausal Egyptian femalesNRNRNRNRNRNRNRNRNRNRCimicifuga rhizome 40mg/dayPlaceboNo difference (p>0.05) between groupsNRNRNRNRNRNo difference in dysuria or stress urinary incontinence between groups (p>0.05)NRNRNRBone aches were significantly improved in phytoestrogen group (p<0.001); no significant difference between groups in vaginal cytology, bone mineral density, or endometrial thickness (p>0.05)NRNRNRBiologically based
Penotti, 200362DB RCTP6 monthsWomen patients attending the outpatient Menopause Clinic at the University of MulanInclusion:Daily diary for hot flash recordingNRNRNRNRNRNRNR23.2 both groups36mg Soy Isoflavones a dayN/ANo change between groups, both groups had a 40% reduction in hot flashesNRNRNRNRNRNRNRNRNRNR6 in soy group1 from soy group due to diarrheaDiarrheaBiologically based
1. High FSH and low BE27 in placebo groupPersistent hot flashes in the rest
2. LDL < 160
3. ≥ 7 hot flashes/day
4. Post menopausal for ≥ 6 months
5. Aged 45–60 years
6. T score > -2.5
Exclusion:
1. Osteoporosis
Rachev, 200164DB RCTP60 daysWomen age 40–60 from the ‘maternity ward’ of the University Hospital in Sofia, Bulgaria; mean age was 51.5 in LF group and 49.5 in placebo group.Inclusion:Hamilton Anxiety Scale (HAMA) and the Climacteric IndexNRNRNRNRNRNRNRWeight was expressed in kilograms, mean of 71.3 for LF group and 79.0 for P groupLiposom Forte (phospholipid liposomes) 28mg/2ml as a single intramuscular injection every other day for a period of 60 daysPlacebo injection every other day for 60 daysSignificant decline in the climacteric index in LF and P groups from baseline (p<0.001); however more significant decline in LF group (p=0.0013) than P group (NOTE: did include questions of asthenia (p=0.05), dizziness (p=0.024) and restlessness (p=0.019)NRNRDecrease in the total HAMA score in both groups was noted (p<0.001); however significantly greater decline in the LF group than the P group (p<0.001); specifically anxious mood (p=0.006), tension (p=0.024) and fear (p=0.009) were significant between groups as well.NRNRNRNRNRSee climacteric index scores under hot flashesNR6/64Allergy = 1NRBiologically based therapiesNot sure that they did a good job of confirming symptoms were related to menopause
1.Evident anxious-depressive symptoms associated with physiological menopause lasting for at least one yearanxiety = 1;
2. No treatment with phospholipids ≥ 4 weeks priorasthenia = 1;
3. No antidepressant or anxiolytic therapy during the studydrowsiness = 2;
Exclusion:hypertension = 1;
1. Sensory organ deficiency not properly corrected by artificial aidspetechia = 1;
2. Signs or symptoms of foci of cerebral lesions,increased sweating = 1;
3. Signs or symptoms of other neurological and/or psychiatric diseases requiring treatment with neuroleptic drugs and/or other antidepressantsparoxysmal tachycardia = 1;
4. Liver or kidney impairment, severe cardiovascular diseases, past or ongoing neoplastic diseases, other sever ongoing internal or surgical pathologiesweight increase = 1
5. Proven hypersensitivity to phospholipid
Rankin, 198940RCTNo treatment2 weeksWomen, age 40–60 who stated they were experiencing menopausal symptoms; referred to the study by other health professionals and recruited from church groups and various women's organizations. Mean age was 49.3 years, range from 40–58Inclusion:Neugarten-Kraines Menopausal Index Scale, Sound Wave Audiotapes41%NRNRNRNRNR5 (2/sound, 3/control) had taken HRT for 1–12 yearsNR20 minute long low frequency sound wave audiotape developed by Halpern (1978); 3 times/week for 2 weeksNo treatmentThe sound wave group has significant improvement over no treatment in decreased frequency of symptoms (p=0.01), somatic symptoms were decreased (p=0.03) and psychological symptoms were decreased (p=0.029).NRNRNRNRNRNRNRNRNRNR6/20 in sound group; 7/20 in the control group4 completed the protocol late, others did not follow instructions, or did not have time.NoneMind-bodyPoor study
1. Understand and write English
