Management Of Hot Flashes Research Articles

Use of Antidepressants for Management of Hot Flashes

A growing body of evidence suggests that antidepressant therapies, particularly selective serotonin reuptake inhibitors and venlafaxine, are effective in the management of hot flash symptoms. Several of these agents have the support of the American College of Obstetricians and Gynecologists and the North American Menopause Society. To review the literature on antidepressants for the treatment of hot flashes in women, we searched the PubMed, International Pharmaceutical Abstracts, and MEDLINE databases from inception through May 2009. All publication types that included human participants and that were published in English were eligible for review. These articles, relevant abstracts, and additional references were used to collect pertinent data. Although initial small pilot trials were conducted solely in breast cancer survivors, additional studies have been conducted both in breast cancer survivors and in relatively healthy menopausal women. Data on the benefits with many of these agents are conflicting. Venlafaxine and paroxetine have been studied more extensively than any of the other antidepressants and are more consistent in effectively reducing the frequency and severity of hot flashes, based on these study results. Desvenlafaxine, sertraline, fluoxetine, and citalopram should be considered second- or third-line options if patients fail therapy with or cannot tolerate venlafaxine or paroxetine, based on the current published data. Duloxetine, escitalopram, fluvoxamine, and mirtazapine should be reserved as last-line therapy until more rigorous studies are conducted assessing their use in the management of hot flashes.

Hot flash placebo responses: Related to baseline hot flash frequency?

9628 Background: As multiple treatments have been studied for the management of hot flashes in randomized, controlled trials, hot flash placebo responses have been quite variable across trials. Based on observations of trial reports, it was hypothesized that the magnitude of placebo effect might correlate with the number of baseline hot flashes in different studies. The current project examines the effect of the baseline hot flash frequency required for study participation and also the actual number of baseline hot flashes observed as these individually relate to the eventual reductions of hot flash frequency observed in patients receiving placebos. Methods: Data were collected from placebo-controlled, double-blinded, randomized trials, identified by a PubMed search, which reported hot flash frequency at baseline, 4–6 weeks and 12 weeks. Trials were excluded if they had less than 20 participants completing the placebo arm. Data gathered, in each study, included the number of hot flashes required to enroll in the study, the average hot flash number during the baseline period, and the hot flash changes in the placebo arms of each study (percent reduction from the baseline period). A simple statistical analysis was conducted in a descriptive fashion since standard deviation was not available in many trials. Scatter plots and Pearson's correlation coefficients demonstrated the relationships between the placebo hot flash percent reduction from baseline and both the minimum required number of hot flashes at baseline, and the mean number of hot flashes at baseline. Results: 45 trials with 49 placebo arms were included in this analysis. A significant positive correlation was seen between the number of hot flashes required to enroll in a study and the percent reduction of hot flashes from baseline at 4–6 weeks (Rho = 0.481, p = 0.003). There was also a significant positive correlation between the number of hot flashes at baseline and the percent reduction of hot flashes from baseline at 4–6 weeks (Rho = 0.481, p= 0.002) and at 12 weeks (Rho = 0.573, p= 0.003). Conclusions: These data support that higher baseline hot flash enrollment requirements and also higher baseline hot flash frequencies are associated with an increased placebo response. No significant financial relationships to disclose.

A phase III randomized, double-blind, placebo-controlled trial of gabapentin in the management of hot flashes in men (N00CB)

