Therapeutic options for the management of hot flashes in breast cancer survivors: an evidence-based review

BACKGROUND: Women with breast cancer may experience treatment-induced menopausal symptoms or natural menopause. Menopausal symptoms, particularly hot flashes, are reported at a high frequency in this group and tend to be more severe, distressing, and of greater duration than in controls. Because of the contribution of sex hormones to breast cancer, the use of hormonal agents for the control of hot flashes is problematic in these women. Safer nonhormonal alternatives are recommended for this patient group. OBJECTIVES: This was a systematic review of the therapeutic options for the treatment of hot flashes in breast cancer survivors. METHODS: MEDLINE was searched from 1990 to July 2006 using the disease-specific term breast neoplasms and the subheadings menopause and hot flashes. EMBASE was searched from 1990 to March 2006 using the disease-specific subject headings breast tumor/ breast cancer and menopause and the key word hot flashes. The reference lists of the identified articles and relevant review articles were examined for additional publications. Pertinent articles and abstracts of large randomized controlled trials focusing on the treatment of hot flashes in breast cancer survivors were selected for review. Pilot studies were excluded. RESULTS: A number of nonpharmacologic approaches are available for the treatment of hot flashes in breast cancer survivors, although they appear to be of limited effectiveness. Complementary alternative medicine therapies and vitamin E have been found to have modest effectiveness at best, and data on their long-term safety are not available. Centrally active agents such as the antidepressants venlafaxine and paroxetine and the anti seizure agent gabapentin have shown clinical effectiveness and appear to be reasonably well tolerated in this population. CONCLUSIONS: Centrally active agents (eg, venlafaxine, paroxetine, gabapentin) are regarded as the most promising nonhormonal treatments for hot flashes in breast cancer survivors. Nonpharmacologic and complementary alternative medicine therapies have limited effectiveness.     

Pilot evaluation of gabapentin for treating hot flashes

OBJECTIVE: To obtain pilot prospective data regarding the efficacy and tolerability of gabapentin for alleviating hot flashes. PATIENTS AND METHODS: This prospective single-arm clinical trial was conducted between July 26, 2001, and November 30, 2001. Patients underwent a baseline week and then 4 weeks of gabapentin treatment, with increasing doses during the first 3 weeks, from 300 to 600 to 900 mg/d. Data were obtained primarily from patient-completed questionnaires. RESULTS: Data from 20 evaluable women (of 24 entered in the trial) were available. Four patients discontinued use of gabapentin for perceived drug-related untoward symptoms, primarily related to light-headedness and dizziness. The 16 patients who completed this clinical trial had a mean reduction in hot flash frequency, in the fourth treatment week compared to the baseline week, of 66%. Their corresponding hot flash score (frequency times average severity) reduction was 70%. Additionally, patients who completed the 4 treatment weeks had a strong tendency to report an improvement in several other symptoms. CONCLUSION: Although a double-blind placebo-controlled clinical trial should be conducted to better elucidate the efficacy and toxicity of gabapentin in patients with hot flashes, the available data suggest that gabapentin is a reasonable treatment to consider in patients with hot flashes if they do not wish to use hormonal therapy.     

Gabapentin for hot flashes in prostate cancer

OBJECTIVE: To report a case of successful treatment of refractory hot flashes with gabapentin in a patient with prostate cancer who was receiving combination antiandrogen and gonadotropin hormone-releasing hormone (GnRH) analog therapy. CASE SUMMARY: A 70-year-old white man with a history of advancing prostate cancer experienced disabling hot flashes from combination therapy with the antiandrogen bicalutamide and the GnRH analog goserelin acetate. He failed to respond to clonidine 0.1 mg twice daily, megestrol acetate 40 mg/d, diethylstilbestrol 1 mg/d, and venlafaxine 25 mg twice daily. The patient was then treated with gabapentin 600 mg once daily, at which time he experienced near-complete resolution of his symptoms. DISCUSSION: This case supports a previous report of the marked improvement in severity and duration of hot flashes associated with antiandrogen or GnRH analog therapy in prostate cancer. The mechanism by which gabapentin reduces hot flashes is unknown. CONCLUSIONS: Hot flashes resulting from antiandrogen or GnRH analog therapy are often difficult to treat and leave many patients disabled. Gabapentin has been shown to markedly reduce the severity, frequency, and duration of these hot flashes. Controlled trials are necessary to evaluate gabapentin against other therapeutic modalities.     