Rao, 200330RCTP2 monthsWomen with menopausal symptomsNRMenopause-specific Quality of LifeNRNRNRNRNRNRNRNRBiogest cream (wild yam)PlaceboSignificant effects were noted with symptoms of hot flushes, night sweats, and emotional symptoms with dramatic reductions in these symptoms occurring in the BioGest group when compared with placebo.NRNRNRNRNRNRNRNRNRNRNRNRNRBiologically basedAbstract only available
Russo, 200350DB RCTP3 monthsWomen who were referred to a clinic in Rome, Italy.Inclusion:Self report questionnaire.NRNRNRExcludedNRSmokers excluded≥ 6 months discontinuationObesity excluded32mg/day of Soy (Fitormil)- Specific formulation described in paperPlacebo11/25 in soy group and 6/25 in placebo group described improvement in symptoms (p<0.05)No significant reductions for either group.No significant reductions for either group.No significant reductions for either group on anxiety.NRNRNRNRNRNRNR31 due to spotting after 15 daysSpottingBiologically basedCross over study, only using data from first 3 months before cross over.
Average age: 53 years1. Aged 48–54 years
Average age at onset of menopause: 51 years2. Recent menopause (1–2 years LMP)
3. Symptomatic
4. Caucasian
5. Negative PAP test
Exclusion:
1. Currently on HRT or off <6 months
2. Arterial hypertension or cardiovascular pathologies
3. Endocrinological pathologies
4. Nicotinism
5. Obesity
6. Alcohol or drug abuse
Salmaggi, 199380DB RCTP30 daysAge 45–59 (mean age is 51) women patients consecutively referred to an Ob/Gyn department in ItalyInclusion:HAM-D-21 (Hamilton Depression Rating Scale) and the RDI (Rome Depression Inventory); MMPI (Minnesota Multiphasic Personality Inventory); CGI-I (Clinical Global Impression Improvement Scale)IncludedIncludedNRNRNRNRNot included if on estrogenNR1600mg SAMe per day divided into 4 dosesPlaceboNRNRNRHAM-D-21 decreased significantly (p<0.01) at both day 10 and 30 compared to placebo; also found in RDI (p<0.01), CGI-I (p<0.01) and depression and psychoasthenia scale of MMPI (p<0.01) compared to placebo.NRQuestions 11–16 on the HAM-D-21 pertaining to somatic symptoms improved significantly from placebo at both day 10 and 30 (p<0.01)NRNRNRNRNR10/40 from each group due to poor complianceNRNRBiologically based
1. Major depression within 6 to 36 months following surgical or natural menopause
2. Free of antidepressants for ≥ 1 week
Exclusion:
1. Considered at risk for suicide
2. On estrogen therapy
3. Major medical illness or bipolar illness
Sammartino, 200370RCTHH12 cycles of 28 daysWomen attending Menopause Clinic.Inclusion:Kupperman scale - Baseline and 6, 12 months0000NRNRExcludedExcluded if >3036mg/day of GenisteinCalcium supplementsSignificant decline in Kupperman Score for Genistein group (p<0.05).NRNRNRNRNRNRNRNRNRAll women in Genistein group had decreased climacteric symptoms (but not specified by symptom).3 in GenisteinNoneNoneBiologically based
Average Age: 51 years1. At least 12 months after spontaneous menopause4 in Calcium
Average time since menopause: 17 months2. FSH > 40
Average BMI: 24–263. Estradiol < 20
4. At least 7 hot flashes of moderate to severe severity in 24 hours during last 2 weeks
Exclusion:
1. Neoplastic, metabolic and infectious diseases
2. Concomitant use of any drug
3. BMI < 30
4. Past or concomitant use of HRT or other drug used for treatment of climacteric symptoms
5. Endometrial thickness of >5mm or endometrial abnormalities
Sandberg, 200230RCTHH14 weeks, Follow-up at 6 monthsWomen age 48–60, natural menopause of at least 6 months were recruited through advertisements in the local press and at gynecological outpatient clinics.Inclusioin:Visual Analog Scale (VAS)UnclearNot includedNot includedNRNRSimilar rates of smoking & exerciseNR how recent, not taken during study26.7 vs. 25.6Electro acupuncture (EA)Extremely superficial needle insertionBoth groups showed improvement in VAS at 3 and 6 monthsNRNRSignificant improvement in mood at 12 weeks in EA group compared to baselineNRNRNRNRNRNRNR4/15 Superficial needle insertionHot flashesHot flashesAlternative health care systems
1. FSH and estradiol levels confirms postmenopausal stateSCL-90Both groups improved in SCL-904/15 EA
