TABLE 2.
Mean systemic estradiol levels at baseline and throughout studies of low-dose and ultralow-lose vaginal estrogen therapies measured by mass spectrometry-based assays
| Assay | Dose | Treatment | n | Study duration | Mean BL (pg/mL) | Mean Cmax (pg/mL) | Mean Cavga (pg/mL) | Mean AUC0-24 (pg h/mL) | Reference |
| GC/MS/MS | 25 μg | E2 softgel insert; Placebo | 18 17 | 12 wks | 3.6 (E2) 4.5 (P) | Day 1 29.8 (E2); 6.6 (P) Day 14 15.7 (E2); 5.5 (P) | Day 1 9.1 (E2); 4.9 (P) Day 14 7.1 (E2); 4.3 (P) | Day 1 217.4 (E2); 116.6 (P) Day 14 171.6 (E2); 104.2 (P) | Archer et al, 201726 |
| LC/MS/MS | 25 μg | E2 softgel insert (single dose) | 36 | 1 d | NR | 31.0 | NR (9.1) | 218.7 | Data on file45b |
| E2 tablet (single dose) | 36 | 1 d | NR | 59.8 | NR (22.7) | 545.4 | Data on file45b | ||
| GC/MS | 25 μg | E2 tablet | 27 | 83 d | 4.0 | Day 1: 43 Day 14: 25 Day 83: 18 | Day 1: 19.8 Day 14: 18.3 Day 83: 9.4 | Day 1: 476.1 Day 14: 438.9 Day 83: 225.9 | Eugster-Hausmann et al, 201027 |
| GC/MS | 25 μg | E2 tablet | 10 | 7 d | 3.1 | 21.4 | 16.7 | 401 | Labrie et al, 200928 |
| GC/MS/MS | 10 μg | E2 softgel insert; Placebo | 19 17 | 12 wks | 4.9 | Day 1 10.9 (E2); 6.6 (P) Day 14: 7.3 (E2) 5.5 (P) | Day 1: 5.8 (E2) 4.9 (P) Day 14: 4.6 (E2) 4.3 (P) | Day 1: 138.2 (E2) 116.6 (P) Day 14: 110.1 (E2) 104.2 (P) | Archer et al, 201726 |
| LC/MS/MS | 10 μg | E2 softgel insert (single dose) | 35 | 1 d | NR | 21.2 | NR (7.4) | 178.2 | Data on file45b |
| E2 tablet (single dose) | 35 | 1 d | NR | 32.5 | NR (14.8) | 355.2 | Data on file45b | ||
| GC/MS | 10 μg | E2 tablet | 29 | 83 d | 3.2 | Day 1: 24 Day 14: 8 Day 83: 7.5 | Day 1: 9.4 Day 14: 6.6 Day 83: 4.6 | Day 1: 225.4 Day 14: 157.5 Day 83: 111.4 | Eugster-Hausmann et al, 201027 |
| GC/MS/MS | 4 μg | E2 softgel insert; Placebo | 18 17 | 12 wks | 3.9 | Day 1: 6.5 (E2); 6.6 (P) Day 14: 4.8 (E2); 5.5 (P) | Day 1: 3.9 (E2); 4.9 (P) Day 14: 3.6 (E2); 4.3 (P) | Day 1: 91.7 (E2); 116.6 (P) Day 14: 87.2 (E2); 104.2 (P) | Archer et al, 201726 |
| GC/MS/MS | 0.3 mg | CEE cream | 24 | 7 d | 3.7 | 12.8 | NR (9.6) | 231 | Dorr et al, 201029 |
AUC0-24, area under the curve over 24 hours; BL, baseline; Cavg, average concentration; CEE, conjugated equine estrogens; Cmax, maximum concentration; E2, 17β-estradiol; GC, gas chromatography; LC, liquid chromatography; MS, mass spectrometry; MS/MS, tandem mass spectrometry; NR, not reported (for average E2 levels with NR, AUC0-24 [if reported] was divided by 24 to calculate the average); P, placebo; UD, undetectable (below limit of detection).
aOr level reported but specified as Cavg.
bFrom same study reported by Pickar et al.50