Continuous transdermal nitroglycerin therapy for menopausal hot flashes: a single-arm, dose-escalation trial.
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.
Alison J
AJ
Huang
Steven R
SR
Cummings
Michael
M
Schembri
Eric
E
Vittinghoff
Peter
P
Ganz
Deborah
D
Grady
D000279:Administration, Cutaneous; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D005996:Nitroglycerin