The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study.

Background: The unexpected results of the Women's Health Initiative study have decreased the use of conventional hormone therapy (HT), changing physicians' and patients' attitudes towards HT and increasing their interest in alternative options. OBJECTIVE: The present study aimed to evaluate the effect of isoflavones contained in red clover extracts (Trifolium pratense) on menopausal symptoms, lipids and vaginal cytology in menopausal women. METHODS: Sixty postmenopausal women aged >40 years, non-users of HT, with Kupperman index score 15, were double-blindly randomized to receive either a commercially available red clover isoflavone supplement (80 mg/day) or placebo for 90 days. Subsequently, after a 7-day washout period, subjects switched to receive the opposite treatment for a further 90 days. Kupperman index score was determined and fasting blood and vaginal cytologic sampling performed at baseline, 90 and 180 days. RESULTS: Fifty-three women (88.3%) completed the trial. Mean age was 51.3 +/- 3.5 years, 69.7% of the women were aged 50 years or more. There was no significant effect on body mass index, weight or blood pressure after either treatment phase. Baseline Kupperman index score decreased significantly after each treatment phase, with the decrease more pronounced after the isoflavone phase (baseline: 27.2 +/- 7.7; after isoflavone: 5.9 +/- 3.9; after placebo: 20.9 +/- 5.3, p < 0.05). Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic, cornification and basal cell maturation indices. Mean total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels also decreased; however, only the latter was significantly lower compared with placebo. CONCLUSIONS: Compared with placebo, red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels.     

Benefits of soy isoflavone therapeutic regimen on menopausal symptoms

OBJECTIVE:To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100-mg soy isoflavone in postmenopausal women. METHODS: In this double-blind, placebo-controlled study, 80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment. The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment. Cardiovascular risk factors were assessed by evaluating plasma lipid levels, body mass index, blood pressure, and glucose levels in the participants. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 17 beta-estradiol were measured. Transvaginal sonography was performed to quantify endometrial thickness. RESULTS: The data showed a decrease in menopausal symptoms (P <.01, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). Total cholesterol and low-density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P <.001, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). The isoflavone treatment appeared to have no effect on blood pressure, plasma glucose, and high-density lipoprotein and triglyceride levels. CONCLUSION: This study suggests that isoflavone 100-mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system.     

The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women.

OBJECTIVE: To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women. DESIGN: Thirty postmenopausal women aged greater than 60 years received either two tablets of an extract of aglycone isoflavones from red clover (each containing formononetin 25 mg, biochanin 2.5 mg and less than 1 mg of daidzein and genistein) for 6 months in a randomized, controlled clinical trial. Cognitive function tests were performed at baseline and at the end of isoflavone or placebo therapy. RESULTS: Isoflavone supplementation was associated with an apparent improvement in block design (a test of visual-spatial intelligence) compared to placebo (isoflavone +12%, placebo -3%; p = 0.03), no improvement in verbal memory compared to an improvement on placebo (isoflavone +1%, placebo +29%; p = 0.023) and a deterioration in digit recall compared to placebo (isoflavone -6%, placebo +12%; p = 0.029). However, these findings were not statistically significant when corrections were made for potential chance findings due to multiple comparisons. CONCLUSION: Isoflavone supplementation does not appear to have major short-term effects on cognitive function in postmenopausal women. However, further clinical trials are required to determine whether small effects or long-term effects on cognitive function occur during isoflavone supplementation.     

Effect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass index

Background. Since current clinical evidence indicates that conventional estrogen hormone therapy (HT) increases cardiovascular risk, alternatives to estrogens are growing in popularity, especially among high-risk populations.

Objective. To determine the effect of Trifolium pratense-derived isoflavone supplementation on the lipid profile of postmenopausal women with increased body mass index (BMI).

Methods. Sixty postmenopausal women aged > 40 years, HT non-users, were randomly assigned to one of two groups: either two capsules of T. pratense (80 mg red clover isoflavones) daily for a 90-day period or placebo of equal design. After a 7-day washout period, medication was crossed-over for another 90 days. Total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein A (LpA) levels were assessed at baseline, 90 and 180 days. Women were divided into two groups: those with increased BMI (≥25 kg/m²) and those with BMI < 25 kg/m².

