Table 4.

Placebo-Controlled Trials of Low-Dose Estrogen Preparations in Hot Flash Relief22–30

Author, Year (Reference)PatientsInterventionsDurationOutcomes
Bachmann, 2007 (22)425 menopausal women with ≥7 hot flashes per day or ≥50 hot flashes per weekTransdermal E2 0.023/levonorgestrel (LNG) 0.0075 mg/d or transdermal E2 0.014 mg/d versus placebo12 weeksReduced 74%, P < .001 for E2/LNG; 55% P = .039 for E2 alone, 39% with placebo
Diem, 2006 (23)417 largely asymptomatic menopausal women aged 60 to 80 yearsTransdermal E2 0.014 mg/d versus placebo2 yearsOnly 16% reported hot flashes at baseline; no significant difference in hot flash improvement versus placebo
Notelovitz, 2000 (29)333 menopausal women with ≥56 hot flashes per weekOral E2 0.5 mg/d or 1 mg/d versus placebo12 weeksReduced, with E2 0.5 mg/d (P = .007) and 1 mg/d (P < .001) versus placebo; more patients on E2 1 mg/d responded
Panay, 2007 (28)575 menopausal women with ≥50 hot flashes per weekOral E2 0.5/NETA 0.1 mg/d, E2 0.5/NETA 0.25 mg/d, or placebo24 weeksReduced 81% with 0.5/0.1 mg/d; 86% with 0.5/0.25 mg/d; 52% with placebo (P ≤ .001 for both treatment groups); significant reduction at week 3 maintained through week 24
Rebar, 2000 (24)204 menopausal womenEE 0.3 mg/d versus placebo12 weeksReduced total symptoms score and Kupperman index versus placebo (P < .05)
Speroff, 1996 (27)324 menopausal women with 56 to 140 hot flashes per weekTransdermal E2 0.02 mg/d or 0.04 mg/d versus placeboTwo 12-week studiesReduced by 84%; with 0.02 mg/d at weeks 2 to 11 and with 0.04 mg/d at weeks 2 to 12 in Study 1.
In Study 2, decrease was significant versus placebo with 0.02 mg/d at weeks 2 to 12 and with 0.04 mg/d at weeks 4 to 12
Speroff, 2000 (30)Study 1: 219 women with ≥10 hot flashes per weekEE/NETA 0.01/0.2 mg/d, 0.025/0.5 mg/d, 0.05/1 mg/d, or 0.1/1 mg/d versus placeboStudy 1: 16 weeksReduced by week 4 in Study 1 and by week 5 in Study 2 (P < .05).
Study 2: 266 women with ≥56 hot flashes per weekStudy 2: 12 weeks (did not include the 0.01/0.2-mg dose)Reductions were dose-related.
Utian, 1999 (26)196 menopausal women with ≥56 hot flashes per weekTransdermal E2 0.025 mg/d, 0.05 mg/d, or 0.1 mg/d versus placebo12 weeksReduced at 12 weeks by 86% with E2 0.025 mg/d and 97% with both E2 0.05 mg/d and E2 0.1 mg/d versus 55% with placebo (P < .05 for all groups)
Utian, 2001 (25)241 menopausal women with ≥7 hot flashes per day or ≥50 hot flashes per weekCEE 0.625 mg/d, 0.45 mg/d, 0.3 mg/d, CEE/MPA 0.625/2.5 mg/d, 0.45/2.5 mg/d, 0.45/1.5 mg/d, 0.3/1.5 mg/d, placebo1 yearReduced with CEE 0.625/MPA 2.5 mg/d and all lower combination doses; CEE 0.625 mg/d reduced hot flashes more than CEE 0.45 mg/d or 0.3 mg/d alone (P < .05). Significant reductions versus placebo over 12 weeks starting at week 2 (0.625 mg/d, 0.45 mg/d, 0.625/2.5 mg/d, 0.45/2.5 mg/d) or week 3 (0.3 mg/d, 0.45/1.5 mg/d, or 0.3/1.5 mg/d)
  • E2, 17β-estradiol; NETA, norethindrone acetate; EE, esterified estrogen; CEE, conjugated equine estrogen; MPA, medroxyprogesterone acetate; LNG, levonorgestrel.