Table 2.
Comparisons of Symptom Rating Scores During Open-Label and Double-blind Treatment
| Meana |
|||||
|---|---|---|---|---|---|
| Measure | Past PMD | Phase | Least Squares (SE) | Arithmetic (SD) | P Valueb |
| CES-D score | Yes | OL Estradiol | 2.4 (1.0) | 2.4 (2.0) | .0004 |
| Placebo | 9.1 (1.0) | 8.8 (4.9) | |||
| Yes | OL Estradiol | 3.1 (0.5) | 3.1 (1.6) | >.99 | |
| DB Estradiol | 2.8 (0.5) | 2.8 (1.5) | |||
| No | OL Estradiol | 0.9 (0.4) | 0.9 (1.5) | >.99 | |
| Placebo | 1.1 (0.4) | 1.1 (1.8) | |||
| No | OL Estradiol | 1.4 (0.5) | 1.4 (2.2) | .13 | |
| DB Estradiol | 0.8 (0.5) | 0.8 (1.4) | |||
| HDRS score | Yes | OL Estradiol | 3.0 (0.9) | 3.0 (2.5) | .0004 |
| Placebo | 7.0 (0.9) | 6.6 (4.5) | |||
| Yes | OL Estradiol | 3.5 (0.7) | 3.6 (1.8) | >.99 | |
| DB Estradiol | 3.1 (0.7) | 3.1 (2.6) | |||
| No | OL Estradiol | 0.9 (0.2) | 0.9 (0.8) | >.99 | |
| Placebo | 0.9 (0.2) | 0.9 (0.9) | |||
| No | OL Estradiol | 0.8 (0.3) | 0.8 (1.1) | >.99 | |
| DB Estradiol | 0.7 (0.3) | 0.7 (1.1) | |||
| BDI score | Yes | OL Estradiol | 1.7 (0.8) | 1.7 (2.3) | .05 |
| Placebo | 4.4 (0.9) | 4.3 (3.7) | |||
| Yes | OL Estradiol | 1.7 (0.5) | 1.7 (1.8) | .42 | |
| DB Estradiol | 1.1 (0.5) | 1.1 (1.5) | |||
| No | OL Estradiol | 0.2 (0.1) | 0.2 (0.3) | .84 | |
| Placebo | 0.2 (0.1) | 0.2 (0.4) | |||
| No | OL Estradiol | 0.2 (0.1) | 0.2 (0.4) | .36 | |
| DB Estradiol | 0.04 (0.1) | 0.04 (0.2) | |||
| Visual analog scale | |||||
| Depression | Yes | OL Estradiol | 5.5 (2.3) | 5.5 (6.1) | .01 |
| Placebo | 14.1 (2.3) | 14.0 (10.2) | |||
| Yes | OL Estradiol | 5.3 (1.7) | 5.5 (3.5) | >.99 | |
| DB Estradiol | 6.7 (1.7) | 6.8 (7.4) | |||
| No | OL Estradiol | 2.8 (0.4) | 2.8 (1.7) | >.99 | |
| Placebo | 2.6 (0.4) | 2.5 (1.8) | |||
| No | OL Estradiol | 3.0 (0.5) | 2.9 (2.2) | .45 | |
| DB Estradiol | 2.4 (0.5) | 2.4 (1.1) | |||
| Anxiety | Yes | OL Estradiol | 8.6 (3.9) | 8.6 (10.4) | .07 |
| Placebo | 18.5 (3.9) | 18.2 (17.6) | |||
| Yes | OL Estradiol | 11.2 (2.7) | 11.5 (9.7) | >.99 | |
| DB Estradiol | 9.7 (2.6) | 9.6 (9.0) | |||
| No | OL Estradiol | 3.0 (0.6) | 3.0 (2.3) | >.99 | |
| Placebo | 2.8 (0.6) | 2.9 (2.3) | |||
| No | OL Estradiol | 4.1 (1.8) | 4.3 (5.7) | >.99 | |
| DB Estradiol | 5.6 (1.8) | 5.3 (8.4) | |||
| Irritability | Yes | OL Estradiol | 10.1 (3.8) | 10.1 (10.4) | .11 |
| Placebo | 20.4 (3.8) | 20.4 (17.5) | |||
| Yes | OL Estradiol | 11.0 (2.3) | 11.1 (8.9) | .11 | |
