Treatment Of Menopausal Vasomotor Symptoms Research Articles

Part I: Interactive case: Menopause

Part I: Interactive case: Menopause

Phytoestrogen Treatment for Menopausal Vasomotor Symptoms after Breast Cancer

Introduction: In breast cancer patients, menopausal symptoms are often reached earlier and in a more severe manner than in healthy women. They can dramatically reduce a patient’s quality of life. Treatment for breast cancer patients remains difficult due to hormone replacement therapy being contraindicated. Therefore, treatment alternatives like herbal phytoestrogen preparations are considered to be a treatment option. Methods: All randomized controlled trials (RCTs) that investigated comparisons of food products, extracts, or dietary supplements containing phytoestrogens in women with a diagnosis of breast cancer were included in the analysis. Results: There was no evidence that phytoestrogen preparations had a benefit over placebo in the treatment of breast cancer patients with menopausal symptoms. Neither the frequency nor severity of menopausal symptoms and the quality of life or occurrence of adverse events were reduced in comparison to a placebo. Conclusion: As we cannot prove a benefit of plant extracts in the treatment of menopausal symptoms in breast cancer patients, different herbal preparations should be analyzed in RCTs in order to find sufficient and safe new treatment options for symptomatic menopausal breast cancer patients. A focus should also be laid on developing a core outcome set to simplify pooling of different studies.

Case Report of Menopausal Vasomotor Symptoms (Heat Flashes and Sleep Disorders) in a Middle-Aged Female Patient Treated with Korean Medicine

Objectives: The purpose of this study is to report on the efficacy of Korean medical treatment for treating menopausal vasomotor symptoms (heat flashes and sleep disorders).Methods: We treated a menopausal female patient with heat flashes and sleep disorders using Korean medical treatments (herbal medicines, acupuncture, pharmacopuncture, moxibustion, and chuna). To evaluate the results of this treatment, we used Kupperman’s Index and the Numerical Rating Scale to measure heat flashes and total sleeping time, respectively. The patient’s general health status was evaluated using the European Quality of Life 5 Dimensions Scale.Results: We observed improvements in Kupperman’s Index, the Numerical Rating Scale, the patient’s total sleeping time, and the European Quality of Life 5 Dimensions Scale following the treatments.Conclusions: This study suggests that Korean medicine may be an effective treatment for menopausal vasomotor symptoms (heat flashes and sleep disorders).

Nonpharmacological therapies for the management of menopausal vasomotor symptoms in breast cancer survivors.

Breast cancer affects millions of women worldwide, and for many, therapy results in treatment-induced menopause. Menopausal symptoms in breast cancer survivors are often more severe, frequent, and of greater duration compared with natural menopause. Hot flushes and night sweats pose a significant burden for many women, with limited therapeutic options as menopausal hormone therapy is contraindicated. Guidelines recommend non-hormonal pharmacological agents including clonidine, gabapentin, and some antidepressants. However, some women may be reluctant to use medications due to concerns about side effects. The aim of this narrative review was to appraise recent evidence for nonpharmacological treatments for vasomotor symptoms in breast cancer survivors including cognitive behavioural therapy, hypnosis, yoga, mindfulness, acupuncture, and lifestyle changes. A literature search was conducted. Studies were included if they were randomised and involved breast cancer survivors and nonpharmacological treatments for menopausal vasomotor symptoms. Twelve studies met the criteria, and three studies of exercise in healthy menopausal women were included. Cognitive behavioural therapy reduces menopausal symptoms and perceived impact of hot flushes and night sweats in breast cancer survivors and is cost effective. The efficacy of hypnosis as a treatment for menopausal vasomotor symptoms in women with breast cancer is supported by two randomised controlled trials. Yoga and acupuncture may reduce vasomotor symptom frequency and/or burden. Studies of exercise as an intervention for vasomotor symptoms in healthy menopausal women have not shown benefit. Evidence for nonpharmacological interventions supports cognitive behavioural therapy and hypnosis in the management of vasomotor symptoms in breast cancer survivors.