2. Natural menopause of ≥ 6 months
3. Aged 48–60 years
Exclusion:
1. Severe metabolic, thromboemboic, endocrine or malignant disease, uncontrolled hypertension
2. Use of medication that could interfere with vasomotor symptoms
Scambia, 200039DB RCTP12 weeksWomen who were outpatients at Italian hospital (mean age was 54 ± 7.1 years)Inclusion:Vasomotor symptoms were evaluted usina a special score card and the Greene climacteric scale. Special score card was filled out daily to evaluate the number and severity of hot flushes and brought it to each visitNR1/501/50NRNRNRNRBMI = 26.2 ± 1.7Standardized soy extract containing 12% isoflavones and 35% saponins in a tablet which was 200mg SOYSELECT 2/day which would correspond to 50mg/day of isoflavones. After 6 weeks of treatment Premarin was also given to each participant at a dose of 0.625 for 4 weeksPlacebo tablet containing lactoseIn the first 6-weeks of treatment, participants who were taking the standardized soy extract had a significant reduction (p<0.01) in the mean number of hot flushes/week as compared with placebo. Once the Premarin was started both groups had a decrease in hot flushes and there was no significant difference between groups.After 6 weeks of treatment, the group that was taking the standardized soy extreact had a significant reduction (p<0.001) in the mean point values 19 and 20 of Greene scale (hot flushes and night sweats) compared with placebo.NRNRNRNRNRNRNRNRNR20 were analyzed in soy extract group suggesting no withdrawalsNausea in 1 placebo memberNRBiologically based
1. Spontaneous amenorrhea ≥ 12 months
2. Surgical or early menopause
3. Normal endometrial thickness by ultrasound, negative mammography, and metabolic and biochemical index within normal range
Simkin-Silverman, 2003535RCTLifestyle vs. assessment only5 yearsWomen were recruited from the WHLP clinical trials and were seen at the Health Studies Clinic at the University of Pittsburg.Inclusion:Weight, BMI and body fat were measured.NRNRNRNRNRNRNR58/535 High BMIBehavioral, dietary and physical activity interventionN/ANRNRNRNo signs of increased stress or depressive symptoms in intervention groupNRNRNRNRNRNRWomen lost significantly more weight in the intervention group (p<0.001), remained more active (p<0.001) and consumed fewer calories (p<0.01) than the control group.14/260 InterventionNRNRMind-body5 year program showed that intense exercise encouragement (cognitive restructuring program) and low fat diet showed decrease of weight and waste circumference
1. Aged 44–50 yearsPaffenbarger Activity Questionnaire12/275 Control
2. Premenopausal by self reportThe Block Food Frequency Questionnaire
3. Not taking HRT
4. BMI was 20–34
Exclusion:
1. Women taking lipid-lowering medication, antihypertensive medication, insulin, thyroid medication, or psychotropic medications
St. Germain, 200169RCTPlacebo24 weeksTelephone interviews of age 42–62 year old women;Inclusion:5 day Menopausal Index (modified from the Blatt instrument, 1953) at baseline, week 12 and week 2411 with intact ovariesExcludedNRNRNRNon smokingNone for 12 months prior to study20–31SPI+ (Supro 675 HG; Protein Technologies International, St. Louis, MO = 80.4 mg/day aglycone components which are the unconjugated parent forms of isoflavones)SPI- (Supro 675 IF; Protein Technologies International) = 4.4 mg/day aglycone components; Group 3 consumed whey protein (control) produced by ProMod; Ross Laboratories, Columbus, OhioNo treatment effect on the change in frequency of hot flushes; time of study from baseline did have a significant effect on hot flush frequency in all groups (p.0.003)No significant difference among the three groups at any time pointNRNo significant difference among the three groups at any time pointNRNRNo significant difference among the three groups at any time pointNRNo significant difference among the three groups at any time pointNRNR1/69NoneNRBiologically based therapies
1. ≥ 10 hot flushes and/or night sweats/week, within 12 months of their last menstrual cycle
