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Hot flash, hot topic: conceptualizing menopausal symptoms from a cognitive-behavioral perspective.

While most healthy women report that the menopausal transition is nondistressing, a subset of women does report that symptoms significantly interfere in their lives. The most common reason that women seek treatment during this time is for vasomotor symptoms, namely, hot flashes and night sweats. Research has suggested that reports of distress during flashing are only weakly related to more objective measures of the flash, including duration and frequency and that differences in treatment-seeking during the menopausal transition may be better accounted for by differences in symptom awareness mediated by a variety of personality and stress factors. This paper discusses hot flashes and night sweats from a cognitive-behavioral perspective, taking into account individual difference variables that may also affect the experience of menopausal symptoms.

Cognitive Behavioral Therapy↗

Tamoxifen-induced hot flashes.

Hot flashes are the most prominent side effect of tamoxifen, the most frequently prescribed antitumor agent in the world. Little detailed information is available to predict who will develop hot flashes on tamoxifen, to describe the natural history of these hot flashes, and/or to predict who will request therapy for such a side effect. This current trial was developed to address these items. Women who were about to begin adjuvant tamoxifen for locally treated breast cancer were approached for this trial. Before initiating tamoxifen, patients completed a short questionnaire designed to inquire about potential prognostic factors. Upon starting tamoxifen, women were asked to complete a hot flash diary daily for 3 months, and then daily for 1 week of each of the subsequent 9 months. Fifty patients, aged 51-83 years, provided data for this report. Approximately half of the women reported that they did not have any substantial hot flashes while the other half reported hot flashes of variable intensity. On average, these hot flashes gradually increased over 3 months and then plateaued. Baseline factors that appeared to predict for subsequent hot flash problems included a prior history of moderate to severe hot flashes with menopause and a history of prior estrogen therapy use. Overall, 16% of the women reported the desire for therapy for their hot flashes. Thirty-seven and one-half percent of the women (6/16) had a history of both prior estrogen use and moderate to severe hot flashes with menopause as compared to none (0/14) of the women without either of these factors. The data from this study can be utilized to better identify and educate women as to their probability of developing hot flashes after starting tamoxifen, to describe the average time frame for these hot flashes, and to predict the likelihood of whether resultant hot flashes will be substantial enough to have a woman request therapy for them.

Aged↗

Pathophysiology and treatment of menopausal hot flashes.

Hot flashes are the most common symptom of menopause. Although the appearance of hot flashes coincides with estrogen withdrawal, this does not entirely explain the phenomenon because estrogen levels do not differ between symptomatic and asymptomatic women. Luteinizing throughout? hormone pulses do not produce hot flashes nor do changes in endogenous opiates. Recent studies suggest that hot flashes are triggered by small elevations in core body temperature (T(c)) acting within a reduced thermoneutral zone in symptomatic postmenopausal women. This narrowing may be due to elevated central noradrenergic activation, a contention supported by observations that clonidine and some relaxation procedures ameliorate hot flashes. Because hot flashes are triggered by T(c) elevations, procedures to reduce T(c), such as lowering ambient temperature, are beneficial. Estrogen ameliorates hot flashes by increasing the T(c) sweating threshold, although the underlying mechanism is not known. Recent studies of hot flashes during sleep call into question their role in producing sleep disturbance.

Adrenergic alpha-Agonists↗

Physiology of hot flashes.

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.

Body Temperature Regulation↗

Pathophysiology and treatment of hot flashes.

Hot flashes affect about three fourths of postmenopausal women and are one of the most common health problems in this demographic group. Dysfunction of central thermoregulatory centers caused by changes in estrogen levels at the time of menopause has long been postulated to be the cause of hot flashes. Treatment should begin with a careful patient history, with specific attention to the frequency and severity of hot flashes and their effect on the individual's function. For mild symptoms that do not interfere with sleep or daily function, behavioral changes in conjunction with vitamin E (800 IU/d) use is a reasonable initial approach. For more severe symptoms, the next step is to determine whether there is a contraindication or a personal reservation to estrogen replacement therapy. For women who are able and willing to use estrogen, it will successfully relieve symptoms by about 80% to 90%. In patients with a history of breast or uterine cancer, treatment with the progestational agent megesterol acetate appears to be a safe alternative that also decreases hot flashes by approximately 80%. For women unwilling or unable to use hormone therapy, one of the newer antidepressant agents can be prescribed. Venlafaxine decreases hot flashes by about 60%. Gabapentin is another drug that appears promising as therapy for women unable or unwilling to use estrogen, and the results of ongoing trials to determine its efficacy are eagerly awaited. The use of clonidine, methyldopa, and belladonna should be discouraged because of their modest efficacy and adverse effects.