Results. Fifty-three women (88.3%) completed the trial. T. pratense isoflavone supplementation had a positive effect on the lipid profile of women with increased BMI, evidenced by a significant decrease in TC, LDL-C and LpA levels.

Conclusions. Isoflavones derived from T. pratense are an attractive alternative therapeutic option for high-risk populations such as postmenopausal women with increased BMI and abnormal lipid profile.     

Phytoestrogens for treatment of menopausal symptoms: a systematic review

OBJECTIVE: To assess the efficacy and tolerability of phytoestrogens for treatment of menopausal symptoms. DATA SOURCES: We searched the Cochrane Library and MEDLINE from 1966 to March 2004, using a detailed list of terms related to phytoestrogens and menopausal symptoms and also hand-searched abstracts from relevant meetings. METHODS OF STUDY SELECTION: Randomized trials were eligible if they involved symptomatic perimenopausal or postmenopausal women, compared phytoestrogen with placebo or control, reported hot flush frequency or menopausal symptom scores, and were at least 4 weeks in duration. TABULATION, INTEGRATION, AND RESULTS: Data were extracted onto standardized forms using a prospectively developed protocol. Twenty-five trials involving 2,348 participants met criteria. At baseline, the mean age was 53.1 years, mean duration of menopause was 4.3 years, and mean daily hot flush frequency was 7.1. Mean study duration was 17 weeks. Trials were grouped into categories according to type of phytoestrogen: soy foods, beverages, or powders (n = 11); soy extracts (n = 9); and red clover extracts (n = 5). Of the 8 soy food trials reporting hot flush frequency outcomes, 7 were negative. Five trials of soy foods provided information to calculate effect sizes; these were in the small-to-medium range, favoring placebo in 3 trials and soy in 2. Of the 5 soy extract trials reporting hot flush frequency, 3 (including the 2 largest trials) were negative. Effect sizes were calculated for 2 soy extract trials: one favored placebo with small effect size and the other favored soy with moderate effect size. Red clover trials showed no improvement in hot flush frequency (weighted mean difference -0.60, 95% confidence interval -1.71 to 0.51). Adverse effects were primarily gastrointestinal and taste intolerance in the soy food and beverage trials. CONCLUSION: The available evidence suggests that phytoestrogens available as soy foods, soy extracts, and red clover extracts do not improve hot flushes or other menopausal symptoms.     

Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial

Objective: To evaluate possible estrogenic effects of dong quai on vaginal cells and on endometrial thickness in postmenopausal women.

Design: Double-blind, randomized, placebo-controlled clinical trial.

Setting: Department of Obstetrics and Gynecology in a large health maintenance organization (HMO).

Patient(s): Seventy-one postmenopausal women (mean age [±SD], 52.4 ± 6 years) who had follicle-stimulating hormone levels (third-generation assay) of >30 mIU/mL with hot flashes.

Intervention(s): Subjects were randomized to treatment with either dong quai or placebo for 24 weeks.

Main Outcome Measure(s): Endometrial thickness was measured by transvaginal ultrasonography; vaginal cells were evaluated for cellular maturation; menopausal symptoms were evaluated by reviewing the Kupperman index and the diary of vasomotor flushes.

Result(s): We observed no statistically significant differences between groups in endometrial thickness, in vaginal maturation index, in number of vasomotor flushes, or in the Kupperman index.

Conclusion(s): Used alone, dong quai does not produce estrogen-like responses in endometrial thickness or in vaginal maturation and was no more helpful than placebo in relieving menopausal symptoms.     

The effect of soy-derived isoflavones over hot flushes,menopausal symptoms and mood in climacteric women with increased body mass index

Background.?Risk-benefit issues raised after the WHI have significantly increased the use of alternative treatments for the menopause. Despite this, data regarding the effect of soy isoflavones over mood and menopausal symptoms in high risk populations is still lacking.

Objective.?To evaluate the effect of soy derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index (BMI).

Methods.?Fifty symptomatic climacteric women aged 40 to 59 with increased BMI (≥25) were recruited to receive oral 100?mg/day of soy derived isoflavones (Climasoy®) for 3 months. Hot flushes (frequency/intensity), menopausal symptoms (Menopause Rating Scale [MRS]) and mood (Hamilton Depressive Rating Scale [HDRS]) were evaluated at baseline and at 90 days.

