Severe Hot Flushes Research Articles

Evaluation of gabapentin in management of hot flushes in postmenopausal women.

This study was conducted to assess the efficacy of gabapentin in controlling hot flushes in postmenopausal women. Fifty postmenopausal patients with hot flushes were randomized in two groups, one receiving gabapentin 900 mg daily along with calcium and another group receiving calcium alone. Frequency, duration and severity of hot flushes were noted and a composite score was calculated. There was around an 80% reduction in composite score in the gabapentin group at 3 and 6 months; significantly more than the placebo group. Gabapentin has a two-fold better response than placebo in reducing hot flushes with the relief starting from the first month and maximum effect at 3 months.

Nature and severity of menopausal symptoms and their impact on quality of life and sexual function in cancer survivors compared with women without a cancer history

After cancer treatment, troublesome menopausal symptoms are common but poorly understood. Using standardized instruments, we measured differences in symptom nature, severity, impact on quality of life, and sexual function between cancer survivors and noncancer participants. The Menopause Symptoms After Cancer Clinic operates within the general menopause service in a large women's hospital, providing menopause advice and management to women with menopausal symptoms and a cancer history. Menopausal symptoms were recorded using the Greene Climacteric Scale, past-week symptoms were recorded using the Functional Assessment of Cancer Therapy breast cancer subscale and endocrine symptom subscale, and sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Cancer survivors (n = 934) and noncancer participants (n = 155) did not significantly differ by age at menopause (46 y) or age at first clinic visit (51 y). Cancer survivors were more likely than noncancer participants to be severely troubled by vasomotor symptoms (hot flushes and night sweats; odds ratio, 1.71; 95% CI, 1.06-2.74) and reported more frequent (6.0 vs 3.1 in 24 h; P < 0.001) and more severe (P = 0.008) hot flushes. In contrast, cancer survivors were significantly less troubled by psychological and somatic symptoms and reported better quality of life than noncancer participants. Groups did not differ significantly in physical or functional well-being, gynecologic symptom severity, or sexual function. Cancer survivors are more troubled by vasomotor symptoms than noncancer participants, but noncancer participants report greater psychological symptoms. Sexual function does not differ. An improved understanding of the nature and impact of menopause on cancer survivors can be used to direct management protocols.

Management of Hot Flushes in Breast Cancer Survivors: Comparison Between Stellate Ganglion Block and Pregabalin

Women who have survived breast cancer have hot flushes that are "significantly more frequent, severe, distressing, and of greater duration" than in other women. We compared the efficacy and safety of stellate ganglion block and pregabalin for the relief of hot flushes in breast cancer survivors. Forty patients who were breast cancer survivors and were suffering from hot flushes to the degree that they seeked for treatment were included in the study and randomly divided into two groups: group I: (N = 20) stellate ganglion block was done for the patients of this group; and group II: (N = 20) in this group, the patients received 75 mg pregabalin twice daily. In both groups self-completed daily hot flush diaries and monthly symptom questionnaires were obtained at baseline and for the following 3 months. Our results showed that group I (stellate ganglion block) had significant (P < 0.05) decline in the frequency of mild, moderate, very severe, and total hot flushes in comparison with group II (pregabalin 75 mg twice daily) throughout the 3 months of follow up period. The stellate ganglion block had superior efficacy in the management of hot flushes in breast cancer survivors.

