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Continuous Transdermal Nitroglycerin for Hot Flashes

Uninterrupted administration of transdermal nitroglycerin (NTG) had no effect on hot flash frequency or severity compared with placebo, researchers report. Adverse effects included early but not persistent headache.

Perimenopausal or postmenopausal women in northern California reporting 7 or more hot flashes per day were recruited for this randomized, double-blinded, placebo-controlled clinical trial between July 2017 and December 2021. Uninterrupted daily use of transdermal NTG with titration by the participant to 0.2 to 0.6 mg/hr was compared with identical placebo patches.

Based on validated symptom diaries assessing changes in any hot flash frequency (primary outcome) and moderate-to-severe hot flash frequency over 5 and 12 weeks, the investigators found: “Among the 141 randomized participants (70 NTG [49.6%], 71 placebo [50.4%]; 12 [85.8%] Asian, 16 [11.3%] Black or African American, 15 [10.6%] Hispanic or Latina, 3 [2.1%] multiracial, 1 [0.7%] Native Hawaiian or Pacific Islander, and 100 [70.9%] White or Caucasian individuals), a mean (SD) of 10.8 (3.5) hot flashes and 8.4 (3.6) moderate-to-severe hot flashes daily was reported at baseline. Sixty-five participants assigned to NTG (92.9%) and 69 assigned to placebo (97.2%) completed 12-week follow-up (P = .27). Over 5 weeks, the estimated change in any hot flash frequency associated with NTG vs placebo was −0.9 (95% CI, −2.1 to 0.3) episodes per day (P = .10), and change in moderate-to-severe hot flash frequency with NTG vs placebo was −1.1 (95% CI, −2.2 to 0) episodes per day (P = .05). At 12 weeks, treatment with NTG did not significantly decrease the frequency of any hot flashes (−0.1 episodes per day; 95% CI, −1.2 to 0.4) or moderate-to-severe hot flashes (−0.5 episodes per day; 95% CI, −1.6 to 0.7) relative to placebo. In analyses combining 5-week and 12-week data, no significant differences in change in the frequency of any hot flashes (−0.5 episodes per day; 95% CI, −1.6 to 0.6; P = .25) or moderate-to-severe hot flashes (−0.8 episodes per day; 95% CI, −1.9 to 0.2; P = .12) were detected with NTG vs placebo. At 1 week, 47 NTG (67.1%) and 4 placebo participants (5.6%) reported headache (P < .001), but only 1 participant in each group reported headache at 12 weeks.”

Source: JAMA Internal Medicine