| DB Estradiol | 7.6 (2.3) | 7.7 (7.1) | |||
| No | OL Estradiol | 2.7 (0.5) | 2.8 (1.6) | .83 | |
| Placebo | 2.8 (0.5) | 2.8 (2.3) | |||
| No | OL Estradiol | 4.5 (1.2) | 4.6 (5.8) | .43 | |
| DB Estradiol | 2.3 (1.2) | 2.3 (1.1) | |||
| Avoid socializing | Yes | OL Estradiol | 5.8 (2.3) | 5.8 (6.3) | .03 |
| Placebo | 12.4 (2.3) | 12.4 (10.5) | |||
| Yes | OL Estradiol | 6.5 (1.7) | 7.0 (8.9) | >.99 | |
| DB Estradiol | 5.0 (1.7) | 4.9 (3.7) | |||
| No | OL Estradiol | 2.3 (0.4) | 2.3 (1.5) | >.99 | |
| Placebo | 2.5 (0.4) | 2.4 (1.8) | |||
| No | OL Estradiol | 2.6 (0.3) | 2.5 (1.4) | >.99 | |
| DB Estradiol | 2.5 (0.3) | 2.5 (1.0) | |||
| Early morning wakening | Yes | OL Estradiol | 9.6 (3.3) | 9.5 (10.0) | .04 |
| Placebo | 15.6 (3.3) | 15.8 (14.4) | |||
| Yes | OL Estradiol | 13.9 (2.7) | 13.7 (7.1) | >.99 | |
| DB Estradiol | 13.1 (2.6) | 13.5 (9.5) | |||
| No | OL Estradiol | 4.0 (1.0) | 4.1 (5.0) | >.99 | |
| Placebo | 3.3 (1.0) | 3.3 (3.2) | |||
| No | OL Estradiol | 3.5 (0.7) | 3.3 (1.7) | >.99 | |
| DB Estradiol | 3.5 (0.7) | 3.3 (3.6) | |||
| Anhedonia | Yes | OL Estradiol | 5.6 (2.3) | 5.6 (5.5) | .07 |
| Placebo | 12.4 (2.3) | 12.4 (11.3) | |||
| Yes | OL Estradiol | 7.3 (2.2) | 8.0 (8.8) | >.99 | |
| DBEstradiol | 6.1 (2.1) | 5.2 (3.7) | |||
| No | OL Estradiol | 2.1 (0.4) | 2.1 (1.3) | >.99 | |
| Placebo | 2.3 (0.4) | 2.3 (1.7) | |||
| No | OL Estradiol | 2.4 (0.3) | 2.4 (1.2) | >.99 | |
| DB Estradiol | 2.3 (0.3) | 2.4 (1.0) | |||
| Decreased energy | Yes | OL Estradiol | 10.9 (3.2) | 10.9 (9.3) | .18 |
| Placebo | 18.9 (3.2) | 18.9 (14.0) | |||
| Yes | OL Estradiol | 12.4 (3.2) | 12.7 (14.7) | >.99 | |
| DB Estradiol | 9.5 (3.1) | 9.6 (7.8) | |||
| No | OL Estradiol | 3.1 (0.6) | 3.1 (2.2) | >.99 | |
| Placebo | 2.9 (0.6) | 2.9 (2.0) | |||
| No | OL Estradiol | 3.2 (0.5) | 3.2 (1.7) | >.99 | |
| DB Estradiol | 3.0 (0.5) | 3.0 (2.0) | |||
| Disturbed sleep | Yes | OL Estradiol | 13.5 (3.8) | 13.5 (11.3) | .09 |
| Placebo | 22.8 (3.9) | 22.7 (17.7) | |||
| Yes | OL Estradiol | 21.6 (4.1) | 22.2 (14.9) | .20 | |
| DB Estradiol | 15.5 (4.1) | 15.6 (13.2) | |||
| No | OL Estradiol | 4.7 (1.7) | 4.8 (7.2) | >.99 | |
| Placebo | 4.3 (1.7) | 4.2 (5.1) | |||
| No | OL Estradiol | 3.6 (0.7) | 3.4 (1.9) | >.99 | |
| DB Estradiol | 3.9 (0.7) | 3.8 (4.2) | |||
| Unmotivated | Yes | OL Estradiol | 6.6 (2.7) | 6.6 (6.5) | .02 |
