Daily Hot Flashes Research Articles

Comparison of hypnotherapy versus gabapentin in the treatment of hot flashes: A pilot study.

168 Background: The purpose of this study is to compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in women with an increased risk or personal history of breast cancer. Methods: In a prospective trial, eligible women were randomized to receive gabapentin (control arm) or hypnotherapy (experimental arm). Eligibility was defined by a personal history of breast cancer or an increased risk of developing breast cancer in women who reported at least one daily hot flash. The duration of participation was eight weeks, and women were asked to keep a daily journal of the number and severity of their hot flashes. The primary endpoints were number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was quality of life, measured using the Hot Flash Related Daily Interference Score (HFRDIS). Results: Twenty-seven women were enrolled (n=14 gabapentin, n=13 hypnotherapy) and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrollment was 4.5 in the gabapentin arm, and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After eight weeks, the median number of daily hot flashes was reduced by 33.3% among women in the gabapentin arm, and 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm, and 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and 55.2% in the hypnotherapy group. Conclusions: Hypnotherapy and gabapentin both demonstrate efficacy in improving hot flashes in women with an increased risk or personal history of breast cancer. Complementary and alternative medicine (CAM) therapies are preferable to many women over hormone therapy due to the perceived risk of breast cancer, but objective data have been lacking comparing its use to conventional therapies. This pilot study provides evidence supporting the use of hypnotherapy for the treatment of hot flashes and emphasizes the need to perform further studies aimed at defining evidence-based recommendations for CAM.

Management of Hot Flashes in Patients Who Have Breast Cancer With Venlafaxine and Clonidine: A Randomized, Double-Blind, Placebo-Controlled Trial

Therapies for breast cancer may induce hot flashes that can affect quality of life. We undertook a double-blind, placebo-controlled trial with the primary objective of comparing the average daily hot flash scores in the twelfth week among patients treated with venlafaxine, clonidine, and placebo. Additional analyses of the hot flash score over the full 12 weeks of treatment were performed. In all, 102 patients with a history of breast cancer were randomly assigned (2:2:1) to venlafaxine 75 mg, clonidine 0.1 mg, or placebo daily for 12 weeks. Questionnaires at baseline and during treatment assessed daily hot flash scores, sexual function, sleep quality, anxiety, and depression. After 12 weeks, a total of 80 patients were evaluable for the primary end point. During week 12, hot flash scores were significantly lower in the clonidine group versus placebo (P = .03); for venlafaxine versus placebo, the difference was borderline not significant (P = .07). However, hot flash scores were equal in the clonidine and venlafaxine groups. Over the course of 12 weeks, the differences between both treatments and placebo were significant (P <.001 for venlafaxine v placebo; P = .045 for clonidine v placebo). Frequencies of treatment-related adverse effects of nausea (P = .02), constipation (P = .04), and severe appetite loss were higher in the venlafaxine group. Venlafaxine and clonidine are effective treatments in the management of hot flashes in patients with breast cancer. Venlafaxine resulted in a more immediate reduction of hot flash scores when compared with clonidine; however, hot flash scores at week 12 were lower in the clonidine group than in the venlafaxine group.

The evaluation of flaxseed for hot flashes: Results of a randomized, controlled trial, NCCTG study N08C7.

CRA9015 Background: Hot flashes are a common symptom during the menopause transition or following breast cancer treatment that can negatively impact the quality of life for many women. Preliminary data have suggested that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment for hot flashes. Methods: A phase III randomized, placebo controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. Postmenopausal women were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks vs a placebo bar. Participants completed daily prospective, self report hot flash diaries during the baseline week and then began eating one study bar per day for 6 weeks, while continuing to record their daily hot flashes. The intra-patient difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Side effects of the bars were evaluated through self report and CTC assessment. Results: Between October and December 2009, 188 women were enrolled onto this trial. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 in the placebo group (p=0.29). In both groups, a little over a third of the women received a 50% reduction in their hot flash scores. Only one side effect was significantly different between groups, that being grade 1 pruritis, which was more common (7%) in the placebo group versus 1% in the flaxseed group. Both groups reported increased abdominal distension, flatulence, diarrhea and nausea. Adherence and ability to detect treatment assignment did not differ between groups. Conclusions: The results of this trial do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were likely due to the fiber content in the flaxseed and placebo bars.

