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PubMed1998

Definitions of hot flashes in breast cancer survivors.

Menopause is an expected event in a woman's life. Treatment for breast cancer can impact the onset of menopause and precipitate symptoms such as hot flashes. Yet this sequelae of events is not well measured, defined or assimilated into quality of life assessments for cancer survivors. Though not life threatening, hot flashes can greatly impact a woman's quality of life or functional ability. It is important for health care professionals to more fully understand the nature of the experience of hot flashes so as not to underestimate their disruptive potential. As part of a larger clinical trial to look at the effectiveness of vitamin E for hot flashes, breast cancer survivors kept a log of both the frequency and intensity of their hot flashes. These women then wrote descriptions to define the severity of those hot flashes. The purpose of this paper is to provide insight into the experience of hot flashes in breast cancer survivors and to describe the severity of hot flashes with narratives given by the women experiencing them.

Adult↗

PubMed2005

Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial.

PURPOSE: In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters. PATIENTS AND METHODS: Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9. RESULTS: 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01). CONCLUSION: Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.

Adult↗

PubMed1994

Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.

PURPOSE: To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS AND METHODS: A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. RESULTS: Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05). CONCLUSION: Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.

Administration, Cutaneous↗

PubMed2001

Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate.

PURPOSE: We evaluated the incidence and frequency of, and distress due to hot flashes after castration therapy with polyestradiol phosphate and complete androgen ablation. MATERIALS AND METHODS: A total of 915 men with metastatic prostate carcinoma enrolled in the Scandinavian Prostatic Cancer Group-5 trial study were randomized to intramuscular injections of 240 mg. Polyestradiol phosphate every 2 weeks for 8 weeks followed by monthly subcutaneous injections or complete androgen ablation, that is bilateral orchiectomy or 3.75 mg. of the gonadotropin-releasing hormone analog triptorelin monthly combined with 250 mg. of the antiandrogen flutamide 3 times daily. The incidence and frequency of, and distress due to hot flashes were recorded at regular intervals using a questionnaire. RESULTS: Of the 915 men 901 were evaluated at a median followup of 18.5 months. The incidence of hot flashes was 30.1% and 74.3% in the polyestradiol phosphate and complete androgen ablation groups, respectively (p <0.001). In the polyestradiol phosphate group the frequency of and distress due to hot flashes were significantly lower than in the androgen ablation group. There was complete relief from hot flashes in 50% of the men on polyestradiol phosphate during followup compared with none on androgen ablation. The incidence of hot flashes did not differ in men with and without tumor progression. CONCLUSIONS: Endocrine treatment with polyestradiol phosphate induced fewer and less distressing hot flashes than complete androgen ablation. Flashes also disappeared to a greater extent during polyestradiol phosphate than during androgen ablation. The data in this study enable us to provide thorough individual information to patients on the risk and grade of expected distress and duration of hot flashes during polyestradiol phosphate or complete androgen ablation treatment.

Androgen Antagonists↗

PubMed1998

Biochemical, metabolic, and vascular mechanisms in menopausal hot flashes.

OBJECTIVE: To determine if increases in core body temperature preceding most hot flashes are caused by increased metabolic rate, peripheral vasoconstriction, or central noradrenergic activation. DESIGN: Laboratory physiological study. SETTING: University medical center. PATIENT(S): Fourteen healthy, postmenopausal women reporting frequent hot flashes. INTERVENTION(S): Data were recorded for 3 hours in a temperature- and humidity-controlled room. MAIN OUTCOME MEASURE(S): Core body temperature, mean skin temperature, respiratory exchange ratio, sternal skin conductance, plasma 3-methoxy-4-hydroxyphenylglycol, and vanillylmandelic acid. RESULT(S): Twenty-nine physiologically defined hot flashes were recorded. Increases in core body temperature, measured with an ingested radiotelemetry capsule, preceded 76% of the flashes. Increased metabolic rate began after increased core temperature. Peripheral vasoconstriction did not occur. Plasma levels of 3-methoxy-4-hydroxyphenylglycol, a metabolite of brain norepinephrine, increased significantly, whereas vanillylmandelic acid, a peripheral metabolite, did not. CONCLUSION(S): Core body temperature elevations preceding menopausal hot flashes are not driven by peripheral vasoconstriction or increased metabolic rate, but probably by a central noradrenergic mechanism.

Analysis of Variance↗

PubMed1985

Hot flashes in postmenopausal women ameliorated by danazol.

