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Changes in neurotensin-like immunoreactivity during menopausal hot flashes.

An elevation of plasma immunoreactive neurotensin (iNT) was found during menopausal hot flashes. The flash-associated increases in iNT were concomitant with several physiological changes, including increased heart rate, finger blood flow, and finger temperature. Plasma iNT during hot flashes increased 245 +/- 65% (+/- SEM; n = 41), peaking 3.6 +/- 0.4 min after the onset of the hot flash. Immunochemical and chromatographic analyses indicated that the components of iNT elevated during a hot flash consisted primarily of C-terminal-related variants of NT, but not NT itself or any of its known metabolites. The three major substances identified using high pressure liquid chromatography and a C-terminal-directed RIA that appeared in women with hot flashes were also present in plasma of women without hot flashes and men. Since NT is a vasoactive and cardioactive peptide that can also affect temperature regulation, our results suggest the active involvement of these variants of NT in hot flashes.

Adult↗

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.

Emotions↗

Oxybutynin for refractory hot flashes in cancer patients.

OBJECTIVE: There is little information available on the treatment of hot flashes in patients refractory to pharmaceutical interventions. Anecdotal evidence led to the use of oxybutynin for the management of hot flashes in refractory cancer patients; therefore, we performed a retrospective chart review of such patients to determine the effect of oxybutynin in treating hot flashes and to observe the side effects of the drug in these patients. DESIGN: A prospective database of all patients treated for hot flashes was started in July 2004 and was retrospectively analyzed as of March 2006. Also included were individual charts preceding July 2004. Fifty-two patient charts were examined. Demographic information was obtained along with baseline severity and frequency of hot flashes, dose and duration of treatment with oxybutynin, patient response to oxybutynin, and side effects. RESULTS: More than 90% of patients analyzed were refractory to hot flash treatments before starting oxybutynin. Seventy percent of patients showed a partial or excellent response to oxybutynin. The duration of oxybutynin use ranged from 2 weeks to 5 years with more than half of patients currently on oxybutynin or taking oxybutynin for longer than 6 months. Of those patients who experienced an excellent or partial response to treatment, 12% stopped because of documented oxybutynin-related side effects within 4 weeks. CONCLUSION: Oxybutynin seems promising in the management of hot flashes with tolerable side effects in the majority of refractory patients. A placebo-controlled, randomized study is being developed to look more closely at the effectiveness of oxybutynin in reducing hot flashes.

Adult↗

Hot flashes: aetiology and management.

Menopause, an event often accompanied by symptoms such as hot flashes, can have a significant impact on a woman's quality of life. A majority of women will experience hot flashes at some point in their life, given a normal life span. Despite multiple theories, the exact pathophysiology of hot flashes is not yet known. Many types of treatment options exist for women with hot flashes, from hormonal and nonhormonal pharmacological therapies to nonpharmacological interventions. Choosing the best treatment option for specific women involves knowledge of the risks and benefits of each treatment. Hormones (estrogen and/or progesterone, or tibolone alone) are still the most effective option available, resulting in an 80 to 90% reduction in hot flashes. The best nonhormonal treatment to date is in the class of newer antidepressants that comprises various selective reuptake inhibitors; for example, venlafaxine provides about a 60% reduction in hot flashes. This article provides evidence-based information about available treatment options for hot flash management, with special consideration of populations such as breast cancer survivors.

Estrogens↗

A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer.

Abrupt onset of hot flashes poses a significant problem for women treated with chemotherapy for breast cancer. Alternatives to hormone replacement, such as the use of the selective serotonin re-uptake inhibitor (SSRI) paroxetine hydrochloride, are being explored as therapies for hot flashes in this patient population. The present study investigated the efficacy of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. This study included 13 patients who were seen in the Psychosocial Clinic at Moffitt Cancer Center. They were referred by their medical oncologist after reporting complaints of significant difficulty with hot flashes. Baseline questionnaires were completed and a structured diagnostic interview for clinical depression was conducted, all of which were repeated 5 weeks after the paroxetine 20 mg daily was started. Significant improvements were seen in the ratings of hot flash severity (P = 0.002). In addition, significant improvements were observed in general, emotional, and mental fatigue. Rates of clinically significant depressive symptomatology also decreased and sleep quality improved significantly as well. Finally, the incidence of clinical depression improved from 39% at baseline to 8% after treatment. These preliminary data suggest that the antidepressant paroxetine can be helpful in the treatment of hot flashes and associated fatigue, sleep disturbance, and depression in women with breast cancer treated with chemotherapy. Further controlled studies are needed to more fully evaluate the efficacy of the SSRIs for hot flashes in women with breast cancer.

