Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tibolone is a synthetic molecule used extensively for the management of menopausal symptoms, with the proposed additional advantage of enhanced mood and libido. Tibolone, after oral administration, is rapidly converted into 3 major metabolites: 3alpha-hydroxytibolone and 3beta-hydroxytibolone, which have estrogenic effects, and the Delta(4)-isomer, which has progestogenic and androgenic effects. The tissue-selective effects of tibolone are the result of metabolism, of enzyme regulation, and of receptor activation which vary in different tissues. Tibolone seems to be effective on estrogen-withdrawal symptoms such as hot flushes, sweating, insomnia, headache, and vaginal dryness, with results generally comparable to the effects exerted by estrogen-based treatments, and the additional property of a progestogenic activity on the endometrium. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves dyspareunia and libido. These effects may depend on both estrogenic and androgenic actions exerted at the genital level and in the central nervous system, and on a reduction of sex-hormone-binding globulin and an increase of free testosterone, without affecting Delta-5 androgens levels. Based on the evidence available, tibolone is a valuable treatment option to relieve menopausal complaints, especially in women suffering persistent fatigue, blunted motivation, and loss of sexual desire despite an adequate estrogen replacement.
Neuropsychiatr Dis Treat 2006 Sep
PMID:Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women. 1941 77

This review assessed the efficacy of isoflavone supplements to reduce vasomotor symptoms in menopausal women by reviewing all published randomized controlled trials. Systematic literature searches were carried out in 70 databases. Randomized and placebo controlled studies were included if they investigated the treatment of isoflavone supplements derived from soy or red clover on vasomotor symptoms in peri- or postmenopausal women for at least 12 wks. Data were analyzed concerning outcome and methodological quality of the study. Twenty-three trials met the inclusion criteria, thereof 17 investigated soy isoflavones and 6 red clover isoflavones. Without exception, selected trials examining the effect of red clover isoflavones were already assessed in several meta-analyses and were therefore excluded from this evaluation. As the soy isoflavone studies were very heterogeneous concerning interventions and outcome measures, meta-analysis could not be performed and trials were systematically assessed in a structured approach. Included soy isoflavone studies had numerous quality deficiencies and did not consistently show a reduction of flushes after treatment with soy isoflavones. Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.
Mol Nutr Food Res 2009 Sep
PMID:Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review. 1965 25

Although most women report vasomotor symptoms (hot flashes, night sweats) during midlife, their etiology and risk factors are incompletely understood. Body fat is positively associated with vasomotor symptoms cross-sectionally, but the longitudinal relation between changes in body fat and vasomotor symptoms is uncharacterized. The study aim was to examine whether gains in body fat were related to vasomotor symptom reporting over time. Measures of bioelectrical impedance for body fat, reproductive hormones, and reported vasomotor symptoms were assessed annually over 4 years from 2002 to 2006 among 1,659 women aged 47-59 years participating in the Study of Women's Health Across the Nation. Body fat change was examined in relation to vasomotor symptoms by using generalized estimating equations. Body fat gains were associated with greater odds of reporting hot flashes in models adjusted for age, site, race/ethnicity, education, smoking, parity, anxiety, and menopausal status (relative to stable body fat, gain: odds ratio = 1.23, 95% confidence interval: 1.02, 1.48; P = 0.03; loss: odds ratio = 1.07, 95% confidence interval: 0.89, 1.29; P = 0.45). Findings persisted controlling for estradiol, the free estradiol index, or follicle-stimulating hormone concentrations. The relations between body fat changes and night sweats were not statistically significant. Body fat gains are associated with greater hot flash reporting during the menopausal transition.
Am J Epidemiol 2009 Sep 15
PMID:Gains in body fat and vasomotor symptom reporting over the menopausal transition: the study of women's health across the nation. 1967 42

Hot flashes are the cardinal symptom of menopause and can be treated with hormonal and nonhormonal prescription medications. However, considering that 6000 women enter menopause daily in the USA, and many of these women are symptomatic, the costs of these treatments can be a significant public health issue. We evaluated annual individual and population costs of hormonal and nonhormonal prescription treatments for hot flashes. Cost information may be helpful to clinicians and consumers in making treatment decisions.
Womens Health (Lond) 2009 Sep
PMID:Costs of hormonal and nonhormonal prescription medications for hot flashes. 1970 49

