Table 4.
Double-Blind Randomized Placebo-Controlled Trials Showing Effect of Estrogen and/or Progestin Therapy on Perceived Sleep Quality
| Author | Study Population | Sample Size | Hormone Preparation | Duration | Treatment Measure | Results*,† |
|---|---|---|---|---|---|---|
| Perceived sleep measures | ||||||
| Welton et al[109] | Postmenopausal 50–69 years No sleep complaints |
3721 | Continuous combined CEE 0.625 mg/day þMPA 2.5/5.0 mg/day versus placebo | Median of 10 years | WHQ (includes three items that address sleep) | HT >placebo |
| Diem et al[123] | Postmenopausal 60–80 years No sleep complaint required |
417 | E2 0.014 mg/day patch versus placebo | 2 years | Likert scale (includes one item that addresses sleep) | HT = placebo |
| Nielsen et al[110] | Postmenopausal 40–65 years No sleep complaint required |
335 | Intranasal E2 150 or 300 •g/day +cyclic-dosed OMP 200 mg/day (if intact uterus) | 2 years | WHQ (includes two items that address sleep) | HT >placebo |
| Heinrich and Wolf[124] | Postmenopausal 58–75 years No sleep complaint required |
35 | Oral E2 2 mg/day +OMP 100 mg/day versus oral E2 2 mg/day versus placebo | 24 weeks | Perceived sleep problems (two items) | HT = placebo |
| Levine et al[120] | Postmenopausal 40–70 years Trial 1: No symptoms Trial 2: ≥8 VMS/day |
Trial 1: 474 Trial 2: 205 |
Trial 1: Continuous combined transdermal E2 50 •g/day +NE 140-, 250-, or 400-•g/day patch versus E2 50 •g/day patch alone Trial 2: Continuous combined transdermal E2 50 •g/day +NE 140-, 250-, or 400 •g/day patch versus placebo |
Trial 1: 52 weeks Trial 2: 12 weeks |
WHI Insomnia Rating Scale (WHIIRS) | Trial 1: All HT preparations >baseline E2 +NE =E2 alone Trial 2: All HT preparations >placebo → Improvement correlated with reduction in VMS |
| Gambacciani et al[119] | Postmenopausal 45–55 years Menopause-related symptoms (VMS, insomnia, anxiety, and/or mood swings) required | 60 | CEE 0.3 mg/day +MPA 2.5 mg/day versus CEE 0.3 mg/day +OMP 100 mg/day versus calcium carbonate 1000 mg/day as control | 12 weeks | Visual Analog Scale of perceived sleep problems | Both HT preparations >calcium control CEE/OMP >CEE/MPA |
| Brunner et al[111] | Postmenopausal 50–79 years No sleep complaint required |
10,739 (subgroup = 1189) | Continuous combined CEE 0.625 mg/day versus placebo | 1 year (3 years for subgroup) | WHI Insomnia Rating Scale (five items) | HT >placebo (at 1 year) HT = placebo (at 3 years) |
| Schürmann et al[112]] | Postmenopausal 45–65 years Reporting VMS but no sleep complaint required |
225 | Continuous combined E2 1 mg/day +DRSP 1 mg/day versus E2 1 mg/day +DRSP 2 mg/day versus E2 1 mg/day +DRSP 3 mg/day versus placebo |
16 weeks | Daily diary rating | All HT preparations >placebo |
| Vestergaard et al[113] | Peri-and postmenopausal 45–58 years No sleep complaint required | 1006 | Continuous oral E2 1–2 mg/day (and cyclic NE 1 mg/day if intact uterus) versus no treatment (i.e., no placebo was used) | 5 years | Modified Greene Climacteric scale (including items that address sleep related and unrelated to VMS) | Both HT preparations >no treatment (sleeping problems related to VMS) Both HT preparations = no treatment (sleeping problems unrelated to VMS) |
| Hays et al[114] | Postmenopausal 50–79 years No sleep complaint required |
16,608 (subgroup = 1511) | Continuous combined CEE 0.625 mg/day +MPA 2.5 mg/day versus placebo | 1 year (3 years for subgroup) | WHI Insomnia Rating Scale (five items addressing sleep) | HT >placebo (at 1 year) HT = placebo (at 3 year) HT >placebo (subgroup with VMS at 3yrs) |
| Gambacciani et al[115] | Postmenopausal Mean age 54 years No sleep complaint required |
50 | Continuous combined oral E2 1 mg/day +NE 0.5 mg/day versus calcium-vitamin control group | 12 weeks | WHQ (includes three items that address sleep) | HT >placebo |
| Polo-Kantola et al,[129] | Postmenopausal 47–65 years No sleep complaint required |
63 | Age <56 years: E2 gel 2.5 g/day versus placebo Age ≥56 years: E2 patch 50 •g/day versus placebo | Crossover trial: 3 months per arm | Visual Analog Scales (eight sleep complaints) | E2 >placebo (<56 years) E2 >placebo (≥56 years) |
*
Effect of first treatment was greater than the effect of second treatment when `>' used.
†
Effect of first treatment was not different than the effect of second treatment when `=' used.
CEE, conjugated equine estradiol; WHQ, Women's Health Questionnaire; HT, hormone therapy (estrogen combined with a progestin); MPA, medroxyprogesterone acetate; E2, 17-β-estradiol; OMP, oral micronized progesterone; VMS, vasomotor symptoms; NE, norethindrone; DRSP, drospirenone; WHI, Women's Health Initiative.