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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↗

Acupuncture for hot flashes: a randomized, sham-controlled clinical study.

OBJECTIVE: Hot flashes are a significant problem in women going through the menopausal transition that can substantially affect quality of life. The world of estrogen therapy has been thrown into turmoil with the recent results of the Women's Health Initiative trial report. Pursuant to a growing interest in the use of alternative therapies to alleviate menopausal symptoms and a few pilot trials that suggested that acupuncture could modestly alleviate hot flashes, a prospective, randomized, single-blind, sham-controlled clinical trial was conducted in women experiencing hot flashes. DESIGN: Participants, after being randomized to medical versus sham acupuncture, received biweekly treatments for 5 weeks after a baseline assessment week. They were then followed for an additional 7 weeks. Participants completed daily hot flash questionnaires, which formed the basis for analysis. RESULTS: A total of 103 participants were randomized to medical or sham acupuncture. At week 6 the percentage of residual hot flashes was 60% in the medical acupuncture group and 62% in the sham acupuncture group. At week 12, the percentage of residual hot flashes was 73% in the medical acupuncture group and 55% in the sham acupuncture group. Participants reported no adverse effects related to the treatments. CONCLUSIONS: The results of this study suggest that the used medical acupuncture was not any more effective for reducing hot flashes than was the chosen sham acupuncture.

Acupuncture Therapy↗

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↗

Menopausal hot flashes and development of cognitive impairment.

Hot flashes have a negative influence on the quality of life in hypogonadal women. There seem to be many regulators of hot flashes that add to the complexity of these profound vasomotor symptoms. In this paper, focus is placed on selected factors that may be involved in the relationship between hot flashes and cognitive status. During the hypogonadal state, the brain becomes relatively deprived of glucose. Hot flashes were found to be associated with transient inadequacies in brain levels of glucose. Neuroglucopenia was shown to initiate a cascade of immediate and delayed reactions leading to neuronal damage. Estrogen is known to diminish neuroglucopenia. In a pilot study on postmenopausal women, it was observed that cognitive performance of women who reported having hot flashes during their menopausal years was better than in women who did not experience hot flashes. It is hypothesized that a hot flash triggers a counterregulatory mechanism of the central nervous system to the insufficiency of glucose delivery to the brain and may have a beneficial effect on cognitive health in postmenopausal women. Possible therapeutic implications of this hypothesis are discussed in the light of current knowledge.

Aging↗

Prospective evaluation of vitamin E for hot flashes in breast cancer survivors.

PURPOSE: Hot flashes represent a substantial clinical problem for some breast cancer survivors. Although estrogen or progesterone preparations can alleviate these symptoms in many patients, concern remains regarding the use of hormonal preparations in such women. Thus, there is a perceived need for nonhormonal treatments for hot flashes for breast cancer survivors. Based on anecdotal evidence that vitamin E was helpful, we designed a trial to investigate this matter. METHODS: We developed and conducted a placebo-controlled, randomized, crossover trial where, after a 1 week baseline period, patients received 4 weeks of vitamin E 800 IU daily, then 4 weeks of an identical-appearing placebo, or vice versa. Diaries were used to measure potential toxicities and hot flashes during the baseline week and the two subsequent 4-week treatment periods. RESULTS: The 120 patients evaluated for toxicity failed to show any. The 105 patients who finished the first treatment period showed a similar reduction in hot flash frequencies (25% v 22%; P = .90) for the two study arms. A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (P < or = .05). At the study end, patients did not prefer vitamin E over the placebo (32% v 29%, respectively). CONCLUSION: Although this trial was able to show a statistically significant hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

Spectrally selective flash early receptor potential (ERP) in dichromats.

The human spectrally selective flash early receptor potential (ERP) was studied in 12 dichromats: 6 protanopes (12 eyes) and 6 deuteranopes (12 eyes). Color filters used were Kodak Wratten filters No.23A, No.57, and No.47 for the red, green, and blue flash ERPs, respectively. The ERP amplitude was measured between the summits of R1 and R2. Mean amplitudes of the red flash ERP and green flash ERP were highly significantly decreased in the protanopes (p less than 0.001) and deuteranopes (p less than 0.01) as compared with the corresponding data in 10 normal subjects (20 eyes). The mean amplitude of the blue flash ERP was significantly lower than normal (p less than 0.001) in the deuteranopes. The mean ratio of the blue flash ERP amplitude to the red flash ERP amplitude showed a highly significant increase in the protanopes (p less than 0.001) and a highly significant decrease in the deutoranopes (p less than 0.001) compared with the mean ratio in the normal subjects, indicating a new, useful index for the objective clinical detection of congenital color defects.

