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PubMedDate not supplied

Acupuncture for hot flashes: a randomized, sham-controlled clinical study.

OBJECTIVE: Hot flashes are a significant problem in women going through the menopausal transition that can substantially affect quality of life. The world of estrogen therapy has been thrown into turmoil with the recent results of the Women's Health Initiative trial report. Pursuant to a growing interest in the use of alternative therapies to alleviate menopausal symptoms and a few pilot trials that suggested that acupuncture could modestly alleviate hot flashes, a prospective, randomized, single-blind, sham-controlled clinical trial was conducted in women experiencing hot flashes. DESIGN: Participants, after being randomized to medical versus sham acupuncture, received biweekly treatments for 5 weeks after a baseline assessment week. They were then followed for an additional 7 weeks. Participants completed daily hot flash questionnaires, which formed the basis for analysis. RESULTS: A total of 103 participants were randomized to medical or sham acupuncture. At week 6 the percentage of residual hot flashes was 60% in the medical acupuncture group and 62% in the sham acupuncture group. At week 12, the percentage of residual hot flashes was 73% in the medical acupuncture group and 55% in the sham acupuncture group. Participants reported no adverse effects related to the treatments. CONCLUSIONS: The results of this study suggest that the used medical acupuncture was not any more effective for reducing hot flashes than was the chosen sham acupuncture.

Acupuncture Therapy↗

PubMed1981

Climacteric hot flash.

No data are available on either quantitative or qualitative aspects of the climacteric hot flash, yet the phenomenon is widely treated despite unknown aetiology. A basic assumption of this study was that a more complete understanding and description of women with hot flashes would identify alternatives to oestrogens used by women for relief of the hot-flash symptom. An exploratory study was undertaken to answer the question: Who is the woman who has hot flashes and what are the characteristics of the hot flashes? The methodology employed was daily self-report by subjects of hot-flash frequency, duration, trigger, origin, spread, intensity and method of coping with it. Analysis of 20 randomly-selected 2 wk self-report record cards revealed no hot-flash pattern among women. A total of 1041 hot flashes were reported. Mean duration of the hot flash was 3.31 min (range 5 sec to 60 min). Neither hot flash origin nor spread was restricted to the upper body in all subjects. Subjects ranked their hot flash as either mild, moderate or severe. Coping strategies used by subjects (external and internal cooling methods) appeared to be related to both duration and severity of the hot flash.

Adult↗

PubMed1984

The effects of naloxone on hot flashes and gonadotropin secretion in postmenopausal women.

Hot flashes have a close temporal relationship with the initiation of LH pulses, suggesting that factors stimulating gonadotropin release are involved in the mechanism of this disturbance. It has been reported that the opiate antagonist naloxone acutely blocked subjective hot flashes, a seemingly paradoxical effect, since the use of this agent in premenopausal women increases the magnitude and frequency of LH pulses. We, therefore, studied the effects of naloxone in 16 postmenopausal women with frequent hot flashes using continuous recordings of finger temperature and skin resistance as objective indices of flushing and perspiration, respectively. After baseline recordings, the subjects were randomized into equal groups, and the recordings were repeated during 8-h infusion of either saline or naloxone (22 micrograms/min). Serum gonadotropin levels were measured at 15-min intervals before and during the last 4 h of the infusion. Naloxone did not change the rate of objectively measured hot flashes, mean serum LH or FSH levels, or the frequencies or amplitudes of gonadotropin pulses. These data suggest that there is a very low input of endogenous opiates on gonadotropin secretion in postmenopausal women and that opioid peptides do not play a role in the initiation of the postmenopausal hot flash.

Aged↗

PubMedDate not supplied

Circadian rhythm of objectively recorded hot flashes in postmenopausal breast cancer survivors.