Results.?A total of 45 women completed the study. After 3 months of soy isoflavone supplementation hot flushes significantly decreased in percentage, number and severity (100% to 31.1%; 3.9?±?2.3 to 0.4?±?0.8 and 2.6?±?0.9 to 0.4?±?0.8, respectively, p?<?0.001). MRS scores (total and for subscales) reflecting general menopausal symptoms also significantly decreased compared to baseline. Regarding mood, after three months total HDRS scores and the rate of women presenting depressed mood (scores?≥?8) significantly decreased (16.3?±?5.4 to 6.9?±?5.2 and 93.3% to 28.9%, respectively, p?<?0.05). There was no effect on blood pressure levels or BMI values after treatment.

Conclusion.?In this high risk climacteric population, soy derived isoflavone treatment improved mood as well as vasomotor and general menopausal symptoms. More research is required to determine if the positive effect over mood is a direct or an indirect one through hot flush alleviation.     

Effects of soy isoflavones on menopausal neurovegetative symptoms

AIM: Dietary soy supplementation may reduce the incidence of hot flushes in postmenopausal women due to the presence of phytoestrogens in soy foods. The aim of this study was to assess the effects of a 3-month administration of different doses of either oral or transdermal soy isoflavones on climacteric complaints in postmenopausal women. METHODS: Sixty postmenopausal women were assigned randomly to one of the following groups: groups A and B received 50 mg/day or 75 mg/day of oral isoflavones respectively, while groups C and D received 6 mg/day or 12 mg/day of transdermal isoflavones. A control group (group E) was composed of 15 patients that did not receive any treatment. Hot flushes, Kupper-man index and vaginal dryness at baseline and then after 5, 9 and 13 weeks were evaluated. RESULTS: The isoflavone treatment led to a progressive significant (p<0.01) reduction of the number of hot flushes in the groups A, B and D with a dose-related effect in group D. At week 13, the Kupperman index and hot flush score decreased significantly in all the treated groups, while vaginal dryness score was reduced only in group B. CONCLUSION: Our findings suggest that both oral and transdermal soy isoflavones are effective to attenuate slight to moderate menopausal neurovegetative symptoms with a dose-related effect.     

不同绝经状态妇女绝经症状与抑郁状态的临床分析

目的:探讨对不同绝经症状妇女的健康保健措施。方法:366例就诊于更年期门诊的妇女按月经状态分成围绝经期组(n=104)、绝经早期组(n=194)、绝经晚期组(n=68),采用改良Kupperman评分法和自评抑郁量表(self-rating depression scale,SDS)对患者进行绝经症状及抑郁症状评分。结果:改良Kupperman评分异常者占46.99%(172/366),Kupperman评分绝经早期组和绝经晚期组比较无显著差异(t=0.393,P>0.05);绝经早期组、绝经晚期组显著高于围绝经期组(t=2.899,P=0.004;t=2.371,P=0.019)。SDS异常者占11.20%,各组间SDS评分无差异。改良Kupperman评分与SDS评分具有相关性(18.58±9.05vs33.60±9.44,Pearson相关系数为0.599,P=0.000)。结论:绝经症状评分绝经妇女高于围绝经妇女,抑郁评分与绝经症状评分存在显著相关性,故需关注妇女的绝经症状,尤其是抑郁症状。     

The relationship between women’s attitude towards menopause and menopausal symptoms among postmenopausal women

Abstract

Objectives: The purpose of this study is to assess the symptoms of menopausal women as well as the relationship between women’s attitude towards menopause and menopausal symptoms.

Method: This studied, following a cross-sectional method, included 349 selected postmenopausal women attending health care centers. The data was collected using the attitude toward menopause (ATM) checklist and Menopause-Specific Quality of Life (MENQOL) questionnaires.

Results: The most common menopausal symptoms were physical with joint and muscle pain. The highest mean score belongs to vasomotor symptoms (1.37?±?1.43), followed by psychosocial (1.32?±?1.16), physical (1.22?±?0.96), and sexual (0.91?±?0.94) symptoms. Attitude toward menopause was significantly influenced by sweat nights, poor memory, and sleeplessness. The marital status and educational level of the husband were the only demographic factors affecting the severity of menopausal symptoms.