A randomized, double-blind, placebo-controlled study of the lowest effective dose of drospirenone with 17β-estradiol for moderate to severe vasomotor symptoms in postmenopausal women

This study aims to investigate the efficacy and safety of daily drospirenone/17β-estradiol in two low-dose combinations (0.25 mg/0.5 mg and 0.5 mg/0.5 mg, respectively) versus 17β-estradiol (0.3 mg) or placebo in postmenopausal women with moderate to severe vasomotor symptoms. Seven hundred thirty-five postmenopausal women aged 40 years or older who experienced a minimum of 7 to 8 moderate to severe hot flushes per day, or 50 to 60 moderate to severe hot flushes per week, participated in a 12-week, double-blind, randomized, placebo-controlled study. The primary efficacy variables were mean changes from baseline to weeks 4 and 12 in the weekly frequency and weekly mean daily severity of moderate to severe hot flushes recorded daily by the participants on diary cards. All active treatments were significantly more effective than placebo for the primary efficacy variables for drospirenone/17β-estradiol (P < 0.0001), and for 17β-estradiol (P < 0.01) at 4 and 12 weeks. Efficacy was greater for both low-dose drospirenone/17β-estradiol combinations versus the lower-dose 17β-estradiol. Change in vaginal pH and vaginal maturation index showed significant improvements (with P values versus placebo of <0.0001 and P ≤ 0.0028, respectively), and exploratory analysis of the Clinical Global Impressions scale score indicated an overall satisfaction of women with active treatments. All active treatments were generally well tolerated with low rates of adverse event-related dropouts, and the safety profile of drospirenone/17β-estradiol in both low-dose combinations was consistent with previous studies. Drospirenone 0.25 mg/17β-estradiol 0.5 mg is concluded to be the lowest dose with demonstrated efficacy in the treatment of postmenopausal women with moderate to severe vasomotor symptoms.

Effects of acupuncture and Chinese herbal medicine (Zhi Mu 14) on hot flushes and quality of life in postmenopausal women

The aim of this study was to evaluate the feasibility of a clinical trial investigating the effects of acupuncture (AP) and Chinese herbal medicine (CHM) on hot flushes and quality of life in postmenopausal women. Forty postmenopausal women reporting at least 20 hot flushes per week were enrolled in a randomized controlled trial. They were randomly allocated to receive traditional Chinese medicine (TCM) AP, sham AP, verum CHM, or placebo CHM for 12 weeks. Follow-up assessment was conducted 12 weeks after intervention. Primary outcome measures included hot flush frequency and severity. As a secondary outcome measure, the severity of menopausal symptoms was assessed using the Menopause Rating Scale (MRS) II. TCM AP induced a significant decline in all outcome measures from pretreatment to posttreatment compared with sham AP (hot flush frequency, P = 0.016; hot flush severity, P = 0.013; MRS, P < 0.001). In the TCM AP group, a larger decrease in MRS scores persisted from pretreatment to follow-up (P = 0.048). No significant differences were noted between the verum CHM group and the placebo CHM group. Compared with the verum CHM group, there was a significant decrease in MRS scores (P = 0.002) and a trend toward a stronger decrease in hot flush severity (P = 0.06) in the TCM AP group from pretreatment to posttreatment. TCM AP is superior to sham AP and verum CHM in reducing menopausal symptoms, whereas verum CHM shows no significant improvements when compared with placebo CHM.

Phytoestrogens for menopausal vasomotor symptoms.

Vasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone therapy has traditionally been used as a highly effective treatment, but concerns about increased risk of some chronic diseases have markedly increased the interest of women in alternative treatments. Some of the most popular of these treatments are foods or supplements enriched with phytoestrogens-plant-derived chemicals that have estrogenic action. To assess the efficacy, safety and acceptability of food products, extracts and dietary supplements containing high levels of phytoestrogens when compared with no treatment, placebo or hormone therapy for the amelioration of vasomotor menopausal symptoms (such as hot flushes and night sweats) in perimenopausal and postmenopausal women. Searches targeted the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials (29 July 2013), the Cochrane Register of Controlled Trials (CENTRAL; 29 July 2013), MEDLINE (inception to 29 July 2013), EMBASE (inception to 29 July 2013), AMED (1985 to 29 July 2013), PsycINFO (inception to 29 July 2013) and CINAHL (inception to 29 July 2013). Attempts were made to access grey literature by sending letters to pharmaceutical companies and performing searches of ongoing trial registers. Reference lists of included trials were also searched. Studies were included if they were randomised, included perimenopausal or postmenopausal participants with vasomotor symptoms (hot flushes or night sweats), lasted at least 12 weeks and provided interventions such as foods or supplements with high levels of phytoestrogens (not combined with other herbal treatments). Trials that included women who had breast cancer or a history of breast cancer were excluded. Selection of trials, extraction of data and assessment of quality were undertaken by at least two review authors. Most trials were too dissimilar for their results to be combined in a meta-analysis, so these findings are provided in narrative 'Summary of results' tables. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts, genistein extracts and other types of phytoestrogens. Five trials used Promensil, a red clover extract; results of these trials were combined in a meta-analysis, and summary effect measures were calculated. A total of 43 randomised controlled trials (4,364 participants) were included in this review. Very few trials provided data suitable for inclusion in a meta-analysis. Among the five trials that yielded data assessing the daily frequency of hot flushes suitable for pooling, no significant difference overall was noted in the incidence of hot flushes between participants taking Promensil (a red clover extract) and those given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to 0.10, I(2) = 31%). No evidence indicated a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08 to 52.38, I(2) = 82%). Four trials that were not combined in meta-analyses suggested that extracts with high (> 30 mg/d) levels of genistein consistently reduced the frequency of hot flushes. Individual results from the remaining trials were compared in broad subgroups such as dietary soy, soy extracts and other types of phytoestrogens that could not be combined. Some of these trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared with placebo, but many trials were small and were determined to be at high risk of bias. A strong placebo effect was noted in most trials, with a reduction in frequency ranging from 1% to 59% with placebo. No indication suggested that discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. Also, no evidence indicated that these treatments caused oestrogenic stimulation of the endometrium or the vagina or other adverse effects when used for up to two years. No conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated.

Effects of sympatholytic therapy on postmenopausal symptoms in hypertensive postmenopausal women

Objective The short-term effects of two sympatholytic antihypertensive drug treatments, β-blocking agent atenolol and imidazoline receptor-1 agonist moxonidine, on postmenopausal symptoms and their relationship to antihypertensive and insulin sensitivity effect were studied.Design This was a double-blind, prospectively randomized study in a multicenter, multinational setting in 112 hypertensive, overweight, postmenopausal women without hormone therapy.Methods Treatment was either with moxonidine, 0.6 mg/day, or with atenolol, 50 mg/day, for 8 weeks. The main outcome measures were blood pressure, insulin sensitivity by Matsuda sensitivity index and postmenopausal symptoms (hot flushes, palpitations, insomnia, irritability, depression and general impression of the symptoms (GIS) through a questionnaire.Results Both atenolol and moxonidine caused a significant reduction in diastolic blood pressure of 9.5 mmHg and 6.2 mmHg, respectively. The severity of hot flushes and palpitations were reduced significantly in both treatment groups. Relief from hot flushes was recorded in 43% of women taking atenolol and in 27% (not significant between the groups) of moxonidine-treated patients. Palpitations were relieved in 41% and 25% (not significant between the groups) of the women in the atenolol- and moxonidine-treated groups, respectively. In the atenolol group, insomnia and GIS were reduced significantly, with relief of symptoms occurring in 33% and 27% of the patients. A change in irritability was seen in blood pressure responders during the treatment in the atenolol group. There was no correlation between improvement of insulin sensitivity and relief of postmenopausal symptoms.Conclusions In this study, two sympatholytic antihypertensives, atenolol and moxonidine, provided relief from hot flushes and palpitations, and atenolol additionally helped with insomnia and improved GIS.

