For many women these symptoms are unbearable and they may benefit from low dose progesterone (e.g. Megace 20 mg, once or twice a day.) Other drugs like clonidine and paxil may be considered.  Herbal supplements are also often tried though some of these (e.g. soy products) are actually plant estrogens and may carry some risk. Some of the studies are noted below...   The whole question of hormone replacement is now quite controversial (go here.)

A recent review article (Support.Onc 1:1:2003) felt that there was only minimal benefit from herbals, or soy and only slight benefit from Vitamin E (800IU/day) so he  felt the best strategy was to start with Effexor or Paxil and if they were not effective then try Neurontin and if that fails then try Megace

Paroxetine (Paxil) Is an Effective Treatment for Hot Flashes: Results From a Prospective Randomized Clinical Trial

Vered Stearns, Lombardi Comprehensive Cancer Center at Georgetown University, Journal of Clinical Oncology, Vol 23, No 28 (October 1), 2005: pp. 6919-6930

Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9. RESULTS: 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01). CONCLUSION: Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.

Our results are consistent with three other reported randomized clinical trials that evaluated the effectiveness of selective serotonin or norandrenergic reuptake inhibitors (SSRI/SNRI) for the treatment of hot flashes. Loprinzi et al compared 3 doses of venlafaxine (Effexor) (37.5 mg, 75 mg, and 150 mg) to placebo. Venlafaxine 75 and 150 mg reduced hot flash composite score by 61% each and was significantly more effective than placebo^.  Venlafaxine 75 mg provided similar benefit to the higher dose and was recommended for clinical use. In a separate trial by the same investigators, fluoxetine was modestly more effective than placebo in reducing hot flash composite score, (50% v 36%, respectively. In another study, we have evaluated the efficacy of two doses of paroxetine controlled release (12.5 mg and 25 mg paroxetine; CR) in reducing hot flashes in women who were postmenopausal, over 90% of whom did not have a history of breast cancer and were not taking a concomitant antiestrogen. Paroxetine CR 12.5 mg and 25 mg provided similar benefit for post menopausal hot flashes, reducing hot flash composite score by 62% and 64%, respectively (respectively). However, the low dose was associated with fewer adverse effects and a smaller likelihood of drug discontinuation. Our results, taken together with other published reports, establish the effectiveness of a low-dose SSRI/SNRI for the control of hot flashes.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial

Megestrol acetate for the prevention of hot flashes.

Loprinzi CL,N Engl J Med 1994 Aug 11;331(6):347-52

Department of Oncology, Mayo Clinic, Rochester, Minn. 55905.

Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients. METHODS. The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patients documented the frequency and severity of hot flashes in daily symptom diaries. RESULTS. After four weeks, hot flashes were reduced by 21 percent in the group receiving placebo first and by 85 percent in the group receiving megestrol acetate first (P < 0.001). Low-dose megestrol acetate is well tolerated and can substantially decrease the frequency of hot flashes in women and men.

Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes.

Quella SK, Cancer 1998 May 1;82(9):1784-8

Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone. RESULTS: A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms. CONCLUSIONS: A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.

Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial.

Quella SK, J Clin Oncol 2000 Mar;18(5):1068-74

Mayo Clinic and Mayo Foundation, Rochester, USA.

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis. PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects. RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed. CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.

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

Stearns V,   Ann Oncol 2000 Jan;11(1):17-22

Breast Cancer Program, Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC, USA.

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.

Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors.

Loprinzi CL,    J Clin Oncol 1998 Jul;16(7):2377-81

Department of Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. cloprinzi@mayo.edu

PURPOSE: Hot flashes can be a prominent clinical problem for breast cancer survivors and men who undergo androgen-deprivation therapy. Anecdotal information suggested a low dose of a relatively new antidepressant, venlafaxine, could abrogate this clinical problem. MATERIALS AND METHODS: This study included 28 consecutive assessable patients entered onto a phase II clinical trial. Hot flash data were collected by daily diary questionnaires during a 1-week baseline period and then for 4 weeks, during which time patients received venlafaxine 12.5 mg orally twice daily. RESULTS: Fifty-eight percent of patients who completed the study had a greater than 50% reduction in hot flash scores (frequency times severity) during the fourth treatment week as compared with the baseline week. Median weekly hot flash scores were reduced by 55% from baseline during the fourth week of venlafaxine therapy. Therapy was generally well tolerated and appeared to alleviate fatigue, sweating, and trouble sleeping. CONCLUSION: Venlafoxine appears to represent an efficacious new method to alleviate hot flashes. Further evaluation of this compound for alleviating hot flashes is indicated.

A New Treatment for Hot Flashes: Antidepressants (from CanCerNet) J Clin Oncol 1998 Jul;16(7):2377-81

Women with breast cancer who suffer hot flashes now have a new option: widely used antidepressant drugs. In a large study presented at the annual meeting of the American Society of Clinical Oncology, venlafaxine (Effexor) substantially reduced hot flashes in 62% of women, and preliminary studies of three other antidepressants indicate similar promising results.