Hot flashes are a disorder of thermoregulation due to the lack of estrogens and are the most common and characteristic climacteric complaint. Hormone replacement therapy is the gold standard treatment but now its use is limited due to several side effects. Need therefore arises to search for non-estrogenic alternatives. It is well established that extracts of Cimicifuga racemosa (CR) ease climacteric complaints but solid animal experimental data supporting such effects are not available. The availability of sensitive transponders which record subcutaneous temperature continuously enables nowadays experiments in rats to establish whether they have hot flashes following ovariectomy (Seidlova-Wuttke et al. 2003) and if so, whether they can be influenced by the extract of CR BNO 1055. Intact Sprague-Dawley rats (n=16) were acclimatized and their subcutaneous body temperature was measured in 5 min intervals and mean values from 3h recordings were calculated. Thereafter, the rats were ovx and fed either with soy free (sf) or CR BNO 1055 (25 mg/animal/day) food. Temperature was recorded again after acute and sub-acute application of CR. In individual intact animals temperature was stable over the 3h recording period. Following ovx temperature pulses appeared with peaks occurring every 20-40 min. These fluctuations were not seen in CR BNO 1055 treated animals resulting in significantly higher mean temperatures in ovx in comparison to intact or ovx CR BNO treated rats. This reduction of hot flashes by BNO 1055 outlasted the experimental period of 3 weeks. These results suggest that the ovx rats and the new temperature-sensitive device may be useful for the study of hot flashes. Furthermore the results prove that the CR BNO 1055 exerts hot flash reducing effects.
Phytomedicine 2010 Sep
PMID:The Cimicifuga racemosa special extract BNO 1055 prevents hot flashes in ovariectomized rats. 2069 60

