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Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial.

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis. PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects. RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed. CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.

Adolescent↗

Methodologic lessons learned from hot flash studies.

PURPOSE: In the course of conducting a series of prospective clinical trials devoted to defining new treatment opportunities for hot flashes in cancer survivors, considerable experience has been acquired with related methodologic issues. This article has been written in response to many queries regarding this methodology. PATIENTS AND METHODS: A series of seven different clinical trials that involved 968 patients was used for this work. Reliable and valid definitions of hot flash intensity were developed from patient-reported descriptions. Concomitant validity and reliability assessment of patient-completed diaries was undertaken to compare hot flash data with toxicity and quality-of-life (QOL) end points and to examine consistency across patient groups using variability analysis and correlation procedures. Parametric data from this meta-analysis was used to examine relative power considerations for the design of phase II and phase III clinical trials. RESULTS: Daily diaries used in these studies exhibited consistency and reliability and had few missing data. Hot flash frequency and hot flash score (frequency multiplied by average severity) variables produced almost identical end point results. For phase III placebo-controlled studies, 50 patients per treatment arm seem appropriate to provide sufficient power specifications to detect a clinically meaningful change in hot flash activity. For phase II trials, 25 patients per trial seem to provide reasonable estimates of eventual hot flash efficacy to screen potential agents for more definitive testing. CONCLUSION: Given the data gained from these experiences, we can plan and carry out more efficient trials to identify efficacious agents for the reduction of hot flash activity.

Analysis of Variance↗

Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials.

OBJECTIVE: Raloxifene, a selective estrogen receptor modulator, is estrogen-like in the skeleton and cardiovascular system and antiestrogenic in reproductive tissues. In contrast to estrogens, raloxifene is not indicated for the treatment of hot flashes. This study was designed to examine the characteristics of hot flashes among healthy postmenopausal women participating in osteoporosis prevention trials who were receiving raloxifene or placebo. METHODS: Adverse event data from three randomized, double-blind trials (N = 876) comparing raloxifene 60 mg/day with placebo for 30 months were integrated and analyzed. Two of the three trials (one European, two North American) were identically designed and were open to healthy postmenopausal women ages 45 through 60 without regard to prior hysterectomy. The third trial was multinational, was open to women ages 40 through 60, and all enrollees had prior hysterectomy at baseline. Women were questioned in general terms about the occurrence of adverse events at 3-6-month intervals. Treatment-emergent adverse events pertaining to hot flashes were included in the current study. RESULTS: At baseline, 12% of women randomly assigned to placebo and 13% assigned to raloxifene reported prevalent hot flashes. After 30 months, the cumulative incidence of hot flashes was 21% for placebo and 28% for raloxifene (P = 0.022), with the difference in incidence rate confined to the first 6 months of therapy. There was no difference between placebo and raloxifene in reported maximum severity of or early discontinuations as a result of hot flashes (< or = 3% per group for both outcomes). Among women whose hot flashes had stopped completely during the 30-month study period, the median total duration of the event prior to becoming symptom-free was 246 days for placebo and 205 days for raloxifene. Among all women reporting a hot flash, the extrapolated total duration of hot flashes was the same for women treated with either raloxifene or placebo. No subgroup-by-therapy interactions were detected. Multivariable regression analysis revealed several factors that were independently weakly predictive of hot flashes. CONCLUSIONS: Raloxifene slightly affects the incidence but not the natural history of hot flashes in healthy postmenopausal women seeking prevention therapy.

Adult↗

Do menopausal hot flashes have any significant effects on arterial blood gas measurements?

OBJECTIVES: To evaluate the effects of menopausal hot flashes on arterial blood gas measurements. METHODS: Twelve postmenopausal women with frequent hot flashes were enrolled in this study. Blood samples from femoral artery were collected before and during menopausal hot flashes in each subject, and all blood samples were analyzed for pH, pCO2, pO2, HCO3 standard, total CO2, and base excess. Arterial blood gas parameters before and during menopausal hot flashes were compared statistically. RESULTS: pH measurements decreased significantly during hot flashes (P < 0.05); although the difference was found to be statistically significant, the amount of decrease and the range in which the change took place led us to conclude that this change was clinically insignificant. Other parameters did not show any statistically significant differences between the preflash and flash measurements. CONCLUSIONS: Our results indicate that menopausal hot flashes do not have any clinically significant effects on arterial blood gas measurements.

Bicarbonates↗

Differential association of modifiable health behaviors with hot flashes in perimenopausal and postmenopausal women.

