Abstract
OBJECTIVE: To evaluate prospective changes in psychological function among menopausal women using continuous nitroglycerin for hot flashes and examine repeated associations between psychological symptoms and hot flashes. METHODS: Menopausal women with ≥7 hot flashes/day were randomized to continuous transdermal nitroglycerin (0.2-0.4 mg/h) or placebo for 12 weeks. Psychological function was evaluated using the Center for Epidemiologic Studies-Depression Scale (CES-D), Generalized Anxiety Disorders-7 (GAD-7), and Menopause-Specific Quality of Life (MENQOL) Psychosocial Subscale. Linear mixed models examined treatment effects on mood symptoms from baseline to 5 and 12 weeks. Based on validated 7-day hot flash diaries, additional models examined associations between mood symptoms and hot flash frequency in both groups combined. RESULTS: Among the 141 randomized participants (mean 10.8±3.5 hot flashes/day), nitroglycerin therapy did not improve CES-D or GAD-7 scores (prespecified secondary outcomes) from baseline to 5 and 12 weeks compared with placebo. Greater hot flash frequency was associated with worse GAD-7 scores across all timepoints (β=0.05 per 1 hot flash, P =0.005), but no associations between hot flashes and CES-D or MENQOL Psychosocial scores were observed. Improvement in hot flash frequency was associated with improvement in MENQOL Psychosocial score (β=0.04 per 1 hot flash, P =0.03), but no associations between improvements in hot flashes and improvements in GAD-7 or CES-D scores were detected. CONCLUSIONS: In a randomized trial of continuous nitroglycerin, improvements in hot flash frequency did not consistently translate into improvements in mood. Clinicians caring for women with overlapping hot flashes and mood symptoms should consider other factors influencing midlife psychological function.