IntroductionHot flashes represent a significant problem in men undergoing androgen deprivation therapy. Materials and methodsVia a prospective, double-blind, placebo-controlled clinical trial, men with hot flashes, on a stable androgen deprivation therapy program for prostate cancer, received a placebo or gabapentin at target doses of 300, 600, or 900 mg/day. Hot flash frequencies and severities were recorded daily during a baseline week and for 4 weeks while the patients took the study medication. ResultsIn the 214 eligible patients who began the study drug on this trial, comparing the fourth treatment week to the baseline week, mean hot flash scores decreased in the placebo group by 4.1 units and in the three increasing dose gabapentin groups by, 3.2, 4.6, and 7.0 units. Comparing the three combined gabapentin arms to the placebo arm did not result in significant hot flash differences. Wilcoxon rank-sum P values for change in hot flash scores and frequencies after 4 weeks of treatment were 0.10 and 0.02, comparing the highest dose gabapentin arm to the placebo arm, respectively. The gabapentin was well tolerated in this trial. ConclusionThese results support that gabapentin decreases hot flashes, to a moderate degree, in men with androgen ablation-related vasomotor dysfunction.

Oxybutynin for refractory hot flashes in cancer patients

There is little information available on the treatment of hot flashes in patients refractory to pharmaceutical interventions. Anecdotal evidence led to the use of oxybutynin for the management of hot flashes in refractory cancer patients; therefore, we performed a retrospective chart review of such patients to determine the effect of oxybutynin in treating hot flashes and to observe the side effects of the drug in these patients. A prospective database of all patients treated for hot flashes was started in July 2004 and was retrospectively analyzed as of March 2006. Also included were individual charts preceding July 2004. Fifty-two patient charts were examined. Demographic information was obtained along with baseline severity and frequency of hot flashes, dose and duration of treatment with oxybutynin, patient response to oxybutynin, and side effects. More than 90% of patients analyzed were refractory to hot flash treatments before starting oxybutynin. Seventy percent of patients showed a partial or excellent response to oxybutynin. The duration of oxybutynin use ranged from 2 weeks to 5 years with more than half of patients currently on oxybutynin or taking oxybutynin for longer than 6 months. Of those patients who experienced an excellent or partial response to treatment, 12% stopped because of documented oxybutynin-related side effects within 4 weeks. Oxybutynin seems promising in the management of hot flashes with tolerable side effects in the majority of refractory patients. A placebo-controlled, randomized study is being developed to look more closely at the effectiveness of oxybutynin in reducing hot flashes.

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

Background: Women with breast cancer may experiencetreatment-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 thetherapeutic 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 treatrment 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 antiseizure agent gabapentin have shown clinical effectiveness and appear to be reasonably well tolerated in this population. Conclusions: Centrally active agents (eg, venlafaxme, paroxetine, gabapentin) are regarded as the most promising nonhormonal treatments for hot flashes in breast cancer survivors. Nonpharmacologic and complementarylalternative medicine therapies have limited effectiveness.

Pilot Evaluation of Flaxseed for the Management of Hot Flashes

The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.

Phase III Trial of Gabapentin Alone or in Conjunction With an Antidepressant in the Management of Hot Flashes in Women Who Have Inadequate Control With an Antidepressant Alone: NCCTG N03C5

Despite the utility of newer antidepressants for alleviating hot flashes, antidepressants do not work adequately enough in many patients. Gabapentin is a nonhormonal agent that also can reduce hot flashes. No data have been available to address whether the combination of both agents would more effectively alleviate hot flashes, compared with gabapentin alone, in patients with inadequate hot flash control with an antidepressant alone. This was a randomized trial in which 118 patients with inadequate hot flash control on an antidepressant were randomly assigned to receive both an antidepressant and gabapentin versus being weaned off the antidepressant and receiving gabapentin alone. Patients were observed for 5 weeks (including a baseline week in which patients continued on their current antidepressant without gabapentin) during which time they completed validated daily hot flash diaries. Ninety-one patients provided complete data at the 5-week assessment. Regardless of whether or not the antidepressant was continued when gabapentin was started, there was an approximately 50% median reduction in hot flash frequencies (54%; 95% CI, 34% to 70% for combined treatment v 49%; 95% CI, 26% to 58% for gabapentin alone) and scores (56%; 95% CI, 26% to 71% for combined treatment v 60%; 95% CI, 33% to 73% for gabapentin alone). Gabapentin seems to decrease hot flashes by approximately 50% in women with inadequate hot flash control who were using an antidepressant. This study saw no significant additional hot flash reduction from continuation of the antidepressant.

