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

In our cross-sectional study we investigated the separate influence of three main factors, namely menopausal and estrogen status, and chronological age, on ten neurovegetative climacteric complaints reported in the scale of Kupperman et al. A multivariate statistical analysis was performed by a multivariate statistical approach on 1161 untreated women seen at the Menopause Center of the Ferrara University Hospital. Ninety women (age range, 41-54 years) were premenopausal; 492 women (age range, 38-55 years) were perimenopausal with irregular periods or amenorrhea for less than 12 months; 468 women (age range, 41-69 years) had a spontaneous menopause (age range, 37-66 years); 111 had had hysterectomy with bilateral ovariectomy while still regularly menstruating. Serum estrone was used as the indicator of the patients' estrogen status. A clear positive trend was demonstrated between menopausal status and the prevalence of depression, hot flushes, insomnia and joint pain. However, only the prevalence of hot flushes amongst these four symptoms was significantly related with the climacteric estrogen decline (beta = -0.006, P = 0.001). Moreover, menopausal status appeared to influence the intensity of fatigue, hot flushes, insomnia and paresthesia. Age was found to significantly (P = 0.053) co-vary only with the intensity of the hot flushes, with a positive relation (beta = 0.092, r = 0.104, P = 0.003), whereas estrone values did not significantly co-vary with any symptom. Furthermore, while neurovegetative symptoms are largely present also in the absence of hot flushes, when these latter are present, they exacerbate both the intensity and the prevalence of all the other symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints. 785 1

This paper reports on an investigation of the homeopathic approach to the management of symptoms of oestrogen withdrawal in women with breast cancer. Forty-five patients entered the study. The most common presenting symptoms were hot flushes (HF) (n=38), mood disturbance (n=23), joint pain (n=12), and fatigue (n=16). Other symptoms included sleeplessness, reduced libido, weight gain, cystitis, vaginal dryness and skin eruptions. The active intervention was an individualised homeopathic medicine. Forty women (89%) completed the study. Significant improvements in mean symptom scores were seen over the study period and for the primary end-point 'the effect on daily living' scores. Symptoms other than HF such as fatigue and mood disturbance appear to be helped. Significant improvements in anxiety, depression and quality of life were demonstrated over the study period. The homeopathic approach appears to be clinically useful in the management of oestrogen withdrawal symptoms in women with breast cancer whether on or off Tamoxifen and improves mood disturbance. A placebo-controlled trial would be the next stage in this line of inquiry.
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PMID:The homeopathic approach to the treatment of symptoms of oestrogen withdrawal in breast cancer patients. A prospective observational study. 1288 92

Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate. Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring. In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.
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PMID:Letrozole: a review of its use in postmenopausal women with breast cancer. 1516 28

The aromatase inhibitors deplete oestrogen by inhibiting aromatase, the enzyme that synthesises oestrogen from androgens. They are effective as therapies for breast cancer only in postmenopausal women whose tumours express oestrogen or progesterone receptors. As adjuvant therapy, tamoxifen and the aromatase inhibitors have similar efficacy in the first 5 years of treatment. Aromatase inhibitors can be used as an alternative to tamoxifen in women with symptomatic intolerance or a contraindication to tamoxifen. Early data suggest that switching to an aromatase inhibitor after 2-5 years of tamoxifen therapy is beneficial in women with high-risk disease. Aromatase inhibitors are associated with more hot flushes than placebo, but with fewer hot flushes, less endometrial toxicity and venous thromboembolism, and more arthralgia, myalgia and bone fracture than tamoxifen.
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PMID:The aromatase inhibitors in early breast cancer: who, when, and why? 1639 38

Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer. Binding of letrozole to the haeme component of the cytochrome P450 subunit of aromatase inhibits estrogen biosynthesis throughout the body. As first-line adjuvant therapy in approximate, equals 8000 postmenopausal women with hormone-responsive, early-stage breast cancer, once-daily letrozole 2.5mg significantly prolonged disease-free survival (DFS; primary endpoint) and reduced the risk of relapse at distant sites relative to once-daily tamoxifen 20mg in the ongoing Breast International Group 1-98, double-blind, multinational trial. The median duration of follow-up for this primary core analysis was 25.8 months. Extended adjuvant therapy with once-daily letrozole 2.5mg significantly prolonged DFS relative to placebo treatment at a median follow-up of 30 months (primary endpoint) in the MA-17 trial in approximate, equals 5000 postmenopausal women who were disease free after 4.5-6 years of tamoxifen therapy for hormone-responsive, early-stage breast cancer. Letrozole treatment for up to 5 years was generally well tolerated in this clinical setting. As first-line treatment, relative to tamoxifen, letrozole was associated with a significantly lower incidence of venous thromboembolitic events, vaginal bleeding, hot flushes and night sweating, whereas the incidence of cardiac failure, bone fractures and arthralgia was higher in letrozole recipients.
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PMID:Letrozole : in postmenopausal hormone-responsive early-stage breast cancer. 1652 26

To summarise the advances in the hormonal treatment of post-menopausal metastatic breast cancer, this paper reviews the published literature regarding the randomised trials comparing aromatase inhibitors (AIs) versus tamoxifen as a first-line therapeutic choice, or AIs versus megestrole acetate (MEG) as a second-line option. The pooled analysis of these authors on AI versus MEG as a second-line option for post-menopausal metastatic breast cancer suggested that AIs do not add any significant benefit over MEG in terms of overall response rate (ORR) and time to progression. According to the Cochrane Database, use of an AI as a second-line therapy versus any other endocrine therapy (mostly MEG) has shown a significant benefit in terms of overall survival, but not for progression-free survival, clinical benefit (CB) or ORR. Concerning the authors' comparisons between AIs versus tamoxifen as a first-line endocrine option in post-menopausal women with metastatic breast carcinoma, AIs seem to be superior to tamoxifen, with a significant benefit in terms of ORR, CB and time to progression being observed in favour of AIs over tamoxifen with fixed effects estimates. According to the Cochrane Database, there was an advantage to the use of AIs over tamoxifen in terms of progression-free survival and CB, but not for overall survival or ORR. With regards to toxicity, AIs show similar levels of hot flushes and arthralgia, increased risks of nausea, diarrhoea and vomiting, but a decreased risk of vaginal bleeding and thromboembolic events compared with other endocrine therapies. Weight gain, dyspnoea and peripheral oedema seem to be more frequent with MEG. At present, there is no proved overall survival difference in patients who are treated first with an AI and then with tamoxifen compared with the opposite sequence. In the metastatic setting, results are limited and are based on retrospective analyses.
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PMID:Aromatase inhibitors in post-menopausal metastatic breast carcinoma. 1759 87

Adjuvant endocrine therapy plays an important role in the management of hormone-receptor-positive early breast cancer, and has increased life expectancy for millions of women. Many patients receive adjuvant treatment for at least 5 years following tumor resection, hence good long-term safety is important for endocrine agents to gain widespread acceptance. Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile limits treatment duration to 5 years. Increased efficacy over tamoxifen and good tolerability have recently made the third-generation aromatase inhibitors (AIs) the first-choice agents for adjuvant endocrine therapy; however, it is currently not known whether AI therapy, like tamoxifen, will be limited to 5 years. Many side effects of endocrine therapy, such as hot flushes and mood disturbances, are related to estrogen deprivation and are common to tamoxifen and AIs, reflecting the mechanism of action of these drugs. In addition, tamoxifen has estrogenic effects that are beneficial in some tissues: tamoxifen lowers serum cholesterol levels and protects against bone loss and cardiovascular disease, but is also associated with potentially life-threatening side effects, such as endometrial cancer and thromboembolic disease. As AIs lack estrogenic activity, they are not associated with these serious adverse events. Clinical trials comparing AIs with tamoxifen in the adjuvant setting have shown that AIs are well tolerated and are associated with a lower incidence of gynecological symptoms and hot flushes than tamoxifen. However, AIs are associated with musculoskeletal side effects, such as arthralgia, myalgia and bone loss, but these events are preventable or manageable. The effects of AIs on lipid metabolism and the cardiovascular system are still debatable, but placebo-controlled trials provide no evidence to suggest that AIs adversely affect these systems. Furthermore, the AIs allow women to maintain a good quality of life, comparable with women receiving tamoxifen or placebo, and are a cost-effective therapeutic option. Ongoing trials will provide more information regarding the long-term effects of AI therapy and will provide comparative data on the efficacy and safety of the different AIs, thereby helping to determine the optimal treatment strategy for these highly effective and well-tolerated drugs.
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PMID:Safety profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer. 1789 Feb 11