Aged↗

Estrogen improves impaired musculocutaneous vascular adrenergic reactivity in pharmacologically ovariectomized rats: a potential peripheral mechanism for hot flashes?

Hot flashes are among the most common complaints of perimenopausal women. Despite the high prevalence of the phenomenon, the background to the development of hot flashes is still not completely understood, through a hypothesized central mechanism, involving norepinephrine and luteinizing hormone-releasing hormone (LH-RH) secretion is widely accepted. We studied the influence of sex steroid deficiency and hormone replacement therapy on the biomechanical properties of musculocutaneous arterioles, to see whether a peripheral mechanism also exists in the development of hot flashes. Fifty adult, nulliparous, non-pregnant female Sprague-Dawley rats received pharmacological ovariectomy, and estradiol, medroxyprogesterone, or both hormones. After 12 weeks the saphenous artery was isolated by microdissection. Norepinephrine-induced tone (active tangential strain) was measured as a function of intraluminal pressure in an organ bath. The norepinephrine-induced arterial tone was significantly different between the control group and the ovariectomized animals in the range of 80-150 mmHg intraluminal pressure (p < 0.05). Also, significant differences were found between the ovariectomized group and the animals receiving estradiol monotherapy (p < 0.01 between 80 and 170 mmHg, and p < 0.05 between 180 and 200 mmHg intraluminal pressure). Neither medroxyprogesterone monotherapy nor combined hormone replacement therapy induced significant changes in the norepinephrine-induced vascular tone. The absence of sex steroids leads to decreased reactivity to norepinephrine in small musculocutaneous arteries, while chronic estradiol replacement therapy restores the impaired responsiveness of the vessels. Our data raise the possibility that in addition to the central mechanism, a previously unknown peripheral background mechanism for perimenopausal hot flashes may exist.

Animals↗

A randomized controlled pilot study of acupuncture for postmenopausal hot flashes: effect on nocturnal hot flashes and sleep quality.

OBJECTIVE: To assess the effectiveness of acupuncture on postmenopausal nocturnal hot flashes and sleep. DESIGN: Prospective randomized placebo-controlled study. SETTING: Stanford University School of Medicine and private acupuncture offices. INTERVENTION(S): Active or placebo acupuncture was administered for nine sessions over seven weeks. MAIN OUTCOME MEASURE(S): Severity and frequency of nocturnal hot flashes from daily diaries and Pittsburgh Sleep Quality Index (PSQI). PATIENT(S): Twenty-nine postmenopausal women experiencing at least seven moderate to severe hot flashes daily, with E(2) <18 pg/mL and FSH 30.0-110.0 IU/L. RESULT(S): Nocturnal hot-flash severity significantly decreased in the active acupuncture group (28%) compared with the placebo group (6%), P=.017. The frequency of nocturnal hot flashes also decreased in the active group (47%, P=.001), though it was not significantly different from the placebo group (24%, P=.170; effect size = 0.65). Treatment did not differentially influence sleep; however, correlations between improvements in PSQI and reductions in nocturnal hot flash severity and frequency were significant (P<.026). CONCLUSION(S): Acupuncture significantly reduced the severity of nocturnal hot flashes compared with placebo. Given the strength of correlations between improvements in sleep and reductions in nocturnal hot flashes, further exploration is merited.

Acupuncture Therapy↗

Measurement of hot flashes by sternal skin conductance and subjective hot flash report in Puebla, Mexico.

OBJECTIVE: To measure hot flashes by sternal skin conductance in an urban Mexican population and to determine variables associated with hot flash reporting and measurement. DESIGN: From June 1999 to August 2000, 67 perimenopausal women aged 40 to 65 years participated in interviews, anthropometric measures, and a 2-h recording of sternal skin conductance. Changes in sweating were used to demonstrate the presence/absence of a hot flash. During the test, women were asked to report if they experienced a hot flash. RESULTS: During the study period, 10 women reported and demonstrated every hot flash, 24 women never reported or demonstrated a hot flash, 7 demonstrated hot flashes but did not report any of them, 7 reported hot flashes but did not demonstrate any of them, and 19 showed a mixture of responses. Women who demonstrated hot flashes by sternal skin conductance were measured in a warmer room, had more years of education, consumed more eggs as a child, recalled a heavier weight at age 18, and had a lower body mass index at interview compared with women who did not demonstrate hot flashes by sternal skin conductance. Women who subjectively reported hot flashes were measured in a warmer room, were more likely to be postmenopausal, reported more frequent consumption of coffee, and spent fewer months breast-feeding their last child compared with women who did not report the experience of hot flashes during the testing period. CONCLUSION: Room temperature explained part of the variation between women who did and did not demonstrate hot flashes via sternal skin conductance, between women who did and did not report the experience of hot flashes, and between women who did and did not demonstrate concordance in objective and subjective measures. In addition to room temperature, coffee intake, months spent breast-feeding the last child, and recalled weight at age 18 were important variables predicting hot flash experience.