The neurokinin 3 receptor antagonist, fezolinetant, is effective in treatment of menopausal vasomotor symptoms: a randomized, placebo-controlled, double-blind, dose-ranging study

The brain's thermoregulatory center is stimulated by neurokinin 3 receptor (NK3R) activation and inhibited by estrogen negative-feedback. In menopause, declining estrogen disturbs this balance and produces vasomotor symptoms (VMS). Fezolinetant is an NK3R antagonist that moderates KNDy neuronal function for treatment of VMS (Fraser et al. Endocr Rev 2017;38:abstr OR16-5). In this phase 2b, double-blind trial (NCT03192176), menopausal women age >40–65 y with moderate/severe VMS (≥50/wk) were randomized to receive fezolinetant 15, 30, 60, or 90 mg BID or 30, 60, or 120 mg QD or placebo (PBO). Efficacy outcomes were frequency and severity of moderate/severe VMS at wk 4 and 12 (primary) and changes in moderate/severe VMS frequency and severity by study wk (secondary). Of 356 women randomized, 352 received ≥1 dose study drug (safety population; mean [SD] age: 54.6 [4.7] y; 73% white) and 287 (81%) completed the study (fezolinetant: 80%; PBO: 84%). Discontinuation occurred most commonly for withdrawal of consent (6.7%) and AEs (5.9%). VMS frequency and severity were reduced in all fezolinetant dose groups at wk 4 and 12. The differences between fezolinetant and PBO in mean changes from baseline in moderate/severe VMS frequency per day at wk 4 were −1.9, −3.0, −2.8, and −3.5 for 15, 30, 60, and 90 mg BID, respectively, and −2.3, −3.0, and −2.4 for 30, 60, and 120 mg QD, respectively (common SE: 0.8; all P < .05). The differences between fezolinetant and PBO in mean changes from baseline in moderate/severe VMS frequency per day at wk 12 were −1.8, −2.1, −2.3, and −2.6, respectively, and −2.1, −2.6, and −2.1, respectively (common SE: ∼0.7; all P < .05). A significant dose response was apparent by wk 1. The majority of TEAEs were mild or moderate in severity, and no deaths or serious treatment-related TEAEs occurred. Fezolinetant was a safe and effective nonhormonal treatment for rapid reduction of moderate/severe menopausal VMS.

The neurokinin 3 receptor antagonist, fezolinetant, is effective in treatment of menopausal vasomotor symptoms: responder analysis results from a randomized, placebo-controlled, double-blind, dose-ranging study

The neurokinin 3 receptor antagonist, fezolinetant, is effective in treatment of menopausal vasomotor symptoms: responder analysis results from a randomized, placebo-controlled, double-blind, dose-ranging study

Trajectories of response to acupuncture for menopausal vasomotor symptoms: the Acupuncture in Menopause study.

To examine the trajectories of responses to acupuncture treatment for menopausal vasomotor symptoms (VMS) and the characteristics of women in each trajectory. Two hundred nine perimenopausal and postmenopausal women aged 45 to 60 years experiencing at least four VMS per day were recruited and randomized to receive up to 20 acupuncture treatments within 6 months or to a waitlist control group. The primary outcome was percent change from baseline in the mean daily VMS frequency. Finite mixture modeling was used to identify patterns of percent change in weekly VMS frequencies over the first 8 weeks. The Freeman-Holton test and analysis of variance were used to compare characteristics of women in different trajectories. Analyses revealed four distinct trajectories of change in VMS frequency by week 8 in the acupuncture group. A small group of women (11.6%, n = 19) had an 85% reduction in VMS. The largest group (47%, n = 79) reported a 47% reduction in VMS frequency, 37.3% (n = 65) of the sample showed only a 9.6% reduction in VMS frequency, and a very small group (4.1%, n = 7) had a 100% increase in VMS. Among women in the waitlist control group, 79.5% reported a 10% decrease in VMS frequency at week 8. Baseline number of VMS, number of acupuncture treatments in the first 8 weeks, and traditional Chinese medicine diagnosis were significantly related to trajectory group membership in the acupuncture group. Approximately half of the treated sample reported a decline in VMS frequency, but identifying clear predictors of clinical response to acupuncture treatment of menopausal VMS remains challenging.

Is desvenlafaxine effective and safe in the treatment of menopausal vasomotor symptoms? A meta-analysis and meta-regression of randomized double-blind controlled studies.