Abstract PD08-04: Management of Hot Flashes in Breast Cancer Patients with Venlafaxine and Clonidine: A Double-Blind Placebo-Controlled Trial

Abstract Background: Therapies for breast cancer may result in symptoms as hot flashes, genitourinary atrophy and psychological distress. Hot flashes are common symptoms that can interfere with quality of life. We undertook a double-blind, placebo controlled trial to assess the efficacy of venlafaxine and clonidine during 12 weeks of treatment. Methods: 102 patients with a history of breast cancer with at least two hot flashes per day were randomly assigned (2:2:1) to venlafaxine 75 mg/d, clonidine 0.1 mg/d or placebo. Daily hot flash scores were recorded at baseline and during treatment. Questionnaires at baseline and during week 4 and 12 assessed sexual function (SAQ), sleep quality (GSQ), anxiety and depression (HADS). The primary endpoint was differences in the average daily hot flash score in the twelfth week between venlafaxine, clonidine and placebo. Secondary objectives were to determine the effect of both drugs on sexual function, sleep quality, anxiety, depression and treatment side effects. Analyses were by intention to treat. Results: 80 patients had evaluable data over the whole study period of 12 weeks. At week 12, treatment was associated with a decrease in the occurrence of hot flashes by 45% versus placebo (p=0.03). There was no significant difference between venlafaxine and clonidine treatment however, over the course of 12 weeks hot flash scores were reduced by 41% in the venlafaxine group and by 26% in the clonidine group (Figure 1). The differences between both treatments and placebo over the 12 week period were significant (p=0.0004 venlafaxine versus placebo, p=0.045 clonidine versus placebo, p=0.002 both treatments versus placebo). Sexual function and sleep quality were not significantly different between the two treatment groups. Adjusting for baseline scores, the week 12 anxiety scores were higher in the clonidine group than in the venlafaxine group (p=0.04) and the depression scores were higher in the venlafaxine group than in the clonidine group (p=0.03). Frequencies of treatment-related side effects, nausea (p=0.02) and constipation (p=0.04) were significantly higher in the venlafaxine group. Only appetite loss (p=0.003) occurred more frequently in the venlafaxine group as severe side effect. Premature discontinuation for adverse events occurred in 2 (5%) patients in the venlafaxine group and 6 (15%) patients in the clonidine group (p=0.26). 41 patients (40%) continued the study treatment after the end of the study. Figure 1. Hot flash score over 12 weeks (blue=placebo, red=clonidine, green=venlafaxine; Discussion: Venlafaxine and clonidine are effective treatments in the management of hot flashes. Venlafaxine treatment resulted in a swifter reduction in the hot flash score in comparison to clonidine. Venlafaxine is more effective than clonidine over the 12 week period of treatment, but at the cost of more side effects. These findings suggest that venlafaxine is to be preferred above clonidine. In case of intolerance clonidine is a realistic treatment alternative. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-04.

Acupuncture for Hot Flashes in Patients With Prostate Cancer

To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer. Men who had a hot flash score > 4 who were receiving androgen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks, using a predefined treatment plan. The primary endpoint was a 50% reduction in the hot flash score after 4 weeks of therapy, calculated from the patients' daily hot flash diaries. The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide, and urinary 5-hydroxyindoleacetic acid, were examined. A total of 25 men were enrolled from September 2003 to April 2007. Of these, 22 were eligible and evaluable. After 4 weeks, 9 (41%, 95% confidence interval 21%-64%) of 22 patients had had a > 50% reduction in the hot flash score. Of the 22 patients, 12 (55%, 95% confidence interval 32%-76%) met this response definition at any point during the therapy course. No patient had a significant increase in hot flash score during therapy. A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality. Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. Of the 22 patients, 41% had responded by week 4 and 55% overall in the present pilot study, providing evidence of a potentially meaningful benefit. Additional studies of acupuncture for hot flashes in this population are warranted.

A randomized crossover trial of venlafaxine (V) versus gabapentin (G) for hot flashes (HF) in breast cancer survivors.