Adult↗

Phase III evaluation of fluoxetine for treatment of hot flashes.

PURPOSE: Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed. PATIENTS AND METHODS: This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis. RESULTS: Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency x average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P =.02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated. CONCLUSION: This dose of fluoxetine resulted in a modest improvement in hot flashes.

Adult↗

Hot flashes revisited: pharmacological and herbal options for hot flashes management. What does the evidence tell us?

BACKGROUND: Hot flashes are the most frequent symptoms of menopause and the most common reason for climacteric women seeking medical advice. Estrogen therapy is by far the most effective therapy. However, fears of side-effect of estrogen therapy urged many patients to seek alternative modalities for symptomatic relief. METHODS: The MEDLINE database for the years 1975-2004 was searched for clinical placebo-controlled trials for the treatment of hot flashes with alternative therapy. Articles reporting the use of progesterone, alpha adrenergic agonists, anti-depressants, anti-convulsants, soy products, black cohosh (BC), red clover, dong quai, ginseng root, evening primrose oil, vitamin E, and wild yam were included. RESULTS AND CONCLUSIONS: A critical review of the literature shows that progesterone may have an independent effect on relieving hot flashes. New nonhormonal agents such as selective serotonin-uptake-inhibitor anti-depressants and a new anti-convulsant gabapentin yielded promising results on small well-conducted studies. Isoflavone's effect on hot flashes is variable and inconsistent, and only modest and delayed improvement of symptoms could be expected by BC and vitamin E. There are insufficient data on the other herbal alternative therapies at this time. Well-designed large studies are needed to further explore new modalities of treatment.

Adrenergic alpha-Agonists↗

Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes.

BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone. RESULTS: A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms. CONCLUSIONS: A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.

Breast Neoplasms↗

The Hot Flash Related Daily Interference Scale: a tool for assessing the impact of hot flashes on quality of life following breast cancer.

To assess the psychometric properties of the Hot Flash Related Daily Interference Scale (HFRDIS), a sample of breast cancer survivors and an age-matched comparison group completed a questionnaire packet and 2-day prospective hot flash diary at an initial time point and again 6 months later. There were 71 breast cancer survivors and 63 comparators at Time 1, and 54 survivors and 46 comparators at Time 2. The HFRDIS was internally consistent, with alphas of 0.96 at times 1 and 2. Validity was supported through 1) correlations with other hot flash variables, 2) correlations with measures of affect and mood, 3) significant differences between women with hot flashes and those without, and 4) demonstrated sensitivity to change over time. The HFRDIS is a psychometrically sound measure for assessing the impact of hot flashes on daily activities and overall quality of life in clinical practice or research protocols.

Breast Neoplasms↗

Thermoregulatory physiology of menopausal hot flashes: a review.

Hot flashes during the climacteric years have long been a frequent clinical complaint, generally considered within the realm of the internist, gynecologist, or endocrinologist. Yet the underlying mechanism of hot flashes remains unknown. Only within the past 10 years has there been significant research on hot flashes as a disturbance of thermoregulation. This paper focuses on thermoregulatory aspects of hot flashes, reviewing current knowledge of the thermoregulatory physiology and endocrinology of hot flashes and discussing future avenues for research. Hot flashes are compared with fever in terms of thermoregulatory changes and speculated mechanisms. Although several substances in the peripheral circulation are found in increased concentrations during hot flashes, none is a trigger for a hot flash. The pattern of hot flash occurrence is striking in its regularity, and the possibility of endogenous rhythmicity is discussed. Recently, investigators have begun to explore a primate model of menopausal hot flashes. These studies are summarized. Finally, the multiple effects of estrogen on various systems of the body and their interrelationships are discussed. An understanding of the mechanism of hot flashes would not only be of importance to women suffering with hot flashes but would further our knowledge of thermoregulatory function and the interactions between thermoregulatory and reproductive systems.

Body Temperature↗

Megestrol acetate for the prevention of hot flashes.