Adolescent↗

Delayed fluorescence from Rhodopseudomonas sphaeroides following single flashes.

Delayed fluorescence from Rhodopseudomonas sphaeroides chromatophores was studied with the use of short flashes for excitation. Although the delayed fluorescence probably arises from a back-reaction between the oxidized reaction center bacteriochlorophyll complex (P+) and the reduced electron acceptor (X-), the decay of delayed fluorescence after a flash is much faster (tau1/2 approximately 120 mus) than the decay of P+X-. The rapid decay of delayed fluorescence is not due to the uptake of a proton from the solution, nor to a change in membrane potential. It correlates with small optical absorbance changes at 450 and 770 nm which could reflect a change in the state of X-. The intensity of the delayed fluorescence is 11-18-fold greater if the excitation flashes are spaced 2 s apart than it is if they are 30 s apart. The enhancement of delayed fluorescence at high flash repetition rates occurs only at redox potentials which are low enough (less than +240 mV) so that electron donors are available to reduce P+X- to PX- in part of the reaction center population. The enhancement decays between flashes as PX- is reoxidized to PX, as measured by the recovery of photochemical activity. Evidently, the reduction of P+X- to PX- leads to the storage of free energy that can be used on a subsequent flash to promote delayed fluorescence. The reduction of P+X- also is associated with a carotenoid spectral shift which decays as PX- is reoxidized to PX. Although this suggests that the free energy which supports the delayed fluorescence might be stored as a membrane potential, the ionophore gramicidin D only partially inhibits the enhancement of delayed fluorescence. With widely separated flashes, gramicidin has no effect on delayed fluorescence. At redox potentials low enough to keep X fully reduced, delayed fluorescence of the type described above does not occur, but one can detect weak luminescence which probably is due to phosphorescence of a protoporphyrin.

Bacteriochlorophylls↗

Photosynthetic control and estimation of the optimal ATP: electron stoichiometry during flash activation of chromatophores from Rhodopseudomonas capsulata.

(1) When chromatophores from Rhodopseudomonas capsulata Ala pho+ are exposed to a train of high-frequency, saturating flashes the kinetics of the reaction centre bacteriochlorophyll absorption change enter a pseudo steady-state in which the extent of oxidation during the flashes is equal to the extent of reduction in between the flashes. The level of the pseudo steady-state is lowered by the presence of a phosphate acceptor system, raised by further addition of oligomycin, lowered by a combination of nigericin and valinomycin and raised by antimycin A. (2) In the pseudo steady-state, the extent of reaction centre bacteriochlorophyll oxidation taking place during the flash may be estimated by subtraction from the total concentration of reaction centre bacteriochlorophyll. This value is equated with the amount of electrons transported through the photosynthetic chain. Comparison with the measured ATP yield per flash in the pseudo steady-state permits calculation of the ATP: two electron ratio. The value of the ratio is 1.1 for flash frequencies between 3 and 12.5 Hz and declines at lower and higher frequencies. The ATP: two electron ratio is approximately halved in the presence of antimycin A. (3) An alternative estimate of the ATP: two electron ratio, based on the assumption that high-frequency flashes approximate to the condition of continuous illumination, was approx. 0.8.

Adenosine Triphosphate↗

Reversing ocular dominance and suppression in a single flash.

An observer views a long (1-2 sec) monocular stimulus. Following stimulus offset there is a dark interstimulus interval (ISI). After the ISI, brief test flashes are presented to both eyes simultaneously. For ISIs less than 100-200 msec, only the test flash contralateral to the stimulated eye is seen. The test flash in the ipsilateral eye is not seen. For ISIs of 200-1000 msec, the contralateral test flash is seen more clearly and completely than the ipsilateral flash (Experiments 1 and 2). The initial and ipsilateral test flash need not be spatially similar. The initial stimulus can be dim but must be longer than 150 msec (Experiment 3). Experiment 3 precludes forward masking or light adaptation as explanation. The effect is relatively independent of the length of the test flash (Experiment 4). The results can be explained in terms of the known properties of binocular rivalry and reinforce the hypothesis (Fox and Check, 1968) that rivalry acts nonselectively, independent of factors such as spatial frequency, luminance, or orientation.