Adult↗

Influence of hot flashes on quality of life in patients with prostate cancer treated with androgen deprivation therapy.

BACKGROUND: We surveyed patients with prostate cancer treated with androgen deprivation therapy to examine the influence of hot flashes on quality of life (QOL). METHODS: Fifty-five outpatients with prostate cancer (M0, 39; M1, 16) treated with androgen deprivation therapy (castration, 15; castration and antiandrogen, 40) were enrolled in this study. Mean duration of androgen deprivation therapy was 21 months (2-91 months). The patients were still being treated with androgen deprivation therapy at the time of the survey. The functional assessment of cancer therapy (FACT) was used as a QOL questionnaire for outpatients with prostate cancer treated with androgen deprivation therapy. Hot flash assessments were used to document the number and severity (mild, moderate, and severe) of daily hot flashes. The patients prescribed fluvoxamine maleate were reassessed for hot flashes 2 weeks after the prescription. RESULTS: Thirty-two of the 55 patients (58.2%) suffered from hot flashes. Hot flashes deteriorated the physical well-being subscale of QOL in patients with prostate cancer treated with androgen deprivation therapy (P = 0.043). There was a significant relationship between the desire to be treated for hot flashes and the hot flash assessments (P = 0.038). Fluvoxamine maleate was significantly effective in reducing hot flashes (P = 0.001). CONCLUSIONS: Hot flashes had adverse effects on the patients' physical status and deteriorated the patients' QOL. New treatment options such as fluvoxamine maleate might help simplify the often difficult management of hot flashes in patients with prostate cancer treated with androgen deprivation therapy.

Aged↗

Hot flashes are associated with increased ambulatory systolic blood pressure.

OBJECTIVE: To determine the association between ambulatory blood pressure (BP) and hot flash experience. DESIGN: The participants in the study were 154 women (mean age=46 years, range=18-65 years), who were evaluated as part of a cross-sectional study on ethnicity, socioeconomic status, and diurnal BP patterns. Participants could be either normotensive or mildly hypertensive. Participants wore an ambulatory BP monitor for 24 hours and recorded their awake and sleep times. Hot flashes were assessed using an everyday complaint questionnaire that embeds symptoms associated with menopause into a list of everyday complaints. RESULTS: Thirty-three percent of participants reported having had hot flashes during the 2 weeks before they completed the questionnaire. Compared with women who did not report hot flashes, mean awake and sleep systolic BP values were significantly higher (P<0.004 and P=0.007, respectively) in women who reported having had hot flashes. Hot flashes continued to independently predict average awake and sleep systolic BP (both P=0.03) after controlling for age, race/ethnicity, body mass index, and menopausal status. Hot flashes were not associated with diastolic BP or nocturnal dipping of BP. CONCLUSIONS: Hot flashes are associated with increased awake and sleep systolic BP independent of menopausal status. Further investigation is warranted to elucidate the mechanisms by which hot flashes are associated with BP.

Adolescent↗

Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial.

