Placebo-Controlled Trials of Low-Dose Estrogen Preparations in Hot Flash Relief22–30
| Author, Year (Reference) | Patients | Interventions | Duration | Outcomes |
|---|---|---|---|---|
| Bachmann, 2007 (22) | 425 menopausal women with ≥7 hot flashes per day or ≥50 hot flashes per week | Transdermal E2 0.023/levonorgestrel (LNG) 0.0075 mg/d or transdermal E2 0.014 mg/d versus placebo | 12 weeks | Reduced 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 years | Transdermal E2 0.014 mg/d versus placebo | 2 years | Only 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 week | Oral E2 0.5 mg/d or 1 mg/d versus placebo | 12 weeks | Reduced, 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 week | Oral E2 0.5/NETA 0.1 mg/d, E2 0.5/NETA 0.25 mg/d, or placebo | 24 weeks | Reduced 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 women | EE 0.3 mg/d versus placebo | 12 weeks | Reduced total symptoms score and Kupperman index versus placebo (P < .05) |
| Speroff, 1996 (27) | 324 menopausal women with 56 to 140 hot flashes per week | Transdermal E2 0.02 mg/d or 0.04 mg/d versus placebo | Two 12-week studies | Reduced 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 week | EE/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 placebo | Study 1: 16 weeks | Reduced by week 4 in Study 1 and by week 5 in Study 2 (P < .05). |
| Study 2: 266 women with ≥56 hot flashes per week | Study 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 week | Transdermal E2 0.025 mg/d, 0.05 mg/d, or 0.1 mg/d versus placebo | 12 weeks | Reduced 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 week | CEE 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, placebo | 1 year | Reduced 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.