Phase III Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Black Cohosh in the Management of Hot Flashes: NCCTG Trial N01CC1

Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.

Symptoms and Treatment in Cancer Therapy-Induced Early Menopause

Young women with breast cancer often experience early menopause as a result of the therapy for their malignant disease. The sudden occurrence of menopause resulting from chemotherapy, oophorectomy, radiation, or gonadal dysgenesis frequently results in hot flashes that begin at a younger age and may occur at a greater frequency and intensity than hot flashes associated with natural menopause. Hormone therapy relieves symptoms effectively in 80%-90% of women who initiate treatment. This therapy, however, is generally contraindicated in estrogen-dependent cancers, such as breast cancer, because of the potentially increased risk for recurrence. Many agents have been investigated as potential means for alleviating hot flashes in survivors of breast cancer, such as progestagens, clonidine, gabapentin, and anti-depressants. Several complementary and alternative medicines frequently used by patients have also been studied. These include black cohosh, phytoestrogens, homeopathy, vitamin E, acupuncture, and behavior strategies. To support the use of one of more of these nonpharmacological or pharmacological options in the treatment of hot flashes in breast cancer patients, more evidence from well-controlled clinical trials is needed. In particular, soundly based scientific research with complementary and alternative medicine therapies is lacking. Pharmacological treatments appear to be more beneficial than nonpharmacological treatments. This article reviews the current literature to assess the epidemiology and diagnosis of hot flashes and the nonpharmacological and pharmacological options for the treatment of hot flashes, in breast cancer patients in particular. When specific treatment options have not been evaluated in breast cancer patients specifically, published data on the management of hot flashes with this modality in healthy postmenopausal women are described.

Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Sertraline (Zoloft) for the Treatment of Hot Flashes in Women with Early Stage Breast Cancer Taking Tamoxifen

We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.

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.

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

Breast cancer accounts for 33% of all incident cancers in women in North America, and there are an estimated >2 million breast cancer survivors in the United States today. Ovarian hormones are intimately involved in the initiation and promotion of breast cancer development, with targeted endocrine therapies being the most widely used as anticancer treatment. It is not surprising that these treatments frequently cause persistent menopausal symptoms in breast cancer survivors. In addition, adjuvant chemotherapy often induces premature menopause in younger patients with breast cancer. Some women at high risk for the development of breast cancer (e.g., precancerous breast disease, carriers of deleterious hereditary predisposition genes) experience vasomotor symptoms as a result of tamoxifen therapy or preventive oophorectomy. Clinical management of menopausal symptoms in these settings is complicated by the relative prohibition of hormonal therapies and the fact that breast cancer-directed therapies often exacerbate these menopausal symptoms. Thus, this special population of women requires unique management strategies and deserves separate consideration.

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

Newer Antidepressants and Other Nonhormonal Agents for the Treatment of Hot Flashes

The reluctance to use estrogen in breast cancer survivors with hot flashes has extended to its use in healthy women since the 2002 publication of the Women's Health Initiative study. This article reviews the clinical development of nonhormonal agents as alternatives to hormonal therapy for the management of hot flashes.

Influence of hot flashes on quality of life in patients with prostate cancer treated with androgen deprivation therapy.