9023 Background: Nonhormonal pharmacologic interventions are recommended for the treatment of HF in breast cancer survivors. Antidepressants (SSRI/SNRI) and G have been shown to be effective, however, it is still unclear which agent is best. Methods: A randomized crossover trial compared 4 weeks of V (37.5 mg × 7 days followed by 75 mg/day) and G (300 mg daily × 3 days, 300 mg BID × 3 days then 300 mg TID). Eligibility included postmenopausal women with at least 14 bothersome HF per week for the prior month. A 2-week baseline period was followed by the first treatment period. Crossover to the alternative treatment occurred following a 2 week dose tapering/wash out period. The primary endpoint was patient preference. Secondary endpoints included change from baseline in HF score (frequency × severity) per a prospective daily HF diary, change in HF frequency, QOL, mood and toxicity. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. A two-stage group sequential design was used with the first analysis pre-planned at 66 patients and the second (if needed) at 131, allowing for drop out/indecision rate of 25%. The design had 80% power to detect a shift from equal preference of ≥ 15 % (2 sided type 1 error at 5%). Results: Data analysis after 66 patients showed the pre-defined stopping rule was satisfied. The study arms were well balanced. Of 56 patients with a preference (8 dropped out and 2 had no preference), 18 preferred G and 38 preferred V (32% and 68% respectively; p = 0.01). Both V and G reduced HF scores (66% reduction) and frequency (55% reduction) similarly and significantly. Satisfaction with the preferred treatment was high. V was associated with more appetite loss, nausea and constipation, and less sleeplessness, nervousness, and negative mood changes than at baseline (all p ≤ 0.03) whereas G was associated with more dizziness and increased appetite, and less sleeplessness (all p ≤ 0.004). Conclusions: Breast cancer survivors prefer V over G for the treatment of HF. Both agents are effective in the management of HF based on recorded diary experience. Preference appears to be driven by the balance between effectiveness and tolerance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, GlaxoSmithKline, Novartis, Roche Amgen, AstraZeneca, GlaxoSmithKline, Novartis, Roche AstraZeneca

Effect of L-methionine on hot flashes in postmenopausal women

Based on a common mechanism of action with gabapentin, we investigated the effects of L-methionine on hot flashes in postmenopausal women. After a 1-week baseline period, 51 postmenopausal women experiencing at least five moderate-severe hot flashes per day were randomized to one of three groups in a 13:13:25 ratio: placebo/placebo, placebo/L-methionine, or L-methionine/L-methionine, respectively (phase 1/phase 2). Phase 1 was 12 weeks long, and phase 2 was 8 weeks long. Participants took 1 g PO BID in phase 1 and 2 g PO BID in phase 2 of either L-methionine or placebo. All participants also took folate 1 mg and methylcobalamin 0.5 mg a day to help minimize the L-methionine-induced elevation in serum homocysteine. The primary outcome variable was the percent change in hot flash composite score from baseline to week 12 obtained from participants' daily hot flash diaries. In phases 1 and 2, there were no significant differences between the L-methionine and placebo groups for any of the hot flash outcome measures. At week 12, there was a mean of 37.4% decrease in hot flash composite score compared with baseline in the L-methionine group and a mean of 33.4% decrease in the placebo group (P = 0.60). There were expected significant increases in fasting serum homocysteine (1.7 and 5.8 micromol/L) and fasting serum methionine (13.9 and 22.3 micromol/L) at weeks 12 and 20, respectively, associated with the two doses of L-methionine therapy relative to placebo therapy. L-methionine therapy seems to be ineffective in the treatment of hot flashes in postmenopausal women.

A study of lavender and tea tree oils on postmenopausal FSH levels and hot flash severity

1516 Background: Products containing lavender and tea tree oil have been linked to prepubertal male gynecomastia.(N Engl J Med 356:479–485) This implies that these products may be phytoestrogens, or plant products with estrogenic effects. Exogenous estrogens increase the risk of developing breast cancer and could counteract benefit from adjuvant hormonal manipulations in women with a history of breast cancer. We designed a study to determine the effects of lavender and tea tree oil on healthy postmenopausal women's FSH as a means to determine the estrogenic effect of both products. Hot flashes are a side effect of decreased endogenous estrogen, and in this study we used hot flash severity as an additional assay of estrogenic effect. Methods: Lavender lotion and tea tree oil products were generously donated by The Body Shop. Nine healthy postmenopausal women suffering from hot flashes were asked to apply lavender lotion and tea tree oil according to product directions for a week each, with a washout period in between. Participants were menopausal with baseline FSH &gt; 26 IU/mL. Serum FSH was obtained at baseline, after each lotion and after the washout period. Participants also recorded daily hot flash number and severity. Average daily hot flash severity was calculated for each patient during each period, with lotion use periods compared to Paired, 2-tailed T-tests were used to compare average hot flash severity for each participant as well as FSH values as compared to the baseline obtained before it. Results: Compliance was excellent. No significant differences were seen between time periods with either product for either measure. In no case did FSH dip to premenopausal levels. No indication of improvement in hot flash frequency or severity was seen. Conclusions: In our population, the lavender and tea tree oil products showed no estrogenic effects. This is similar to clinical trials of phytoestrogens, which as used by humans are not potent enough to affect FSH or hot flash severity. Both lotions can probably be used without increasing the risk of recurrent or de novo breast cancer. We intend one more study period in which participants will use a large daily amount of lavender lotion, again tracking hot flash severity and FSH. No significant financial relationships to disclose.