The impact of improved treatments for the management of hormone-sensitive breast cancer extends beyond clinical responses. Thanks to appropriate literature and access to the internet, patient awareness of treatment options has grown and patients are now, in many cases, able to engage their oncologists in informed conversations regarding treatment and what to expect in terms of efficacy and safety. Indeed, patients realize that although there is no cure for metastatic disease, treatment can greatly reduce the risk of progression and in the adjuvant setting, where treatment is administered with a curative intent, current treatment options reduce the risk of relapse. The approval of letrozole throughout the breast cancer continuum has provided patients with many reassuring options. The improvement in outcome with letrozole is achieved without a detrimental effect on overall quality of life. Adverse events such as hot flushes, arthralgia, vaginal dryness, and potential osteoporosis are most significant from the patient's perspective, and it is important that caregivers pay attention to patients experiencing these events, as they can impact compliance unless effectively explained and managed. The major benefits of letrozole are to improve prospects for long-term survivorship in the adjuvant setting and to delay progression and the need for chemotherapy in the metastatic setting.
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PMID:The patient experience. 1791 39

Third-generation aromatase inhibitors (AIs) are replacing tamoxifen as adjuvant therapy in postmenopausal women with hormone-sensitive breast cancer due to their superiority shown in several recent head-to-head trials. Healthy postmenopausal women normally experience age-related side effects, and in postmenopausal women with breast cancer, these symptoms may be exacerbated by adjuvant endocrine therapy. This review evaluates the current literature regarding bone health, lipid metabolism, cardiovascular disease, gynecologic health, and cognition in postmenopausal women receiving adjuvant AI therapy. The AIs -- anastrozole, exemestane, and letrozole -- are generally well tolerated: most adverse events are mild to moderate and common to menopause. Common short-term AI-associated toxicities are hot flushes, musculoskeletal complaints/arthralgia, and bone loss, all of which can be effectively managed. AIs may lack the cardioprotective and lipid-lowering effects of tamoxifen but, in contrast to tamoxifen, do not increase the risk of serious life-threatening thromboembolic or cerebrovascular events or endometrial cancer. Every patient should be individually assessed with respect to therapy risks and benefits. Lifestyle, comorbidities, and concomitant medications must be considered, and the importance of compliance to adjuvant therapy should be discussed before selecting a treatment regimen. The superior efficacy of adjuvant AI therapy will in most cases outweigh the risk of bothersome side effects that can be prevented or easily managed.
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PMID:Menopausal symptoms and adjuvant therapy-associated adverse events. 1831 Feb 77

We report an open-label, prospective, crossover study involving 184 post-menopausal women experiencing hot flushes on adjuvant tamoxifen (T). Six weeks after switching to an AI, the primary end point, hot flush score, improved by 47.3% (P<0.001) compared to those reported on T. The mean mood rating scale (MRS) score improved by 9.7% (P=0.01). The total mean combined FACT (b+es) score improved from 134.2 (95% CI +/-2.96) to 143.5 (95% CI +/-2.96 <0.001), and the endocrine subscale improved by 9.8% from 51.73 (95% CI +/-1.38) to 57.34 (CI +/-1.38, P<0.001). At 6 weeks, significantly more women chose to remain on an AI: 133 (72%), vs 40 (22%) (P<0.001) preferring T. At 3 months, 107 (58%) preferred to remain on an AI, 55(30%) on T, and 22 (12%) withdrew. The overall arthralgia rate at 3 months was 47% on AI and 30% on T (P=0.001). In all 182 (99%) women reported appreciating the opportunity to experience both drugs. These data suggest that if patients suffering significant adverse effects on T are given the opportunity to try an AI, this empowers them to prioritize relative side-effects, improving wellbeing in a significant proportion. These data also highlight the need for hospital follow-up in this intolerant cohort.
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PMID:Switching to letrozole or exemestane improves hot flushes, mood and quality of life in tamoxifen intolerant women. 1839 53


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