2. Free from chronic diseases (cardiovascular disease or osteoporosis) or chronic medication use
3. Not taking HRT or ERT at the time of the study or 12 months previously
4. 1 or both ovaries remaining
5. BMI 20–31
6. FSH>30.
Teoman, 200481RCTControl Usual care6 weeksVolunteer postmenopausal women (average age 51.0 ± 3.9 years)Inclusion:6 minute walking test, vertical jump test, static back extension test, sit up test, side bending test, sit and reach test, balance test, quality of life using the Nottingham Health ProfileNRExcludedNRNRNRNRMust be on for 12 months27.0 ± in exercise group and 25.4 ± 4.0 in control group6 weeks aerobic exercise programmeNon-exercise control groupNRNRNRNRNRNRNRNRNRAt the end of the 6 weeks, there was a statistically significant change in the exercise group according to NHP, indicating an improvement in the quality of life (<0.05). Only the increase in social isolation parameter was not statistically significant.NRNRNRNRExerciseTurkey
1. Natural menopauseMind/body
2. Taking HRT ≥ 1 year (0.625 mg estrogen and 2.5 mg medroxyprogesterone/day)
3. Aged 45–65 years old
4. No health problems that may prevent from doing exercise
5. No high cardiac risk
Thompson, 2002 (Abstract only)53DB RCTP16 weeksWomen with breast cancer with menopausal symptomsNRMeasure Yourself Medical Outcome Profile (MYMOP), Hospital Anxiety and Depression score, European Organization for Research and Treatment in Cancer Quality of Life Score, Menopausal Symptom ScaleNRNRNRIncludedNRNRNRNRHomeopathic interventionPlaceboBoth groups showed significant improvement over the study period by an average of 80%. No statistically significant difference betweeen groupsNRNRNRNRNRNRNRNRNRNR8/43NRNRBiologically based therapiesAbstract only; included as only homeopathic RCT that could be found.
Tice, 2003252DB RCTHH12 weeksWomen were recruited from 3 academic clinical research sites in Oakland, CA; Minneapolis, MN, and Iowa City, Iowa from the general population through newspaper and radio advertising, flyers posted in clinics and at health fairs, and directed mailingsInclusion:Greene Climacteric Scale; used the psychological (anxiety and depression), somatic, vasomotor, and sexual desire; hot flash diary cardsNRAllowedNRNRNRExcluded if drank >2 alcoholic beverages/ dayNone for 3 months prior26.3 ± 5.1 in Promensil group; 25.6 ± 4.2 in Rimostil group; 26.5 ± 5.4 in placebo groupPromensil contains an average of 41.0 mg of total isoflavones/tablet (red clover containing a higher proportion of biochanin A and genistein); Rimostil contains average of 28.6 mg of total isoflavones and a higher proportion of formononetin and daidzein. Participants took two tablets daily.Placebo that had less than 0.04 mg total isoflavoneDecrease in hot flush count was significant for all three groups (p<0.001), however, the hot flash reductions in the phytoestrogen groups were not statistically different from placebo at 12 weeks (p>0.20).NRNRNRNRNRNRNRNRNRGreene Symptom Scales; over the 12-week treatment period, there were significant improvements from baseline in all three groups, but there was no statistically significant differences between groups on any of the Greene scales6/252 withdrew 2 from each of the 3 arms; 84 participants were in Promensil group; 83 participants were in Rimostil group; 85 participants were in placebo group1 from the Rimostil groupThere was no statistically significant association of either of the dietary supplements with adverse eventsBiologically based
1. Age 45–60 years old
2. Experiencing ≥ 35 hot flashes/week
3. FSH > 30