PURPOSE: Vasomotor symptoms, such as hot flashes and night sweats, in breast cancer survivors are often worsened by chemotherapy and tamoxifen, and/or the discontinuation of hormone replacement therapy at diagnosis. This study evaluated the acceptability and effectiveness of a soy beverage containing phytoestrogens as a treatment for hot flashes in postmenopausal women with breast cancer. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted in postmenopausal women with moderate hot flashes who were previously treated for early-stage breast cancer. Women were stratified for tamoxifen use and randomized to a soy beverage (n = 59) containing 90 mg of isoflavones or to a placebo rice beverage (n = 64). Women recorded the number and severity of hot flashes daily with a daily menopause diary for 4 weeks at baseline and for 12 weeks while consuming 500 mL of a soy or placebo beverage. RESULTS: There were no significant differences between the soy and placebo groups in the number of hot flashes or hot flash scores. However, presumably because of a strong placebo effect, both groups had significant reductions in hot flashes. Mild gastrointestinal side effects were experienced by both groups but occurred with greater frequency and severity with soy. The mean serum genistein concentration at 6 weeks was significantly higher in women who consumed soy (0.61 +/- 0.43 micromol/L) compared with placebo (0.43 +/- 0.37 micromol/L) (P =.02). Overall acceptability and compliance were high and similar in both groups. CONCLUSION: The soy beverage did not alleviate hot flashes in women with breast cancer any more than did a placebo. Future research into other compounds is recommended to identify safe and effective therapies for hot flashes in breast cancer survivors.

Breast Neoplasms↗

Pilot evaluation of mirtazapine for the treatment of hot flashes.

This prospective, single-arm, pilot clinical trial, developed to evaluate the efficacy and tolerability of mirtazapine for alleviating hot flashes, was conducted between May 2001 and January 2002. Patients' baseline characteristics were collected during the first week of the study. At the beginning of the second week, patients were started on mirtazapine at a dose of 7.5 mg at bedtime. The dose of mirtazapine was then increased to 15 mg at week 3 and to 30 mg at week 4. For week 5, patients could choose whether to take 15 mg/d or 30 mg/d. Data were obtained primarily from patient-completed questionnaires. Data from 22 evaluable women were available. For the 16 patients who completed the study, the median reductions in total daily hot flashes and weekly hot-flash scores from their baselines were 52.5% and 59.5%, respectively. Patients reported improvements in tension, trouble sleeping, abnormal sweating, distress from hot flashes, satisfaction with hot-flash control, overall quality of life, and impact of hot flashes on quality of life. Patients also reported increases in appetite and dry mouth. Although data from a double-blind, placebo-controlled clinical trial would be necessary to more definitively elucidate the efficacy and toxicity of mirtazapine in patients with hot flashes, the available data suggest that mirtazapine is a reasonable treatment to consider in patients with hot flashes, particularly in those with anxiety and sleep disturbances.

Administration, Oral↗

Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.

BACKGROUND: Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. OBJECTIVE: To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University of Rochester Cancer Center Community Clinical Oncology Program. PATIENTS: 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy. INTERVENTION: Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks. MEASUREMENTS: In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study. RESULTS: Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups. CONCLUSION: Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.

Administration, Oral↗

Pilot evaluation of citalopram for the treatment of hot flashes in women with inadequate benefit from venlafaxine.

BACKGROUND: While newer antidepressants, such as venlafaxine and paroxetine, substantially decrease hot flashes, there is no published information with regards to whether a different antidepressant will be effective when one antidepressant does not adequately relieve hot flashes. OBJECTIVE: The objective of this trial was to provide pilot information with regards to whether citalopram would effectively reduce hot flashes in patients who did not receive adequate enough hot flash reduction with venlafaxine. DESIGN: This was a prospective pilot trial. MEASUREMENTS: Validated patient-completed hot flash diary questionnaires were utilized for measuring hot flashes. SUBJECTS: Thirty patients were recruited to this trial, 22 of whom were fully evaluable. RESULTS: Compared to a baseline week, hot flash scores were reduced by 53% 4 weeks later. The citalopram appeared to be well tolerated with many quality-of-life and potential toxicity symptoms much improved compared to the baseline week. At the end of the 4-week treatment, 19 patients (63% of patients entering the study and 86% of the patient completing the study treatment) chose to continue to use citalopram. CONCLUSION: This pilot information supports the hypothesis that citalopram will reduce hot flashes in patients with inadequate hot flash relief while taking venlafaxine.

Adult↗

Hot flashes and androgens: a biological rationale for clinical practice.