Conclusion: This study provides deeper insights about the relationship between attitudes towards menopause and menopausal symptoms, which can guide health-care professionals towards providing an optimal package.     

Lowest effective transdermal 17beta-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial

OBJECTIVE: To investigate the efficacy of micro-dose transdermal estrogen in relieving menopausal vasomotor symptoms. METHODS: A randomized, double-blind, placebo-controlled, multi-center trial. Healthy postmenopausal women with at least seven moderate or severe hot flushes per day for at least 1 week, or at least 50 per week, applied transdermal patches with a nominal delivery of 0.023 mg/d 17beta-estradiol and 0.0075 mg/d levonorgestrel (low-dose E2/levonorgestrel; n=145), 0.014 mg/d E2 (micro-dose; n=147), or placebo (n=133) for 12 weeks. The coprimary efficacy variables were the mean changes from baseline in frequency and severity of moderate and severe hot flushes at the week 4 and 12 endpoints. RESULTS: At the week 12 endpoint, mean weekly frequencies of moderate and severe hot flushes were significantly reduced compared with placebo with low-dose E2/levonorgestrel (-51.80; P<.001) and micro-dose E2 (-38.46; P<.001). Severity scores were also significantly reduced with both treatments compared with placebo. At week 12 endpoint, 41.3% of women receiving micro-dose E2 were treatment responders (75% or more reduction from baseline in hot flush frequency; P=.003 compared with 24.2% placebo). In this group, the mean reduction in moderate and severe hot flushes from baseline was approximately 50% after 2, 70% after 4, 90% after 8, and 95% after 12 weeks. There were no differences between active treatments and placebo regarding adverse events. CONCLUSION: Micro-dose E2 (0.014 mg/d) was clinically and statistically significantly more effective than placebo in reducing the number of moderate and severe hot flushes, with a 41% responder rate, supporting the concept of the lowest effective dose. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00206622     

Optimizing soy isoflavones effect in postmenopausal women: the impact of timing on climacteric symptoms

Background.?The most common complaints during climacteric are vasomotor symptoms. A circadian rhythm has been observed when hot flashes start; however, not much information is available in this field.

Aims.?To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome.

Trial design.?Multicentric, observational, open, prospective, longitudinal and cross-sectional study.

Subjects and methods. One thousand six hundred eighty-two postmenopausal women with climacteric symptoms were allocated in two groups in order to receive the treatment in the morning (Group 1) or in the evening (Group 2), switching administration time after 3 months. Clinical evaluation was carried out at 0, 3 and 6 months of follow-up using Blatt–Kupperman and Greene scales

Results.?233 (13.9%) women dropped out from the study. Both administration times improved the climacteric symptoms after 3 and 6 months of treatment, showing a reduction in the scores of Blatt–Kupperman and Greene scales (p?<?0.001). No differences between both groups during the follow-up were identified.

Conclusions.?The time of administration of isoflavones does not modify its effect on climacteric symptoms.     

A comparison of acupuncture and oral estradiol treatment of vasomotor symptoms in postmenopausal women.

OBJECTIVE: To compare the effects of electro-acupuncture with oral estradiol and superficial needle insertion on hot flushes in postmenopausal women. MATERIAL AND METHODS: Forty-five postmenopausal women with vasomotor symptoms were randomized to electro-acupuncture, superficial needle insertion or oral estradiol treatment during 12 weeks, with 6 months' follow-up. The number and severity of flushes were registered daily and the Kupperman index and a general estimate of climacteric symptoms were completed before, during and after therapy. RESULTS: In the electro-acupuncture group, the mean number of flushes/24 h decreased from 7.3 to 3.5 (ANOVA, p < 0.001). Eleven of the 15 women had at least a 50% decrease in number of flushes (with a mean decrease of 82%). Superficial needle insertion decreased the number of flushes/24 h from 8.1 to 3.8 (p < 0.001). In seven out of 13 women, the number of flushes decreased by at least 50% (mean decrease 83%). In the estrogen group, the number of flushes decreased from 8.4 to 0.8 (p < 0.001). The decrease in number of flushes persisted during the 24-week follow-up period in all treatment groups. The Kupperman index and the general climacteric symptom score decreased, and remained unchanged 24 weeks after treatment in all groups (p < 0.001). Electro-acupuncture decreased the number of flushes/24 h significantly over time, but not to the same extent as the estrogen treatment. No significant difference in effect was found between electro-acupuncture and the superficial needle insertion. CONCLUSION: We suggest that acupuncture is a viable alternative treatment of vasomotor symptoms in postmenopausal women and cannot recommend superficial needle insertion as an inactive control treatment.     