A pilot study of magnetic therapy for hot flashes after breast cancer

The purpose of this randomized placebo-controlled crossover pilot study was to evaluate the effectiveness and acceptability of magnetic therapy for hot flashes among breast cancer survivors. Participants completed a 24-hour baseline hot-flash monitoring session, wore the magnetic devices or placebo for 3 days, completed an after-treatment hot-flash monitoring session, experienced a 10-day washout period, and then crossed over to the opposite study arm. Magnetic devices and placebos were placed on 6 acupressure sites corresponding to hot-flash relief. Complete data were available from 11 survivors of breast cancer. Results indicated magnetic therapy was no more effective than placebo in decreasing hot-flash severity, and contrary to expectations, placebo was significantly more effective than magnets in decreasing hot-flash frequency, bother, interference with daily activities, and overall quality of life. Implications for clinical practice and future research include the need to explore alternative interventions aimed at alleviating hot flashes in this population.     

Pilot evaluation of paroxetine for treating hot flashes in men

OBJECTIVE: To provide prospective information on the potential utility of paroxetine for treating hot flashes In men receiving androgen ablation therapy for prostate cancer. PATIENTS AND METHODS: Men with symptomatic androgen ablation therapy-related hot flashes were entered into this clinical trial between August 2001 and October 2003. After a baseline week of documentation of the frequency of hot flashes, patients were assigned to receive paroxetine; the initial dosage was 12.5 mg/d, and it was increased to 37.5 mg/d over the ensuing 4 weeks. RESULTS: Of the 24 patients in whom medication was initiated, 18 completed the 5-week study. In these patients, the median frequency of hot flashes decreased from 6.2 per day during the baseline week to 2.5 per day during the last study week. Hot flash scores (frequency x mean severity) during the same period decreased from 10.6 per day to 3.0 per day. Overall, paroxetine was well tolerated by most patients. CONCLUSION: The results from this trial suggest that paroxetine Is an effective agent for diminishing hot flashes in men receiving androgen ablation therapy.     

Qigong for women with breast cancer: An updated systematic review and meta-analysis

ObjectiveThe purpose of this review was to evaluate the effectiveness of Qigong in improving the quality of life and relieving fatigue, sleep disturbance, and cancer-related emotional disturbances (distress, depression, and anxiety) in women with breast cancer.MethodsThe PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Sinomed, Wanfang, VIP, and China National Knowledge Infrastructure databases were searched from their inceptions to March 2020 for controlled clinical trials. Two reviewers selected relevant trials that assessed the benefit of Qigong for breast cancer patients independently. A methodological quality assessment was conducted according to the criteria of the 12 Cochrane Back Review Group for risk of bias independently. A meta-analysis was performed by Review Manager 5.3.ResultsThis review consisted of 17 trials, in which 1236 cases were enrolled. The quality of the included trials was generally low, as only five of them were rated high quality. The results showed significant effectiveness of Qigong on quality of life (n = 950, standardized mean difference (SMD), 0.65, 95 % confidence interval (CI) 0.23–1.08, P = 0.002). Depression (n = 540, SMD = −0.32, 95 % CI −0.59 to −0.04, P = 0.02) and anxiety (n = 439, SMD = −0.71, 95 % CI −1.32 to −0.10, P = 0.02) were also significantly relieved in the Qigong group. There was no significant benefit on fatigue (n = 401, SMD = −0.32, 95 % CI 0.71 to 0.07, P = 0.11) or sleep disturbance relief compared to that observed in the control group (n = 298, SMD = −0.11, 95 % CI 0.74 to 0.52, P = 0.73).ConclusionThis review shows that Qigong is beneficial for improving quality of lifeand relieving depression and anxiety; thus, Qigong should be encouraged in women with breast cancer.     

Acupuncture for treating hot flushes in men with prostate cancer: a systematic review

Goals of work  The goal of the study was to assess the effects of acupuncture as a treatment for hot flushes in prostate cancer (PC) patients. Materials and methods  The literature was searched using 14 databases with dates ranging from their inceptions to December 2008 and without language restrictions. All clinical studies of any type of acupuncture in PC patients were included. Their main outcome measures had to be vasomotor symptoms. Their methodological quality was assessed using the modified Jadad score. Results  Six studies met all the inclusion criteria. One randomised clinical trial compared the effects of manual acupuncture with acupuncture plus electro-acupuncture. The other five studies were uncontrolled observational studies and therefore had limitations. Conclusion  The evidence is not convincing to suggest acupuncture is an effective treatment for hot flush in patients with PC. Further research is required to investigate whether acupuncture has hot-flush-specific effects.     