Changes in bone mineral density are correlated with bone markers and reductions in hot flush severity in postmenopausal women treated with bazedoxifene/conjugated estrogens

A post hoc exploratory analysis was conducted to examine correlations between changes in bone density, bone markers, and hot flushes after the treatment of postmenopausal women with bazedoxifene (BZA)/conjugated estrogens (CE). In a 2-year phase 3 study, 3,397 postmenopausal women were randomized to BZA 10 mg/CE 0.45 mg, BZA 20 mg/CE 0.45 mg, BZA 40 mg/CE 0.45 mg, BZA 10 mg/CE 0.625 mg, BZA 20 mg/CE 0.625 mg, BZA 40 mg/CE 0.625 mg, raloxifene 60 mg, or placebo. In this analysis, bone density changes at 2 years were compared with baseline levels of the bone markers serum C-telopeptide and osteocalcin. Correlations between changes in bone density and changes in 12-week hot flush composite scores in symptomatic women were also analyzed. Treatment with BZA 20 mg/CE 0.45 mg or BZA 20 mg/CE 0.625 mg increased lumbar spine bone density more in women with higher bone resorption and formation, categorized by baseline levels of C-telopeptide and osteocalcin (P < 0.001, both BZA/CE doses). With placebo, larger decreases in lumbar spine bone density were seen in the highest tertile of serum C-telopeptide. There was no correlation between changes in total hip bone density and baseline bone markers. There were significant correlations between percent change in hot flush score at week 12 and percent changes in lumbar spine (r = -0.31, P = 0.006) and total hip (r = -0.23, P = 0.044) bone densities at month 24. With 2-year BZA/CE treatment, women with larger increases in lumbar spine and total hip densities also have higher baseline bone markers. Early reductions in hot flush score (12 wk) are predictive of long-term increases in bone density (24 mo).

Acupuncture for menopausal hot flushes

Hot flushes are the most common menopausal vasomotor symptom. Hormone therapy (HT) has frequently been recommended for relief of hot flushes, but concerns about the health risks of HT have encouraged women to seek alternative treatments. It has been suggested that acupuncture may reduce hot flush frequency and severity. To determine whether acupuncture is effective and safe for reducing hot flushes and improving the quality of life of menopausal women with vasomotor symptoms. We searched the following databases in January 2013: the Cochrane Menstrual Disorders and Subfertility Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, PsycINFO, Chinese Biomedical Literature Database (CBM), Chinese Medical Current Content (CMCC), China National Knowledge Infrastructure (CNKI), VIP database, Dissertation Abstracts International, Current Controlled Trials, Clinicaltrials.gov, National Center for Complementary and Alternative Medicine (NCCAM), BIOSIS, AMED, Acubriefs, and Acubase. Randomized controlled trials comparing any type of acupuncture to no treatment/control or other treatments for reducing menopausal hot flushes and improving the quality of life of symptomatic perimenopausal/postmenopausal women were eligible for inclusion. Sixteen studies, with 1155 women, were eligible for inclusion. Three review authors independently assessed trialeligibility and quality, and extracted data. We pooled data where appropriate and calculated mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Eight studies compared acupuncture versus sham acupuncture. No significant difference was found between the groups for hot flush frequency (MD -1.13 flushes per day, 95% CI -2.55 to 0.29, 8 RCTs, 414 women, I(2) = 70%, low-quality evidence) but flushes were significantly less severe in the acupuncture group, with a small effect size (SMD -0.45, 95% CI -0.84 to -0.05, 6 RCTs, 297 women, I(2) = 62%, very-low-quality evidence). There was substantial heterogeneity for both these outcomes. In a post hoc sensitivity analysis excluding studies of women with breast cancer, heterogeneity was reduced to 0% for hot flush frequency and 34% for hot flush severity and there was no significant difference between the groups for either outcome.Three studies compared acupuncture versus HT. Acupuncture was associated with significantly more frequent hot flushes than HT (MD 3.18 flushes per day, 95% CI 2.06 to 4.29, 3 RCTs, 114 women, I(2) = 0%, low-quality evidence). There was no significant difference between the groups for hot flush severity (SMD 0.53, 95% CI -0.14 to 1.20, 2 RCTs, 84 women, I(2) = 57%, low-quality evidence).One study compared electroacupuncture versus relaxation. There was no significant difference between the groups for either hot flush frequency (MD -0.40 flushes per day, 95% CI -2.18 to 1.38, 1 RCT, 38 women, very-low-quality evidence) or hot flush severity (MD 0.20, 95% CI -0.85 to 1.25, 1 RCT, 38 women, very-low-quality evidence).Four studies compared acupuncture versus waiting list or no intervention. Traditional acupuncture was significantly more effective in reducing hot flush frequency from baseline (SMD -0.50, 95% CI -0.69 to -0.31, 3 RCTs, 463 women, I(2) = 0%, low-quality evidence), and was also significantly more effective in reducing hot flush severity (SMD -0.54, 95% CI -0.73 to -0.35, 3 RCTs, 463 women, I(2) = 0%, low-quality evidence). The effect size was moderate in both cases.For quality of life measures, acupuncture was significantly less effective than HT, but traditional acupuncture was significantly more effective than no intervention. There was no significant difference between acupuncture and other comparators for quality of life. Data on adverse effects were lacking. We found insufficient evidence to determine whether acupuncture is effective for controlling menopausal vasomotor symptoms. When we compared acupuncture with sham acupuncture, there was no evidence of a significant difference in their effect on menopausal vasomotor symptoms. When we compared acupuncture with no treatment there appeared to be a benefit from acupuncture, but acupuncture appeared to be less effective than HT. These findings should be treated with great caution as the evidence was low or very low quality and the studies comparing acupuncture versus no treatment or HT were not controlled with sham acupuncture or placebo HT. Data on adverse effects were lacking.