OBJECTIVE: Similar to the circadian rhythm of core body temperature, hot flashes have been found to exhibit a circadian rhythm in healthy, naturally postmenopausal women, with a peak in frequency at 18:25 h. However, to date, no studies have evaluated whether this same pattern is found among breast cancer survivors reporting hot flashes. DESIGN: Daily hot flash frequencies were measured among 21 postmenopausal breast cancer survivors using validated 24-h sternal skin conductance monitoring. RESULTS: Hot flashes were noted in all women, ranging in frequency from 1 to 30 per 24-h period. A majority of the sample (86%) experienced > or = 1 nighttime hot flash, with 48% exhibiting > or = 3 but < or = 7 nighttime hot flashes. For the total sample, a modest circadian rhythm was noted with a peak in hot flash frequency occurring at 16:10 h. However, significant variability was observed across individual women, and, as a whole, breast cancer survivors demonstrated distorted to obliterated rhythms. CONCLUSIONS: Data suggest that hot flashes in postmenopausal breast cancer survivors do not follow the same circadian pattern as previously seen in healthy, naturally postmenopausal women. Findings have implications for (1) understanding the potential for sleep disturbances and fatigue in breast cancer survivors experiencing hot flashes, and (2) future research examining circadian rhythms of core body temperature and hot flashes in breast cancer survivors.

Body Temperature↗

PubMedDate not supplied

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.

Adult↗

PubMedDate not supplied

Hot flashes in the late reproductive years: risk factors for Africa American and Caucasian women.

Hot flashes are a primary reason that midlife women seek medical care, but there is little information about the onset or the predictors of hot flashes in the years before the menopause. This study examines women's experience of hot flashes in the late reproductive years, comparing African American and Caucasian women, and identifies hormonal, behavioral, and environmental risk factors for hot flashes associated with ovarian aging. Data are from a population-based prospective cohort study of ovarian aging in women who were ages 35--47, in general good health, and had regular menstrual cycles at study enrollment. Hot flashes were assessed by subject report in a structured interview at the first follow-up period and correlated highly with previous prospective daily ratings of hot flashes (p = 0.0001). Blood samples were obtained in the first 6 days of the menstrual cycle in two consecutive cycles at enrollment and two consecutive cycles at follow-up. Predictor variables include hormone measures, structured interview, and standard questionnaire data. Thirty-one percent of the sample (n = 375) reported hot flashes (mean age 41 years). In bivariate analysis, more African American than Caucasian women reported hot flashes (38% vs. 25%, p = 0.01). Significant predictors of hot flashes in the final multivariable logistic regression model were higher follicle-stimulating hormone (FSH) levels (odds ratio [OR] 3.19), anxiety (OR 1.06), baseline menopausal symptoms (OR 4.91), alcohol use (OR 1.09), body mass index (BMI) (OR 1.04), and parity (OR 1.20). Race did not predict hot flashes after adjusting for these variables. Hot flashes commonly occur before observable menstrual irregularities in the perimenopause and are associated with both hormonal and behavioral factors. The association of hot flashes with increased body mass (BMI) challenges the current "thin" hypothesis and raises important questions about the role of BMI in hormone dynamics in the late reproductive years.

Adult↗

PubMed2004

Hot flashes and sleep in women.

Sleep disturbances during menopause are often attributed to nocturnal hot flashes and 'sweats' associated with changing hormone patterns. This paper is a comprehensive critical review of the research on the relationship between sleep disturbance and hot flashes in women. Numerous studies have found a relationship between self-reported hot flashes and sleep complaints. However, hot flash studies using objective sleep assessment techniques such as polysomnography, actigraphy, or quantitative analysis of the sleep EEG are surprisingly scarce and have yielded somewhat mixed results. Much of this limited evidence suggests that hot flashes are associated with objectively identified sleep disruption in at least some women. At least some of the negative data may be due to methodological issues such as reliance upon problematic self-reports of nocturnal hot flashes and a lack of concurrent measures of hot flashes and sleep. The recent development of a reliable and non-intrusive method for objectively identifying hot flashes during the night should help address the need for substantial additional research in this area. Several areas of clinical relevance are described, including the effects of discontinuing combined hormone therapy (estrogen plus progesterone) or estrogen-only therapy, the possibility of hot flashes continuing for many years after menopause, and the link between hot flashes and depression.

Climacteric↗

PubMed2003

Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial.

CONTEXT: Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective. OBJECTIVE: To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics. PATIENTS: A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy. INTERVENTION: After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks. MAIN OUTCOME MEASURES: Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity). RESULTS: Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P =.007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P =.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group. CONCLUSION: Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.