The association between nocturnal hot flashes and sleep in breast cancer survivors

This study examined the relationship between objectively measured nocturnal hot flashes and objectively measured sleep in breast cancer survivors with insomnia. Twenty-four women who had completed treatment for non-metastatic breast cancer participated. All were enrolled in a study of cognitive–behavioral treatment for chronic insomnia. Nocturnal hot flashes and sleep were measured by skin conductance and polysomnography, respectively. The 10-minute periods around hot flashes were found to have significantly more wake time, and more stage changes to lighter sleep, than other 10-minute periods during the night. Nights with hot flashes had a significantly higher percentage of wake time, a lower percentage of Stage 2 sleep, and a longer REM latency compared to nights without hot flashes. Overall, hot flashes were found to be associated with less efficient, more disrupted sleep. Nocturnal hot flashes, or their underlying mechanisms, should be considered as potential contributors to sleep disruption in women with breast cancer who report poor sleep.     

A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients

Background  

We tested if magnesium would diminish bothersome hot flashes in breast cancer patients.     

The influence of breast cancer treatment on the occurrence of hot flashes

Approximately 65% of women report hot flashes (HFs) during or following breast cancer treatment. However, few studies have compared the occurrence of vasomotor symptoms according to the type of adjuvant treatment received, and little is known about other risk factors for HFs among this population. This longitudinal study aimed to: 1) compare the frequency and severity of HFs in breast cancer patients according to treatment regimen; 2) evaluate the potential contribution of hormone therapy on the frequency and severity of HFs; and 3) identify other potential risk factors for HFs in breast cancer patients. Forty-one women receiving radiation therapy and chemotherapy and 40 women receiving radiation therapy without chemotherapy completed a daily diary of HFs for seven days, and the vasomotor scale of the Menopause-Specific Quality of Life Questionnaire prior to and following each type of treatment, and at a three-month follow-up evaluation. Z-scores and percentiles computed from an age-matched control group (n=45) without a history of cancer revealed a higher frequency and severity of HFs among breast cancer patients compared with control participants. Chemotherapy and hormone therapy were both associated with increased HFs. Past use of hormone replacement therapy (HRT) and a lower body mass index (BMI) were significantly associated with more severe vasomotor symptoms. This study highlights the clinical significance of HFs among breast cancer patients, particularly in women receiving chemotherapy and hormone therapy, and the necessity to offer effective therapeutic strategies to relieve HFs in this population.     

Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations

Purpose

Breast cancer patients frequently report hot flashes. Given that conventional hormone replacement therapy is generally contraindicated for them, other therapeutic modalities must be considered. The purpose of this review was to develop evidence-based recommendations on non-hormonal pharmacological interventions, including natural health products, for managing hot flashes in women undergoing treatment for breast cancer or with a history of breast cancer.

Methods

A review of the scientific literature published between January 2000 and December 2011 was performed. A total of 26 randomized trials were identified.

Results

Studies showed that serotonin–norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, antihypertensives and anticonvulsants significantly reduced the frequency and severity of hot flashes in breast cancer patients.

Conclusions

Considering the evidence available to date, the CEPO recommends the following: (1) for breast cancer patients being treated with tamoxifen: (a) the use of venlafaxine, citalopram, clonidine, gabapentin and pregabalin be considered effective in treating hot flashes and (b) the use of paroxetine and fluoxetine be avoided, given that they may reduce the efficacy of tamoxifen; (2) for breast cancer patients not being treated with tamoxifen: (a) the use of venlafaxine, paroxetine, citalopram, clonidine, gabapentin and pregabalin be considered effective in treating hot flashes and (b) fluoxetine not be used to treat hot flashes, given that there is insufficient evidence for its therapeutic efficacy and (3) for breast cancer survivors, sertraline, phytoestrogens, black cohosh and St. John’s wort not be used to treat hot flashes.     