OBJECTIVE: To determine the association of modifiable factors, such as smoking, body mass index, and alcohol use, with hot flashes, and to ascertain whether the association with hot flashes varies by menopausal stage. DESIGN: A written survey completed by perimenopausal and postmenopausal women enrolling in a randomized, controlled trial of a menopause risk management program in 1999. Survey items included questions on demographics, health status, and health behaviors. SETTING: A Massachusetts-based health maintenance organization. PATIENTS/PARTICIPANTS: Female members, age 40 to 65, excluding women with chronic conditions precluding study participation, were randomly selected from an automated medical record system. MEASUREMENTS AND MAIN RESULTS: The majority of the 287 postmenopausal and 468 perimenopausal women participating in the study were white, college educated, and nonsmoking. Approximately 30% of both groups reported experiencing hot flashes. Separate multivariable logistic regression models were developed for perimenopausal and postmenopausal women to identify correlates of reporting any versus no hot flashes. After controlling for age, race, oral contraceptive use, hormone replacement therapy use, and depression, correlates of hot flashes in perimenopausal women were body mass index >/=25 kg/m(2) (odds ration [OR], 2.00; 95% confidence interval [CI], 1.28 to 3.12) and alcohol use of 1 to 5 drinks per week (OR, 0.52; 95% CI, 0.31 to 0.86). The only significant correlate of hot flashes in the postmenopausal population was high dietary fat intake (OR, 0.35; 95% CI, 0.15 to 0.81). CONCLUSION: Although study respondents were from similiar sociodemographic groups and received their health care in the same health maintenance organization, modifiable factors associated with hot flashes were different for perimenopausal and postmenopausal women.

Adult↗

State of the science: hot flashes and cancer. Part 1: definition, scope, impact, physiology, and measurement.

PURPOSE/OBJECTIVES: To critically evaluate and synthesize multidisciplinary research related to hot flashes in the context of cancer. Topics include the definition, scope, and impact of hot flashes; physiologic mechanisms; and measurement issues. DATA SOURCES: Published, peer-reviewed articles and textbooks; editorials; unpublished data; and computerized databases. DATA SYNTHESIS: Hot flashes can affect a diverse group of men and women diagnosed with or at high risk for certain cancers with a resulting negative impact on quality of life. Although the exact physiologic mechanisms underlying hot flashes remain unclear, a complex interplay of thermoregulatory, gluconeuroendocrine, genetic, and behavioral factors appears to be involved. Measurement of hot flashes should be considered carefully because they can be operationalized objectively and subjectively. CONCLUSIONS: The large and diverse evidence base and current national attention on measurement of hot flashes highlight the importance of the symptom to healthcare professionals, including oncology nurses. IMPLICATIONS FOR NURSING: Careful attention to assessment and measurement of hot flashes in patients with cancer is needed.

Body Temperature Regulation↗

Pilot evaluation of paroxetine for treating hot flashes in men.

OBJECTIVE: To provide prospective information on the potential utility of paroxetine for treating hot flashes In men receiving androgen ablation therapy for prostate cancer. PATIENTS AND METHODS: Men with symptomatic androgen ablation therapy-related hot flashes were entered into this clinical trial between August 2001 and October 2003. After a baseline week of documentation of the frequency of hot flashes, patients were assigned to receive paroxetine; the initial dosage was 12.5 mg/d, and it was increased to 37.5 mg/d over the ensuing 4 weeks. RESULTS: Of the 24 patients in whom medication was initiated, 18 completed the 5-week study. In these patients, the median frequency of hot flashes decreased from 6.2 per day during the baseline week to 2.5 per day during the last study week. Hot flash scores (frequency x mean severity) during the same period decreased from 10.6 per day to 3.0 per day. Overall, paroxetine was well tolerated by most patients. CONCLUSION: The results from this trial suggest that paroxetine Is an effective agent for diminishing hot flashes in men receiving androgen ablation therapy.

Aged↗

Hot flashes and their management in breast cancer.

OBJECTIVES: To review literature relevant to defining and managing hot flashes in women with breast cancer. DATA SOURCES: Published literature on hot flashes in women with breast cancer and in healthy women. CONCLUSIONS: The etiology of hot flashes is influenced by several breast cancer treatment-related factors. Hot flashes are a prevalent, severe problem that can negatively impact quality of life. Certain women are at higher risk for hot flashes following breast cancer treatment. Little research supports the safety or effectiveness of treatments in women with breast cancer. IMPLICATIONS FOR NURSING PRACTICE: Implications include the need to improve patient education, perform comprehensive symptom assessments, and counsel women about various treatment alternatives.

Adult↗

Hot flashes in patients with hypogonadism and low serum gonadotropin levels.

