Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial

doi:10.1016/S0029-7844(02)02712-6

Obstetrics & Gynecology

Volume 101, Issue 2, February 2003, Pages 337-345

https://doi.org/10.1016/S0029-7844(02)02712-6 Get rights and content

Abstract

Objective

To evaluate whether treatment with the anticonvulsant gabapentin may be effective in reducing hot flash frequency and severity.

Methods

A randomized, double-blind, placebo-controlled trial was conducted in 59 postmenopausal women with seven or more hot flashes per day examining the effects of gabapentin 900 mg per day on hot flash frequency after 12 weeks of treatment. Subsequently, study patients were enrolled in a 5-week, open-label treatment phase, during which patients could increase the dose of gabapentin to 2700 mg per day, if needed.

Results

After 12 weeks of double-blind treatment, intention-to-treat analysis showed that gabapentin 900 mg per day was associated with a 45% reduction in hot flash frequency and a 54% reduction in hot flash composite score (frequency and severity combined into one score) from baseline, compared with 29% (P = .02) and 31% (P = .01) reductions, respectively, for placebo. Four patients (13%) in the gabapentin group and one (3%) in the placebo group withdrew from the double-blind study because of adverse events. Fifteen patients (50.0%) in the gabapentin group reported at least one adverse event, compared with eight patients (27.6%) in the placebo group. Higher, open-label gabapentin dosing was associated with 54% and 67% reductions in hot flash frequency and composite score from baseline, respectively.

Conclusion

Gabapentin is effective in reducing hot flash frequency and severity in postmenopausal women.

Section snippets

Materials and methods

Study participants were recruited by advertisements and from a local news program about alternative hot flash therapies. We enrolled 59 postmenopausal women meeting the following entry criteria: an average of seven or more hot flashes per day accompanied by sweating; amenorrhea for more than 12 months or amenorrhea for 6–12 months with a serum follicle-stimulating hormone level greater than 40 mIU/mL and estrogen less than 20 pg/mL or status post-bilateral oophorectomy for 2 months; no

Results

A total of 246 women were screened by phone conversation. Most were ineligible because of insufficient hot flash frequency or occurrence of menses within the past 6 months. Fifty-nine patients were enrolled from July to November 2000 (Figure 1), and follow-up continued until March 2001. Patient baseline characteristics are summarized in Table 1.

Of the 54 patients who completed the double-blind study, 26 of 26 (100%) and 26 of 28 (93%) of gabapentin-treated and placebo-treated patients,

Discussion

The results of this randomized, double-blind, placebo-controlled trial have confirmed our previous open-label findings that low-dose gabapentin is effective in treating hot flashes in postmenopausal women. A significant difference between the gabapentin and placebo groups was apparent after 12 weeks of therapy, and this difference was consistent throughout the double-blind study. Subsequent, open-label data showed that most patients (86.4%) were satisfied with moderate gabapentin doses (up to

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Citation Excerpt :
Nineteen RCTs and 2 randomized crossover trials, reporting results from 3519 participants, were included (Table 1, online Supplemental Table 1). Thirteen studies were conducted in American countries,28–40 6 in Asia,41–46 1 in Europe,47 and 1 in Africa.48 Nine RCTs compared gabapentin with placebo,28,30–33,37,38,41,42 2 RCTs compared pregabalin with placebo or ganglion block.34,48
Vasomotor symptoms are common among postmenopausal women and patients receiving hormone deprivation therapies, and emerging studies are exploring gabapentin’s and pregabalin’s effects as nonhormonal treatment options. We aimed to assess the efficacy and safety of these 2 drugs.
Based on a preregistered protocol (Prospective Register of Systematic Reviews -CRD42019133650), we searched 10 databases (PubMed, Embase, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese Biological Medical Literature, Chinese National Knowledge Infrastructure, Chinese Journals Full-text Database [VIP], and Wanfang) as well as the World Health Organization international clinical trials registry platform and reference lists of related literatures.
Randomized controlled trials and randomized crossover studies exploring gabapentin and pregabalin among women patients with vasomotor symptoms were included.
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. Two reviewers independently selected studies, assessed bias, and extracted data. Mean difference and standardized mean difference with 95% confidence intervals were assessed by random-effects models. Heterogeneities were assessed by I² statistics, and the quality of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach.
Nineteen randomized controlled trials and 2 randomized crossover trials reporting results from 3519 participants were included. Gabapentin could reduce hot flash frequency (mean difference, –1.62, 95% confidence interval, –1.98 to –1.26 after 4 weeks; mean difference, –2.77, 95% confidence interval, –4.29 to –1.24 after 12 weeks) and composite score (standardized mean difference, –0.47, 95% confidence interval, –0.71 to –0.23 after 4 weeks; standardized mean difference, –0.77, 95% confidence interval, –1.15 to –0.40 after 12 weeks) compared with placebo. Both menopausal participants and patients with breast cancer benefited from treatment. Higher risks of dizziness and somnolence were found in the gabapentin group than in the control group (risk ratio, 4.45, 95% confidence interval, 2.50–7.94; risk ratio, 3.29, 95% confidence interval, 1.97–5.48, respectively). Estrogen was more effective in reducing hot flash frequency than gabapentin. No statistically significant difference in reduction of hot flash severity score was found between gabapentin and antidepressants. The trials comparing gabapentin or pregabalin with the other interventions were too limited to make a conclusion.
Favorable effects of gabapentin in relieving vasomotor symptoms were observed, compared with controls, but were less effective than those of estrogen. Evidence supporting the therapeutic effect of pregabalin is still lacking.

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^☆

The authors thank David S. Guzick, MD, for critical review of the manuscript.

This study was funded by a General Clinical Research Center grant, 5 M01 RR00044 from the National Center for Research Resources, National Institutes of Health (NIH); an Experimental Therapeutics in Neurological Disease NIH Grant #5 T32 NS07338-12; and University of Rochester institutional research funds.

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Original researchGabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial☆

Abstract

Objective

Methods

Results

Conclusion

Section snippets

Materials and methods

Results

Discussion

Am J Obstet Gynecol

Maturitas

Obstet Gynecol

Psychiatry Res

Lancet

Obstet Gynecol

Maturitas

Ann Oncol

Neuropharmacology

J Biol Chem

Brain Res

Association of waking episodes with menopausal hot flushes

JAMA

The use of estrogens and progestins and the risk of breast cancer in postmenopausal women

N Engl J Med

Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled trial

JAMA

Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group

JAMA

Effects of estrogen replacement on the progression of coronary-artery atherosclerosis

N Engl J Med

Cardiovascular disease outcomes during 6.8 years of hormone therapyHeart and Estrogen/Progestin Replacement Study follow-up (HERS II)

JAMA

Gabapentin for the treatment of postherpetic neuralgiaA randomized controlled trial

JAMA

Original research
Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial☆