Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial.
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BACKGROUND: Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. METHODS: 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. FINDINGS: Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. INTERPRETATION: Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer. (+info)
Natural history of menopause symptoms in primary care patients: a MetroNet study.
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BACKGROUND: The association between changes in menopausal status and menopause-related symptom reporting over the course of the menopause transition is not well understood, especially whether there are any racial differences in this association. OBJECTIVE: To determine (1) the prevalence and the natural history of menopause symptoms among primary care patients approaching, or at menopause; (2) the relationship between self-reported symptoms and menopausal status; and (3) whether this relationship varies in African American and white women. STUDY DESIGN: Cross-sectional self-report survey of 342 women aged 40 to 55 years (31.6% African American) were recruited from 8 family practice centers in 2000 and 2001. RESULTS: Among 251 women without surgical menopause, 133 (53.0%) were premenopausal, 72 (28.7%) were peri-menopausal, and 46 (18.3%) were postmenopausal. The most commonly reported symptoms were joint/muscle pain and headache, which did not vary by menopausal status. As many as 28.6% of the women with regular menstruation reported hot flashes, and 18.8% had night sweats; although both symptoms were strongly associated with changes in menopausal status (P < .01). During the natural menopausal transition, white women had increasing trends of nervousness, memory loss, vaginal dryness, loss of sexual interest, hot flashes, and night sweats while African American women only had increasing trend of painful sex and hot flashes. In multivariate analyses, loss of sexual interest was associated with postmenopause status in white but not in African American women. CONCLUSIONS: Symptoms are not uncommon among premenopausal women and become more prevalent as the transition through menopause occurs. The prevalence of vasomotor symptoms in premenopausal women may be an under-recognized aspect of the natural history of the menopause transition. African American and white women may present different symptoms through menopause transition. (+info)
The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.
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Hormone replacement therapy (HRT) is contraindicated in women with a history of breast cancer or a high risk of breast cancer development. Recent results from large clinical trials, such as the Women's Health Initiative, have demonstrated increased risks of thromboembolic events and a moderate increased risk of breast cancer in women using conjugated estrogens and progestogens. There is a need for viable non-hormonal alternative treatments to HRT, such as nutritional and botanical therapies, in this population of women, who tend to experience more significant vasomotor symptoms. Safe and effective therapies that do not stimulate breast cell proliferation could prove extremely useful for the management of such symptoms for women in both low- and high-risk breast cancer populations. As a non-hormonal treatment, anti-depressants, such as selective serotonin reuptake inhibitors (SSRIs), have been shown to improve hot flash symptoms in women. The proposed mechanism is related to an increase in serotonin allowing for an increase in the set point of the brain's thermoregulator. In small clinical studies, the administration of tryptophan and 5-hydroxytryptophan (5HTP), the precursors of serotonin, have been shown to reduce depressive symptoms, possibly by enhancing the synthesis of serotonin. Thus, increased serotonin levels may have the ability to decrease hot flashes in a mechanism similar to that of SSRIs without the risks of breast cell stimulation. This would be particularly desirable for menopausal women with breast cancer or with risks of breast cancer. This article discusses the background information on hot flashes, SSRIs, tryptophan, and 5HTP, and possible clinical application of 5HTP for menopausal women with breast cancer risk. (+info)
Botanical and dietary supplements for menopausal symptoms: what works, what does not.