A randomized, double-blind, controlled trial of a Chinese herbal formula (Er-Xian decoction) for menopausal symptoms in Hong Kong perimenopausal women

The aim of this study is to investigate the effectiveness and safety of a Chinese herbal formula, Er-Xian decoction (EXD), in the treatment of menopausal symptoms among Hong Kong perimenopausal women. A randomized, double-blind, controlled trial was conducted for 12 weeks among 108 Hong Kong perimenopausal women who reported Menopause Rating Scale (MRS) total scores of 28 or higher. Posttreatment follow-up was performed 3 months after the intervention. The primary outcome measure was the frequency and severity of hot flushes. The secondary outcome measures included the MRS, the Menopause-Specific Quality of Life questionnaire, and serum hormone levels. Among 108 participants, 101 participants finished the study. EXD significantly reduced the mean (SD) frequency of hot flushes from 5.8 (5.0) to 2.2 (3.0) in the treatment group and from 5.0 (3.8) to 2.4 (2.5) in the placebo group (P = 0.04). The mean (SD) hot flush score was also reduced from 19.6 (6.6) to 4.9 (7.8) in the treatment group and from 16.6 (5.4) to 7.0 (6.4) in the placebo group (P = 0.02). The superiority of EXD to placebo was also observed with greater improvement in the total scores for the MRS (P = 0.03) and the Menopause-Specific Quality of Life questionnaire (P < 0.01). There were no differences in serum hormone levels between the EXD group and the placebo group. There were no serious adverse events, and the safety indices of whole blood counts, renal function, and liver function were within the normal range before and after treatment. The Chinese herbal formula EXD is superior to placebo in reducing the frequency and severity of hot flushes and in improving menopausal symptoms in Hong Kong perimenopausal women. It is well tolerated, with no serious adverse events noted during the study period.

Non-hormonal interventions for hot flushes in women with a history of breast cancer

BACKGROUND Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain. OBJECTIVE To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer. METHODS Search methods: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library), Medline, Embase, Lilacs, CINAHL, PsycINFO (August 2008) and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts. Selection criteria: Randomized controlled trials (RCTs) comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer. Data collection and analysis: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies. MAIN RESULTS Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin) reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies had a significant benefit. Side-effects were inconsistently reported. AUTHORS' CONCLUSIONS Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to moderate effect on reducing hot flushes in women with a history of breast cancer.