We surveyed patients with prostate cancer treated with androgen deprivation therapy to examine the influence of hot flashes on quality of life (QOL). Fifty-five outpatients with prostate cancer (M0, 39; M1, 16) treated with androgen deprivation therapy (castration, 15; castration and antiandrogen, 40) were enrolled in this study. Mean duration of androgen deprivation therapy was 21 months (2-91 months). The patients were still being treated with androgen deprivation therapy at the time of the survey. The functional assessment of cancer therapy (FACT) was used as a QOL questionnaire for outpatients with prostate cancer treated with androgen deprivation therapy. Hot flash assessments were used to document the number and severity (mild, moderate, and severe) of daily hot flashes. The patients prescribed fluvoxamine maleate were reassessed for hot flashes 2 weeks after the prescription. Thirty-two of the 55 patients (58.2%) suffered from hot flashes. Hot flashes deteriorated the physical well-being subscale of QOL in patients with prostate cancer treated with androgen deprivation therapy (P = 0.043). There was a significant relationship between the desire to be treated for hot flashes and the hot flash assessments (P = 0.038). Fluvoxamine maleate was significantly effective in reducing hot flashes (P = 0.001). Hot flashes had adverse effects on the patients' physical status and deteriorated the patients' QOL. New treatment options such as fluvoxamine maleate might help simplify the often difficult management of hot flashes in patients with prostate cancer treated with androgen deprivation therapy.

Management of hot flashes in breast cancer survivors and men with prostate cancer.

Hot flashes are a significant complaint among many breast cancer survivors and many men undergoing androgen deprivation therapy for prostate cancer. Several therapeutic approaches are available to the suffering man or woman. Many of these individuals have tried nonpharmacologic and nonconventional approaches. However, most nonpharmacologic treatments have not been compared with placebo or were not more effective than placebo in prospective, randomized clinical trials. The most effective nonhormonal treatments for hot flashes include agents from the selective serotonin or noradrenergic reuptake inhibitor (SSRI/SNRI) family. Paroxetine, 10 mg/d, or venlafaxine, 37.5 mg/d, are reasonable initial dosages, and if symptoms do not improve within a week or two, the dosage can be doubled. Gabapentin appears to provide similar benefits, but direct comparisons have not been reported. Because of the strong association between gonadal hormones and breast and prostate cancer, the use of hormonal agents to treat hot flashes in these patients has been limited. However, such hormonal therapies as depomedroxyprogesterone acetate can be prescribed for an informed individual who experiences bothersome symptoms despite nonhormonal treatments.

Hot flashes in breast cancer survivors.

Hot flashes can be a major problem for patients with a history of breast cancer. The precipitation of menopause in premenopausal women who undergo chemotherapy for breast cancer can lead to the rapid onset of hot flash symptoms that are more frequent and more severe than those associated with natural menopause. In addition, tamoxifen, historically the most commonly prescribed pharmacologic agent for the treatment of breast cancer, is associated with hot flashes in more than 50% of its users. Although estrogen relieves hot flashes in 80-90% of women who initiate treatment, its use in women with a history of breast cancer is controversial, and most physicians in the community will not use this treatment modality. In addition, the results of the long-awaited Women's Health Initiative study and other recent studies suggest that long-term estrogen therapy should not be recommended for most women for a variety of reasons. However, hot flashes in breast cancer survivors should no longer be considered untreatable, as there are many pharmacologic and nonpharmacologic treatments that can help alleviate this problem. This article reviews the current strategies for the management of hot flashes in breast cancer survivors and the evidence supporting their use.

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.

Hot flashes: aetiology and management.

Menopause, an event often accompanied by symptoms such as hot flashes, can have a significant impact on a woman's quality of life. A majority of women will experience hot flashes at some point in their life, given a normal life span. Despite multiple theories, the exact pathophysiology of hot flashes is not yet known. Many types of treatment options exist for women with hot flashes, from hormonal and nonhormonal pharmacological therapies to nonpharmacological interventions. Choosing the best treatment option for specific women involves knowledge of the risks and benefits of each treatment. Hormones (estrogen and/or progesterone, or tibolone alone) are still the most effective option available, resulting in an 80 to 90% reduction in hot flashes. The best nonhormonal treatment to date is in the class of newer antidepressants that comprises various selective reuptake inhibitors; for example, venlafaxine provides about a 60% reduction in hot flashes. This article provides evidence-based information about available treatment options for hot flash management, with special consideration of populations such as breast cancer survivors.

Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial

Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer. Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks. 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group. Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.