| Placebo | 14.9 (2.7) | 14.0 (12.8) | |||
| Yes | OL Estradiol | 5.8 (1.6) | 5.6 (4.7) | >.99 | |
| DB Estradiol | 6.7 (1.6) | 7.0 (7.4) | |||
| No | OL Estradiol | 3.3 (0.8) | 4.3 (7.8) | >.99 | |
| Placebo | 3.1 (0.8) | 2.7 (1.6) | |||
| No | OL Estradiol | 2.8 (0.4) | 3.4 (2.0) | >.99 | |
| DB Estradiol | 2.6 (0.4) | 2.6 (1.1) | |||
| Excess worry | Yes | OL Estradiol | 5.4 (3.0) | 5.4 (5.0) | .07 |
| Placebo | 14.2 (3.0) | 14.0 (16.4) | |||
| Yes | OL Estradiol | 7.9 (1.6) | 8.4 (7.6) | .55 | |
| DB Estradiol | 5.0 (1.5) | 5.1 (4.4) | |||
| No | OL Estradiol | 3.4 (0.9) | 3.5 (3.5) | >.99 | |
| Placebo | 3.5 (0.9) | 3.4 (3.9) | |||
| No | OL Estradiol | 2.7 (0.4) | 2.7 (1.6) | >.99 | |
| DB Estradiol | 2.7 (0.4) | 2.8 (1.8) | |||
| Decreased concentration | Yes | OL Estradiol | 9.1 (3.6) | 9.1 (8.2) | .18 |
| Placebo | 17.9 (3.6) | 17.9 (17.6) | |||
| Yes | OL Estradiol | 9.5 (2.5) | 9.9 (11.9) | .82 | |
| DB Estradiol | 7.6 (2.5) | 7.6 (6.4) | |||
| No | OL Estradiol | 3.5 (0.8) | 3.5 (3.4) | .82 | |
| Placebo | 2.9 (0.8) | 2.8 (2.4) | |||
| No | OL Estradiol | 2.7 (0.3) | 2.6 (1.6) | .82 | |
| DB Estradiol | 2.3 (0.3) | 2.3 (1.1) | |||
| Nighttime hot flushes | Yes | OL Estradiol | 1.2 (0.1) | 1.1 (0.3) | .43 |
| Placebo | 1.5 (0.1) | 1.4 (0.5) | |||
| Yes | OL Estradiol | 1.4 (0.2) | 1.4 (0.8) | .51 | |
| DB Estradiol | 1.3 (0.2) | 1.1 (0.3) | |||
| No | OL Estradiol | 1.1 (0.1) | 1.1 (0.2) | .43 | |
| Placebo | 1.2 (0.1) | 1.2 (0.3) | |||
| No | OL Estradiol | 1.1 (0.1) | 1.1 (0.3) | .20 | |
| DB Estradiol | 1.1 (0.1) | 1.0 (0.1) | |||
| Daytime hot flushes | Yes | OL Estradiol | 1.2 (0.1) | 1.2 (0.3) | .26 |
| Placebo | 1.5 (0.1) | 1.5 (0.5) | |||
| Yes | OL Estradiol | 1.2 (0.1) | 1.2 (0.3) | >.99 | |
| DB Estradiol | 1.1 (0.1) | 1.1 (0.3) | |||
| No | OL Estradiol | 1.2 (0.1) | 1.2 (0.2) | >.99 | |
| Placebo | 1.2 (0.1) | 1.2 (0.3) | |||
| No | OL Estradiol | 1.1 (0.03) | 1.1 (0.2) | .38 | |
| DB Estradiol | 1.0 (0.03) | 1.0 (0.1) | |||
Abbreviations: BDI, Beck Depression Inventory; CES-D, Center for Epidemiologic Studies-Depression Scale; DB, double-blind; HDRS, Hamilton Depression Rating Scale; OL, open-label; PMD, perimenopausal depression.
a
Least squares means were adjusted by PROC MIXED (SAS Institute Inc) using residual maximum likelihood methods, whereas arithmetic means are not adjusted.
b
P values represent post hoc Bonferroni comparisons of least squares means.