Transdermal nitroglycerin yields modest, inconsistent hot flash relief

Continuous transdermal nitroglycerin reduced daily hot flash frequency by up to 69% at the maximum dose in a small single-arm study, but randomized data showed modest, imprecise reductions compared with placebo, according to results of a systematic review presented at The Menopause Society 2026 Annual Meeting in San Diego, California.¹

Hot flashes are the most frequent symptom of perimenopause and menopause, affecting 75% to 85% of women. An estimated 10% to 30% of women have symptoms severe enough to impair daily activities, work performance, and overall quality of life. Hormone therapy is widely considered the most effective treatment for moderate-to-severe hot flashes, but not all women are willing or able to take hormones, and the number of nonhormone treatments on the market has grown as a result.²

Review drew on 4 publications from 2 trials

Investigators followed PRISMA guidelines and searched PubMed, Embase, and the Cochrane Library from inception to March 2026. They assessed the effect of continuous transdermal nitroglycerin on hot flash frequency and related quality-of-life outcomes.

Four studies were included, with 89 participants receiving nitroglycerin and 71 receiving placebo. Three of the publications reported different outcomes from the same randomized controlled trial of 141 participants (70 nitroglycerin, 71 placebo). The fourth was a single-arm dose-escalation study of 19 participants who received nitroglycerin only.

Randomized data show imprecise reductions

In the randomized trial, the change in overall hot flashes at 12 weeks for the nitroglycerin group compared with placebo was −0.5 episodes/day (95% CI, −1.6 to 0.6). The change in moderate-to-severe hot flashes was −0.8 episodes/day (95% CI, −1.9 to 0.2).

Improvements in sleep and psychological function were inconsistent. Higher hot flash frequency was associated with worse sleep and anxiety, and hot flash patterns were associated with psychosocial quality of life.

In the single-arm study, hot flashes recurred after nitroglycerin was discontinued. Headache was the most frequent adverse event, affecting up to two-thirds of participants early in treatment.

The authors reported that continuous transdermal nitroglycerin may provide modest reductions in hot flash frequency and represents a potential nonhormonal option for postmenopausal women with contraindications to hormone therapy. They characterized the evidence as limited, imprecise, and inconsistent. They called for well-powered trials to clarify the efficacy, safety, and clinical utility of the treatment in this population.¹

Experts see promise but call for larger trials

"Finding effective nonhormonal treatments for hot flashes is important because many women are unable or prefer not to use hormone therapy, yet these symptoms can significantly affect sleep, daily functioning, and quality of life. Our findings suggest that transdermal nitroglycerin is an interesting potential nonhormonal approach, but the current evidence is still limited. Larger, well-designed trials are needed to determine whether this treatment can provide a meaningful benefit for patients," said Flavia Fairbanks Ruano, MD, PhD, lead author from the University of Miami Miller School of Medicine.

"Hot flashes can have a profound effect on sleep, daily functioning, work productivity, and quality of life. Although hormone therapy remains the most effective treatment for most women, there is an ongoing need for safe and effective nonhormone options. This review highlights transdermal nitroglycerin as a potentially promising approach, but the available evidence remains limited and inconsistent. Larger, well-designed studies are needed before its role in clinical practice can be determined," said Stephanie Faubion, MD, medical director for The Menopause Society, in a statement.²

References:

1. Ruano FF, Queiroz LF, Lemos M, Diniz AF, Ruano AH, Ruano R. Transdermal nitroglycerin for hot flashes in postmenopausal women: a systematic review. Poster. Presented at: The Menopause Society Annual Meeting. October 20-24, 2026. San Diego, California.
2. Transdermal nitroglycerin shows limited but potential benefit for menopausal hot flashes. News release. The Menopause Society. Accessed October 20, 2026.