Six postmenopausal women with hot flashes were studed for two 8-week periods during which they received low-dose danazol (100 mg/24 hours) for one time interval and placebo for the other in a randomized double-blind manner. The patients recorded the number and severity of their hot flashes daily. On the last day of each period the patients were admitted to the research center overnight for an 8-hour monitoring of forehead skin temperatures and for continuous withdrawal of blood to determine 20-minute integrated levels of luteinizing hormone. Three of the six patients responded to danazol with a mean reduction of 88% in the number of hot flashes and a 53% decrease in the severity of hot flashes. Responders differed from nonresponders in that on treatment the frequency of nocturnal pulses of luteinizing hormone was reduced more (36.1% versus 14.4%), the increase in amplitude of the pulses was greater (+30.7% versus -11.8%), and the fall in the mean level of luteinizing hormone was more marked (19.0% versus 10.5%). The findings suggest that danazol may be a reasonable alternative to estrogen in the treatment of postmenopausal women with severe vasomotor symptoms.

Danazol↗

PubMed1975

Body temperatures during menopausal hot flashes.

Body temperatures during hot flashes were measured in a menopausal woman. Internal temperatures fell after each flash; lowest: rectal, 35.6 degrees C; vaginal, 35.6 degrees C; tympanic, 35.2 degrees C. Where sweating occurred, the skin temperature fell during the flash and rose after it. Finger and toe temperatures always showed a sharp rise at the onset of a flash with a slower fall after the flash. Only the cheeks showed additional temperature rises; maximum, 0.7 degrees C. The heart accelerated 13% at the onset of the flash but slowed immediately thereafter. The flash interval was sharply demarcated by undulations in the ECG baseline. There was never any premonitory sign of the imminence of a flash. A central excitatory state seemed to build up, perhaps by the accumulation of a chemical compound, but not of heat, which was explosively dischargedmthe thermal distress was probably evoked by vascular warming in the cheeks. Dabbing the malar prominences with cold water brought prompt relief.

Body Temperature↗

PubMed2001

Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer.

PURPOSE: Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients. PATIENTS AND METHODS: Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits. RESULTS: Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups. CONCLUSION: Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.

Antineoplastic Agents, Hormonal↗

PubMed2006

Cognitive behavior therapy for menopausal hot flashes: two case reports.

Two case reports of women treated with an individual cognitive behavioral treatment (CBT) for menopausal hot flashes are presented. Both women reported substantial improvements in the number of hot flashes experienced as well as in their quality of life as measured by the Menopause Quality of Life Scale (MENQOL), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Improvements in hot flashes and quality of life were maintained 6 months after treatment ended. It is hypothesized that CBT reduces hot flashes by reducing central sympathetic activation, perceptions of stress, and self-critical thoughts. The long-term efficacy of CBT for hot flashes should be examined in large controlled clinical trials.

Cognitive Behavioral Therapy↗

PubMed2002

Pilot evaluation of gabapentin for treating hot flashes.

OBJECTIVE: To obtain pilot prospective data regarding the efficacy and tolerability of gabapentin for alleviating hot flashes. PATIENTS AND METHODS: This prospective single-arm clinical trial was conducted between July 26, 2001, and November 30, 2001. Patients underwent a baseline week and then 4 weeks of gabapentin treatment, with increasing doses during the first 3 weeks, from 300 to 600 to 900 mg/d. Data were obtained primarily from patient-completed questionnaires. RESULTS: Data from 20 evaluable women (of 24 entered in the trial) were available. Four patients discontinued use of gabapentin for perceived drug-related untoward symptoms, primarily related to light-headedness and dizziness. The 16 patients who completed this clinical trial had a mean reduction in hot flash frequency, in the fourth treatment week compared to the baseline week, of 66%. Their corresponding hot flash score (frequency times average severity) reduction was 70%. Additionally, patients who completed the 4 treatment weeks had a strong tendency to report an improvement in several other symptoms. CONCLUSION: Although a double-blind placebo-controlled clinical trial should be conducted to better elucidate the efficacy and toxicity of gabapentin in patients with hot flashes, the available data suggest that gabapentin is a reasonable treatment to consider in patients with hot flashes if they do not wish to use hormonal therapy.

Acetates↗

PubMed1983

Induction of hot flashes in premenopausal women treated with a long-acting GnRH agonist.

