TABLE 1.
Assay | Dose | Treatment | n | Study duration | Mean BL (pg/mL) | Mean Cmax (pg/mL) | Mean Cavga (pg/mL) | Mean AUC0-24 (pgh/mL) | Reference |
RIA | 25 μg | E2 tablet | 59 | 48 wks | 4.1 | NR | Weeks 24 & 48: 9.8 | NR | Weisberg et al, 200515 |
RIA | 25 μg | E2 tablet | 19 | 12 wks | 7.0 | Day 1: 51 Week 12: 49 | Day 1: 22 Week 12: 23 | Day 1: 538 Week 12: 563 | Notelovitz et al, 200216 |
RIA | 25 μg | E2 tablet | 6 | 12 wks | 7.5 | 20.4 | Week 2: NR (15.8) Week 12: NR (16.4) 13.6 (after last tablet) | Week 2: 380.0 Week 12: 392.5 | Nilsson and Heimer, 199519 |
RIA | 25 μg | E2 tablet | 24 | 14 d | 9.5 | Day 1: 42.8 Day 14: 21.8 | Day 14: 16 (24 h) | NR | Nilsson and Heimer, 199220 |
RIA | 25 μg | E2 tablet (1x/wk) | 17 | 52 wks | 10.5 | NR | Week 2: 10.1 Week 12: 9.9 Week 52: 10.8 | NR | Mettler and Olsen, 199121 |
RIA | 25 μg | E2 tablet (2x/wk) | 34 | 52 wks | 9.6 | NR | Week 2: 9.3 Week 12: 9.6 Week 52: 11.3 | NR | Mettler and Olsen, 199121 |
RIA | 25 μg | E2 tablet | 80 | 24 wks | NR (≤30)b | NR | Week 24: 5% of women >49b | NR | Rioux et al, 200075 |
RIA | 10 μg | E2 tablet | 23 | 12 wks | 7.6 | Day 1: 35 Week 12: 22 | Day 1: 15 Week 12: 11 | Day 1: 349 Week 12: 264 | Notelovitz et al, 200216 |
RIA | 10 μg | E2 tablet | 24 | 14 d | 9.5 | Day 1: 24.5 Day 14: 15.0 | Day 14: 13, hour 24 | NR | Nilsson and Heimer, 199220 |
RIA | 10 μg | E2 tablet | 336 | 52 wks | 5.2 | NR | Week 52: 6.1 | NR | Ulrich et al, 201014 |
RIA | 0.3 mg | CEE cream | 20 | 4 wks | 8 (with placebo) | NR | 13 | NR | Mandel et al, 198322 |
RIA | 7.5 μg/d | E2 ring; Untreated | 27 27 | 12 mos | 3.7 (E) 4.2 (U) | NR | 4.2 (E2) 4.1 (U) | NR | Naessen and Rodriguez-Macias, 200217 |
RIA | 7.5 μg/d | E2 ring; Untreated | 20 10 | 6 mos | 4.4 (E) 3.5 (U) | NR | 6 mos: 5.7 (E2); 3.0 (U) | NR | Naessen et al, 199718 |
RIA | 8.0 μg/d | E2 ring | 126 | 48 wks | 4.4 | NR | Week 24: 13.3 Week 48: 5.5 | NR | Weisberg et al, 200515 |
RIA | 9.0 μg/d | E2 ring | 222 | 24 wks | <5.5 (UD) | NR | Within postmenopausal rangec | NR | Smith et al, 199323 |
RIA | 6.6 μg/d | E2 ring | 11 | 84 d | <12.3 (UD) | Median at 2 h: 63.5 (range 29.4-158.8) | Median Day 2: 19.1 Days 7, 14, 28, 84: <12.3 (UD) | NR | Holmgren et al, 198924 |
RIA | 20.2 μg/d | E2 ring | 11 | 84 d | <12.3 (UD) | Median at 2 h: 96.4 (range 72.7-231.8) | Median Day 2: 51.8 Days 7, 14, 28, 84: <12.3 (UD) | NR | Holmgren et al, 198924 |
Bioassay | 10 μg | E2 creamd | 7 | 12 wks | 2.0 (E2) 1-3 (U) | Initial: 3.1 Week 3: 3.8 Week 12: 5.7 | NR | NR | Santen et al, 200276 |
ELISA | 25 μg | E2 tablet | 27 | 12 wks | 7.6 | NR | 8.9 | NR | Manonai et al, 200125 |
IC | 25 μg | E2 tablet; Placebo | 828 784 | 12 mos | 15.7 (E) 14.2 (P) | NR | 4 mos: 17.3 (E); 15.1 (P) 12 mos: 15.5 (E); 13.8 (P) | NR | Simunic et al, 200377 |
NR | 25 μg | E2 tablet | 48 | 24 wks | <2.7 | NR | <2.7e | NR | Dugal et al, 200078 |
AUC0-24, area under the curve over 24 hours; BL, baseline; Cavg, average concentration; CEE, conjugated equine estrogens; Cmax, maximum concentration; E2, 17β-estradiol; ELISA, enzyme-linked immunosorbent assay; GC, gas chromatography; IC, immunochemical (Ortho-Clinical Diagnostics); 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; RIA, radioimmunoassay; U, untreated; UD, undetectable (below limit of detection).
aOr level reported but specified as Cavg.
bReported percentage of women who had levels > postmenopausal range (>49 pg/mL); basal level of ≤30 pg/mL based on inclusion criteria.
cE2 levels were in postmenopausal range (27.2-68.1 pg/mL) and below limit of detection (5.5 pg/mL) before and during (time not specified) treatment.23
dDiluted Estrace given daily during first 3 weeks then twice weekly for 9 weeks.76
eBlood E2 levels were within the normal range for postmenopausal women (<2.7 pg/mL) after 24 weeks of treatment.78