Genistein reduces the number and duration of hot flashes in peri/post menopausal women in a randomized, double‐blind, placebo‐controlled, multi‐center trial

ObjectiveTo evaluate the effectiveness of a safe, high‐purity, non‐plant derived, non‐allergenic, patent‐protected, proprietary genistein (geniVida) in alleviating hot flashes in peri/post menopausal women.Methods84 peri/post menopausal women (minimum 7 hot flashes/day or 40/week) were enrolled in a randomized, placebo‐controlled, parallel, multi‐center ICH/GCP trial and given a 30 mg capsule of geniVida or a 30 mg placebo capsule daily with breakfast for 12 weeks. Measurements included daily hot flashes, FSH, 17 beta‐estradiol, endometrial thickness and adverse events.ResultsWomen on geniVida had fewer hot flashes/day from baseline to 8 and 12 weeks vs. women on the placebo (p=0.045 and p=0.015, respectively). 61.5% of women on geniVida had 50% or greater reduction in daily hot flashes vs. 25.9% of women on placebo. 88.5% of women on geniVida had 25% or greater reduction in duration of daily hot flashes vs. 59.3% of women on placebo. Severity of hot flashes was not different between groups. There were no differences between the groups for FSH, 17 beta‐estradiol, endometrial thickness and adverse events.ConclusionsgeniVida genistein was demonstrated to have a significant benefit in reducing the number and duration of daily hot flashes in peri/post menopausal women and may be used to manage menopausal symptoms without hormone replacement. Supported by DSM Nutritional Products, Inc.

Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women

The aim of this pilot double-blind, randomized clinical trial, which initially targeted breast cancer survivors, was to obtain preliminary evidence of the effect of Hypericum perforatum extract (St. John's wort extract) compared with placebo on symptoms and quality of life of symptomatic perimenopausal women. We also assessed practical difficulties in recruiting women to such a trial. Symptomatic perimenopausal women aged 40 to 65 years who experience hot flashes (three or more per day, Heart and Estrogen/Progestin Replacement Study scale) were randomly assigned to receive ethanolic St. John's wort extract (900 mg TID) or placebo. The women were asked to keep a daily diary during the week before randomization and during the week before the 3-month follow-up (primary outcome) to record hot flash frequency and intensity. A hot flash score (frequency x severity) was calculated. The Menopause-Specific Quality of Life questionnaire was used to assess menopause-specific quality of life. Forty-seven women were randomized. After 12 weeks of treatment, a nonsignificant difference favoring the St. John's wort group was observed in the daily hot flash frequency (St. John's wort, -2.3 +/- 3.6; placebo, -1.0 +/- 2.2; P = 0.11) and the hot flash score (-3.8 +/- 8.3 and -1.8 +/- 6.5, respectively; P = 0.10). After 3 months of treatment, compared with the placebo group, women in the St. John's wort group reported significantly better menopause-specific quality of life (P = 0.01) and significantly fewer sleep problems (P = 0.05). Hypericum perforatum may improve quality of life in ways that are important to symptomatic perimenopausal women, but these results need to be confirmed by a larger clinical trial.

A phase III trial evaluating three doses of citalopram for hot flashes: NCCTG trial N05C9

9538 Background: Hot flashes are experienced by up to 75% of women and can negatively impact quality of life. Estrogen treatment has fallen out of favor, so new options are needed. Based on encouraging pilot data, this trial was designed to evaluate three doses of citalopram for effects on hot flashes. Methods: A randomized trial evaluated citalopram at doses of 10, 20 or 30 mg/day versus placebo for 6 weeks. Women recorded hot flashes for one week before starting treatment, then were titrated up to their assigned dose. The primary endpoint was change from baseline in hot flash score (frequency × severity) per a prospective daily hot flash diary. Secondary endpoints included hot flash frequency and activity interference. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. Eligibility included postmenopausal women with at least 14 bothersome hot flashes per week for the past month. A total of 50 patients per arm (N=200), provided 80% power for a two-sample t-test...