BACKGROUND: Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients. METHODS: The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patients documented the frequency and severity of hot flashes in daily symptom diaries. RESULTS: After four weeks, hot flashes were reduced by 21 percent in the group receiving placebo first and by 85 percent in the group receiving megestrol acetate first (P < 0.001). An intention-to-treat analysis of data for all eligible treated patients showed that 74 percent of the megestrol acetate group, as compared with 20 percent of the placebo group, had a decrease of 50 percent or more in the frequency of hot flashes during the first four weeks (P < 0.001). The degree of efficacy was similar in men and women. The only side effect was withdrawal menstrual bleeding in women, generally occurring one to two weeks after the megestrol acetate had been discontinued. CONCLUSIONS: Low-dose megestrol acetate is well tolerated and can substantially decrease the frequency of hot flashes in women and men.

Breast Neoplasms↗

Menopausal Vasomotor Symptoms (MVS) survey for assessment of hot flashes.

OBJECTIVES: During the menopause, 65%-80% of women experience hot flashes. Hot flashes can also occur after hysterectomy and may be experienced during cancer therapy. A very limited assessment of hot flashes is provided by currently available menopausal instruments. This study was performed to evaluate a new Menopausal Vasomotor Symptoms (MVS) survey as an instrument for a comprehensive and subjective assessment of hot flashes. METHODS: The MVS survey was designed to assess multiple dimensions of hot flashes and to be simple and easy to administer. Hot flashes and associated conditions were addressed with 39 closed-ended questions. Sixty-one qualified women, 40-58 years old, from the Dallas, Fort Worth Metroplex area were enrolled. Women experiencing hot flashes took the survey at baseline and then 14 days, 2 months, and 6 months later. Factor analysis was performed. Face and content validity, internal consistency, test-retest reliability, and sensitivity to changes were evaluated. RESULTS: Fifty-two women (85.2%) completed all study sessions. The MVS survey was found to have good face and content validity and good internal consistency (rhoKR = 0.87). Spearman rank-order correlation coefficients at the 14-day retest varied from 0.58 to 1.00. As a result of these analyses, the MVS survey was further refined. CONCLUSIONS: The MVS survey was found to be comprehensive, simple, valid, reliable, sensitive, and a convenient instrument for subjective assessment of various characteristics of hot flashes. The MVS survey may serve as a valuable clinical and research tool for measurement of hot flashes.

Adult↗

Pilot evaluation of black cohosh for the treatment of hot flashes in women.

BACKGROUND: Hot flashes cause significant morbidity in postmenopausal women, including women with breast cancer. We undertook a pilot study to estimate the effectiveness of black cohosh to reduce hot flashes. METHODS: Women who reported significant hot flashes (> or = 14 per week) were enrolled. Black cohosh was given in the form of the commercial product Remifemin. The first week was a no-treatment baseline period, and therapy was given for the subsequent 4 weeks. Hot flash data were collected by daily questionnaires during baseline and treatment weeks. Adverse effects were recorded. RESULTS: Twenty-one women completed the study. Their mean age was 56 years (range, 38-80). Thirteen patients had a history of breast cancer. Six patients were taking tamoxifen or raloxifene. Patients reported an average of 8.3 hot flashes per day during the baseline week. The reduction in mean daily hot flash frequency was 50% (95% CI, 34%-65%), while weekly hot flash scores were reduced 56% (95% CI, 40%-71%) at completion of the study. Overall, patients reported less trouble with sleeping, less fatigue, and less abnormal sweating. No patients stopped therapy because of adverse effects. CONCLUSIONS: Black cohosh appeared to reduce hot flashes and had a low toxicity. The efficacy found in this trial seems to be more than would be expected by a placebo effect (20%-30% hot flash reduction in previous trials). These results suggest that further evaluation of this black cohosh preparation with a phase III randomized trial is indicated.

Adolescent↗

Incidence and management of hot flashes in prostate cancer.

Hot flashes are as common in men who have been castrated due to prostate cancer as hot flashes are in women after menopause. The symptom can cause significant discomfort for a considerable length of time. The hot flashes are most likely caused by a reduction in sex-hormone levels, which, in turn, causes an instability in the hypothalamic thermoregulatory center. Calcitonin gene-related peptide is involved in menopausal hot flashes in women and possibly also in castrated men. The mainstays of treatment for castrated men with hot flashes remain estrogens, progesterone, and cyproterone acetate, each of which has different side effects. Other treatments for hot flashes include clonidine and antidepressants and, according to one uncontrolled study, electrostimulated acupuncture. Nonetheless, there is a need for more effective and less toxic treatments. In this review, we will discuss the prevalence, duration, distress, physiology, and treatment options of hot flashes in men subjected to castration therapy due to prostate cancer.

Hot Flashes↗