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Hot flashes--physiology, hormonal therapy, and alternative therapies.

Hormone replacement therapy should be discussed with every postmenopausal woman and should be the first therapy offered to treat hot flashes owing to its high efficacy and other beneficial properties. Women who are ineligible for or uncomfortable with estrogen replacement therapy and who suffer from hot flashes that interfere with the quality of life should be offered other regimens as discussed in this article.

Adrenergic alpha-Agonists↗

Further delineation of hypothalamic dysfunction responsible for menopausal hot flashes.

An association exists between pulsatile LH release and hot flashes (HFs). To further delineate the hypothalamic mechanism(s) responsible for HF, the basal levels and pulsatile release of LH, FSH, estradiol, and estrone and the rate of occurrence of HFs (measured objectively) were evaluated in patients with a defect of GnRH secretion [isolated gonadotropin deficiency (IGD)], patients with abnormalities of afferent input to GnRH neurons [hypothalamic amenorrhea (HA)], and postmenopausal women with severe HFs. Patients with IGD had received estrogens, which were discontinued before study. Patients with HA had experienced regular menses before disease onset, which followed emotional stress or weight loss. Studies were limited to HA patients with estrogen levels in the postmenopausal range. Pulsatile LH release was absent in patients with IGD and was absent or greatly reduced in women with HA. Objectively measured and subjectively experienced HFs occurred in IGD but not in HA patients. These results suggest that HFs are not an obligatory consequence of low endogenous estrogen levels and that the absence of episodic LH and GnRH release (IGD) does not influence the occurrence of HFs. It is possible that the dysfunction of afferent input to GnRH neurons in HA somehow prevents HFs in these women with low endogenous estrogen secretion.

Adult↗

Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes.

PURPOSE: Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. METHODS: We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling. RESULTS: Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes. CONCLUSION: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.

Adult↗

Gabapentin's effects on hot flashes and hypothermia.

The author describes six cases in which gabapentin treatment reduced the frequency of hot flashes. In addition, gabapentin treatment enhanced the frequency of hypothermic episodes in a separate patient with known hypothalamic dysfunction. Gabapentin may act directly upon temperature regulatory centers.

Acetates↗

Treatment options for menopausal hot flashes.

Although alternatives exist, hormone therapy remains the most effective treatment for menopausal symptoms such as hot flashes, and it is the only treatment approved by the US Food and Drug Administration (FDA) for this indication. The FDA recommends using the lowest effective dose of hormones. New low-dose preparations and new dosage forms of hormone therapy are available.

Drug Approval↗

A pilot study of mindfulness-based stress reduction for hot flashes.

OBJECTIVE: A variety of results from both population and laboratory studies suggest that stress and hot flashes (HFs) are correlated and that HFs are more severe in women with lower coping abilities. The objective of this pilot study was to obtain information on the feasibility and effect of participation in a mindfulness-based stress reduction (MBSR) program on HF severity and menopause-related quality of life. DESIGN: Fifteen women volunteers reporting a minimum of seven moderate to severe HFs per day at study intake attended the eight weekly MBSR classes at the University of Massachusetts Medical School. Participants were assessed for menopause-related quality of life before beginning and at the conclusion of the MBSR program. Women also kept a daily log of their HFs through the course of the 7 weeks of the MBSR program and for 4 weeks after it. RESULTS: Women's scores on quality-of-life measures increased significantly, and the median reported HF severity, calculated as the weekly average of a daily HF severity score, decreased 40% over the course of the 11 weeks of the assessment period. The women were individually interviewed at the completion of their participation, and the results of the interviews were consistent with the results from daily diaries. CONCLUSIONS: These results provide preliminary positive evidence of the feasibility and efficacy of MBSR in supporting women who are experiencing severe HFs, and it warrants further investigation.

Female↗

[Selective serotonin reuptake inhibitors (SSRIs) antidepressants use in hot flashes in oncology].

INTRODUCTION: Menopausal women or patients treated by chemotherapy or hormonotherapy for breast cancer have often disabled hot flashes. Men with prostate cancer confronted to castration can also suffer from the same problem. In both situations, many arguments go against implementation of estrogenic treatment. Albeit, many complementary therapeutics exist, they are often unsatisfying. CURRENT KNOWLEDGE AND KEY POINTS: Since some years, anecdotal case reports and controlled studies have reported interest of selective serotonin reuptake inhibitors (SSRIs) antidepressants in this indication. These treatments often appear efficient and well tolerated. FUTURE AND PROJECTS: Through a review of literature and clinical vignette, we will specify physiopathology and prescription modalities in this new type of indication.

Female↗

Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life.

BACKGROUND: Research on hot flashes (HFs) after the diagnosis and treatment of breast carcinoma (BC) is scarce. To our knowledge, this research represents the second study of HF prevalence and severity in women with BC and the first study of 1) correlates of HF prevalence and severity, 2) use of HF management strategies, and 3) the relation between HFs and quality of life (QOL) among women with BC. METHODS: Eligible women (n = 136) participated in structured telephone interviews. RESULTS: Of the 114 postmenopausal women interviewed, 65% reported HFs, with 59% of women with HFs (n = 74) rating the symptom as severe. Multivariate analysis revealed that 1) HFs were most common in women with a high school education or less and those who were younger at diagnosis and 2) HFs were most severe in women with a higher body mass index, those who were younger at diagnosis, and those receiving tamoxifen. Among women with HFs, 37% were not using any HF management strategies and 63% expressed interest in learning more regarding > or = 1 strategy. HFs marginally were related to decreased mental and physical QOL using the SF-12 Health Survey (P < 0.10). CONCLUSIONS: The results of the current study significantly contribute to knowledge regarding HFs in women with BC and support the need for carefully controlled clinical trials evaluating interventions for relieving HFs in this population.