Comparison of Menopausal Symptoms During the First Year of Adjuvant Therapy With Either Exemestane or Tamoxifen in Early Breast Cancer: Report of a Tamoxifen Exemestane Adjuvant Multicenter Trial Substudy

Hormonal breast cancer treatment increases menopausal symptoms in women. This study investigated differences between the symptoms associated with either adjuvant tamoxifen or exemestane. Ten common symptoms were assessed by self-report questionnaire administered to 1,614 consecutive patients at baseline and every 3 months during the first year of a double-blind, randomized trial of postmenopausal women with early hormone receptor-positive breast cancer. Symptoms were categorized as none, mild, moderate, or severe. A hot flash score was calculated at each time point. Symptoms were analyzed by repeated-measures analysis of variance. Each time period was tested repeatedly against the baseline; an overall P value was assigned for each reported symptom. Compliance was excellent, with 7,286 questionnaires analyzed. Baseline symptom prevalence ranged from 2% (vaginal bleeding) to 60% to 70% (bone/muscle aches and low energy). There were no significant differences in vaginal bleeding, mood alteration, or low energy. Patients receiving tamoxifen had significantly more vaginal discharge (P < .0001). Exemestane patients reported more bone/muscle aches (P < .0001), vaginal dryness (P = .0004), and difficulty sleeping (P = .03). In both groups, the hot flash score peaked at 3 months and decreased thereafter. At 12 months, patients receiving tamoxifen had a significantly higher mean hot flash score (P = .03), with daily hot flashes increasing from baseline by 33% compared with a 7% increase from baseline with exemestane. At 12 months, exemestane was associated with fewer hot flashes and less vaginal discharge than tamoxifen, but with more vaginal dryness, bone/muscle aches, and difficulty sleeping. Symptoms were common in both groups.

A pilot study of mindfulness-based stress reduction for hot flashes

A variety of results from both population and laboratory studies suggest that stress and hot flashes (HFs) are correlated and that HFs are more severe in women with lower coping abilities. The objective of this pilot study was to obtain information on the feasibility and effect of participation in a mindfulness-based stress reduction (MBSR) program on HF severity and menopause-related quality of life. Fifteen women volunteers reporting a minimum of seven moderate to severe HFs per day at study intake attended the eight weekly MBSR classes at the University of Massachusetts Medical School. Participants were assessed for menopause-related quality of life before beginning and at the conclusion of the MBSR program. Women also kept a daily log of their HFs through the course of the 7 weeks of the MBSR program and for 4 weeks after it. Women's scores on quality-of-life measures increased significantly, and the median reported HF severity, calculated as the weekly average of a daily HF severity score, decreased 40% over the course of the 11 weeks of the assessment period. The women were individually interviewed at the completion of their participation, and the results of the interviews were consistent with the results from daily diaries. These results provide preliminary positive evidence of the feasibility and efficacy of MBSR in supporting women who are experiencing severe HFs, and it warrants further investigation.

A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause

To compare the effects of daily ingestion of soy flour (S), ground flaxseed (F), or wheat flour (W) muffins, on quality of life and hot flash frequency and severity in postmenopausal women. This was a double-blind, randomized, controlled, intention-to-treat trial. Ninety-nine women, 1 to 8 years after menopause, ingested muffins with 25 g of flaxseed (50 mg of lignans), 25 g of soy (42 mg of isoflavones), or wheat (control) daily for 16 weeks. Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries. Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly. Eighty-seven women (28, ground flaxseed muffins; 31, soy flour muffins; and 28, wheat flour muffins) completed the trial. Multivariate analysis of variance of all quality-of-life domains yielded an insignificant treatment x time interaction (F46,122 = 0.92, P = 0.62) but a significant time main effect (P <.0001). Repeated-measures analyses of covariance controlling for body mass index showed no significant group x time interaction nor time nor group differences on all quality-of-life domains and hot flash measures except severity. Hot flashes were less severe with flaxseed (P = 0.001) compared to placebo; however, the group x by time interaction was not significant. Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination. Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study.