Adult↗

PubMed2006

Association between race and hot flashes in midlife women.

OBJECTIVE: Studies suggest that African American women may have a greater risk of hot flashes compared to Caucasian women, but the reasons for this are unknown. This study tested the hypothesis that African American women have an increased risk of hot flashes due to racial differences in risk factors for hot flashes, including high body mass index (BMI) and lower estrogen levels. METHODS: A population-based study was conducted among women aged 45-54 years. Participants were divided into women who reported ever experiencing hot flashes (n=356) and women who reported never experiencing hot flashes (n=257). Participants provided a blood sample for hormone assays, were weighed and measured, and completed a questionnaire. RESULTS: Among peri-menopausal women, African American women were more likely than Caucasian women to report any hot flashes (RR=2.08), severe hot flashes (RR=2.19), and hot flashes for more than 5 years (RR=1.61). The risk ratios for the associations between race and the hot flash outcomes were attenuated after controlling for other important hot flash risk factors (i.e. obesity and low estrogen levels). CONCLUSIONS: African American women have an increased risk of hot flashes compared to Caucasian women due to racial differences in a number of risk factors for hot flashes, including advanced age, obesity, current smoking, less than 12 drinks in the past year, and lower estrogen levels.

Age Distribution↗

PubMed2002

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.

Adult↗

PubMed2004

Making sense of the evidence regarding nonhormonal treatments for hot flashes.

The demand for nonhormonal interventions for hot flashes is increasing because of the number of patients diagnosed with hormone-sensitive cancers and the results of the Women's Health Initiative indicating that hormone replacement therapy is not as beneficial as originally believed. Since 2002, numerous studies testing nonhormonal treatments for hot flashes have been conducted. Clinicians need to be able to use these research findings to help patients make treatment decisions. Because hot flashes can interfere with activities of daily living such as sleep and work, clinicians first should assess the extent to which hot flashes are disruptive to a woman's life. The evidence for nonhormonal interventions is summarized, and a decision treatment algorithm is offered for use in clinical practice. This algorithm includes nonhormonal options of the antidepressants available in addition to gabapentin, an antiseizure medication. A short review of the evidence for possible complementary therapies also is included.

Acetates↗

PubMed2005

Stellate ganglion blockade provides relief from menopausal hot flashes: a case report series.

OBJECTIVE: To investigate whether standard C6 stellate ganglion blockade (SGB) might provide relief from hot flashes associated with menopause. METHODS: Six women were referred for severe menopausal hot flashes and elected to undergo standard SGB (5 ml 0.375% Marcaine, Abbott Labs, Abbott Park, IL) to evaluate a novel intervention for hot flash relief. Hot flashes were assessed by self-reporting before and after stellate ganglion block. RESULTS: Initial SGB (SGB1) was successful in all 6 subjects, as evidenced by a positive Horner's syndrome and anhydrosis. Successful SGB caused complete alleviation of hot flashes for times ranging from 2 to 5 weeks. Patients returned for follow-up SGB after mild hot flashes returned. A second SGB produced additional asymptomatic periods of relief ranging from 4 to 18 weeks. In each case, repeated block provided hot flash relief equal to or greater than that of the initial block. Two patients who submitted for a third SGB reported 15 and 48 weeks of relief. CONCLUSION: Successful SGB appears to be related to relief of hot flashes. Repeat SGB results in efficacious multiple week relief of severe hot flashes associated with menopause.

Anesthesia, Local↗

PubMed1999

Racial differences in menopause information and the experience of hot flashes.

OBJECTIVE: To compare the prevalence of hot flashes and health education regarding menopause in African-American and white American women in the late reproductive years. DESIGN: Cross-sectional study. SETTING: Population-based sample recruited through random digit dialing. PARTICIPANTS: The sample was 436 women between the ages of 35 and 48 years with regular menses. Half the sample was African American and half was white American. MAIN RESULTS: African-American women (53%) were more likely than white American women (29%) to have experienced hot flashes (p < .001). The difference remained after adjustment for body-mass index, education, menstrual cycle characteristics, and gynecologic and medical history. Despite the high prevalence of symptoms, few women had discussed menopausal management with their physicians. For white women the media were the primary source of menopause-related information, whereas African-American women reported that their family was the primary source of information. CONCLUSIONS: These results indicate that hot flashes occur commonly among women in their thirties and forties who have regular menstrual cycles and that the prevalence of hot flashes appears to differ by race. Studies should be designed to evaluate the hormonal and physiologic implications of these symptoms among women in their late reproductive years. Few of these women had discussed menopause with their physicians. Given the differences in sources of information about menopause, development of culture-specific health education programs should be considered.