Quality-of-life assessment in community-dwelling, middle-aged, healthy women in Japan.

OBJECTIVES: To determine the quality of life (QOL) of middle-aged Japanese healthy women during the menopausal transition, to identify the correlation between decreasing quality of life and the severity of menopausal symptoms in those women, and to evaluate the number of women who sought treatment/health-care support and their expectations for health-care services. METHODS: This was a community-based study, performed in collaboration with the Munakata Women's Midlife Health Project. The participants attended an annual medical check-up and cancer screenings, and led an everyday life without receiving medical treatment. Their quality of life was assessed with the World Health Organization QOL assessment (WHOQOL) and the severity of menopausal symptoms was assessed with the Kupperman index. Their expectations for health-care services were determined with an open-ended questionnaire. RESULTS: The mean scores of the Kupperman index in the peri- and postmenopausal states were significantly higher than that in the premenopausal states, whereas there was no significant difference of quality of life scored by the WHOQOL in the three groups. In spite of recruiting healthy middle-aged women, 24.4% of the perimenopausal and 26.6% of the postmenopausal women suffered from moderate or severe menopausal symptoms. The decreasing level of quality of life was correlated with the severity of the menopausal symptoms in the peri- and postmenopausal women. The participants did not receive medical support except in two cases, but 83.0% of them wished to participate in a seminar concerning menopause. Several of them sought treatment, health-care support and advice on how to maintain their health during and after the menopausal transition. CONCLUSIONS: Nearly one-quarter of Japanese community-dwelling, healthy women in the peri- and postmenopausal states suffered from menopausal symptoms, which decreased their quality of life in everyday life.     

Use of alternative and complementary medicine in menopause.

OBJECTIVES: To review the clinical evidence available for the treatment of menopausal symptoms with alternative and complementary medicine. METHODS: The MEDLINE, PREMEDLINE and COCHRANE electronic databases for the years 1980-2002 were searched for articles concerning soy products, black cohosh, dong quai, acupuncture, ginseng and evening primrose oil. Studies pertaining to menopausal vasomotor symptoms, lipid profiles and bone mineral densities of postmenopausal women were included. The data from clinical trials were reviewed. RESULTS: Soy isoflavones slightly decrease total cholesterol and LDL levels. The clinical significance of this small change is yet to be determined. The synthetic isoflavone derivative ipriflavone increases bone mineral density in healthy peri- and postmenopausal women with moderate bone mineral densities. Although earlier reports have claimed that soy is beneficial for the improvement of vasomotor symptoms, recent data do not support this claim. There are insufficient data on the other alternative therapies for treating menopausal symptoms at this time. CONCLUSION: Alternative and complementary medicine may play a role in the management of menopause, however, well-designed large studies are still needed.     

A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients

OBJECTIVE: Phytoestrogens are popular in treatment of menopause, although scientific evidence is insufficient as to their efficacy. We studied the effects of daily use of isoflavonoids on climacteric symptoms and quality of life in patients with a history of breast cancer. METHODS: Sixty-two postmenopausal symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for 3 months; the treatment regimens were reversed after a 2-month washout period. Fifty-six women completed the study. Menopausal symptoms were recorded on the Kupperman index and the visual analogue scale, and working capacity and mood changes were assessed via validated questionnaires. In addition, we followed the levels of phytoestrogens, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and sex hormone-binding globulin. Liver enzymes and creatinine were also assessed at each visit. RESULTS: The phytoestrogen regimen raised the circulating levels of phytoestrogens (daidzein, genistein, equol) 19- to 106-fold. The Kupperman index was reduced by 4.2 +/- 9.6 (mean +/- standard deviation) (15.5%) during phytoestrogen use and similarly by 4.0 +/- 8.1 (14.7%) during placebo use (P nonsignificant). The quality of life parameters (working capacity, mood changes) were unaffected by phytoestrogen. In addition, the phytoestrogen regimen caused no changes in FSH, LH, estradiol, or sex hormone-binding globulin. Phytoestrogen treatment was well tolerated and caused no changes in liver enzymes, creatinine, body mass index, or blood pressure. Of the 56 women, 25 (44.6%) preferred the phytoestrogen regimen, 15 preferred the placebo (26.8%), and 16 (28.6%) reported no preference (nonsignificant). CONCLUSION: Pure isoflavonoids did not alleviate subjective menopausal symptoms in breast cancer patients.     

