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Continuous transdermal nitroglycerin therapy for menopausal hot flashes

a single-arm, dose-escalation trial

Huang, Alison J. MD, MAS; Cummings, Steven R. MD, MPH; Schembri, Michael BA; Vittinghoff, Eric PhD; Ganz, Peter MD; Grady, Deborah MD, MPH

doi: 10.1097/GME.0000000000000520
Brief Report

Objective: To describe the efficacy and tolerability of continuous nitroglycerin for treatment of hot flashes.

Methods: Perimenopausal and postmenopausal women reporting at least seven hot flashes per day were recruited into a single-arm, dose-escalation trial of continuous transdermal nitroglycerin. Participants were started on a generic 0.1 mg/hour nitroglycerin patch applied daily without patch-free periods. During 4 weeks, participants escalated dosage weekly to 0.2, 0.4, or 0.6 mg/hour as tolerated, then discontinued nitroglycerin during the final week. Changes in hot flash frequency and severity were assessed using symptom diaries. Paired t tests examined change in outcomes between baseline and maximal-dose therapy and after discontinuation of nitroglycerin.

Results: Of the 19 participants, mean age was 51.4 (±4.3) years. Women reported an average 10.6 (±3.0) hot flashes and 7.1 (±3.8) moderate-to-severe hot flashes per day at baseline. Eleven women escalated to 0.6 mg/hour, three to 0.4 mg/hour, two to 0.2 mg/hour, and one remained on 0.1 mg/hour nitroglycerin. Two discontinued nitroglycerin before the first outcomes assessment. Among the remaining 17 women, the average daily frequency of hot flashes decreased by 54% and the average frequency of moderate-to-severe hot flashes decreased by 69% from baseline to maximum-dose therapy (P < 0.001 for both). After discontinuing nitroglycerin, participants reported an average 23% increase in frequency of any hot flashes (P = 0.041) and 96% increase in moderate-to-severe hot flashes (P < 0.001).

Conclusions: Continuous nitroglycerin may substantially and reversibly decrease hot flash frequency and severity. If confirmed in a randomized blinded trial, it may offer a novel nonhormonal hot flash treatment.

1Department of Medicine, University of California, San Francisco, California

2San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California

3Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California

4Department of Epidemiology and Biostatistics, University of California, San Francisco, California.

Address correspondence to: Alison J. Huang, MD, MAS, Women's Health Clinical Research Center, University of California San Francisco, 1545 Divisadero Street, Box 0320, San Francisco, CA 94115. E-mail:

Received 15 April, 2015

Revised 4 June, 2015

Accepted 4 June, 2015

Funding/support: This research was supported by a grant from the Mt. Zion Health Fund. A.J.H. is additionally supported by the Paul B. Beeson Career Development Award in Aging Research from the National Institute on Aging (1K23AG038335) and the American Federation for Aging Research. D.G. is additionally supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through University of California San Francisco Clinical and Translational Science Institute (UCSF-CTSI) Grant Number UL1 TR000004.

Financial disclosure/conflicts of interest: A.J.H. has received funding from Pfizer, Inc., to conduct research unrelated to hot flashes through research grants awarded through UCSF.

© 2016 by The North American Menopause Society.