Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes

Abstract

Study objectives: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes.

Design: 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks.

Setting: Academic research centers.

Participants: 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day.

Measurements and results: Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine).

Conclusions: Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality.

Clinical trial registration: NCT01418209 at www.clinicaltrials.gov.

Keywords: estradiol; hot flashes; menopause; randomized trial; sleep; venlafaxine.

© 2014 Associated Professional Sleep Societies, LLC.

Figures

Figure 1

Participant flow diagram for data collection of sleep outcome measures.

Figure 2A

Mean change in ISI from Baseline to Week 8 by treatment assignment overall and within risk subgroups. The dotted vertical line indicates the overall absolute mean difference between treatment groups. * Adjusted absolute mean differences and interaction P-values are computed from a repeated measures model estimating mean week 4 and 8 ISI as a function of treatment arm, site, baseline ISI, the subgroup of interest, and the interaction between treatment assignment and subgroup. ** Mean week 8 ISI – baseline ISI difference.

Figure 2B

Mean change in ISI from Baseline to Week 8 by treatment assignment overall and within risk subgroups. The dotted vertical line indicates the overall absolute mean difference between treatment groups. * Adjusted absolute mean differences and interaction P-values are computed from a repeated measures model estimating mean week 4 and 8 ISI as a function of treatment arm, site, baseline ISI, the subgroup of interest, and the interaction between treatment assignment and subgroup. ** Mean week 8 ISI – baseline ISI difference.

Figure 3A

Mean change in PSQI from Baseline to Week 8 by treatment assignment overall and within risk subgroups. The dotted vertical line indicates the overall absolute mean difference between treatment groups. * Adjusted absolute mean differences and interaction P-values are computed from a repeated measures model estimating mean week 4 and 8 PSQI as a function of treatment arm, site, baseline PSQI, the subgroup of interest, and the interaction between treatment assignment and subgroup. ** Mean week 8 PSQI – baseline PSQI difference.

Figure 3B

Mean change in PSQI from Baseline to Week 8 by treatment assignment overall and within risk subgroups. The dotted vertical line indicates the overall absolute mean difference between treatment groups. * Adjusted absolute mean differences and interaction P-values are computed from a repeated measures model estimating mean week 4 and 8 PSQI as a function of treatment arm, site, baseline PSQI, the subgroup of interest, and the interaction between treatment assignment and subgroup. ** Mean week 8 PSQI – baseline PSQI difference.