Study on Hot Flashes and Nitroglycerin Therapy

Hot flashes, also known as vasomotor symptoms, are one of the most common symptoms among menopausal women, with more than two-thirds of women in Western nations reporting hot flashes during the menopausal transition. However, its management is crucial. Does uninterrupted transdermal nitroglycerin (NTG) therapy decrease the frequency and severity of menopause-related hot flashes?

A new study in JAMA Internal Medicine reveals that perimenopausal and postmenopausal women who experienced at least 7 hot flashes per day saw a decrease in hot flash frequency by more than 40% over 12 weeks in both the nitroglycerin and placebo groups. However, early reductions in moderate-to-severe hot flash frequency or hot flash severity scores associated with nitroglycerin at 5 weeks did not persist at 12 weeks relative to placebo.

Researchers conducted a randomized, double-blinded, placebo-controlled clinical trial that included perimenopausal or postmenopausal women reporting 7 or more hot flashes per day. These women were recruited from northern California by study personnel at a single academic center. The study involved uninterrupted daily use of transdermal NTG (participant-directed dose titration from 0.2-0.6 mg/h) or identical placebo patches. Validated symptom diaries assessed changes in any hot flash frequency (primary outcome) and moderate-to-severe hot flash frequency over 5 and 12 weeks.

Key Findings of the Study

• Among the 141 randomized participants (70 NTG [49.6%], 71 placebo), 65 participants assigned to NTG (92.9%) and 69 assigned to placebo (97.2%) completed the 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 episodes per day, and the change in moderate-to-severe hot flash frequency with NTG vs placebo was −1.1 episodes per day.
• At 12 weeks, treatment with NTG did not significantly decrease the frequency of any hot flashes (−0.1 episodes per day) or moderate-to-severe hot flashes (−0.5 episodes per day) 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) or moderate-to-severe hot flashes (−0.8 episodes per day) 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.

Researchers concluded that “This randomized clinical trial found that continuous use of NTG did not result in sustained improvements in hot flash frequency or severity relative to placebo and was associated with more early but not persistent headache.”

Reference: Huang AJ, Cummings SR, Ganz P, et al. Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal Women: A Randomized Clinical Trial. JAMA Intern Med. 2023;183(8):776–783. doi:10.1001/jamainternmed.2023.1977