Effects of Pharmacologically Induced Hypogonadism on Mood and Behavior in Healthy Young Women

The relationship between depression and estrogen withdrawal remains controversial. The authors examined the effects of gonadotropin-releasing hormone agonist-induced ovarian suppression on mood, sleep, sexual function, and nighttime hot flushes. They focused on whether participating women experienced clinically significant depressive symptoms and whether specific symptoms associated with hypogonadism (nighttime hot flushes and disturbed sleep) increased susceptibility to depression. Participants were 72 healthy premenopausal women, ages 19-52 years, with no current or past axis I psychiatric diagnosis or gynecological or other medical illness. After 2 months of baseline screening, women received monthly injections of leuprolide acetate (3.75 mg) for 2-3 months. Outcomes were measured using the Beck depression inventory (BDI) and a daily rating scale measuring the severity of several affective and behavioral symptoms. Data were analyzed by repeated-measures analysis of variance using PROC MIXED (for mixed models). BDI scores ≥10 were reported in four of the 72 women (5.6%). Relative to baseline, induced hypogonadism was associated with significantly decreased sexual interest, disturbed sleep, and more severe nighttime hot flushes, but no significant change in any mood-related symptom score. Hot flush severity was significantly correlated with disturbed sleep. These data demonstrate that clinically significant depressive symptoms were rare accompaniments of short-term estradiol withdrawal and induced hypogonadism in healthy premenopausal women. Additionally, neither nighttime hot flushes nor disturbed sleep were sufficient to cause depressive symptoms in hypogonadal women.

Folic acid supplementation: The new dawn for postmenopausal women with hot flushes

Hot flushes, experienced by 75% of menopausal women, are associated with estrogen deprivation. Estrogen was shown to ameliorate hot flushes by interacting with monoamine neurotransmitters in the brain; reducing noradrenaline and increasing serotonin. Hormone replacement therapy(HRT), the first treatment option, causes concerns over possible increased risks particularly breast cancer. Folic acid is involved in the biosynthesis of serotonin and nordrenaline, which is responsible for its effects on mood and cognition, and degrees of folate inadequacy, not severe enough to produce megaloblastic anaemia, were found to be associated with depression and cognitive malfunctioning. Also, increased age was observed to relate to reduced serum and cerebrospinal fluid folic acid levels. There is emerging evidence that folic acid supplementation ameliorates hot fl ushes by the same mechanism as estrogen. To explore this hypothesis, a multi-centre, double-blind, placebo-controlled randomized is being set up to compare the effect of 5 mg folic acid vs placebo in reducing the frequency and severity of hot fl ushes in postmenopausal women, and on the blood level of serotonin and noradrenaline. If folic acid supplementation is demonstrated to be effective, this will be a turning point in the clinical practice since it represents a cheap, safe and well-tolerated alternative to HRT.

Increased Vascular Inflammation in Early Menopausal Women Is Associated With Hot Flush Severity

Context: Menopause has been related to an increased atherosclerotic risk. Presence and severity of hot flushes in menopausal women have been associated with impaired endothelial function and advanced subclinical atherosclerosis. Objective: The objective of the study was to evaluate the effect of menopausal transition on vascular inflammation indices and investigate the association of hot flush severity with these indices in early menopausal women. Design, Setting, and Participants: This was a cross-sectional study that included 120 early menopausal women (age range 42–55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women (controls). Main Outcomes: Serum high-sensitivity C-reactive protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured. Results: P-selectin and sCD40L were increased in early menopausal compared with control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C-reactive pr...