During perimenopause, vasomotor symptoms are known to have a detrimental effect on women's functional ability and quality of life. For symptomatic women not eligible for hormonal therapy, desvenlafaxine is an option, but its safety margin and tolerability are not yet determined. A computer-based literature search was done in the databases of MEDLINE, Cochrane library, and HINARI (Health InterNetwork Access to Research Initiative). Meta-analysis was conducted by including double-blind randomized controlled studies on the effectiveness and safety of desvenlafaxine in the treatment of hot flashes. The effectiveness, safety and tolerability of desvenlafaxine were determined by standardized mean differences (SMDs) and Mantel-Haenszel odds ratio. Subgroup analysis based on doses of desvenlafaxine and linear meta-regression analyses were performed for several covariates. Heterogeneity testing, the risk of bias assessment and sensitivity analyses were done. Desvenlafaxine was associated with a statistically significant reduction in the number and severity of daily moderate to severe hot flashes. The number of nighttime awakenings because of hot flashes was also significantly decreased. However, the rate of desvenlafaxine treatment discontinuation because of adverse events was a significantly higher than placebo treated women and the risk ratios of adverse events like asthenia, hypertension, anorexia, constipation, diarrhea, dry mouth, nausea, dizziness, insomnia, somnolence and mydriasis were very high. Desvenlafaxine is effective in the treatment of hot flashes but it is strongly associated with several adverse events and treatment discontinuation. Further clinical trials focusing only on desvenlafaxine related adverse events are highly warranted before it is approved for public use.

Relaxation for perimenopausal and postmenopausal symptoms.

Since the time of publication of the Women's Health Initiative (WHI) study, menopausal symptom management has become more complex because of increased awareness of the risks associated with hormone replacement therapy (HRT). Currently, a wide range of management options is available. Some women take prescription drugs, and others use self care strategies, including lifestyle modifications, over-the-counter preparations and complementary and alternative therapies, such as herbal preparations, exercise programmes and relaxation techniques. Relaxation techniques consist of a group of behavioural interventions. They are considered relatively harmless, but their effectiveness in treating vasomotor symptoms and sleep disturbances remains debatable. To determine the effectiveness of relaxation techniques as treatment for vasomotor symptoms and associated sleep disturbances in perimenopausal and postmenopausal women. Searches of the following electronic bibliographic databases were performed in February 2014 to identify randomised controlled trials (RCTs): the Cochrane Menstrual Disorders and Subfertility Group Specialised Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, PsycINFO, Social Science Citation Index and CINAHL. Handsearches of trial registers, relevant journals and published conference abstracts were also performed. RCTs were included if they compared any type of relaxation intervention with no treatment or other treatments (except hormones) for vasomotor symptoms in symptomatic perimenopausal/postmenopausal women. Two review authors selected studies, assessed quality and extracted data. Included studies were combined, if appropriate, by using a random-effects model to calculate pooled mean differences and 95% confidence intervals. Four studies were eligible for inclusion (281 participants): Two studies compared relaxation with electroacupuncture or superficial needling, one study compared relaxation with paced respiration or placebo control (α-wave electroencephalographic biofeedback) and one study compared relaxation with no treatment.No evidence was found of a difference between relaxation and acupuncture or superficial needle insertion in the number of hot flushes per 24 hours (mean difference (MD) 0.05, 95% confidence interval (CI) -1.33 to 1.43, two studies, 72 participants, I(2) = 0%; very low-quality evidence). Nor did any evidence suggest a difference between the two interventions in hot flush severity, measured using the Kupperman Index (MD -1.32, 95% CI -5.06 to 2.43, two studies, 72 participants, I(2) = 0%; very low-quality evidence).The other two studies found no clear evidence of a difference in hot flush frequency between relaxation and paced respiration, placebo or no treatment. The data for these comparisons were unsuitable for analysis.None of these studies reported night sweats, sleep disturbances associated with night sweats or adverse effects as an outcome.The main limitations of identified evidence were lack of data, imprecision and failure to report study methods in adequate detail. Evidence is insufficient to show the effectiveness of relaxation techniques as treatment for menopausal vasomotor symptoms, or to determine whether this treatment is more effective than no treatment, placebo, acupuncture, superficial needle insertion or paced respiration.

Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms

The efficacy and safety of low-dose paroxetine 7.5 mg for the treatment of menopausal vasomotor symptoms were evaluated in two multicenter, double-blind, placebo-controlled, phase 3 studies of 12 and 24 weeks' duration. Postmenopausal women were randomly assigned 1:1 to receive paroxetine 7.5 mg or placebo once daily. The four primary efficacy endpoints included mean changes in the frequency and severity of moderate to severe vasomotor symptoms on weeks 4 and 12; an additional endpoint was persistence of treatment benefit on week 24. Five hundred ninety-one participants were randomly assigned to treatment with paroxetine 7.5 mg, and 593 participants were randomly assigned to treatment with placebo. All primary endpoints were met in the 24-week study; three of four primary endpoints were met in the 12-week study. In both studies, paroxetine 7.5 mg significantly reduced the mean weekly vasomotor symptom frequency compared with placebo on week 4 (P < 0.0001 for both studies) and week 12 (P = 0.0090, 12-wk study; P = 0.0001, 24-wk study). Mean weekly reduction in vasomotor symptom severity was significantly greater for paroxetine 7.5 mg than for placebo on week 4 (P = 0.0048) in the 12-week study and on week 4 (P = 0.0452) and week 12 (P = 0.0114) in the 24-week study. Persistence of treatment benefit was demonstrated in the 24-week study. Most treatment-emergent adverse events were mild or moderate in severity. No clinically significant changes in laboratory values or vital signs were noted, and no short-term discontinuation of symptoms followed treatment cessation. Paroxetine 7.5 mg is well-tolerated, is effective in reducing the frequency and severity of menopausal vasomotor symptoms, and demonstrates persistence of treatment benefit through 24 weeks of treatment.

Cardiovascular, cerebrovascular, and hepatic safety of desvenlafaxine for 1 year in women with vasomotor symptoms associated with menopause

A previous trial of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine (administered as desvenlafaxine succinate) raised concerns on potential serious cardiovascular and hepatic events. The current study was designed to estimate these events in desvenlafaxine versus placebo in a larger population followed for 1 year. Healthy postmenopausal women seeking treatment of vasomotor symptoms were randomized to placebo or desvenlafaxine 100 mg/day in a 1-year, multicenter, double-blind study. Safety was monitored throughout. Potential ischemic cardiovascular events (coronary heart disease-related death, new-onset myocardial infarction or unstable angina requiring hospitalization, and unscheduled revascularization procedures) and cerebrovascular events (definite stroke or probable stroke) identified by investigator reports and periodic adverse event review based on Standardized medical dictionary for regulatory activities Query were reviewed by blinded adjudication boards. Hepatic events (aspartate aminotransferase or alanine aminotransferase >5 times the upper limit of normal) were evaluated. A total of 2,118 participants (1,066 desvenlafaxine, 1,052 placebo) took one or more doses of study medication (mean, 280 d). There was one cardiovascular event; a placebo-treated participant was adjudicated to have had a myocardial infarction. One desvenlafaxine-treated participant was adjudicated to have had a probable stroke. Two participants in each treatment group had hepatic events. The excess risk (90% CI) of desvenlafaxine over placebo per 1,000 woman-years was -1.07 (-2.86 to 0.72) for cardiovascular events, 1.11 (-0.68 to 2.9) for cerebrovascular events, and 0.08 (-3.51 to 3.67) for hepatic events. There is no evidence for an increased risk of cardiovascular, cerebrovascular, or hepatic events associated with desvenlafaxine 100 mg/day compared with placebo for the treatment of menopausal vasomotor symptoms.

Desvenlafaxine compared with placebo for treatment of menopausal vasomotor symptoms

The aim of this study was to assess the 12-week efficacy of desvenlafaxine in treating moderate to severe vasomotor symptoms and the clinical relevance of improvements in postmenopausal women experiencing 50 or more moderate to severe hot flashes per week. Participants were randomized to placebo or desvenlafaxine 100 mg/day in the 12-week efficacy substudy of a year-long, multicenter, parallel-group, double-blind study. Coprimary outcomes were changes from baseline in the daily number and severity of hot flashes on weeks 4 and 12. The percentage of women achieving the minimal clinically important difference (MCID) in the number of hot flashes on week 12 was determined. The efficacy substudy modified intent-to-treat population included 365 women (desvenlafaxine, n = 184; placebo, n = 181). Desvenlafaxine 100 mg/day significantly reduced the number and severity of hot flashes versus placebo on week 4 (P < 0.001) and week 12 (P < 0.001). On week 12, desvenlafaxine reduced the number of moderate and severe hot flashes by 7.3 (62%) per day (placebo, -4.5 [38%] per day) and the severity score by 0.59 (25%) per day (placebo, -0.28 [12%] per day). MCID-a reduction of 5.35 moderate and severe hot flashes per day-was achieved by 64% of desvenlafaxine-treated women (placebo, 41%; P < 0.001). In all, 17.2% (67/390) of participants discontinued, 10.0% (20/200) of participants taking desvenlafaxine and 3.7% (7/190) of participants taking placebo discontinued because of adverse events (P = 0.016), and 2.5% (5/200) of participants taking desvenlafaxine and 8.4% (16/190) of participants taking placebo discontinued because of lack of efficacy (P = 0.012). Postmenopausal women with moderate to severe hot flashes who are treated with desvenlafaxine achieve rapid symptom reduction that is clinically relevant based on MCID.

