HOT FLASHES AND SLEEP DISRUPTION IN A RANDOMIZED TRIAL IN MENOPAUSAL WOMEN.

BACKGROUND: Hot flashes, common during menopause, affect up to 80% of Western menopausal women and are reported to contribute to sleep disturbances in midlife. Few prospective data are available to confirm the specific role of hot flashes in disrupting sleep in midlife women, however, or confirm whether changes in hot flashes in response to clinical therapies result in improvement in sleep. OBJECTIVE: To examine the effects of continuous nitroglycerin therapy on sleep quality in peri- and postmenopausal women with frequent hot flashes (pre-specified secondary trial endpoint), and to examine prospective associations between hot flashes and sleep disruption in this population. STUDY DESIGN: Sleep data were analyzed from a randomized, double-blinded, placebo-controlled trial of continuous transdermal nitroglycerin (NTG) therapy to suppress nitric oxide-mediated vasodilation in peri- or postmenopausal women with hot flashes. Participants were randomized to uninterrupted use of transdermal NTG (0.2-0.6 mg/hour) or placebo for 12 weeks. Nocturnal hot flashes awakening participants from sleep were evaluated using 7-day symptom diaries at baseline, 5 weeks, and 12 weeks. Sleep disruption (wake time after sleep onset, WASO) was assessed using validated sleep diaries, and global sleep quality was assessed by the validated Pittsburgh Sleep Quality Index (PSQI: range 0 [best] 21 [worst]) questionnaire. Mixed linear models examined changes in sleep quality and disruption, as well as the strength of associations between nocturnal hot flash frequency and sleep outcomes, over 5 and 12 weeks, adjusting for baseline values, age, race, and ethnicity. RESULTS: Among the 141 participants (70 to NTG and 71 to placebo, mean age 54.6 [±3.9] years), the mean baseline hot flash frequency was 10.8 (±3.5) per day, including 2.6 (±1.7) nocturnal hot flashes awakening participants. At baseline, hot flashes were the most commonly reported reason for nocturnal awakening, with 62.6% of participants reporting waking due to hot flashes at least twice nightly. Over 5 and 12 weeks, 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 WASO also decreased (NTG: -10.1 minutes, placebo: -7.3 minutes), and mean PSQI score improved (NTG: -1.3 points, placebo: -1.2 points). No significant between-group differences in change in sleep outcomes were detected from baseline to 5 and 12 weeks, including PSQI sleep quality score as a pre-specified secondary trial endpoint (P ≥ .05 for all). Greater improvement in nocturnal hot flash frequency over 5 and 12 weeks was associated with greater improvement in PSQI sleep quality score (ß= -0.30, P=.01) and sleep disruption reflected by WASO (ß= -1.88, P=.02) in the combined sample. CONCLUSION: Among menopausal women in a randomized trial of continuous NTG therapy for hot flashes, hot flashes were the most frequently reported cause of nocturnal awakenings. Compared to placebo, continuous NTG therapy did not result in greater improvements in sleep quality from baseline to 5 and 12 weeks. Based on night-by-night symptom diaries and questionnaires, however, greater improvement in nocturnal hot flash frequency in both groups was associated with greater improvement in sleep quality and disruption.

Recurrent Urinary Tract Infection in Older Outpatient Women.

This Clinical Insights discusses special considerations in recurrent urinary tract infection diagnosis and management in older women.

Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal Women: A Randomized Clinical Trial.

Importance: Due to the potential risks of long-term systemic estrogen therapy, many menopausal women are interested in nonhormonal treatments for vasomotor symptoms. Physiologic studies indicate that nitric oxide plays a key role in mediating hot flash-related vasodilation, suggesting that nonhormonal medications that induce nitrate tolerance in the vasculature may offer therapeutic benefit for vasomotor symptoms. Objective: To determine whether uninterrupted administration of transdermal nitroglycerin (NTG) to induce nitrate cross-tolerance decreased the frequency or severity of menopause-related hot flashes. Design, Setting, and Participants: This randomized, double-blinded, placebo-controlled clinical trial included perimenopausal or postmenopausal women reporting 7 or more hot flashes per day who were recruited from northern California by study personnel at a single academic center. Patients were randomized between July 2017 and December 2021, and the trial ended in April 2022 when the last randomized participant completed follow-up. Interventions: Uninterrupted daily use of transdermal NTG (participant-directed dose titration from 0.2-0.6 mg/h) or identical placebo patches. Main Outcome Measures: Validated symptom diaries assessing changes in any hot flash frequency (primary outcome) and moderate-to-severe hot flash frequency over 5 and 12 weeks. Results: 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. Conclusions and Relevance: 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. Trial Registration: Clinicaltrials.gov Identifier: NCT02714205.