Adult↗

Feasibility and psychometrics of an ambulatory hot flash monitoring device.

OBJECTIVE: To assess the feasibility and psychometric properties of a lightweight, automated, ambulatory sternal skin conductance monitor to measure frequency of hot flashes (HFs) among breast cancer survivors (BCSs). DESIGN: A total of 19 postmenopausal BCSs and 5 premenopausal healthy comparison women participated by wearing the monitor for 24 h during their normal daily activities, including sleep. HFs were assessed using subjective (diaries, event markers) and objective (skin conductance) methods. RESULTS: Problems with subjective reporting of HFs were reported by 35% of BCSs. Technological problems and discomfort related to wearing the monitor were minimal. A total of 243 HFs were recorded using the skin conductance monitor by 17 BCSs and 5 premenopausal women (BCS group M = 13.4; range, 1-30). Subjective reporting of HFs was associated with a 31-33% false-positive rate. Skin conductance monitoring during waking hours was associated with a 30% false-negative rate. CONCLUSIONS: The monitor is a feasible method for objectively assessing HFs in BCSs. Data support continued use of sternal skin conductance as an objective measure of HF frequency. This technology should prove useful as an objective measure of HFs in future intervention research aimed at alleviating the symptom and improving quality of life among BCSs.

Adult↗

Paroxetine treatment of mood disorders in women: premenstrual dysphoric disorder and hot flashes.

With the relatively recent introduction of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, increased attention has been focused on the use of antidepressants in the treatment of mood disorders across the female life cycle. Evidence for the efficacy of antidepressants in the treatment of premenstrual dysphoric disorder (PMDD) and hot flashes associated with menopause and breast cancer has emerged. The clinical trials experience with paroxetine and the controlled-release (CR) formulation of paroxetine is reviewed.

Antidepressive Agents, Second-Generation↗

Postmenopausal estrogen for treatment of hot flashes: clinical applications.

Use of postmenopausal estrogen has changed since the release of the first results from the Women's Health Initiative in 2002. Professional organizations, the US Food and Drug Administration, and the US Preventive Services Task Force have issued new recommendations against use of estrogen and progestin or progesterone for prevention of chronic conditions. This article applies the current state of evidence for postmenopausal estrogen use to management decisions in 2 clinical scenarios initiating therapy in a perimenopausal woman with hot flashes and discontinuing estrogen use in a long-term user.

Climacteric↗

The menopausal hot flash: a procrustean bed of research.

There are several scientific researchers from a variety of academic disciplines investigating the menopausal hot flash (MHF). Synthesis of all MHF research findings results in contradictory and inconclusive information available to health care providers and perimenopausal women. This study used epistemological construction and hermenuetical understanding to explore this information problem. Specific MHF exemplars, the problem-solutions, were constructed from extant scientific literature; two models of health guiding MHF research were generated from these exemplars. These models, health as a shared and communicable experience and health as a medical-physiological concept, provided a focus for hermeneutical understanding of the MHF information problem. Cooperative-collaborative inquiry was proposed as an approach for future MHF research.

Climacteric↗

Biophysical and endocrine-metabolic changes during menopausal hot flashes: increase in plasma free fatty acid and norepinephrine levels.

Thermocutaneous, vascular, metabolic and hormonal changes were investigated during 11 hot flashes from 6 postmenopausal women. The first detectable change was an increase in finger blood flow with a concomitant enhancement of skin conductance. The increase in skin conductance was followed rapidly by a sharp rise in finger temperature. The main endocrine-metabolic changes associated with the above phenomena were a sharp increase in plasma free fatty acids (approximately 65%), norepinephrine (approximately 100%) and LH (approximately 20%) levels. Plasma glucose and cortisol tended to be increased but did not reach statistical significance; on the other hand, plasma insulin, glucagon, growth hormone, epinephrine and dopamine remained unchanged.

Adult↗

Hot flashes and sleep.

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Clinical Trials as Topic↗

Treatment of hot flashes with transdermal estradiol administration.

A randomized prospective double blind study was performed to assess the ability of a transdermal therapeutic system (TTS) delivering estradiol (E2) to suppress hot flashes (HFs) in symptomatic postmenopausal women. Patients were given placebo or E2 in four doses for a 20-day period, and serum gonadotropin and estrogen levels and the occurrences of HFs were measured. Administration of placebo had no measurable effect on either estrogen or gonadotropin levels or the occurrence of HFs. A dose-response relationship was found between the rate of E2 administered and the circulating level of E2, with 25, 50, 100, and 200 micrograms/24 h dosages raising the mean E2 concentrations from mean baseline levels of 5-8 pg/ml to 18, 38, 73, and 100 pg/ml, respectively. Estrone levels also increased with TTS application, but to a lesser extent than did E2 levels. Dose-response reductions of FSH and LH with increasing amounts of E2 administration occurred, but gonadotropin levels were not lowered in any of the patients into the ranges found in premenopausal women. TTS application significantly suppressed the occurrence of HFs at the 50 micrograms/24 h dosage and higher. A significant negative correlation (r = 0.6045; P less than 0.001) between E2 levels and the rates of occurrence of HFs was found during hormone administration. Based on this regression, 50% and 100% reductions of HFs should occur at 61 and 122 pg/ml E2. These data indicate that the transdermal delivery of E2 with these systems significantly reduced the occurrence of HFs and allowed definition of the therapeutic range of hormone replacement in terms of lost ovarian function, as reflected by circulating E2 levels.

Administration, Topical↗