Table III. BMD trials—oral estradiol, estradiol valerate, esterified estrogens, estrone sulphate, estriol
| HRT regimesa |
Sample size |
Femoral |
Total |
Lumbar |
Reference |
|
(drop-outs) (n) |
neck (%)b |
hip (%)b |
spine (%)b |
|
|
| 10 years |
|
|
|
|
|
| Estradiol 2 + NETA 1 |
50 (19) |
NA |
NA |
15.9 |
1Eiken et al. (1996) |
| Estradiol 2 + cyclic NETA 1c |
50 (11) |
NA |
NA |
11.1 |
|
| Placeboc |
|
|
|
|
|
|
| 5 years |
|
|
|
|
|
| Estradiol valerate 2 + cyclic CPA |
115 (NA)d |
2.9 |
NA |
4.7 |
1Komulainen et al. (1999) |
| 93 calcium |
116 (NA)d |
|
|
|
|
|
| 4 years |
|
|
|
|
|
| Estradiol 2 + cyclic NETA 1 + calcium |
<110 (28) |
6.6 |
NA |
10.4 |
1Ravn et al. (1999)e,f |
| Placebo + calcium |
501 (134) |
|
|
|
|
|
| 3 years |
|
|
|
|
|
| Estradiol 2 + NETA 1 |
50 (NA)g |
NA |
NA |
19 |
2Nielsen et al. (1994) |
| Estradiol 2& + cyclic NETA 1 |
50 (NA)g |
NA |
NA |
15 |
|
| Placebo |
51 (NA)g |
|
|
|
|
| Estradiol 2 + cyclic NETAc |
20 (6) |
NA |
NA |
1.8 |
2Hasling et al. (1994) |
| 2000 calcium + 400 IU vitamin D |
17 (8) |
|
|
|
|
|
| 2 years |
|
|
|
|
|
| Estradiol valerate 2 + cyclic CPA |
115 (NA)d |
3.4 |
NA |
5.5 |
1Komulainen et al. (1997)i |
| 93 calcium |
116 (NA)d |
|
|
|
|
| Estradiol 2 + cyclic NETA 1 + calcium |
<110 (19) |
4.8 |
NA |
6.9 |
1Hosking et al. (1998)f |
| Placebo + calcium |
501 (93) |
|
|
|
|
| Estradiol 0.5 |
40 (3) |
4.0 |
NA |
–3.3 |
1Giske et al. (2002) |
| Estradiol 1 |
41 (6) |
4.2 |
NA |
4.3 |
|
| Estradiol 2 |
42 (5) |
4.1 |
NA |
5.3 |
|
| Placebo |
43 (12) |
|
|
|
|
| Estradiol 1 + NETA 0.25 |
44 (15) |
2.5 |
4.3 |
6.1 |
1Delmas et al. (2000) |
| Estradiol 1 + NETA 0.5 |
46 (17) |
1.7 |
4.5 |
6.3 |
|
| Placebo |
45 (12) |
|
|
|
|
| Estradiol valerate 2 + cyclic MPA |
26 (3) |
5.0 |
7.5 |
NA |
1Heikkinen et al., (1997) |
| Estradiol valerate 2 + long-cycle MPAj |
26 (5) |
3.5 |
7.0 |
NA |
|
| Placebo |
26 (1) |
|
|
|
|
| Estradiol 1.5 + cyclic desogestrel |
25 (5) |
NA |
NA |
10.0 |
2,1Marslew et al. (1991) |
| Estradiol valerate 2 + cyclic MPA |
25 (7) |
NA |
NA |
8.0 |
|
| Placebo |
|
|
|
|
|
| Estradiol valerate 2 + cyclic CPA |
25 (6) |
NA |
NA |
5.0 |
2,1Marslew et al. (1992) |
| Estradiol valerate 2 + cyclic LNG |
25 (6) |
NA |
NA |
6.0 |
|
| Placebo |
25 (1) |
|
|
|
|
| Estradiol 2 + estriol 1 + NETA |
70 (17) |
NA |
NA |
20.0 |
3Dören et al. (1995) |
| Estradiol valerate 2 + cyclic MPA |
70 (26) |
NA |
NA |
1.0 |
|
| No treatment |
70 (31) |
|
|
|
|
| Esterified estrogens 0.3 + |
101 (35) |
1.4 |
2.3 |
4.3 |
1Genant et al. (1997) |
| 1000 calcium |
|
|
|
|
|
| Esterified estrogens 0.625 + |
102 (48) |
2.6 |
3.2 |
5.3 |
|
| 1000 calcium |
|
|
|
|
|
| Esterified estrogens 1.25 + |
100 (64) |
3.1 |
4.2 |
7.6 |
| 1000 calcium |
|
|
|
|
|
| Placebo + 1000 calcium |
103 (41) |
|
|
|
|
| Estrone sulphate 0.3 + 1000 calcium |
28 |
NA |
NA |
–1.5 |
3Harris et al. (1991)k |
| Estrone sulphate 0.625 + 1000 calcium |
30 |
NA |
NA |
2.8 |
|
| Estrone sulphate 1.25 + 1000 calcium |
32 |
NA |
NA |
4.3 |
|
| Placebo + 1000 calcium |
30 |
|
|
|
|
| Estriol 2 + MPA 2.5 |
15 (0) |
NA |
NA |
9.9 |
3Itoi et al. (1997)l |
| 250 calcium supplement |
17 (0) |
|
|
|
|
| |
BMD1,2,3 = 1DEXA, 2DPA, 3QCT.
All daily doses in mg; MPA = medroxyprogesterone acetate; NETA = norethisterone (norethindrone) acetate; CPA = cyproterone acetate; LNG = levonorgestrel.
aOnly HRT treatment groups shown, other treatment within one trial (clodronate) not shown.
bPercentage change, relative to comparator treatment, no treatment or placebo, respectively, at the end of the study period.
cEstradiol 2 mg for 22 days and 1 mg for 6 days, respectively, of a 28-day cycle; placebo for the first 2 years only.
dOverall n = 29 (Komulainen et al., 1999) and n = 73 (Komulainen et al., 1997) drop-outs in four groups; identical baseline population.
eSame study as Hosking et al. (1998), see also Table II for second HRT group, actual number of patients assigned to each HRT regimen unknown.
fCounselling to improve dietary calcium intake if necessary.
gDrop-outs after 5 years: n = 22 (E + NETA), n = 25 (E + cyclic NETA), n = 21 (placebo); same baseline groups: Eiken et al. (1996) and Nielsen et al. (1994).
hHRT regimen also contains cyclic estriol (two doses), additionally 400 IU of vitamin D and 120 mg of calcium.
iStudy duration: 2.5 years, same baseline groups: Komulainen et al. (1997,1999).
jCyclic MPA given at 3 months interval only.
kOverall n = 32 drop-outs in four groups.
lSee also Table II for second HRT group.