Hot flashes are the most prevalent symptom of menopause. Although the etiology of hot flashes has yet to be determined, it is increasingly apparent that the physiology of the underlying vasomotor instability is multifactorial. Estrogen and androgen receptors are present in the areas of the central nervous system relevant to hot flashes. Androgens are central to the synthesis of estrogen and to the bioavailability of free estrogen in peripheral tissues. In addition, androgens have direct central nervous system effects that modulate other endocrine factors associated with hot flashes. The pharmacodynamic differences of testosterone and methyltestosterone are briefly reviewed in the context of choice for individualized clinical use.

Algorithms↗

Pathophysiology and management of hot flashes.

Depending on their frequency and severity, hot flashes can be a major source of distress for individuals with cancer, particularly women with a history of breast cancer and men with prostate cancer. Characterized by increased skin temperature, skin conductance, and heart rate, hot flashes are associated with somatic, behavioral, and emotional manifestations. In this article, the authors review the prevailing theories on the pathophysiology of hot flashes and assess the major treatment interventions, such as hormonal agents, nonhormonal pharmacotherapy (including antidepressants), and complementary/alternative medicine options.

Antidepressive Agents↗

Sleep, fatigue, and depressive symptoms in breast cancer survivors and matched healthy women experiencing hot flashes.

PURPOSES/OBJECTIVES: To compare sleep quality and disturbance, fatigue, and depressive symptoms between breast cancer survivors and healthy women experiencing hot flashes and to examine relationships among sleep and remaining variables (fatigue, depressive symptoms, and frequency of hot flashes). DESIGN: Cross-sectional, descriptive, comparative pilot study. SETTING: University-based outpatient setting. SAMPLE: 15 breast cancer survivors and 15 healthy women matched on age, race, and menopausal status. All women had untreated hot flashes (no hormone replacement therapy or other hot flash treatments). METHODS: Questionnaires (sleep quality and disturbance, fatigue, and depression); two ambulatory, 24-hour sternal skin conductance monitoring sessions (hot flash frequency); and medical records review. MAIN RESEARCH VARIABLES: Sleep quality and disturbance, fatigue, depressive symptoms, and objective hot flash frequency. FINDINGS: The majority of participants evidenced poor sleep quality and high sleep disturbance (73% of breast cancer survivors and 67% of healthy women above a cutoff score of 5). Sleep duration was significantly shorter for breast cancer survivors in contrast to healthy women. Nighttime flashes were experienced by 67% of breast cancer survivors and 37% of healthy women. No group differences were found in fatigue, depressive symptoms, or objective hot flash frequency. Global sleep scores were significantly positively correlated with fatigue and depression but not with hot flash frequency. CONCLUSIONS: Findings suggest that sleep disturbance is common in menopausal breast cancer survivors and healthy women, is not necessarily related to hot flashes, and may stem from a multifactorial etiology. IMPLICATIONS FOR NURSING: Menopausal breast cancer survivors who present with any one of these symptoms should be screened for all symptoms both during and after treatment.

Breast Neoplasms↗

Menopausal hot flash frequency changes in response to experimental manipulation of blood glucose.

OBJECTIVE: Although a majority of women (80%) at menopause experience hot flashes, the symptoms' physiological trigger has yet to be identified. To determine the relationship between glucose availability and hot flashes in menopausal women, hot flash frequency was compared between intervals while the subjects were fasting and/or infusing in a sample of menopausal women (38-55 years of age). DESIGN: An experimental study was conducted in 10 postmenopausal women taking hormone therapy (HT) between the ages of 38 and 55. Following a clinic visit to screen for general health and absence of diabetes, HT participants were asked to stop the medication for 7 to 10 days and to maintain a diary of hot flash frequency. When hot flashes were experienced at least four times per day in a consecutive 3-day period, participants were admitted to the General Clinical Research Center for a 30-hour experimental protocol, including frequent blood sampling and two experimental periods of intravenous infusion of glucose or normal saline. Blood glucose levels were manipulated to provide conditions of postprandial versus fasting states. RESULTS: There was a significant reduction in the incidence of hot flashes during the experimental elevation of glucose concentrations (130 to 140 mg/dl) compared to the fasting state (<110 mg/dl) (t= -2.4, df= 9, p=.04). CONCLUSIONS: Conditions of fasting may stimulate the trigger mechanism for menopausal hot flashes.