Estrogen receptor beta and its selective ligands: an option for treatment of menopausal vasomotor symptoms?

Abstract In the human female, menopause is the permanent end of fertility, defined as occurring 12 months after the last menstrual period. During peri- and postmenopausal stages, the vast majority of women experience moderate-to-severe vasomotor symptoms, such as hot flashes and night sweats, which interfere with sleep and may be severe enough to affect quality of life. The only treatment approved by national health authorities is hormone therapy with estrogen alone or in combination with a progestagen. However, this therapeutic regimen is associated with severe side effects, such as stimulation of growth of breast cancer or cardiovascular events. Thus, there is a demand for efficient and safe alternative treatments for menopausal complaints. After the discovery of estrogen receptor beta in many organs, and confirmation of its presence in the brain, many researchers raised the question of whether ERβ-specific ligands may be novel therapeutic agents for treatment of menopausal complaints with the desirable effects of estrogen but without increased risk of tumor incidence. This minireview will briefly summarize the relevance of estrogen receptor beta and its specific ligands for the treatment of menopausal symptoms with a focus on vasomotor menopausal symptoms. At present, estrogen receptor beta-selective ligands do not seem to be active in models of prevention or reversal of osteoporosis. However, data from animal experiments suggest that estrogen receptor beta-selective ligands might be safe therapeutics for the treatment of vasomotor menopausal symptoms.

Update on genistein and thyroid: an overall message of safety

Genistein aglycone, one of the soy isoflavones, has been reported to be beneficial in the treatment of menopausal vasomotor symptoms, osteoporosis, and cardiovascular diseases, as well as in a variety of cancers. However, issues of potential harm on thyroid function resulting from soy isoflavones consumption have been raised. Much of the evidence for the goitrogenic effects of isoflavones is derived from experimental in vitro and in vivo studies. Goitrogenic effects were also noted in infants fed non-iodine-fortified, soy-based formula, a problem that was easily solved with iodine fortification. Recent studies suggest that genistein shows a good profile of safety on the thyroid although definitive conclusions have not reached. The aim of this brief review is to summarize and better clarify the effects of genistein on human thyroid health.

Tissue-Selective Estrogen Complex Bazedoxifene and Conjugated Estrogens for the Treatment of Menopausal Vasomotor Symptoms

Menopause occurs on average at age 51.4 years. Most, but not all, women who undergo menopause experience significant vasomotor symptoms (VMS). Although single agent estrogen therapy can relieve VMS, over time estrogen can stimulate the endometrial lining leading to an increased risk for endometrial hyperplasia and adenocarcinoma. Although a progestin has traditionally been given in combination with estrogen to 'protect' the endometrium, a new and innovative approach to this traditional combination hormone therapy is to substitute the progestin with an alternative agent. One such alternative agent is bazedoxifene, an estrogen agonist-antagonist. Based on data from randomized trials, when bazedoxifene is given in combination with oral conjugated estrogens to post-menopausal women, the risk of estrogen-associated endometrial stimulation is significantly reduced. The combination of bazedoxifene and conjugated estrogens has also been shown to relieve menopause-associated VMS and vaginal atrophy, and has been shown to be safe for short-term use. Long-term studies of this combination are needed to determine if the combination of conjugated estrogens/bazedoxifene can be used for >3 years without increasing the risk of breast cancer, stroke, cognitive deficit, pulmonary embolism or coronary heart disease. Short-term data regarding this combination has been submitted to the FDA and is currently under review for clinical use, with the relief of VMS as its primary indication. Data regarding the effects of combination conjugated estrogens/bazedoxifene therapy on bone are promising in terms of the prevention and treatment of post-menopausal osteoporosis.