The treatment of primary breast cancer usually consists of surgery often followed by adjuvant therapy (radiotherapy, chemotherapy, hormonal treatment, etc.) to reduce the risk of recurrence. The cancer diagnosis and the treatments may have significant impact on the patients' quality of life. This thesis deals with scientific aspects and clinical results of a study aimed at assessing the impact of breast cancer (and its treatment) on the patients' quality of life. Studies such as this assessing the problems and symptoms experienced by the patients are often referred to as health-related quality of life (HRQL) research. HRQL research deals with subjective experiences and raises challenging, scientific questions. Therefore, much attention was directed towards methodological issues in this clinically motivated project. The study was a prospective, longitudinal, questionnaire-based investigation of women with newly diagnosed breast cancer registered in the Danish Breast Cancer Co-operative Group's DBCG 89 Program. The patients were sub-divided into low-risk and high-risk patients. High-risk patients were offered randomisation in one of three randomised adjuvant therapy trials involving chemotherapy, ovarian ablation, and endocrine therapy. After a literature study and interviews with breast cancer patients, a questionnaire was composed that included two widely used standard questionnaires (EORTC QLQ-C30 and Hospital Anxiety and Depression (HAD) Scale) and a DBCG 89 Questionnaire developed for this study. A total of 1,898 eligible patients were invited by post to participate in the study involving six assessments over a 2-year period, and 1,713 patients (90%) completed the first questionnaire. Furthermore, a questionnaire was sent to 872 women selected at random from the general population; 608 (70%) responded. The multi-item scales of the two standard questionnaires were analysed for so-called differential item functioning (DIF) in order to investigate whether the (summary) scale scores were adequate representations of the information obtained by the individual items. The DIF analyses identified a number of cases of DIF, which, among other things, contributed to detection of possible problems in the HAD Scale. It was concluded that DIF analyses are relevant when important analyses based on multi-item scales are made. A new way to evaluate the validity of questionnaires was developed. The results from questionnaires completed by patients were compared against results from open ended interviews with the same patients rated by observers. The idea was that if results were similar, the patients had then probably understood and completed the questionnaire items as intended. On the other hand, if results from self-assessment and interviews deviated, misunderstandings or other errors might have taken place, and the study would give insight into possible problems. Of 57 breast cancer patients, 46 (81%) were successfully interviewed. In general, the agreement between patient-completed questionnaires and interviews was excellent, indicating very good validity. The median weighted kappa for the EORTC QLQ-C30 was 0.85 (range 0.49-1.00); it was 0.79 (range 0.65-0.95) for the HAD Scale, and 0.92 (range 0.51-1.00) for the DBCG 89 Questionnaire. However, the study identified a mechanism called selective reporting, which may affect results from most HRQL questionnaires: in order to provide correct and useful answers some patients do not report symptoms they believe are irrelevant to the study, e.g., symptoms unrelated to cancer. This mechanism may lead to bias if results from patients are compared to results from populations reporting their symptoms more completely, e.g., general population samples. In contrast, this mechanism has little importance when results from different sub-groups of cancer patients are compared. In this study multiple variables were assessed at multiple points in time and we did not have a priori hypotheses for all these potential comparisons. Therefore, a staff survey involving experienced doctors and nurses was conducted in order to generate hypotheses that could be tested in the data from patients. We contacted 46 health care professionals and 36 (78%) responded. Overall, the staff survey did not prove very useful for the intended purpose. The main reason for this was probably that the health care professionals had limited insight into the patients' HRQL. A different approach to the problem of multiple hypothesis testing proved more useful. Hypotheses generated from the initial literature review were tested in the comparison of patients in chemotherapy against patients not in chemotherapy. The study of women selected at random from the general population showed that these women experienced a considerable degree of "morbidity" according to all three questionnaires. This shows that symptoms and problems reported by cancer patients may have causes other than cancer, and thus constitutes a good justification for the use of data from general population studies when interpreting data from cancer patients. The levels of anxiety and depression of low-risk breast cancer patients were found to be lower than those from the general population sample. After careful consideration we concluded that this finding was probably incorrect. The most important explanations were thought to be the wording of some HAD Scale items as well as two mechanisms that are not specific to the HAD Scale, the "selective reporting mechanism" found in the validation study, and the response-shift problem. These findings indicate - in contrast to the conclusion above - that the comparability of HRQL data from cancer patients and general population data must be questioned. However, as this is the first study to raise the problem, this issue needs further investigation. Based on the initial literature review and interviews we hypothesised that 30 different HRQL issues would be impaired in patients undergoing CMF chemotherapy compared to patients not in chemotherapy; 23 of these hypotheses were confirmed. In addition, our study and other research suggest that other HRQL aspects may also be affected by chemotherapy. Thus, there is considerable evidence that patients in chemotherapy may experience effects on a wide spectrum of HRQL issues. Most other studies have assessed surprisingly few of the HRQL issues shown in our study to be impaired in patients receiving chemotherapy. Similarly, current review articles on HRQL effects of adjuvant chemotherapy mention only relatively few of these topics. Concerning HRQL after the treatment period, our main finding was that many symptoms and problems had declined or disappeared, but some persisted: anticipatory nausea, weight gain, endocrine effects (e.g., hot flushes/sweats, irregular bleedings/amenorrhea, vaginal dryness), disturbed sleep, and sexual dysfunction. These findings are in agreement with the literature. The staff study showed that experienced physicians and nurses did not expect many of the "scientifically well documented" consequences of chemotherapy. Taken together, our findings suggest that information to patients about chemotherapy should be more comprehensive than that which has been practised in most places. When compared against ovarian ablation, chemotherapy was associated with more impact on HRQL during the treatment period; only hot flushes/sweats were more pronounced in the ovarian ablation group. Thus, from an overall "HRQL perspective" ovarian ablation or suppression may be preferable. However, younger women may preserve their premenopausal status (including fertility) by having chemotherapy, and this may be an argument for chemotherapy or for temporary ovarian ablation via goserelin, rather than permanent ovarian ablation. Furthermore, while ovarian ablation/suppression may be preferable because of less impairment of HRQL, contemporary chemotherapeutic regimens may be more effective. These results indicate that for some patients, the HRQL data and results on treatment efficiency may be in conflict. There is no simple, universally correct solution to this dilemma. More research into patients' views and expectations to the health-care system in cases where medical decision-making involves complex trade-offs between treatment efficiency and HRQL issues is needed. Contrary to expectations, the analyses showed that fatigue and emotional function predicted the risk of recurrence and death independently of biological and clinical prognostic variables. In multivariate Cox regression analyses patients who were more fatigued or had poorer emotional function had a worse prognosis. These results are consistent with one small study, but are inconsistent with five similar studies in patients with primary breast cancer, which found no such associations. The reasons for these important differences are currently unknown. In conclusion, this study consisted of methodological and clinical investigations of HRQL in primary breast cancer patients. The initial questionnaire development resulted in a combination of questionnaires that was more comprehensive than in other similar studies. The results of the methodological studies generally supported the validity of the questionnaires but also gave important insights into potential scientific problems that are probably not restricted to the present study. These insights helped to prevent misinterpretations of the clinical data. The study provided the most detailed description of HRQL during and after breast cancer adjuvant chemotherapy to date, and compared results of chemotherapy against ovarian ablation. It also provided controversial results concerning the prognostic value of HRQL data. The combination of a large empirical study and several methodological sub-studies thus proved useful and gave new results.
Dan Med Bull 2010 Sep
PMID:Health-related quality of life in early breast cancer. 2081 24

During the climacteric period, several symptoms exist that motivate women to seek medical advice; one of the most common is the hot flush, which presents in 75%-85% of these during a variable time span. For the treatment of hot flush, several non-hormonal treatments exist; among them, veralipride has shown to be a useful treatment of vasomotor symptoms during the climacteric period. In recent times, several medical societies have discredited its use. The purpose of this review, therefore, is to define a measured position in relation to the use of this drug. On completion of this review, it was possible to conclude that this drug has an antidopaminergic mechanism of action. The recommended schedule is: 100 mg/day for 20 days, with 10 days drug free. Since the risk of undesirable secondary effects such as galactorrhea, mastodynia, and extrapyramidal can increase with use, no more than 3 treatment cycles are recommended. This drug has a residual effect that can allow drug-free intervals, which permit a longer time between schedules.
Clin Interv Aging 2010 Sep 07
PMID:Actual status of veralipride use. 2085 74