To examine the relationship between the occurrence of menopausal hot flashes and the pulsatile release of LH, we have investigated the serum hormone levels and the occurrence of hot flashes by objective recordings in five women with endometriosis given daily injections of a long-acting GnRH agonist (GnRH-a) for 28 days. Results were compared to the findings made in 25 young women 6-8 weeks after bilateral oophorectomy. Serum levels of estrone and estradiol were similar in the subjects given GnRH-a and the women who underwent a surgical castration. In comparison with values before GnRH-a administration, the mean FSH level was lower whereas the mean LH concentration was significantly higher (P less than 0.01) on the last day of therapy. The coefficients of variations of both gonadotropins measured during 4-h sampling periods at 20-min intervals before and at the end of GnRH-a administration were significantly reduced (P less than 0.01) with therapy. During the total of 20 h of frequent sampling in the 5 subjects, 15 pulses (20% rise from nadir) of LH and 12 pulses of FSH were detected before GnRH-a, whereas only 2 and 8 pulses, respectively, were observed on day 28 of treatment. Hot flashes were observed in both groups of patients. The proportion of women experiencing hot flashes, the rate of occurrence/h and the characteristics of the physiological changes were similar in the 2 groups of women. These data indicate that hot flashes can occur in the absence of prominent LH pulses, suggesting the pulsatile release of this hormone is merely associated with the hot flash rather than being etiological.

Castration↗

PubMed1984

Pituitary hormones during the menopausal hot flash.

Eighteen postmenopausal women with severe hot flashes had continuous recordings of finger temperature and skin resistance as objective indexes of flushing episodes, and serial measurements of anterior pituitary hormones as indirect indexes of hypothalamic neurotransmitter activity. Significant increases of growth hormone, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH) occurred with maximal concentrations at 30, five, and 15 minutes, respectively, after the onset of the skin temperature rises. No significant fluctuations of prolactin (PRL), thyroid-stimulating hormone (TSH), or follicle-stimulating hormone (FSH) were observed. The mean serum cortisol concentration increased 15 minutes after the hot flash, presumably consequent to the preceding elevation of ACTH. Pituitary ACTH release may be secondary to hypothalamic cooling, whereas increased growth hormone and LH output and the thermoregulatory adjustments comprising the flushing episodes are all consistent with cyclic episodes of increased hypothalamic norepinephrine activity.

Adrenocorticotropic Hormone↗

PubMed1984

Menopausal hot flashes: thermoregulatory, cardiovascular, and circulating catecholamine and LH changes.

Thermoregulatory, cardiovascular and endocrine changes were simultaneously monitored in 11 post-menopausal women with frequent hot flashes (catecholamine and LH levels were measured in 5 and 6 subjects respectively). Plasma samples were obtained at 1- and 5-min intervals. Hot flashes were accompanied by abrupt increases in plasma epinephrine (about 150%) and concomitant decreases in norepinephrine (about 40%). Increased luteinizing hormone was associated with most hot flashes. A detailed sequence of hot flash-associated changes was established. An aura preceded the onset of the hot flash by several seconds. HR and FBF increased just before the onset of the flash and reached peak levels of 10-20 beats/min and 30-fold respectively. Coincident with vasodilation and sweating, finger temperature increased an average of 3.9 degrees C and esophageal temperature fell 0.2-0.6 degrees C. Flashes of both discrete and prolonged intervals were observed. Sensation was a reliable index of flash occurrence and intensity as measured physiologically. Our observations are consistent with the hypothesis that hot flashes are due to a change in the thermoregulatory set point. Furthermore, the changes in catecholamine levels are consistent with the cardiovascular changes accompanying hot flashes.

Body Temperature Regulation↗

PubMedDate not supplied

Pilot evaluation of citalopram for the relief of hot flashes.

Symptoms associated with premature menopause are a significant problem for women with a history of breast cancer who cannot take hormone replacement therapy. Thus, effective nonhormonal alternatives are needed to manage hot flashes, the most prevalent symptom of menopause. Previous studies have defined that venlafaxine, an anti-depressant, is an effective treatment for such hot flashes. Based on suggestive anecdotal information, we set out to evaluate, in a pilot trial, whether the antidepressant citalopram might be a good nonhormonal treatment option to add to our armamentarium for controlling hot flashes. A prospective pilot study was developed in which patients were studied for 5 weeks, with the first week used to establish a baseline, followed by 4 weeks of treatment with citalopram. During the first week of treatment, 10 mg/day of citalopram was taken while 20 mg/day was taken during each of the following three weeks. Hot-flash diaries were completed daily, symptom diaries and quality-of-life items were completed weekly and the Profile of Mood States was completed at baseline and at week 5. Evaluable patients who completed the study had a mean hot-flash frequency reduction of 58% and a mean hot-flash score reduction of 64% from baseline to week 5. The patients finishing the study also reported decreased anger, tension and depression, as well as improved mood. This pilot trial suggests that citalopram may be an effective non-hormonal treatment for hot flashes in women who can tolerate it.