Safety, efficacy and patient acceptability of drospirenone and estradiol in the treatment of menopausal vasomotor symptoms: a review

During menopause vasomotor symptoms are one of the main complaints about which women seek medical advice. For symptom control, several therapies have been used, among which hormone therapy has produced good results. One of these is estrogen monotherapy, which unfortunately may induce endometrial hyperplasia in women with an intact uterus. A progestin must be added to avoid this risk. Progestins may induce several secondary effects such as breast tenderness, hirsutism, edema and unfavorable lipid profile modifications. Recently a new progestin called drospirenone has been synthesized and used in combination with estradiol for the treatment of postmenopausal women. This progestin is derived from spironolactone, and lacks estrogenic, androgenic and glucocorticoid activities. Several studies have evaluated safety, efficacy and patient tolerability, and have shown a good profile in all these parameters. All studies agree that the combination of estradiol 1 mg plus drospirenone 2 mg is a good choice for postmenopausal women with vasomotor symptoms.

Desvenlafaxine: Future Nonhormonal Treatment for Menopausal Hot Flashes

Estrogen is the most effective treatment for menopausal vasomotor symptoms, but results from recent randomized trials have raised questions about its

Efficacy and Tolerability of Desvenlafaxine Succinate Treatment for Menopausal Vasomotor Symptoms

To compare efficacy and safety of desvenlafaxine succinate (desvenlafaxine) with placebo for the treatment of vasomotor symptoms. 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. 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. 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. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00421031 I.

Desvenlafaxine succinate (DVS) efficacy for the relief of vasomotor symptoms (VMS) associated with menopause: a double-blind, placebo-controlled trial

To compare the efficacy of DVS with placebo in the treatment of menopausal VMS. 12-week, multicenter, randomized, double-blind, placebo-controlled trial with dose titration and tapering. Efficacy was evaluated at 4 and 12 weeks. Postmenopausal women with ≥50 moderate-to-severe hot flushes (HFs) per week received placebo or DVS 100 or 150 mg, titrated up from 50 mg/d during week 1 and tapered down at the end of the study. Efficacy endpoints were analyzed using ANCOVA and included reduction from baseline (BL) in the average daily number and severity of moderate-to-severe HFs, reduction in number of nighttime awakenings, 75% responder analysis, and time to reach ≥50% decrease in number of HFs from BL. Safety data are presented elsewhere. Of the 458 subjects randomly assigned to DVS or placebo, 436 were included in the efficacy evaluation for primary endpoints. There were no significant differences between groups for demographic and BL characteristics. All groups had a significant decrease from BL in the number of moderate-to-severe HFs at all time points. Both DVS dose groups had significant reductions in number of HFs compared with placebo at weeks 4 and 12 (all comparisons P≤0.012). The DVS 100-mg and 150-mg groups achieved 65.4% and 66.6% reductions from BL in the number of HFs at week 12, respectively, compared with a 50.8% reduction in the placebo group. All groups had significant decreases from BL in HF severity at all time points; both DVS dose groups had a significantly greater decrease than placebo at weeks 4 and 12 (all comparisons P<0.001). The proportion of subjects with ≥75% reduction from BL in number of HFs was significantly higher at week 12 in the DVS 100-mg (50%) and DVS 150-mg (53%) groups compared with placebo (29%; all comparisons P<0.001). The median time to reach a 50% reduction from BL in the number of HFs was significantly shorter with both DVS doses (100 mg, 7 days; 150 mg, 8 days) compared with placebo (25 days; both comparisons, P<0.001). Both DVS dose groups had significantly greater reductions from BL in the number of nighttime awakenings due to HFs compared with placebo at weeks 4 and 12 (all comparisons P≤0.048) DVS is an effective non-hormonal treatment for VMS and nighttime awakenings associated with menopause and has a rapid onset of action at both 100 and 150 mg doses.

Non-hormonal therapy of post-menopausal vasomotor symptoms: a structured evidence-based review

Interest in non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. To provide information on the efficacy of non-hormonal therapies for menopausal vasomotor symptoms based on evidence from published randomised controlled studies. The Cochrane Database of Systematic Reviews (CDSR), MEDLINE, Alternative Therapies in Health and Medicine database (ATHMD) and Allied and Complementary Medicine database (AMED) were searched for randomised controlled trials in the English language reporting data on treatment of menopausal vasomotor symptoms. Trials including cancer breast patients were included. Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose, one for dong quai and one for vitamin E. Most trials had methodological deficiencies. There is evidence that clonidine, paroxetine, venlafaxine, gabapentin and black cohosh may be beneficial in the treatment of menopausal vasomotor symptoms in some women. Current evidence does not support the use of fluoxetine, red clover, phytoestrogens, Ginseng, evening primrose, dong quai and vitamin E. The side effects profile of these therapies should be considered.