Continuous nitroglycerin therapy fails to improve sleep quality in postmenopausal women with nocturnal hot flashes: Study

Despite this, data from daily symptom diaries and questionnaires revealed an important finding: women in the NTG and placebo groups who experienced fewer nighttime hot flashes also reported better sleep quality and less disruption. This highlights the strong link between managing hot flashes and improving sleep during menopause. The findings were published online in the American Journal of Obstetrics and Gynecology.

Hot flashes, a common symptom during menopause affecting up to 80% of Western women, are often linked to sleep disturbances in midlife. Despite this, limited prospective data confirm the exact role of hot flashes in disrupting sleep or whether clinical therapies that alleviate hot flashes also improve sleep.

To address this gap, Alison J. Huang, Department of Medicine, University of California San Francisco, San Francisco, CA, and colleagues conducted a study to evaluate the effects of continuous nitroglycerin therapy on sleep quality in perimenopausal and postmenopausal women experiencing frequent hot flashes. The study also aimed to explore the relationship between changes in hot flashes and sleep disruption in this population, providing valuable insights into how symptom management might influence sleep outcomes.

For this purpose, the researchers analyzed sleep data from a randomized, double-blinded, placebo-controlled trial that evaluated continuous transdermal NTG therapy to suppress nitric oxide-mediated vasodilation in perimenopausal and postmenopausal women experiencing hot flashes. Participants were randomly assigned to receive uninterrupted transdermal NTG (0.2–0.6 mg/hour) or a placebo over 12 weeks. Nocturnal hot flashes that awakened participants were evaluated using 7-day symptom diaries at baseline, 5 weeks, and 12 weeks.

Sleep disruption, measured as wakefulness after sleep onset (WASO), was evaluated through validated sleep diaries. In contrast, global sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), where scores ranged from 0 (best) to 21 (worst). Mixed linear models were employed to examine changes in sleep quality and disruption, and the relationship between nocturnal hot flash frequency and sleep outcomes over the study period. These analyses accounted for baseline values, age, race, and ethnicity, providing a comprehensive understanding of how managing hot flashes might influence sleep quality.

The following were the key findings of the study:

• The study included 141 participants (70 assigned to NTG and 71 to placebo) with a mean age of 54.6 years.
• At baseline, participants experienced an average of 10.8 hot flashes per day, including 2.6 nocturnal hot flashes that caused awakenings.
• Hot flashes were the most frequently reported cause of nocturnal awakenings, with 62.6% of participants waking due to hot flashes at least twice nightly.
• Over 5 and 12 weeks, the mean frequency of nocturnal hot flashes causing awakenings decreased in both groups (NTG: −0.9 episodes/night; placebo: −1.0 episodes/night).
• Sleep disruption, as measured by average nightly wakefulness after sleep onset (WASO), decreased in both groups (NTG: −10.1 minutes; placebo: −7.3 minutes).
• Global sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI), also improved in both groups (NTG: −1.3 points; placebo: −1.2 points).
• There were no significant differences between the NTG and placebo groups in changes in sleep outcomes, including PSQI sleep quality scores, from baseline to 5 and 12 weeks (P≥.05 for all).
• Greater reductions in nocturnal hot flash frequency over 5 and 12 weeks were associated with greater improvements in PSQI sleep quality scores (β= −0.30) and reduced sleep disruption measured by WASO (β= −1.88) in the combined sample.

"The findings showed that continuous NTG therapy did not improve sleep quality more than placebo, but reductions in nocturnal hot flash frequency were linked to better sleep quality and reduced disruptions in both groups," the researchers concluded.

Reference:

Pei, M., Gibson, C. J., Schembri, M., Raghunathan, H., Grady, D., Ganz, P., & Huang, A. J. (2024). Hot flashes and sleep disruption in a randomized trial in menopausal women. American Journal of Obstetrics and Gynecology, 232(1), 102.e1-102.e9. https://doi.org/10.1016/j.ajog.2024.07.022