Affect↗

PubMed2003

Menopausal hot flash and calciotonin gene-related peptide; effect of Keishi-bukuryo-gan, a kampo medicine, related to plasma calciotonin gene-related peptide level.

OBJECTIVES: The purpose of this study is to investigate relationship of menopausal hot flash and calcitonin gene-related peptide (CGRP). Furthermore, this study evaluated the effect of the Japanese herbal (kampo) medicine Keishi-bukuryo-gan from the aspect of CGRP regulation. METHODS: Plasma CGRP and vasoactive intestinal peptide (VIP) levels were measured during hot flash and CGRP reactivity was studied by cold load test in subjects with/without hot flashes. The effect of Keishi-bukuryo-gan was assessed in comparison with plasma CGRP level. RESULTS: Only plasma CGRP but not VIP significantly elevated at the occurrence of hot flash (P=0.002). Stress by cold load significantly enhanced the over-secretion of CGRP in subjects with flash compared with those without flash (P=0.003) 3 min after the load. Keishi-bukuryo-gan decreased plasma CGRP level in subjects with hot flash. CONCLUSIONS: CGRP but not VIP was mainly related to the occurrence of hot flash. Keishi-bukuryo-gan, Japanese herbal medicine, improves hot flash possibly affecting plasma CGRP level.

Calcitonin Gene-Related Peptide↗

PubMed1985

The prevalence of hot flash and associated variables among perimenopausal women.

A telephone survey of a random sample of 594 perimenopausal women was done to study the prevalence of hot flashes, use of estrogen, age of menopause onset, and, among those subjects experiencing hot flashes, the frequency of occurrence and number of years of hot flashes. The prevalence of hot flashes was 88%. Surgical menopause women had a prevalence rate of 92% and had the highest estrogen utilization rate. The median age of onset for natural menopause women was 49 years. The frequency of occurrence and number of years of hot flash experience was variable across all groups.

Adolescent↗

PubMed2004

Nonhormonal alternatives for the treatment of hot flashes.

OBJECTIVE: To review the literature on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin for the treatment of hot flashes. DATA SOURCES: A MEDLINE search (January 1966-July 2003) was conducted to identify English-language literature available on the treatment of hot flashes that focused on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin. These articles, relevant abstracts, and additional references listed in articles were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA SYNTHESIS: In women unable or unwilling to take hormonal therapies, several nonhormonal alternatives have been evaluated in small controlled and uncontrolled trials. Oral and transdermal formulations of clonidine are moderately effective in reducing hot flashes. Results of studies evaluating venlafaxine, paroxetine, and gabapentin suggest greater reductions in hot-flash frequency and severity compared with those of clonidine. Fluoxetine appears to display a modest benefit compared with paroxetine, although no comparative trials have been conducted. Most women studied in these trials had a history of breast cancer, and many were taking concurrent tamoxifen. All of these agents were fairly well tolerated. CONCLUSIONS: Clonidine, venlafaxine, paroxetine, fluoxetine, and gabapentin are nonhormonal agents that have demonstrated efficacy in small controlled and uncontrolled trials in reducing hot flashes and should be considered in patients unwilling or unable to take hormonal therapies.

Complementary Therapies↗

PubMed2001

Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate.

PURPOSE: In women the vasodilatory neuropeptides calcitonin gene-related peptide and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed whether plasma calcitonin gene-related peptide and neuropeptide Y change during hot flashes in men after castration. MATERIALS AND METHODS: We evaluated 10 men 61 to 81 years old who underwent castration due to cancer of the prostate and had frequent hot flashes for changes in plasma calcitonin gene-related peptide and neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples were obtained between flashes and 4 were obtained during each flash. The samples were analyzed for calcitonin gene-related peptide and neuropeptide Y using radioimmunoassay technique. Hot flashes were objectively recorded by measuring peripheral skin temperature and skin conductance. RESULTS: Plasma calcitonin gene-related peptide increased 46% (95% confidence interval 21 to 71) during flashes in the 6 men in whom it was measurable. This change was statistically significant (p = 0.028). The concentration of neuropeptide Y was below the detection limit. Skin conductance and temperature increased significantly during flashes. CONCLUSIONS: Calcitonin gene-related peptide is involved in the mechanisms of hot flashes in men who underwent castration due to prostate carcinoma. Thus, there may be a similar mechanism of hot flashes in women and in men deprived of sex steroids.

Aged↗