Incidence Of Hot Flashes Research Articles

Long-term safety of aromatase inhibitors in the treatment of breast cancer

Following promising data for metastatic breast cancer in terms of efficacy and safety profile, third-generation aromatase inhibitors (AI), anastrozole, letrozole, and exemestane, underwent a full development in early setting. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting are still debated. Beyond the choice of clinical strategy, the long duration of exposure to AI in adjuvant setting required a full determination of the long-term toxicity profile of these agents. While all three AIs have either favorable (decreased incidence of hot flashes, gynecologic and thromboembolic side-effects) or unfavorable (skeletal complications, arthralgia, musculoskeletal pain, sexual dysfunction) class adverse events, some variability between AIs has been reported in side-effects as well as gastrointestinal, urogenital, neurologic, and visual disturbances, confirming the lack of interchangeability between the three AIs. The overall therapeutic index of AIs appears today superior to that of tamoxifen with proven improved efficacy and better toxicity profile. This review will explore the results from the available adjuvant AIs trials with a particular emphasis on safety profiles, quality of life, and therapeutic index, helping to define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.

進行前立腺癌に対する内分泌療法における患者QOLの検討

There were few studies which reported the longitudinal quality of life (QOL) for Japanese men who received endocrine therapy for advanced or metastatic prostate cancer. A pilot randomized trial was conducted to assess QOL and the incidence of hot flash following endocrine therapy using luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate 1-month or 3-month depot alone in patients with advanced or metastatic prostate cancer. A total of 28 patients with advanced or metastatic prostate cancer who received LH-RH analogue goserelin acetate depot alone for 12 months were randomized (1:1) to two different formulations. Fifteen patients received the 1-month depot and thirteen patients received 3-month depot, namely Zoladex 3.6 mg depot and Zoladex LA 10.8 mg depot, respectively. We measured health related QOL using European Organization for Research and Treatment of Cancer (EORTC) and EuroQol (EQ-5D) questionnaire and evaluated the incidence of hot flashes between the two groups for one year after diagnosis. Moreover, we evaluated the incidence of hot flashes between the 1M and 3M depot. A baseline interview was conducted before treatment. Follow-up interviews were conducted in person at scheduled study visits of 3, 6, 9 and 12 months after treatment. Five (18%) patients dropped out of the study. Thus, we analyzed 23 eligible patients (11 in the 1M arms and 12 in the 3M arms). No significant differences between the two treatment arms were detected in categories of age, average pre- PSA values, Gleason scores and clinical T stage. According to EORTC, each treatment group showed similar QOL scores in all domains before and after treatment. With regard to EQ-5D, the 1M-treatnent arm reported better utility scores than 3M treatment arm, which was no significant statistically. The overall incidence of hot flash was 61% (58% in 1M group and 64% in 3M group). There were no differences with regard to general and disease specific HRQOL between the both formulations of goserelin acetate. Hot flashes are the major adverse effects of endocrine therapy for Japanese patients with prostate cancer.

Mental Workload under Time Pressure can Trigger Frequent Hot Flashes in Menopausal Women

The aim of this study is to examine the relationship between mental workload and occurrence of hot flashes. Twelve women with moderate to severe menopausal hot flashes participated in the study. Subjects participated in both a mental arithmetic task (Task) and control (Non-task) experiments. We measured heart rate, heart rate variability, blood pressure, near infrared spectroscopy, skin temperature, and skin potential level. The incidence of hot flashes was greater in Task than in Non-task. No significant differences between before, during and after hot flashes emerged for the percentage of correct responses and reaction time. However, the percentage of correct responses for two subjects among the ten who experienced hot flashes in Task substantially declined during hot flashes. Chest skin temperatures increased in both Task and Non-task during hot flashes, and regional oxygen saturation was significantly higher in Non-task than in Task. The present study suggested that mental workload under time pressure might be a risk factor for menopausal hot flashes, and the performance of most people who experienced hot flashes was not affected by hot flashes, however, work-related difficulties due to cognitive disturbance during hot flashes might arise in some people.

Germline Pharmacogenetics of Tamoxifen Response: Have We Learned Enough?

Germline Pharmacogenetics of Tamoxifen Response: Have We Learned Enough?