Hot flush symptom-free days with bazedoxifene/conjugated estrogens in postmenopausal women

ABSTRACTObjective The aim of this study was to examine the number of hot flush symptom-free days in symptomatic postmenopausal women treated with bazedoxifene/conjugated estrogens (BZA/CE).Methods In this 12-week, randomized, double-blind, placebo-controlled, phase-3 study, 322 postmenopausal women aged 40–65 years with an intact uterus who had ≥ seven moderate-to-severe daily hot flushes (or ≥ 50 per week) were randomized to BZA 20 mg/CE 0.45 or 0.625 mg or placebo. Subjects recorded the incidence and severity of hot flushes on daily diary cards. In this secondary analysis, the number of days per week without hot flushes from baseline to week 12 was determined. The percentage of women who experienced no hot flushes at week 12 was also evaluated.Results From baseline to week 12, the number of days per week without moderate-to-severe hot flushes or without any hot flushes steadily increased for women treated with BZA 20 mg/CE 0.45 or 0.625 mg versus placebo. In addition, the rate of increase in days per week without any hot flushes was significantly greater with either BZA/CE dose than with placebo (p < 0.0001). Compared with placebo, the percentage of women who experienced no moderate-to-severe hot flushes or no severe hot flushes at week 12 was greater with BZA 20 mg/CE 0.45 mg (p < 0.01 and p < 0.05, respectively) and BZA 20 mg/CE 0.625 mg (p < 0.001 for both).Conclusions BZA/CE increased the number of hot flush symptom-free days and the proportion of women without hot flushes over 12 weeks of therapy.

The tissue selective estrogen complex: a promising new menopausal therapy.

Menopause is associated with health concerns including vasomotor symptoms, vulvar/vaginal atrophy (VVA), and osteoporosis. Estrogen therapy or combined estrogen-progestin therapy (EPT) are primary treatment options for menopausal symptom relief and osteoporosis prevention. Because EPT has been associated with some safety/tolerability concerns relating to undesirable effects of estrogen and progestin, alternative options are needed. The tissue selective estrogen complex (TSEC) is a novel class of agents pairing a selective estrogen receptor modulator (SERM) with 1 or more estrogens. The TSEC combines the established efficacy of estrogens on menopausal symptoms and bone with the protective effects of a SERM on the reproductive tract. The pairing of bazedoxifene (BZA) with conjugated estrogens (CE) has been evaluated in a series of phase 3 clinical trials. BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg have shown efficacy in reducing the frequency and severity of hot flushes, relieving VVA symptoms, and maintaining bone mass while protecting the endometrium and breast. These BZA/CE doses have been associated with a favorable safety/tolerability profile, with higher rates of cumulative amenorrhea and lower incidences of breast pain than those reported for EPT. Thus, BZA/CE may be a promising alternative to conventional EPT for treating non-hysterectomized, postmenopausal women.

The Portuguese Version of the Perceived Control over Hot Flushes Index: Evaluation of its Psychometric Properties

Aim : This research aims at validating an instrument to assess the perception of control over hot flushes, frequent symptoms during menopause. Method : A sample of 243 symptomatic women completed the Perceived Control over Hot Flushes Index, PCoHFI (Reynolds, 1997), two subscales from the Menopause Symptoms’ Severity Inventory, MSSI-38 (Pimenta et al., 2011) to assess perceived loss of control and vasomotor symptoms, as well as a socio-demographic questionnaire. The construct, criterion and external validity, reliability and sensitivity were explored. Results : The exclusion of item 15 is suggested since it presents a negative factorial weight (λ = -.105; p = .134) and only 1.1% of its variance is explained by the construct. The PCoHFI manifested two factors: internal and external control attribution. It does not present convergent validity, but it has discriminant validity. Criterion validity is confirmed by a significant correlation with other similar constructs. Moreover, the PCoHFI evidences a good reliability and sensitivity. Conclusion : The PCoHFI manifests good psychometric properties and is an adequate instrument to assess this variable, which has been identified as a strong predictor of vasomotor symptoms’ severity. Research and interventions with women who evidence severe hot flushes can benefit from the assessment of such construct.