Pilot Evaluation of Bupropion for the Treatment of Hot Flashes

Bupropion is commonly used in the treatment of nicotine dependence and depression, and in most people, does not cause sexual dysfunction, weight gain, or sedation. Given its attractive side effect profile, the efficacy of other newer antidepressants against hot flashes and anecdotal observations of resolution of hot flashes in some patients taking bupropion for nicotine dependence, it was decided to explore its clinical activity as a hot flash remedy in a pilot study. Between January 1999 and October 2004, 21 patients (7 men and 14 women) were enrolled in the study. Self-completed daily hot flash diaries were used to document the frequency and severity of hot flashes at baseline (week 1) and during the treatment period (weeks 2 through 5). Participants received bupropion 150 mg every morning for the first 3 days and then 150 mg twice per day for a total of 4 weeks. One woman did not provide any hot flash information and was excluded from the analysis. Five women could not complete the study because of side effects. The study did not show a reduction in hot flash frequency and/or severity significantly higher than what would be expected with a placebo. Even though the sample size was small, these results are consistent with bupropion's mechanism of action (norepinephrine reuptake inhibition without serotonergic effects) and what it is now hypothesized about the pathophysiology of hot flashes (increased noradrenergic activity and decreased serotonergic activity). These data suggest that bupropion should not be further investigated as a remedy for hot flashes.

Association between hot flashes, sleep complaints, and psychological functioning among healthy menopausal women

Self-report data suggest that sleep hot flashes among menopausal women are associated with sleep problems and in turn impaired psychological functioning. However, few studies have examined these relations with physiologic hot flash measures. A total of 41 perimenopausal and postmenopausal women with daily hot flashes underwent nighttime sternal skin conductance monitoring to quantify hot flashes. Participants completed sleep diaries; the Sleep-Wake Experience List (van Diest, 1990); and depression, anxiety, and daily stress measures. Participants experienced a median of 2 physiologically monitored and 1 reported sleep hot flash nightly. Although sleep complaints were significantly and positively associated with psychological functioning, neither sleep complaints nor psychological functioning was significantly related to frequency of physiologically monitored sleep hot flashes. Conversely, results indicate an association between reported sleep hot flashes and acute sleep problems. The frequency of physiologically monitored sleep hot flashes, as opposed to reported sleep hot flashes, may be independent of problems with sleep and mood among menopausal women.

Nonhormonal Therapies for Menopausal Hot Flashes

Concern regarding the adverse effects of estrogen and other hormones for treating menopausal symptoms has led to demand for other options; however, the efficacy and adverse effects of nonhormonal therapies are unclear. To assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials. MEDLINE (1966-October 2005), PsycINFO (1974-October 2005), and the Cochrane Controlled Clinical Trials Register Database (1966-October 2005) were searched for relevant trials that provided data on treatment of menopausal hot flashes using 1 or more nonhormonal therapies. All English-language, published, randomized, double-blind, placebo-controlled trials of oral nonhormonal therapies for treating hot flashes in menopausal women measuring and reporting hot flash frequency or severity outcomes. Trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Data on participants, interventions, and outcomes were extracted and trials were rated for quality based on established criteria. A meta-analysis was conducted for therapies with sufficient trials reporting hot flash frequency outcomes. From 4249 abstracts, 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily hot flashes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference, -1.13; 95% confidence interval [CI], -1.70 to -0.57), 4 trials of clonidine (-0.95; 95% CI, -1.44 to -0.47), and 2 trials of gabapentin (-2.05; 95% CI, -2.80 to -1.30). Frequency was not reduced in meta-analysis of trials of red clover isoflavone extracts and results were mixed for soy isoflavone extracts. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined. The SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.

Dehydroepiandrosterone for the Treatment of Hot Flashes: A Pilot Study

BackgroundPublished data regarding the negative risk-benefit ratio of traditional estrogen/progesterone hormone replacement therapy for menopausal symptoms have indicated the need for alternative treatments. Dietary supplements and herbal products are popularly used for menopausal control without a large evidence base. Therefore, a prospective pilot trial using 50 mg of dehydroepiandrosterone (DHEA) once daily for 4 weeks following a baseline week was developed to explore whether DHEA has any efficacy in reducing hot flashes. Safety issues were also evaluated. Patients and MethodsTwenty-eight women were enrolled in this study, 22 of whom are evaluable. The primary outcome was the reduction in hot flash score (frequency multiplied by average severity) from baseline as measured by validated self-report daily hot flash diaries. ResultsThe mean hot flash score decreased 50% from baseline, and there were no side effects that were significantly worse compared with baseline. Quality of life related to hot flashes showed statistically significant improvement after 4 weeks of DHEA therapy. ConclusionThis pilot study provides data supporting the hypothesis that DHEA is well tolerated and can reduce hot flashes. Dehydroepiandrosterone should be studied further in a larger, placebo-controlled trial.