Tamoxifen or Raloxifene in Postmenopausal Women for Prevention of Breast Cancer: A Tale of Two Choices—Counterpoint

Postmenopausal women 50 years or older with an estimated 5-year Gail model breast cancer risk of >1.66% or prior history of lobular carcinoma in situ now have two choices of prevention drug therapy: approved by the Food and Drug Administration for breast cancer risk reduction tamoxifen and

The Association between Soy Nut Consumption and Decreased Menopausal Symptoms

Epidemiological studies suggest a low incidence of hot flashes in populations that consume dietary soy. The present study examined the effect of soy nuts on hot flashes and menopausal symptoms. Sixty healthy postmenopausal women were randomized in a crossover design to a therapeutic lifestyle changes (TLC) diet alone and a TLC diet of similar energy, fat, and protein content in which one-half cup soy nuts divided into three or four portions spaced throughout the day (containing 25 g soy protein and 101 mg aglycone isoflavones) replaced 25 g of nonsoy protein. During each 8-week diet period, subjects recorded the number of hot flashes and amount of exercise daily. At the end of each 8-week diet period, subjects filled out the menopausal symptom quality of life questionnaire. Compared to the TLC diet alone, the TLC diet plus soy nuts was associated with a 45% decrease in hot flashes (7.5 +/- 3.6 vs. 4.1 +/- 2.6 hot flashes day, respectively, p < 0.001) in women with >4.5 hot flashes/day at baseline and 41% in those with <or=4.5 hot flashes/day (2.2 +/- 1.2 vs. 1.3 +/- 1.1, respectively, p < 0.001). Soy nut intake was also associated with significant improvement in scores on the menopausal symptom quality of life questionnaire: 19% decrease in vasomotor score (p = 0.004), 12.9% reduction in psychosocial score (p = 0.01), 9.7% decrease in physical score (p = 0.045), and a trend toward improvement in the sexual score, with a 17.7% reduction in symptoms (p = 0.129). The amount of exercise had no effect on hot flash reduction. Substituting soy nuts for nonsoy protein in a TLC diet and consumed three or four times throughout the day is associated with a decrease in hot flashes and improvement in menopausal symptoms.

NCIC CTG MA.17: Tolerability of letrozole among ethnic minority women

6018 Background: Disease free survival was significantly improved in women receiving letrozole after standard adjuvant tamoxifen in the MA.17 trial. Based on the results of MA.17 and of other trials of aromatase inhibitors in early stage breast cancer, chronic aromatase inhibitor therapy, in postmenopausal women free of breast cancer recurrence, is now being widely employed. We analyzed the toxicity of letrozole according to ethnic status among women enrolled in MA.17. Methods: The chi-square test was used for comparison of rates of side effects between the two groups, Caucasian vs. ethnic minority (defined as all non-Caucasians). In a subset of women, quality of life (QOL) was assessed by the SF-36 Health Survey. Mean change scores in QOL from baseline were compared between groups for summary measures and domains using the Wilcoxon test. Results: 352 minority women and 4,708 Caucasians were enrolled in MA.17, of which 183 minority women and 2,339 Caucasians were randomized to receive letrozole. Caucasians were older than minority women and had a slightly longer duration of treatment with prior tamoxifen. Tumor size and nodal status were not significantly different between the two groups. In women who received letrozole, minority women had significantly lower incidence of hot flashes (49% vs. 58%; p = 0.02), fatigue (29% vs. 39%; p = 0.005), and arthritis (2% vs. 7%; p = 0.006) compared with Caucasians. Mean QOL change scores of SF-36 domains for women who received letrozole were not different but minority women had better mental health at 6 month assessment (p = 0.02) and worse bodily pain at 12 month assessment (p = 0.046). Conclusions: Minority women tolerated letrozole considerably better than Caucasians in the MA.17 trial. These preliminary findings suggest that minority women respond differently to letrozole in terms of toxicity. Recent demonstration of genotypic variations in the aromatase gene in different ethnic groups plus likely pharmacogenomic differences suggests that further research is needed to clarify the clinical outcomes of aromatase inhibition in women of diverse ethnicities. Future research strategies should focus on examining in vivo genotype-phenotype correlations to determine the effects of genetic variation on response to anticancer therapy and on toxicities and end-organ effects. [Table: see text]

Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer

Aromatase inhibitors are widely employed in the adjuvant treatment of early stage breast cancer. The impact of aromatase inhibitors has not been established in ethnic minority women. The purpose of this study was to evaluate the impact of letrozole on minority women in MA.17, a placebo-controlled trial of letrozole following 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Retrospective comparison of disease-free survival (DFS), side effects, and mean changes in quality of life (QOL) scores from baseline between Caucasian and minority women was performed. Minority (n = 352) and Caucasian (n = 4708) women were analyzed. There was no difference between these groups in DFS (91.6% versus 92.4% respectively for 4 year DFS). Letrozole, compared with placebo, significantly improved DFS for Caucasians (HR = 0.55; P < 0.0001) but not for minorities (HR = 1.39; P = 0.53). Among women who received letrozole, minorities had a significantly lower incidence of hot flashes (49% versus 58%; P = 0.02), fatigue (29% versus 39%; P = 0.005), and arthritis (2% versus 7%; P = 0.006) compared with Caucasians. Mean change in QOL scores for minority women who received letrozole demonstrated improved mental health at the 6-month assessment (P = 0.02) and less bodily pain at the 12-month assessment (P = 0.046). Letrozole improved DFS in Caucasians but a definite benefit in minority women has not yet been demonstrated. Minority women tolerated letrozole better than Caucasians in terms of toxicity. These results need confirmation in other trials of aromatase inhibitors.

Raloxifene: A Selective Estrogen-Receptor Modulator for Postmenopausal Osteoporosis – a Clinical Update on Efficacy and Safety

Selective estrogen-receptor modulators are molecules with specific estrogen-receptor binding affinity. Each selective estrogen-receptor modulator induces a unique conformation in the ligand-receptor complex, which leads to transcriptional activation and/or inhibition. Raloxifene 60 mg/day, a benzothiophene selective estrogen-receptor modulator, is approved for the prevention and treatment of postmenopausal osteoporosis. This article provides an update on new studies and further analyses of clinical trial data for raloxifene. The Multiple Outcomes of Raloxifene Evaluation (MORE) trial of women with osteoporosis has described the efficacy of raloxifene in decreasing vertebral fracture risk over 4 years. The Continuing Outcomes Relevant to Evista((R)) (CORE) trial, designed to assess the effects of raloxifene on breast cancer prevention, is a 4-year continuation of MORE. The skeletal and cardiovascular effects of raloxifene in the CORE study were similar to those observed in MORE. The relative risk of developing breast cancer was significantly decreased in women treated with raloxifene, compared with placebo, after 4 years in MORE and 8 years in the CORE trial. The incidence of uterine bleeding, endometrial hyperplasia and endometrial cancer was similar between raloxifene and placebo after 8 years of treatment. Raloxifene use is associated with a higher incidence of hot flashes and leg cramps, and an increased risk of venous thromboembolic events.

Pharmacogenetics of Tamoxifen Biotransformation Is Associated With Clinical Outcomes of Efficacy and Hot Flashes

Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. 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. 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. 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.

Centrally active nonhormonal hot flash therapies

Given the problems associated with hormonal therapy, and the prominent problem of hot flashes in menopausal women, there is a need for nonhormonal agents to alleviate hot flashes. Several compounds that appear to act on the central nervous system have been investigated. Potential mechanisms for their effects on hot flashes have been described. Bellergal (no longer available on the US market, where it was known as Bellergal-S), a combination preparation sedative that consists of low-dose phenobarbital, ergotamine tartrate, and levorotatory alkaloids of belladonna, is an old agent that was popular approximately 20 years ago; however, there is limited suggestion of efficacy for this agent. Clonidine, an older antihypertensive drug, is another centrally active agent that has been studied. Randomized trials have demonstrated that it clearly works for reducing hot flashes, but the magnitude of efficacy is somewhat limited. Toxicity from this agent limits its utility in the clinic. Methyldopa is another centrally active agent that has been studied but to a more limited degree. It appears to have minimal efficacy and too much toxicity to make it clinically useful. Anecdotal observations from a number of sources suggested that newer antidepressants can alleviate hot flashes. This led to pilot trials of venlafaxine and paroxetine, with results suggesting benefit from both drugs. Subsequently, randomized, placebo-controlled, double-blind clinical trials of venlafaxine, paroxetine, and fluoxetine were conducted. All 3 of these clinical trials demonstrated statistically significant reductions in hot flashes with these newer antidepressants compared with placebo. Pilot trials of citalopram and mirtazapine, 2 other newer antidepressants, have also suggested efficacy. Toxicity evaluations have suggested that these agents are, again, well tolerated by the majority of patients. A recent trial, however, was unable to demonstrate any benefit for fluoxetine or citalopram over a placebo. Anecdotal observations also suggested that gabapentin was helpful for alleviating hot flashes. This led to pilot trials that again suggested efficacy. Subsequently, 2 large placebo-controlled, randomized, double-blind clinical trials were conducted. Both of these demonstrated statistically significant efficacy for gabapentin compared with a placebo. This drug is relatively well tolerated by most patients. Thus, centrally active nonhormonal agents clearly do decrease hot flashes in women. The most efficacious and clinically appropriate agents for use are newer antidepressants and gabapentin. Continued evaluation of the efficacy and toxicity of these agents is ongoing.