Adult↗

PubMed2000

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Antidepressive Agents, Second-Generation↗

PubMedDate not supplied

Ambulatory blood pressure and heart rate in relation to hot flash experience among women of menopausal age.

OBJECTIVE: The purpose of this study was to evaluate whether ambulatory blood pressure and heart rate varied with hot flash experience among women of menopausal age. SUBJECTS AND METHODS: A total of 1149 ambulatory blood pressure and heart rate measurements from 20 women aged 44-55 were examined. Women were categorized by hot flash experience as (1) having had hot flashes during the study period (Symptomatic during Study; n = 5; 302 measurements), (2) having a past history of hot flashes, but no hot flashes during the study period (Historically Symptomatic; n = 7; 385 measurements), and (3) never having had a hot flash (Asymptomatic; n = 8; 462 measurements). Using repeated measures, nested ANOVA models that also adjusted for posture, the variation in blood pressure and heart rate associated with hot flash experience over the whole day and by location of measurement (microenvironment) was evaluated. RESULTS: The results show that, overall, systolic pressure did not differ among the hot flash experience groups although the Symptomatic during Study group had higher pressures at work than the other two groups (p<0.01), and tended to have higher pressures during sleep (p<0.08). The sleep diastolic pressure of the Asymptomatic group was significantly lower than that of the women who had hot flashes on the study day (p<0.01), but women who had a past history of hot flashes had slightly lower diastolic pressure (p<0.01) than those in the other two groups overall. Heart rates of the Asymptomatic group, however, were significantly lower (4-6 b.p.m.; p<0.001) in each microenvironment and over the whole day than both groups who had hot flash experience. CONCLUSIONS: These data suggest first that there may be a relationship between the experience of hot flashes and accelerated heart rate, and second that women who do not experience hot flashes may have lower sleep blood pressures than women who do.

Adult↗

PubMed2000

A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer survivors.

BACKGROUND: Many breast cancer survivors suffer debilitating hot flashes. Estrogen, the drug of choice in perimenopausal women, is generally not recommenced to breast cancer survivors. Nonhormonal treatments are mostly disappointing. Anecdotal reports in our institution suggested that the selective serotonin-reuptake inhibitor, paroxetine hydrochloride, might be efficacious in alleviating hot flashes. PATIENTS AND METHODS: Thirty women with prior breast cancer who were suffering at least two hot flashes a day entered a single institution pilot trial to evaluate paroxetine's efficacy in reducing the frequency and severity of hot flashes. After completing daily diaries for one week on no therapy, the women received open-label paroxetine, 10 mg daily for one week, followed by four weeks of paroxetine, 20 mg daily. The women completed hot-flash daily diaries throughout the study period, and a health-related symptom-assessment questionnaire and a quality-of-life rating scale in the first and sixth week of the study. RESULTS: Twenty-seven women completed the six-week study period. The mean reduction of hot flash frequency was 67% (95% confidence interval (95% CI): 56%-79%). The mean reduction in hot flash severity score was 75% (95% CI: 66%-85%). There was a statistically significant improvement in depression, sleep, anxiety, and quality of life scores. Furthermore, 25 (83%) of the study participants chose to continue paroxetine therapy at the end of study. The most common adverse effect was somnolence, resulting in drug discontinuation in two women, and dose reduction in two women. One woman discontinued drug due to anxiety. CONCLUSIONS: Paroxetine hydrochloride is a promising new treatment for hot flashes in breast cancer survivors, and warrants further evaluation in a double-blind randomized placebo-controlled trial.

Adult↗

PubMed2026

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans↗

PubMed2005

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.

Amines↗