To find another way to control hot flashes, the Mayo team tested several other agents, including vitamin E, without much luck. Pilot tests of sertraline (Zoloft), flouxotine, and venlafaxine, which are all chemically related and which researchers say work in similar ways, showed promise in reducing hot flashes, so Loprinzi decided to do a large, controlled clinical trial comparing venlafaxine to placebo. His team enrolled 229 patients, giving them either the placebo or one of three doses of venlafaxine.

The dose of 75 milligrams per day gave the best benefit-to-side effect profile, said Loprinzi, reducing a hot flash "score" by three quarters or more in 29% of women, and by half or more in 62%. The score accounted for both the number and severity of hot flashes each day.

Patients being treated for depression typically receive 150 milligrams of the drug per day, but this dose tended to elevate side effects without increasing the number of women helped. Common side effects reported included dry mouth, a drop in appetite, and temporary nausea. Other studies of velafaxine have identified a decrease in sexuality as a problem in women who took the drug, but Loprinzi said decreased sexual drive or other sexual side effects were not a problem in his study.

Alternatives to estrogen for the treatment of hot flashes.

Lucero MA, McCloskey WW   Ann Pharmacother 1997 Jul-Aug;31(7-8):915-7

Department of Pharmacy Services, University of Massachusetts Medical Center, Worcester 01655, USA.

Postmenopausal women experiencing hot flashes in whom estrogen replacement is contraindicated have alternatives available to them; however, there is no clearly defined treatment modality. The literature addressing many of these alternatives has serious limitations, which include the small number of women enrolled and lack of comparative studies between agents. Each patient needs to be assessed in terms of her current medical status, concomitant medications, and the degree to which vasomotor instability interferes with everyday activities. The literature suggests that megestrol acetate 20 mg bid may provide significant relief. Women who opt to use megestrol acetate must be told in advance that the effects will not be felt immediately particularly if tamoxifen is used concomitantly. Clonidine and medroxyprogesterone may constitute potential alternatives, but patients may not be able to tolerate the adverse effects. Because of the lack of literature supporting their clinical use, options such as vitamin E and ginseng need to be approached cautiously. Exercise has a role in alleviating some of the complications associated with menopause, such as heart disease and osteoporosis, but its effect on neurotransmitters and hormone concentrations, and how this relates to the treatment of hot flashes have not been characterized. Patients should be told that regular physical activity, a balanced diet, avoidance of alcohol and caffeine, and stress reduction may be of additional help in decreasing vasomotor flushing.

Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.

Pandya KJ,   Ann Intern Med 2000 May 16;132(10):788-93

University of Rochester Cancer Center Community Clinical Oncology Program Research Base, New York 14642, USA.

BACKGROUND: Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. OBJECTIVE: To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University of Rochester Cancer Center Community Clinical Oncology Program. PATIENTS: 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy. INTERVENTION: Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks. MEASUREMENTS: In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study. RESULTS: Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups. CONCLUSION: Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.

Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life.

Carpenter JS, Cancer 1998 May 1;82(9):1682-91

Department of Behavioral Science, University of Kentucky, Lexington 40536-0086, USA.

BACKGROUND: Research on hot flashes (HFs) after the diagnosis and treatment of breast carcinoma (BC) is scarce. Of the 114 postmenopausal women interviewed, 65% reported HFs, with 59% of women with HFs (n = 74) rating the symptom as severe. Multivariate analysis revealed that 1) HFs were most common in women with a high school education or less and those who were younger at diagnosis and 2) HFs were most severe in women with a higher body mass index, those who were younger at diagnosis, and those receiving tamoxifen.

Hormone replacement therapy and breast cancer: revisiting the issues.

DeGregorio MW, Taras TL   J Am Pharm Assoc (Wash) 1998 Nov-Dec;38(6):738-44; quiz 744-6

Department of Internal Medicine, University of California, Sacramento

OBJECTIVE: To assess current ideas about the benefits and risks of estrogen and hormone replacement therapy (ERT/HRT) in postmenopausal women. Review of meta-analyses of clinical trials showed that ERT/HRT ever-users (patients who have ever used ERT/HRT) did not have an increased risk of breast cancer, but current users did have an increased risk, with some studies reporting increasing risk with duration of ERT. No relationship was found between dose or the addition of progestin to ERT and increased breast cancer risk. Overall breast cancer mortality rates associated with HRT were decreased in current users. In general, HRT does not increase the risk of breast cancer in women with a family history of the disease, compared with those without a family history. New HRT strategies that could potentially prevent breast cancer are now being developed. The SERMs tamoxifen and toremifene appear to have positive clinical effects on bone and serum lipids; they are currently being investigated for use as breast cancer chemopreventive agents. Raloxifene, a new SERM used for the prevention of osteoporosis, is an alternative for women who cannot tolerate HRT. Unfortunately, these SERMS have anti-estrogenic effects and thus cause vasomotor adverse effects such as hot flashes and vaginal dryness. In addition, SERMs do not protect against heart disease or prevent osteoporosis as well as does HRT. CONCLUSION: Presently, SERMs will not become first-line HRT, as the positive effects of ERT/HRT may outweigh any potentially increased risk of breast cancer. The development of new agents with pharmacodynamic profiles similar to that of ERT/HRT but lacking its adverse effects would be greatly beneficial for postmenopausal women.