Nonsedating neurotransmitter-modulating supplement for nonvasomotor sleep disturbance in menopause

OBJECTIVE: To evaluate a GABAergic, melatonergic, and glutamatergic supplement for enhancing sleep quality in perimenopausal and postmenopausal women with low vasomotor symptom (VMS) burden. METHODS: A randomized, double-blind, placebo-controlled, decentralized trial (NCT07375095) was performed in healthy perimenopausal and postmenopausal women with moderate-to-severe sleep disturbance (patient-reported outcome measure information system sleep disturbance [PROMIS SD] SF 8b T-score ≥60) and minimal VMS (≤5 hot flashes and ≤2 night sweats/wk). Participants were randomized to a neurotransmitter-modulating supplement (NMS; L-theanine, gamma-aminobutyric acid, magnesium, S-adenosyl methionine, propyl gallate) or placebo for three weeks. Primary outcomes were changes in PROMIS SD and sleep-related impairment T-scores and responder rates. Secondary outcomes included diary-based total sleep time, sleep efficiency, and visual analog ratings of sleepiness and daytime functioning. RESULTS: Of 128 randomized participants, 127 completed the trial (NMS, n = 65; placebo, n = 62). Baseline characteristics and VMS frequency were similar between groups (3.0 ± 4.0 hot flashes and 1.9 ± 1.7 night sweats/wk). At week 3, NMS significantly improved PROMIS SD T-score (LS mean difference: -11.1 [95% CI, -13.6 to -8.6]; P = 0.0012) and responder rate (90.9% vs. 45.2%; P < 0.001) versus placebo. PROMIS sleep-related impairment T-score (-4.8 [95% CI, -7.3 to -2.3]; P < 0.001) and responder rate (50.8% vs. 32.2%; P = 0.047) also improved. All primary endpoints reached significance by week 2. NMS increased total sleep time by 40.9 minutes versus a 14.9-minute decrease with placebo (P < 0.001), and sleep efficiency improved by 7.4% versus 3.4% (P = 0.021). No between-group differences in adverse events were observed. CONCLUSION: In perimenopausal and postmenopausal women with disrupted sleep but minimal VMS, a NMS significantly improved sleep quality and duration.