An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women

The aim of this study was to derive an empirically validated definition of treatment responders for the reduction of moderate to severe hot flushes in postmenopausal women. This study used prospective blinded data analysis from a placebo-controlled study to investigate the efficacy of a treatment of moderate to severe hot flushes in postmenopausal women. Seven hundred ten postmenopausal women with at least 50 moderate to severe hot flushes per week participated in the study. The participants recorded the number of moderate to severe hot flushes each day in a diary. They also assessed their satisfaction with treatment on a Clinical Global Impression-improvement rating scale. Changes in the weekly number of moderate to severe hot flushes were compared with participants' self-assessments to derive an empirically validated minimal clinically important difference. This anchor-based value was compared with the conventional half-SD rule for minimal clinically important difference in participant-reported outcomes. Anchor- and distribution-based minimal clinically important differences between "no change/worse" and "minimally improved" were an absolute reduction of 19.1 and 18.6 in the weekly number of moderate to severe hot flushes, respectively. In addition, the threshold between "minimally improved" compared with "much improved or better" was determined, based on the anchor method, as an absolute reduction of 40.3 in the weekly number of moderate to severe hot flushes. A responder was defined as having at least an improvement of 19.1 hot flushes per week at week 4 and an improvement of 40.3 hot flushes per week at week 12.

Transdermal estradiol gel for the treatment of symptomatic postmenopausal women

The aim of this study was to determine the efficacy, safety, and lowest practical dose of a transdermal estradiol gel in the treatment of symptomatic postmenopausal women. Healthy postmenopausal women with seven or more moderate to severe hot flushes per day or 50 to 60 or more per week were randomized to transdermal gel containing 1.5 mg (n = 73) or 0.75 mg (n = 75) estradiol (EstroGel 0.06%) or placebo (n = 73) in a phase 3 study, or to 0.375 mg (n = 119) or 0.27 mg (n = 118) estradiol (0.03% gel) or placebo (n = 114) in a phase 4 study. The frequency of moderate to severe hot flushes and severity of all hot flushes significantly decreased versus placebo at weeks 4 and 12 with 1.5, 0.75, and 0.375 mg estradiol. Overall participant responder rates were generally lower in the phase 4 study than those in the phase 3 study with the approved 0.75-mg estradiol dose. Vaginal maturation index (VMI) shifts from baseline to week 12 were significant (P < 0.001) with 0.75 and 1.5 mg estradiol versus placebo; VMI improved (P < 0.001), superficial cells increased (P = 0.005), and parabasal cells decreased (P = 0.002) with 0.375 mg estradiol vs placebo but not with 0.27 mg estradiol. The most frequently reported treatment-emergent adverse events, although not necessarily treatment related, were headache, infection, breast pain, and nausea (phase 3 study) and insomnia and headache (phase 4 study). No serious adverse events were related to treatment; no deaths occurred. A transdermal gel with 0.75 mg estradiol was the lowest practical dose that effectively reduced the frequency and severity of moderate to severe hot flushes, improved VMI, and was well tolerated.

Using bazedoxifene plus conjugated estrogens for treating postmenopausal women

The objective of this article was to review clinical outcomes reported with the tissue selective estrogen complex containing bazedoxifene (BZA) and conjugated estrogens (CE) in postmenopausal women. PubMed was searched from inception to June 2011 using the key words bazedoxifene and conjugated estrogens. We reviewed six published articles reporting the clinical efficacy and safety outcomes of three different level I evidence, multicenter, blind, randomized, placebo-controlled studies. BZA/CE reduced hot flush frequency and severity, prevented loss of bone mass, and treated vulvar-vaginal atrophy and its symptoms without endometrial stimulation and provided amenorrhea and breast tenderness rates similar to those with placebo. Overall safety was not different from that observed with placebo, and no unexpected findings were reported. The tissue selective estrogen complex composed of BZA/CE is a new progestin-free therapy that alleviates hot flushes and prevents the loss of bone mass in postmenopausal women with endometrial hyperplasia and amenorrhea rates comparable with those of placebo.