Acupuncture for the management of hot flashes in women with early stage breast cancer treated with tamoxifen or an aromatase inhibitor: A pilot study of efficacy, safety and feasibility

703 Background: With the increasing use and duration of endocrine therapies in the treatment of adjuvant breast cancer (BC), the control of vasomotor symptoms is paramount. Complementary and alternative therapies are popular and widely available, but rigorous data evaluating their safety and efficacy are lacking. Given concerns regarding the use of hormone replacement therapy in BC symptom management, other nonhormonal means for treating hot flashes (HF) are required. Based on anecdotal information regarding the efficacy of acupuncture (AP) for treating HF, the trial was developed. Methods: We are evaluating the efficacy of 30-minute AP treatments given for 10 weeks in patients with early BC. Eligible patients had at least 14 HF/week of sufficient severity for therapeutic intervention. Use of antidepressants at a stable dose for at least 3 months was allowed. The primary objective was efficacy as measured by HF frequency (number of HF reported per day) and HF score (average intensity x frequency). The secondary objectives were safety and quality of life. The AP treatment plan was based on 6 recognized Traditional Chinese Medicine patterns of disharmony and treated accordingly by a licensed AP physician. The incidence of HF was recorded with the use of a HF diary for 14 weeks. Results: Data from 14 patients are available from 20 enrolled in this ongoing study. Nine (64%) patients had been treated with tamoxifen and 5 (36%) with an aromatase inhibitor. Six (43%) patients were taking venlafaxine when they started the study. The median HF frequency went from 6.5 (range 3.0–26.0) to 3.0 (range 1.0 to 9.0) for a 54% reduction. The mean HF score went from 19.4 to 8.7 for a 55% reduction. An improvement in HF score was greater that 30% in 11 (79%) patients and greater than 50% in 9 (64%) patients. Grade I bruising and pain were reported at the AP site in 5 patients (36%) and in 1 (7%) respectively. Patients reported improvement in several other symptoms such as night sweats and insomnia. Conclusion: The available data suggest that AP is a safe and effective therapy in BC patients with HF. This study is being sponsored by the AVON foundation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Avon Foundation

Menopausal hot flash frequency changes in response to experimental manipulation of blood glucose.

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). 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. 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). Conditions of fasting may stimulate the trigger mechanism for menopausal hot flashes.

Side effects of androgen deprivation therapy: monitoring and minimizing toxicity

The current trends in favor of androgen deprivation therapy (ADT) for nonmetastatic prostate cancer at the stage of biochemical recurrence or increasing prostate-specific antigen (PSA) raises the issue of exposing otherwise asymptomatic patients to potential side effects over the longer term. Some of these side effects can have deleterious effects on quality of life, and others may contribute to increased risks for serious health concerns associated with aging. Sexual side effects are the most well-recognized adverse effects from ADT and include loss of libido, erectile dysfunction (ED), and hot flashes. Loss of libido is distressing to many men, and they may not pursue treatments for ED. However, for those who do maintain sexual interest, various remedies are available. The incidence of hot flashes, which may not abate over the course of ADT, is close to 80%. Estrogens, progestin megestrol acetate, medroxyprogesterone acetate, venlafaxine, and cyproterone acetate have been shown to alleviate hot flashes and associated symptoms. Physiologic effects, including gynecomastia, changes in body composition (weight gain, reduced muscle mass, increase in body fat), and changes in lipids, are less commonly recognized as side effects of ADT. These may lead to an exacerbation of potentially more serious conditions, such as hypertension, diabetes, and coronary artery disease. Loss of bone mineral density, anemia, and hair changes also may occur. Additionally, both the diagnosis of prostate cancer and the hormonal therapy can cause psychological distress. These side effects need more systematic study in clinical trials. Physicians should be aware of far-reaching consequences of ADT and should incorporate strategies for preventing and managing toxicities into routine practice.