Menopause: a review of botanical dietary supplements

Since the release of the Women's Health Initiative (WHI) findings, an increasing number of dietary supplement products specifically targeting women in menopause have appeared in the American marketplace. This growth highlights the need for a critical evaluation of the tolerability and effectiveness of these products. The purpose of this article is to assess the evidence for safety and benefit of botanical monopreparations used for relief of menopause-related symptoms. The Cochrane Library and Medline databases were searched from January 1966 to October 2004, using a detailed list of terms related to botanicals and menopausal symptoms. Studies were considered eligible (1) if they were controlled trials of a botanical monopreparation administered orally for a minimum of 6 weeks to perimenopausal or postmenopausal women with hot flashes and (2) if they included a placebo or comparative treatment arm. Topical preparations, botanical combinations, and dietary interventions, such as soy food or protein, were not included. No language restrictions were imposed on the search. A total of 19 studies met the inclusion criteria. The majority of studies indicate that extract of black cohosh (Actaea racemosa L.) improves menopause-related symptoms; however, methodologic shortcomings in the trials were identified. To date, 4 case reports of possible hepatotoxicity have been published, although previous safety reviews suggest that black cohosh is well tolerated and that adverse events are rare when it is used appropriately. The results of 6 clinical studies on soy (Glycine max L.) isoflavone extracts are mixed. Moreover, the composition and dose of soy supplements varies widely across studies, making comparisons and definitive conclusions difficult. One study challenged the long-term safety of high-dose soy isoflavone extract (150 mg/day for 5 years) on the uterine endometrium. Clinical data from 5 controlled trials assessing the efficacy of semipurified isoflavone red clover (Trifolium pratense L.) leaf extracts to reduce hot flash frequency and severity or to relieve symptoms associated with the domains of the Greene Menopausal Symptom Scale are contradictory. The largest study showed no benefit for reducing symptoms associated with menopause for 2 different red clover isoflavone products compared with placebo. No significant adverse events have been reported in the literature. Single clinical trials do not support the use of dong quai (Angelica sinensis L.), ginseng (Panax ginseng C.A. Mey), or evening primrose seed oil (Oenothera biennis L.) for improving menopausal symptoms. We conclude that black cohosh extracts appear to ease menopausal symptoms; ongoing studies funded by the National Institutes of Health (NIH) will provide more definitive safety and efficacy data. Soy isoflavone extracts appear to have minimal to no effect, although definitive conclusions are difficult given the wide variation in product composition and dose. Long-term safety of higher dosage (150 mg/day) soy isoflavone extracts is uncertain. Semipurified isoflavone red clover leaf extracts have minimal to no effect in reducing menopausal symptoms. Dong quai, ginseng extract, and evening primrose seed oil appear to be ineffective in ameliorating menopausal symptoms at the dosages and in the preparations used in these studies.

Is sternal skin conductance monitoring a valid measure of hot flash intensity or distress?

To examine the validity of using sternal skin conductance monitoring as a measure of hot flash intensity and hot flash distress. Descriptive, prospective, longitudinal data from the 2-week baseline of a larger hot flash intervention study; 73 breast cancer survivors with daily hot flashes wore a hot flash monitor and completed a hot flash diary during two 24-hour assessment periods that were separated in time by 1 week. Data consisted of 569 diary rated hot flashes; 46.9% had magnitude of less than 2.0 micromhos (insufficient to meet objective hot flash criterion) and 26.3% had magnitude of 0.0 micromho (no change in skin conductance). Results from mixed-linear modeling indicated that, although magnitude significantly predicted hot flash intensity and distress, effect sizes were very small: less than 2% when using all observations, and less than 1% when using only the subset meeting objective hot flash criteria. Even after adjusting for covariates that were associated with intensity or distress, magnitude explained very little variance in intensity or distress (<2.2%). Scatterplots and locally weighted smooth regression curves also revealed very little relationship between magnitude and either intensity or distress. Findings indicate that objective change in sternal skin conductance, an indicator of sweat gland activity, should not be used as a proxy measure of subjective hot flash intensity or distress. Future research should continue to subjectively measure hot flash intensity and distress when these are important outcome variables to consider.