Nonhormonal Alternatives for the Treatment of Hot Flashes

Brigitte L. Sicat, Pharm.D.; Deborah K. Brokaw, Pharm.D.

Disclosures

Pharmacotherapy. 2004;24(1) 

In This Article

Abstract and Introduction

Abstract

Objective: To review the literature on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin for the treatment of hot flashes.
Data Sources: A MEDLINE search (January 1966–July 2003) was conducted to identify English-language literature available on the treatment of hot flashes that focused on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin. These articles, relevant abstracts, and additional references listed in articles were used to collect pertinent data.
Study Selection: All controlled and uncontrolled trials were reviewed.
Data Synthesis: In women unable or unwilling to take hormonal therapies, several nonhormonal alternatives have been evaluated in small controlled and uncontrolled trials. Oral and transdermal formulations of clonidine are moderately effective in reducing hot flashes. Results of studies evaluating venlafaxine, paroxetine, and gabapentin suggest greater reductions in hot-flash frequency and severity compared with those of clonidine. Fluoxetine appears to display a modest benefit compared with paroxetine, although no comparative trials have been conducted. Most women studied in these trials had a history of breast cancer, and many were taking concurrent tamoxifen. All of these agents were fairly well tolerated.
Conclusions: Clonidine, venlafaxine, paroxetine, fluoxetine, and gabapentin are nonhormonal agents that have demonstrated efficacy in small controlled and uncontrolled trials in reducing hot flashes and should be considered in patients unwilling or unable to take hormonal therapies.

Introduction

Hot flashes affect approximately 75% of postmenopausal women and are one of the most distressing symptoms women experience as they enter menopause. Symptoms typically begin a few years before natural menopause and usually continue for 0.5–5 years, although a small percentage of women may have symptoms for up to 15 years.[1,2] Hot flashes occur not only in women undergoing natural menopause, but also in women experiencing premature menopause due to bilateral oophorectomy or cytotoxic chemotherapy. This abrupt decline in estrogen often results in hot flashes that are more frequent and severe than those associated with natural menopause. In addition, 50% of postmenopausal women with breast cancer who are receiving tamoxifen experience hot flashes as an adverse effect of the drug.[3]

Hormone replacement therapy effectively reduces hot-flash symptoms by 80–90%[4,5]; however, many patients may be unable or unwilling to undergo hormonal treatment. Patients with a history of endometrial cancer, venous thromboembolism, or breast cancer, or with a family history of breast cancer often are advised to avoid hormonal agents. Although several recent reports suggest some breast cancer survivors may be safely treated for hot flashes with estrogen or progesterone,[6–8] their use remains controversial because of concerns about stimulating cancer growth. In addition, the estrogen and progestin arm of the Women's Health Initiative[9] and other recent reports[10–12] suggest that hormone replacement therapy may increase the risk for coronary heart disease events, strokes, venous thromboembolism, and invasive breast cancer. Many expert groups recommend that combination hormonal therapy for the management of vasomotor symptoms should be limited to the shortest duration consistent with treatment goals and benefits versus risks for individual women.[13–15] All of these concerns have generated interest in nonhormonal treatment of hot flashes.

Numerous nonhormonal alternatives for the treatment of hot flashes have been evaluated, including clonidine, belladonna-ergotamine-phenobarbital, methyldopa, vitamin E, and complementary and alternative agents.[16–18] However, adverse effects or insufficient efficacy limits the use of these agents. Accumulating evidence suggests that several antidepressants including venlafaxine and selective serotonin reuptake inhibitors (SSRIs), as well as gabapentin, may be effective in reducing hot flashes. We conducted a MEDLINE search (January 1966–July 2003) to identify English-language literature available on the treatment of hot flashes that focused on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin. These articles, relevant abstracts, and additional references listed in articles were used to collect pertinent data.

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