Low-dose mifepristone for uterine leiomyomata

Objective To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms, and to measure side effects. Methods Forty premenopausal women with large, symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study. Uterine volume was measured at bimonthly intervals by sonography. Serum concentrations of hemoglobin levels, follicle-stimulating hormone, and liver enzymes were obtained, and endometrial samples, symptoms, and menstrual bleeding were also assessed. Results Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study. Mean uterine volume shrank by 48% ( P < .001) in the 5-mg group and 49% ( P < .001) in the 10-mg group, a nonsignificant difference. Leiomyoma-related symptoms were comparably reduced in both groups. Amenorrhea occurred in 60–65% of both groups. Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group. Simple endometrial hyperplasia occurred in 28% of all subjects, with no difference between groups. No atypical hyperplasia was noted. Conclusion Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression, improvement in symptoms, and few side effects. Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone.

Low-Dose Mifepristone for Uterine Leiomyomata

In Brief OBJECTIVE To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms, and to measure side effects. METHODS Forty premenopausal women with large, symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study. Uterine volume was measured at bimonthly intervals by sonography. Serum concentrations of hemoglobin levels, follicle-stimulating hormone, and liver enzymes were obtained, and endometrial samples, symptoms, and menstrual bleeding were also assessed. RESULTS Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study. Mean uterine volume shrank by 48% (P < .001) in the 5-mg group and 49% (P < .001) in the 10-mg group, a nonsignificant difference. Leiomyoma-related symptoms were comparably reduced in both groups. Amenorrhea occurred in 60–65% of both groups. Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group. Simple endometrial hyperplasia occurred in 28% of all subjects, with no difference between groups. No atypical hyperplasia was noted. CONCLUSION Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression, improvement in symptoms, and few side effects. Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone. Mifepristone in daily 5- and 10-mg doses administered over 6 months shrinks uterine leiomyomata and ameliorates symptoms, with a low frequency of side effects.

Vaginal rings delivering progesterone and estradiol may be a new method of hormone replacement therapy

Objective: To determine whether a low dose of P delivered together with E 2 from a vaginal ring on a continuous schedule can prevent endometrial proliferation and yield a bleeding pattern dominated by amenorrhea. Design: Longitudinal clinical study. Setting: Three university hospitals. Patient(s): Fifty-five women 45 to 75 years of age, not hysterectomized, with E 2 levels of <20 pg/mL and hot-flash incidence of two or more per day in the past week. Intervention(s): A vaginal ring delivering approximately 150 μg/d of 17β-E 2 and approximately 5 mg/d or approximately 9 mg/d of P used continuously for 4 and 6 months. Main Outcome Measure(s): Endometrial thickness, bleeding pattern, and hot flash incidence. Result(s): Endometrial proliferation was prevented by both P doses. Bleeding incidence decreased. In months 4, 5, and 6, 8 of 12 women had no bleeding. Incidence of hot flashes and night sweats decreased quickly and significantly. Conclusion(s): A vaginal ring delivering E 2 and a low dose of P merits further study as a method for long-term hormone replacement therapy.

Sleep quality, estradiol levels, and behavioral factors in late reproductive age women

OBJECTIVE: To estimate the prevalence of perceived poor sleep in women aged 35–49 years and to correlate sleep quality with levels of gonadal steroids and predictors of poor sleep. METHODS: A cohort of 218 black and 218 white women aged 35–47 years at enrollment (aged 37–49 at final follow-up) with regular menstrual cycles was identified through random digit dialing for a longitudinal study of ovarian aging correlates. Data obtained at four assessment periods, including enrollment, over a 2-year interval were collected between days 1 and 6 (mean = 3.9) of the menstrual cycle. The primary outcome measure was subjects’ rating of sleep quality at each assessment period. Associations of sleep quality with hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral, and demographic variables were examined in bivariable and multivariable analyses. RESULTS: Approximately 17% of subjects reported poor sleep at each assessment period. Significant independent associations with poor sleep included greater incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.08, 2.12, P = .02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P = .04), higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P < .001), greater caffeine consumption (OR 1.25; 95% CI 1.04, 1.49, P = .02), and lower estradiol levels in women aged 45–49 (OR 0.53; 95% CI 0.34, 0.84, P = .006), after adjustment for current use of sleep medications. CONCLUSION: Both hormonal and behavioral factors were associated with sleep quality. Estradiol levels are an important factor in poor sleep reported by women in the 45–49 age group. Further evaluation of estrogen treatment for poor sleep of women 45 years and older is warranted.