Adult↗

Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5.

PURPOSE: Despite the utility of newer antidepressants for alleviating hot flashes, antidepressants do not work adequately enough in many patients. Gabapentin is a nonhormonal agent that also can reduce hot flashes. No data have been available to address whether the combination of both agents would more effectively alleviate hot flashes, compared with gabapentin alone, in patients with inadequate hot flash control with an antidepressant alone. PATIENTS AND METHODS: This was a randomized trial in which 118 patients with inadequate hot flash control on an antidepressant were randomly assigned to receive both an antidepressant and gabapentin versus being weaned off the antidepressant and receiving gabapentin alone. Patients were observed for 5 weeks (including a baseline week in which patients continued on their current antidepressant without gabapentin) during which time they completed validated daily hot flash diaries. RESULTS: Ninety-one patients provided complete data at the 5-week assessment. Regardless of whether or not the antidepressant was continued when gabapentin was started, there was an approximately 50% median reduction in hot flash frequencies (54%; 95% CI, 34% to 70% for combined treatment v 49%; 95% CI, 26% to 58% for gabapentin alone) and scores (56%; 95% CI, 26% to 71% for combined treatment v 60%; 95% CI, 33% to 73% for gabapentin alone). CONCLUSION: Gabapentin seems to decrease hot flashes by approximately 50% in women with inadequate hot flash control who were using an antidepressant. This study saw no significant additional hot flash reduction from continuation of the antidepressant.

Adult↗

Parenteral medroxyprogesterone for the management of luteinizing hormone releasing hormone induced hot flashes in men with advanced prostate cancer.

PURPOSE: Luteinizing hormone releasing hormone (LHRH) agonist therapy for advanced prostate cancer can manifest significant side effects affecting quality of life, most notably hot flashes. This study evaluated the effectiveness of parenteral medroxyprogesterone acetate (MPA) in reducing the frequency and severity of these hot flashes. MATERIALS AND METHODS: A multi-institutional retrospective review of hot flashes from LHRH therapy for prostate cancer was conducted. The hot flashes were quantified and the severity was graded (3-point analogue scale) before and after treatment with MPA. Two doses of MPA (400 or 150 mg intramuscularly) were administered. Statistical analysis (Student's t test) evaluated the quantity of hot flashes, the quality of hot flashes, and dose effectiveness. RESULTS: A total of 48 men (40 at 400 mg, 8 at 150 mg) with a mean age of 71.4 years (range 54 to 87) from 3 institutions were evaluated. There were 91% with symptomatic improvement with MPA, and half (46%) had a complete response defined as total elimination of hot flashes. The median number of the hot flashes per day decreased from 4 to 1 and the median severity score decreased from 2 to 1 (p <0.05). Significance was not achieved comparing the 2 doses. Complete responders were not noted with the 150 mg dose. Anticipated response to MPA did not correlate with the number or severity of the hot flashes. CONCLUSIONS: This study is the first multi-institutional evaluation of hot flashes demonstrating significant reduction in quantity and severity with MPA. Based on these data we now manage hot flashes associated with LHRH analogues with 400 mg of MPA.

Androgen Antagonists↗

Risk factors for hot flashes in midlife women.

OBJECTIVE: To review the scientific literature pertaining to potential risk factors for hot flashes in midlife women. METHODS: Scientific publications reporting on risk factors for hot flashes were identified through a systematic Medline search and are summarized in this review paper. RESULTS: Although few studies have investigated risk factors for hot flashes in midlife women, consistent evidence suggests that smoking is associated with an increased risk for hot flashes. In addition, some studies suggest that other factors, such as hormone levels, body size, tubal ligation, surgical menopause, and race/ethnicity, may be associated with the occurrence of hot flashes. CONCLUSIONS: Future studies are needed to confirm previous findings and to identify additional risk factors for hot flashes. Such studies will increase our understanding of the etiology of hot flashes and may lead to better treatments and preventive measures for this condition.

Body Constitution↗