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BACKGROUND: Approximately two thirds of women who reach menopause develop menopausal symptoms, primarily hot flashes. Hormone therapy long was considered the first-line treatment for vasomotor symptoms. However, given the results of the Women's Health Initiative (WHI), many women are reluctant to use exogenous hormones for symptomatic treatment and are turning to botanicals and dietary supplement (BDS) products for relief. Despite the fact that there is limited scientific evidence describing efficacy and long-term safety of such products, many women find these natural treatments appealing. Perimenopausal and postmenopausal women are among the highest users of these products, but 70% of women do not tell their healthcare providers about their use. Compounding this issue is the fact that few clinicians ask their patients about use of BDS, largely because they have not been exposed to alternative medical practices in their training and are unfamiliar with these products. METHODS: This paper reviews the botanicals and dietary supplements commonly used in menopause (such as black cohosh, red clover, and soy products) as well as the available data on efficacy and safety. We searched the MEDLINE database from 1966 to December 2004 using terms related to BDS and menopausal symptoms for perimenopausal or postmenopausal women. Abstracts from relevant meetings as well as reference books and websites on herbal supplements were also searched. Randomized, controlled trials (RCTs) were used if available; open trials and comparison group studies were used when RCTs were not available. RESULTS AND CONCLUSIONS: The evidence to date suggests that black cohosh is safe and effective for reducing menopausal symptoms, primarily hot flashes and possibly mood disorders. Phytoestrogen extracts, including soy foods and red clover, appear to have at best only minimal effect on menopausal symptoms but have positive health effects on plasma lipid concentrations and may reduce heart disease. St. John's wort has been shown to improve mild to moderate depression in the general population and appears to show efficacy for mood disorders related to the menopausal transition. Other commonly used botanicals have limited evidence to demonstrate safety and efficacy for relief of symptoms related to menopause. (+info)
Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial.
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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. (+info)
Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis.
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PURPOSE: Significant regression of radiation (RT) -induced fibrosis (RIF) has been achieved after treatment combining pentoxifylline (PTX) and alpha-tocopherol (vitE). In this study, we focus on the maximum response, how long it takes to achieve response, and changes after treatment discontinuation. PATIENTS AND METHODS: Measurable superficial RIF was assessed in patients treated by RT for breast cancer in a long-treatment (24 to 48 months) PTX-vitE (LPE) group of 37 patients (47 RIFs) and in a short-treatment (6 to 12 months) PTX-vitE (SPE) group of seven patients (eight RIFs). Between April 1995 and April 2000, women were treated with a daily combination of PTX (800 mg) and VitE (1,000 IU). RESULTS: Combined PTX-vitE was continuously effective and resulted in exponential RIF surface area regression (-46% for LPE and -68% for SPE at 6 months, -58% for LPE and -69% for SPE at 12 months, -63% for LPE and -62% for SPE at 18 months, and -68% for LPE at 24 and 36 months). The mean estimated maximal treatment effect was 68% RIF surface area regression. The mean time to this effect was 24 months and was shorter (16 months) in more recent RIF (< 6 years since RT) than in older RIF (28 months; P = .0003). Symptom severity (Subjective Objective Medical Management and Analytic Evaluation score) was halved in both groups. After treatment discontinuation, mean RIF surface area at 1 year had increased by +40% in the SPE group (rebound) and +8.5% in the LPE group. CONCLUSION: Under combined PTX-vitE treatment, RIF regression was exponential, with a two-thirds maximum response after a mean of 2 years. There was a risk of a rebound effect if treatment was too short. Long treatment (>/= 3 years) is recommended in patients with severe RIF. (+info)
Plasma adenosine levels in peri-menopausal women having frequent hot flushes.
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BACKGROUND: The effect of hormone replacement therapy (HRT) on plasma adenosine levels was investigated in climacteric women experiencing hot flushes. METHODS AND RESULTS: Plasma adenosine levels were measured in 13 peri-menopausal women with frequent hot flushes (>5 per day) before and 3-4 months after initiating HRT. Thirteen healthy pre-menopausal, 9 peri-menopausal women with few hot flushes (<1 or 2 per day) and 10 healthy postmenopausal women were enrolled as controls. The average plasma adenosine level in the peri-menopausal women was 0.20+/-0.09 micromol/L, which was significantly higher than in the pre-menopausal (0.12+/-0.07 micromol/L, p<0.05), peri-menopausal with few hot flushes (0.10+/-0.09 micromol/L, p<0.05) and postmenopausal women (0.13+/-0.06 micromol/L, p<0.05). Both the increased adenosine level and the hot flushes were decreased by HRT (plasma adenosine: 0.13+/-0.06 micromol/L). CONCLUSIONS: Increased plasma adenosine in peri-menopausal women may be associated with frequent hot flushes. (+info)
Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes.
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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. (+info)