PROSPECTIVE EVALUATION OF HOT FLASHES DURING TREATMENT WITH PARENTERAL ESTROGEN OR COMPLETE ANDROGEN ABLATION FOR METASTATIC CARCINOMA OF THE PROSTATE

We evaluated the incidence and frequency of, and distress due to hot flashes after castration therapy with polyestradiol phosphate and complete androgen ablation. A total of 915 men with metastatic prostate carcinoma enrolled in the Scandinavian Prostatic Cancer Group-5 trial study were randomized to intramuscular injections of 240 mg. Polyestradiol phosphate every 2 weeks for 8 weeks followed by monthly subcutaneous injections or complete androgen ablation, that is bilateral orchiectomy or 3.75 mg. of the gonadotropin-releasing hormone analog triptorelin monthly combined with 250 mg. of the antiandrogen flutamide 3 times daily. The incidence and frequency of, and distress due to hot flashes were recorded at regular intervals using a questionnaire. Of the 915 men 901 were evaluated at a median followup of 18.5 months. The incidence of hot flashes was 30.1% and 74.3% in the polyestradiol phosphate and complete androgen ablation groups, respectively (p <0.001). In the polyestradiol phosphate group the frequency of and distress due to hot flashes were significantly lower than in the androgen ablation group. There was complete relief from hot flashes in 50% of the men on polyestradiol phosphate during followup compared with none on androgen ablation. The incidence of hot flashes did not differ in men with and without tumor progression. Endocrine treatment with polyestradiol phosphate induced fewer and less distressing hot flashes than complete androgen ablation. Flashes also disappeared to a greater extent during polyestradiol phosphate than during androgen ablation. The data in this study enable us to provide thorough individual information to patients on the risk and grade of expected distress and duration of hot flashes during polyestradiol phosphate or complete androgen ablation treatment.

Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials

Objective: Raloxifene, a selective estrogen receptor modulator, is estrogen-like in the skeleton and cardiovascular system and antiestrogenic in reproductive tissues. In contrast to estrogens, raloxifene is not indicated for the treatment of hot flashes. This study was designed to examine the characteristics of hot flashes among healthy postmenopausal women participating in osteoporosis prevention trials who were receiving raloxifene or placebo. Methods: Adverse event data from three randomized, double-blind trials ( N=876) comparing raloxifene 60 mg/day with placebo for 30 months were integrated and analyzed. Two of the three trials (one European, two North American) were identically designed and were open to healthy postmenopausal women ages 45 through 60 without regard to prior hysterectomy. The third trial was multinational, was open to women ages 40 through 60, and all enrollees had prior hysterectomy at baseline. Women were questioned in general terms about the occurrence of adverse events at 3–6-month intervals. Treatment-emergent adverse events pertaining to hot flashes were included in the current study. Results: At baseline, 12% of women randomly assigned to placebo and 13% assigned to raloxifene reported prevalent hot flashes. After 30 months, the cumulative incidence of hot flashes was 21% for placebo and 28% for raloxifene ( P=0.022), with the difference in incidence rate confined to the first 6 months of therapy. There was no difference between placebo and raloxifene in reported maximum severity of or early discontinuations as a result of hot flashes (≤3% per group for both outcomes). Among women whose hot flashes had stopped completely during the 30-month study period, the median total duration of the event prior to becoming symptom-free was 246 days for placebo and 205 days for raloxifene. Among all women reporting a hot flash, the extrapolated total duration of hot flashes was the same for women treated with either raloxifene or placebo. No subgroup-by-therapy interactions were detected. Multivariable regression analysis revealed several factors that were independently weakly predictive of hot flashes. Conclusions: Raloxifene slightly affects the incidence but not the natural history of hot flashes in healthy postmenopausal women seeking prevention therapy.