Transition from estrogen-progestin to raloxifene in postmenopausal women: effect on vasomotor symptoms

OBJECTIVE: To compare vasomotor symptoms after transition from estrogen-progestin therapy to raloxifene 60 mg/d with and without a placebo washout. METHODS: Postmenopausal women currently taking continuous combined estrogen-progestin therapy (conjugated equine estrogen, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg) daily for 5 or more months were enrolled. Women were randomized to 1 of 4 blinded regimens: 1) 12 weeks estrogen-progestin; 2) 12 weeks placebo; 3) 4 weeks placebo, then 8 weeks raloxifene; or 4) 12 weeks raloxifene. For the final 36 weeks, all subjects received raloxifene. Vasomotor symptoms were assessed by patient diaries. RESULTS: A total of 266 women (mean age 57.5) were enrolled. Mean hot flush frequency at baseline was approximately 1 per week in the entire population, with 16% of women reporting hot flushes. Mean frequency and severity of hot flushes during the first 12 weeks of the study were statistically greater in the 3 groups transitioned off estrogen-progestin (range of hot flushes per week: 4 weeks, 11-12; 8 weeks, 18-24; 12 weeks, 13-16), as compared with those continuing estrogen-progestin, with no difference between these 3 groups (P> or =.1). Approximately 50-70% of these women reported hot flushes, generally rated as mild to moderate by participants, after estrogen-progestin discontinuation. CONCLUSION: A large proportion of women discontinuing estrogen-progestin experience hot flushes. Raloxifene does not appear to increase the frequency or severity of vasomotor symptoms in women discontinuing estrogen-progestin more than that observed with placebo treatment after estrogen-progestin discontinuation. Transition from estrogen-progestin to raloxifene with no washout period therefore may be acceptable. LEVEL OF EVIDENCE: I     

Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial

OBJECTIVE: To compare efficacy and safety of desvenlafaxine succinate (desvenlafaxine) with placebo for the treatment of vasomotor symptoms. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 707 healthy, postmenopausal women experiencing 50 or more moderate-to-severe hot flushes per week. Participants randomly received desvenlafaxine 50, 100, 150, or 200 mg or placebo daily. Trial duration was 52 weeks. Primary outcomes were change from baseline in average daily number of moderate-to-severe hot flushes and in daily hot flush severity score at weeks 4 and 12. RESULTS: Six hundred twenty women with an average of 11 moderate-to-severe hot flushes per day at baseline completed at least one on-therapy evaluation for primary efficacy end points; 519 participants completed 12 weeks of treatment, and 368 completed the study. Desvenlafaxine 100 mg/d achieved a significantly greater reduction compared with placebo in average daily number of hot flushes at weeks 4 (P=.013) and 12 (P=.005), reaching a 64% decrease from baseline at week 12, and the 75% responder rate was significantly higher for desvenlafaxine 100 mg (50%) compared with placebo (29%; P=.003; number needed to treat=4.7) at week 12. Average daily severity of hot flushes was significantly lower in the desvenlafaxine 100-mg group compared with placebo at week 12 (P=.020). Desvenlafaxine-treated women reported significantly more treatment-emergent adverse events than placebo-treated women during the first week of therapy only. CONCLUSION: Desvenlafaxine is an effective nonhormonal treatment for vasomotor symptoms in postmenopausal women. Its tolerability profile is consistent with that of other serotonin-norepinephrine reuptake inhibitors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00421031 LEVEL OF EVIDENCE: I.