Adolescent↗

Rod and cone system contributions to oscillatory potentials: an explanation for the conditioning flash effect.

The oscillatory potentials (OPs) of the human electroretinogram (ERG) are smaller in response to the initial flash of a series than to subsequent flashes. To investigate a possible rod system contribution to this "conditioning flash effect," we have examined OPs in normals and rod monochromats. The OPs recorded from rod monochromats were similar to those recorded from normals under test conditions that selectively stimulate rods. However, under conditions that in normals stimulate both rods and cones and that result in maximal amplitude of the OPs, the rod monochromats exhibit markedly reduced OPs. This finding suggests that the initial (conditioning) flash operates by adapting the rod system contribution to the OPs, so that the OPs in response to subsequent flashes result primarily from the cone system. In agreement with this hypothesis, the conditioning flash effect did not occur when flashes were presented against a background which eliminated the rod system response nor during the cone plateau phase of dark adaptation.

Color Vision Defects↗

The evolutionary change of flash visual evoked potentials in preterm infants with periventricular leukomalacia.

OBJECTIVE: The aim of this study was to prospectively investigate flash visual evoked potential (VEP) findings and their chronological changes in preterm infants with cystic periventricular leukomalacia (PVL) during the early neonatal period. METHODS: The subjects of this study were 14 preterm infants with cystic PVL. The patients underwent serial cranial ultrasonography and diagnosed as having cystic PVL. Flash VEPs were diagnosed at least twice within the first 3 weeks of life. RESULTS: All infants had at least one or more flash VEP abnormalities. The most common finding was 'absent VEP', which was seen in 13 infants (93%). 'Delayed latency' was seen in two infants and 'abnormal waveform' was seen in one infant. Concerning the chronological changes, all records were abnormal in 4 infants, and the other 10 had transient normal VEP findings. Among them, flash VEPs changed from normal to abnormal within 10 days after birth in most cases. CONCLUSIONS: Almost all infants with cystic PVL had abnormal flash VEPs within the first 3 weeks of life, but chronological changes of flash VEP findings were seen during the period. SIGNIFICANCE: This manuscript may be useful as a reference to the flash VEPs in preterm infants with cystic PVL.

Cerebral Cortex↗

FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors.

We previously reported that tumor necrosis factor alpha receptor- and Fas-associated FLASH interacts with one of the p160 nuclear receptor coactivators, glucocorticoid receptor-interacting protein (GRIP) 1, at its nuclear receptor-binding (NRB) domain, and that inhibits the transcriptional activity of the glucocorticoid receptor (GR) by interfering with association of GR and GRIP1. Here, we further examined the specificity of FLASH suppressive effect and the physical/functional interactions between this protein and two other p160 family subtypes. The suppressive effect of FLASH on GR transactivation was observed in several cell lines and on the chromatin-integrated mouse mammary tumor virus (MMTV) promoter. FLASH strongly interacted with the NRB domain of the thyroid hormone receptor activator molecule (TRAM) 1, a member of the steroid hormone receptor coactivator (SRC) 3/nuclear receptor coactivator (N-CoA) 3 subtypes, as well as with SRC2/N-CoA2 p160 coactivator GRIP1, while its interaction with SRC1a, one of the SRC1/N-CoA1 proteins, was faint in yeast two-hybrid assays. Accordingly, FLASH strongly suppressed TRAM1- and GRIP1-induced enhancement of GR-stimulated transactivation of the MMTV promoter in HCT116 cells, while it did not affect SRC1a-induced potentiation of transcription. Furthermore, FLASH suppressed androgen- and progesterone receptor-induced transcriptional activity, but did not influence estrogen receptor-induced transactivation, possibly due to their preferential use of p160 coactivators in HCT116 and HeLa cells. Thus, FLASH differentially suppresses steroid hormone receptor-induced transcriptional activity by interfering with their association with SRC2/N-CoA2 and SRC3/N-CoA3 but not with SRC1/N-CoA1.

Animals↗