Treating hot flashes in breast cancer survivors: a review of alternative treatments to hormone replacement therapy

As the number of breast cancer survivors continues to grow, factors associated with quality of life are receiving increased clinical and research attention. This attention is imperative given the aftermath of psychological and physiologic side effects that commonly result from a cancer diagnosis and cancer-related treatments, including menopausal symptoms. Hot flashes, the most prevalent of these symptoms, have been shown to significantly decrease quality of life in women. Although manageable with hormone replacement therapy (HRT), hot flashes often are especially problematic in breast cancer survivors, a population that typically is not treated with HRT because of controversial evidence of a relationship among estrogen and/or progesterone and breast cancer recurrence and mortality. Furthermore, hot flashes commonly are more severe in premenopausal women who experience acute menopause as a result of chemotherapy treatment. In recent years, several treatment alternatives to HRT have been investigated. Given the significant number of women affected by breast cancer and the negative impact that hot flashes can have on their quality of life, this article reviews alternatives to HRT for reducing hot flash symptoms in breast cancer survivors.     

Impact of hot flashes on quality of life among postmenopausal women being treated for breast cancer

Hot flashes are among the most commonly reported symptoms among women who have completed treatment for breast cancer. Relatively little is known, however, about hot flashes among women while they are undergoing breast cancer treatment. The present study investigated the prevalence and severity of hot flashes of women during chemotherapy and radiotherapy for breast cancer. We also sought to identify the medical, demographic, and treatment correlates of hot flashes during treatment and to document the impact of hot flashes on quality of life. Seventy postmenopausal women with breast cancer completed a self-report questionnaire packet during chemotherapy and radiotherapy. Forty percent (n = 28) reported hot flashes during the week prior to assessment. Of the 28 women endorsing hot flashes, 25% (n = 7) rated them as severe, 39% (n = 11) rated them as moderate, and 36% (n = 10) rated them as mild. Women with hot flashes were significantly (p < 0.05) younger and reported significantly (p < 0.001) more fatigue, poorer sleep quality, and poorer physical health compared to women without hot flashes. Multivariate analyses revealed that, even after controlling for relevant medical, demographic, and treatment variables, the prevalence of hot flashes significantly (p < 0.05) predicted poorer sleep quality, more fatigue, and worse physical health. The results indicate that hot flashes are experienced by a sizable percentage of postmenopausal breast cancer patients as they undergo treatment. Hot flashes during cancer treatment appear to have a negative impact upon patient quality of life that may be due, in part, to fatigue and interference with sleep. Future research should seek to evaluate interventions to relieve hot flashes during breast cancer treatment as a means of improving patient quality of life.     

An updated meta-analysis: repetitive transcranial magnetic stimulation for treating tinnitus

ObjectiveTo undertake an updated meta-analysis to obtain more evidence from randomized controlled trials (RCTs) to assess the effect of repetitive transcranial magnetic stimulation (rTMS) for the treatment of tinnitus.MethodsPubMed®, Embase®, Web of Science, Cochrane Database of Systematic Reviews, CBM, CNKI and Wanfang were searched for RCTs from inception up to March 2020. Studies meeting the eligibility criteria were included in the meta-analysis. The mean difference was calculated and the effect size was evaluated using a Z test.ResultsThe analysis included 12 randomized sham-controlled clinical trials with a total of 717 participants. Active rTMS was superior to sham rTMS in terms of the short-term and long-term effects (6 months) on the tinnitus handicap inventory scores, but an immediate effect was not significant. There was no significant immediate effect on the tinnitus questionnaire (TQ) and Beck depression inventory (BDI) scores.ConclusionsThis meta-analysis demonstrated that rTMS improved tinnitus-related symptoms, but the TQ and BDI scores demonstrated little immediate benefit. Future research should be undertaken on large samples in multi-centre settings with longer follow-up durations.     

Depomedroxyprogesterone acetate for hot flashes

To evaluate the efficacy of a long-acting preparation of medroxyprogesterone acetate for hot flash management, 3 men receiving androgen ablation therapy for prostate cancer and 15 women with a history of breast cancer were treated as part of clinical practice with three biweekly intramuscular injections of 500 mg depomedroxyprogesterone. A review of hot flash diaries and patient charts were completed to evaluate the effectiveness and tolerability of these injections for managing hot flashes. Treatment was associated with an approximate 90% decrease in hot flashes (95% CI 82–97%). Daily hot flash frequency decreased from a mean of 10.9 on the first day of treatment (95% CI 8.0–13.8 hot flashes per day) to a mean of 1.1 hot flashes 6 weeks later (95% CI 0.5–1.8 hot flashes) and to a mean of 0.7 hot flashes 12 weeks following therapy initiation (95% CI 0.1–1.2). Improvement in the hot flashes remained for months after discontinuing the injections in many patients. Reported side effects were minimal. This experience suggests that treatment with depomedroxyprogesterone may be an effective and well-tolerated option for the treatment of hot flashes.