Menopause has been associated with vasomotor symptoms, vulvar-vaginal atrophy and osteoporosis. One of the goals in exploring the potential of selective estrogen receptor modulators (SERMs) was to determine if they could prevent fractures, reduce menopausal symptoms and treat vaginal atrophy, while being neutral or protective on the uterus, breast and cardiovascular system. However, no SERM to date has achieved this goal. More recently, the idea of pairing a SERM with estrogen(s), known as a tissue-selective estrogen complex (TSEC), has been studied in postmenopausal women. A TSEC combines the complementary tissue-selective activities of a SERM and estrogen(s), in an attempt to gain the benefits of each with better overall tolerability. The Selective estrogen Menopause And Response to Therapy (SMART) trials were multicentre, randomized, double-blind, placebo- and active-controlled phase 3 studies evaluating the safety and efficacy of the SERM, bazedoxifene (BZA) paired with conjugated estrogens (CEs) in healthy postmenopausal women. In the first SMART trial, BZA/CE protected the endometrium from estrogenic stimulation, relieved hot flushes and maintained bone mass, with rates of amenorrhea, breast pain and overall adverse events similar to those with placebo in more than 3400 women over two years. BZA 20 mg was the lowest effective dose of BZA in BZA/CE to protect the endometrium and maintain bone mass when paired with CE 0.625 mg and CE 0.45 mg. In SMART-2, these BZA/CE doses significantly reduced the frequency and severity of hot flushes over 12 weeks. Collectively, these data support the TSEC containing BZA/CE as a new paradigm for treating menopausal symptoms and preventing osteoporosis while protecting the endometrium from unopposed estrogenic stimulation.
Menopause Int 2010 Sep
PMID:Tissue-selective agents: selective estrogen receptor modulators and the tissue-selective estrogen complex. 2095 88

Treatments for postmenopausal osteoporosis are generally safe, but are linked to some rare serious adverse drug reactions, for which causality is not always certain. The bisphosphonates are associated with gastrointestinal effects, acute phase reactions, and musculoskeletal pain, and, more rarely, cases of atrial fibrillation, subtrochanteric fracture, osteonecrosis of the jaw, cutaneous hypersensitivity reactions and renal impairment. It is too soon for pharmacovigilance data on denosumab, but it has been associated with cutaneous effects and possibly osteonecrosis of the jaw (to date, only in metastatic cancer). The selective estrogen receptor modulators may induce hot flushes and leg cramps, and--more rarely--venous thromboembolism and stroke. Strontium ranelate is associated with headache, nausea and diarrhea, and, more rarely, cutaneous hypersensitivity reactions and venous thromboembolism, while teriparatide and parathyroid hormone(1-84) are associated with headache, nausea, dizziness and limb pain. The management of osteoporosis should entail weighing the probability of adverse reactions against the benefits of therapy--that is, reduction of fracture risk.
Expert Rev Clin Pharmacol 2011 Sep
PMID:Adverse drug reactions to osteoporosis treatments. 2222 Mar 6

Epidemiological studies suggest that consumption of isoflavones rich diets can improve several postmenopausal complications. The aim of this study was to investigate the absorption and the efficacy of isoflavonic supplementation in the treatment of menopausal symptoms.36 postmenopausal women received 75 mg/day of isoflavones in the form of tablets, for six months. 21 subjects concluded the treatment. Plasmatic and urinary samples were collected before and after the treatment, along with a dietary interview. Isoflavones were determined in biological samples and in commercial administered supplements by a HPLC/DAD system.Results showed the presence of genistein (from 0.043 to 1.820 micromol/L) in plasma samples, and of genistein (from 2.486 to 20.363 micromol/24h) and daidzein (from 11.106 to 98.091 micromol/24h) in the urines of the treated women. In the 21 completers the Greene Climateric scale value for hot flushes changed from 3 to 1 or 0. No changes of the endometrial thickness and of the breast tissue were detected. The analysis of the supplement content in the tablets was in agreement with what declared by the producer.Administration of isoflavone supplements produced a decrease of symptoms in this cohort of postmenopausal women monitored for isoflavone absorption.
Clin Cases Miner Bone Metab 2009 Sep
PMID:Absorption and bioeffects of an isoflavone-based supplementation in postmenopausal women. 2246 Dec 55


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