OBJECTIVE: To augment the number of cases in the literature describing patients with hot flashes due to hypopituitarism or hypothalamic hypogonadism. METHODS: We reviewed medical records for hot flashes in our patients with low sex hormone levels and low or inappropriately normal gonadotropin levels, and we inquired about hot flashes in new patients with these hormone patterns. A comprehensive literature review on this subject was also completed. RESULTS: In our medical records, we found 14 patients with hot flashes, low sex hormone levels, and low or inappropriately normal gonadotropin levels. In this group of patients, 10 had hypopituitarism and 6 had hypothalamic hypogonadism; 2 patients had both conditions. Hormone replacement therapy successfully relieved or substantially decreased the hot flashes in all 8 patients treated. A review of the literature revealed 17 patients with hot flashes and hypopituitarism and another 5 patients with hypothalamic hypogonadism. CONCLUSION: Hot flashes as a manifestation of low sex hormone levels and associated with low or inappropriately normal gonadotropin levels occur in patients with hypopituitarism and hypothalamic hypogonadism. Sex hormone replacement therapy alleviates the symptoms.

Female↗

Gabapentin's effects on hot flashes in postmenopausal women: a randomized controlled trial.

OBJECTIVE: To evaluate whether treatment with the anticonvulsant gabapentin may be effective in reducing hot flash frequency and severity. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 59 postmenopausal women with seven or more hot flashes per day examining the effects of gabapentin 900 mg per day on hot flash frequency after 12 weeks of treatment. Subsequently, study patients were enrolled in a 5-week, open-label treatment phase, during which patients could increase the dose of gabapentin to 2,700 mg per day, if needed. RESULTS: After 12 weeks of double-blind treatment, intention-to-treat analysis showed that gabapentin 900 mg per day was associated with a 45% reduction in hot flash frequency and a 54% reduction in hot flash composite score (frequency and severity combined into one score) from baseline, compared with 29% (P =.02) and 31% (P =.01) reductions, respectively, for placebo. Four patients (13%) in the gabapentin group and one (3%) in the placebo group withdrew from the double-blind study because of adverse events. Fifteen patients (50.0%) in the gabapentin group reported at least one adverse event, compared with eight patients (27.6%) in the placebo group. Higher, open-label gabapentin dosing was associated with 54% and 67% reductions in hot flash frequency and composite score from baseline, respectively. CONCLUSION: Gabapentin is effective in reducing hot flash frequency and severity in postmenopausal women.

Acetates↗

Differential diagnosis of hot flashes.

OBJECTIVE: The purpose of this study is to present the physiology and differential diagnosis of hot flashes, other than associated with menopause, in order to facilitate the proper evaluation of symptomatic patients with hot flashes. STUDY DESIGN: Literature search using Med-Line computer access. RESULTS: Interest in flushing reaction began in historic times. With the rapidly expanding population of women over the age of 45 and prevalence of hot flashes as menopausal symptoms, physicians need to be aware of other medical conditions which may mimic hot flashes. These include flushing due to systemic diseases, carcinoid syndrome, systemic mast cell disease, pheochromocytoma, medullary carcinoma of the thyroid, pancreatic islet-cell tumors, renal cell carcinoma, neurological flushing, emotional flushing, spinal cord injury, flushing reaction related to alcohol and drugs, flushing associated with food additives and eating. CONCLUSION: There is a wide variety of disease processes that can cause hot flashes. Knowledge of the nature of these disease processes is necessary for quick recognition of patients with hot flashes who do not respond to estrogen replacement treatment, and to facilitate the proper evaluation of atypical patients.

Body Temperature Regulation↗

Circadian rhythms in hot flashes in natural and surgically-induced menopause.

The aim of this study was to investigate circadian and ultradian variations in menopausal hot flash. The number of hot flashes per 2-hr period was collected from 25 diurnally-active, perimenopausal women for 1 week in January or February of each year for 3 consecutive years. Fourteen women were experiencing natural menopause (NM) (mean age 51.9 years) and 11 were experiencing surgically-induced menopause (SIM) (mean age 52.0 years). The difference in the number of hot flashes between the two types of menopause at each clock time was not statistically significant; neither was the mean number of hot flashes per 24 hr different between the two groups (Student's t-test). Data when normalized for each woman and placed end-to-end revealed by cosinor analysis circadian rhythmicity in the SIM group (P = 0.02) but not in the NM group. A 12-hr periodicity was detected in both groups (P less than 0.001 for both). An 8-hr rhythm was detected only for the NM group (P = 0.04). Both groups combined exhibited statistically significant rhythmicities with periods of 24 hr (P = 0.003), 12 hr (P less than 0.001) and 8 hr (P = 0.005). Regardless of the type of menopause, the women could be separated into two groups based on the temporal pattern of hot flashes during the day. One group was defined by the occurrence of peak frequency of flashes during the morning (0400-0959), while the second group was defined by the occurrence of the peak in the evening (1600-2159).(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles↗

A pilot study of magnetic therapy for hot flashes after breast cancer.

