Nitroglycerin patch does not reduce hot flashes during menopause

Key takeaways:

• Transdermal nitroglycerin and placebo had similar outcomes for hot flash frequency and severity at 12 weeks.
• Nitroglycerin was linked to headaches, although this association did not persist.

Continuous use of transdermal nitroglycerin did not result in sustained improvements in hot flash frequency or severity compared with placebo among peri- and postmenopausal women, according to results of a randomized clinical trial.

“Nitroglycerin has been used for decades to treat chest pain in patients with coronary disease because it can increase blood flow to the heart when used for only 12 hours at a time,” Alison J. Huang, MD, an internal medicine physician at the University of California, San Francisco, said in a press release. “But lab studies suggested that if nitroglycerin is used continuously, it could prevent or suppress the type of rapid, increased blood flow under the skin that causes sensations of heat and flushing during hot flashes during menopause. In this line of research, we repurposed a medication that has been used for close to a century for a different indication.”

Writing in JAMA Internal Medicine, Huang and colleagues noted that recent efforts evaluating hot flash treatments have focused on central nervous system (CNS) mechanisms.

“To our knowledge, few nonhormonal medications directed at CNS mechanisms have been found effective, and none yet appear as potent as estrogen therapy,” they wrote. “As a result, mechanisms underlying peripheral vasodilation may offer a more direct target for hot flash treatment.”

Huang and colleagues conducted a double-blinded, randomized clinical trial called the Flushing Reduction Associated With Nitrates study — to compare the safety and efficacy of transdermal nitroglycerin (NTG) with placebo over 12 weeks in 141 women aged 40 to 62 years who experienced at least seven hot flashes per day. Among them, 70 were assigned to receive a NTG patch (Mylan Pharmaceuticals) and the rest were assigned to placebo.

The initial NTG dose was 0.2 mg/h at baseline and ranged from 0.2 to 0.6 mg/h daily throughout the study period. The researchers hypothesized that NTG may decrease “vasomotor symptoms by suppressing [nitric oxide]-mediated peripheral vasodilation.”

Over the first 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 a day. Meanwhile, the change in moderate to severe hot flashes with NTG vs. placebo was -1.1 (95% CI, -2.2 to 0) episodes per day.

At 12 weeks, however, NTG treatment did not show a significant decrease in the frequency (-0.1; 95% CI, -1.2 to 0.4) nor the severity of hot flashes (-0.5; 95% CI, -1.6 to 0.7) compared with placebo, according to the researchers.

Additionally, Huang and colleagues reported that 47 NTG participants reported headaches in the first week compared with four placebo participants. Only one participant in each group reported headaches by 12 weeks.

The researchers noted that NTG remained associated with reductions in hot flash frequency and severity at 12 weeks, but they also observed reductions in the placebo group, eliminating treatment outcome differences.

“It is possible that continuous NTG therapy was initially more efficacious in suppressing hot flashes, but participants assigned to the placebo group experienced progressive, natural resolution of their hot flashes (i.e., greater reversion to the mean) over time,” they wrote. “Alternately, early treatment benefits associated with NTG could have plateaued if sustained administration of NTG eventually brought about compensatory increases in alternate peripheral vasodilation mechanisms independent of [nitric oxide].”

Huang and colleagues concluded the findings do not support the use of NTG as treatment for menopause-associated vasomotor symptoms.

“The bottom line is that our study doesn’t allow us to recommend nitroglycerin skin patches as a strategy for consumers to suppress hot flashes in the long term,” Huang said in the release. “But our study suggests that there may be promise in this overall approach to treating a common condition in midlife women. The menopause field is still lacking in effective treatment approaches that don’t involve hormones.”

References:

• Doctors test chest pain medication to treat hot flashes. https://www.ucsf.edu/news/2023/06/425476/doctors-test-chest-pain-medication-treat-hot-flashes. Published June 5, 2023. Accessed June 5, 2023.
• Huang A, et al. JAMA Intern Med. 2023;doi:10.1001/jamainternmed.2023.1977.