The purpose of this randomized placebo-controlled crossover pilot study was to evaluate the effectiveness and acceptability of magnetic therapy for hot flashes among breast cancer survivors. Participants completed a 24-hour baseline hot-flash monitoring session, wore the magnetic devices or placebo for 3 days, completed an after-treatment hot-flash monitoring session, experienced a 10-day washout period, and then crossed over to the opposite study arm. Magnetic devices and placebos were placed on 6 acupressure sites corresponding to hot-flash relief. Complete data were available from 11 survivors of breast cancer. Results indicated magnetic therapy was no more effective than placebo in decreasing hot-flash severity, and contrary to expectations, placebo was significantly more effective than magnets in decreasing hot-flash frequency, bother, interference with daily activities, and overall quality of life. Implications for clinical practice and future research include the need to explore alternative interventions aimed at alleviating hot flashes in this population.

Aged↗

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial.

BACKGROUND: Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. METHODS: 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. FINDINGS: Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. INTERPRETATION: Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.

Amines↗

Type of menopause, patterns of hormone therapy use, and hot flashes.

OBJECTIVE: To examine the associations between the type of menopause (natural, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy) and the experiencing of hot flashes while accounting for different patterns of hormone therapy (HT) use among the menopausal groups. DESIGN: Cross-sectional study. SETTING: Women who reported their history of hot flashes and HT use through a mailed survey. PATIENT(S): Postmenopausal women ages 40-60 years residing in the Baltimore metropolitan area. INTERVENTION(S): No interventions were administered. MAIN OUTCOME MEASURE(S): Associations between type of menopause and the experiencing of hot flashes. RESULT(S): Among all participants, both types of surgical menopause were associated with a decreased risk of experiencing any, moderate or severe, and daily hot flashes. After taking into account HT use patterns, women who underwent bilateral oophorectomy were at increased risk of experiencing any, moderate or severe, and daily hot flashes compared with women with natural menopause, although only the results for moderate or severe hot flashes were statistically significant. Women who underwent hysterectomy with ovarian conservation remained at significantly lower odds of experiencing any hot flashes than women with natural menopause. CONCLUSION(S): Women who undergo bilateral oophorectomy and who are not given HT to prevent the onset of menopausal symptoms are at increased risk of experiencing hot flashes, especially those that are moderate to severe in nature, compared with women with natural menopause.

Adult↗

Venlafaxine hydrochloride for the treatment of hot flashes.

OBJECTIVE: To review the literature evaluating venlafaxine for the treatment of hot flashes. DATA SOURCES: Clinical literature accessed through MEDLINE (1966-August 2002), PubMed, Harrison's Online, and references of reviewed articles. Key terms used were venlafaxine, Effexor, hot flashes, and vasomotor symptoms. DATA SYNTHESIS: Not all patients experiencing hot flashes are candidates for traditional hormonal therapy. Nonhormonal alternatives have long been explored, but conflicting evidence of efficacy exists. CONCLUSIONS: Venlafaxine is an effective nonhormonal alternative for relief from uncontrolled hot flashes.

Clinical Trials as Topic↗

Current alcohol use is associated with a reduced risk of hot flashes in midlife women.

AIMS: To examine the relation between current alcohol use, estradiol, estrone, and testosterone levels, and hot flashes in midlife women using a case-control study design. METHODS: Cases were midlife women (45-54 years) who reported ever experiencing hot flashes. Controls were midlife women (45-54 years) who reported never experiencing hot flashes. Each participant completed a questionnaire and provided a blood sample that was used to measure estradiol, estrone, and testosterone levels by enzyme-linked immunosorbent assay. RESULTS: The results indicate that current alcohol use (at least one day per month) was significantly associated with a reduced risk of hot flashes compared to non-use of alcohol, independent of age and smoking habits. The hot flashes experienced by current alcohol users were less severe and less frequent than those experienced by non-users of alcohol. Further, current alcohol users had similar levels of estradiol, estrone, and testosterone compared to non-users of alcohol. CONCLUSIONS: These data suggest that current alcohol use is associated with a reduced risk of any, severe, and frequent hot flashes in midlife women by a mechanism that may not include changes in sex steroid hormone levels.

Alcohol Drinking↗

Effect of clonidine on hot flashes in postmenopausal women.

The effectiveness of clonidine in suppressing the occurrence of postmenopausal hot flashes was examined using a dose-response study design and objective recordings of hot flashes. Patients with frequent flashes were studied before and after oral administration of placebo and 0.1, 0.2, and 0.4 mg of clonidine daily for 2 weeks at each dose level. Finger temperature and skin resistance were recorded as indices of hot flash episodes. Four of 10 subjects beginning the study withdrew because of drug-related side effects. Clonidine was found to reduce significantly the frequency of hot flashes as compared with baseline (P less than .005) and with effects of the placebo (P less than .05). At the maximum dosage the mean rate of hot flash occurrence decreased 46%. It was concluded that clonidine does reduce the frequency of postmenopausal flashes.

Body Temperature↗