Table 1 Characteristics of studies and population baseline

David M et al

2000

309

E:66.3(7.6)

E + P:65.6(6.5)

C:65.6(7.3)

0.625 mg conjugated estrogen+ 2.5 mg medroxyprogesterone acetate

Placebo

3.2 y

All-cause death,

CVE,stroke,VT

DOPS

2012

1006

E/E + P:50(2.8)

C:49.5(2.7)

2 mg 17-β-estradiol+ 1 mg norethisterone acetate or

2 mg 17-β-estradiol (hysterectomy)

NT

16 y

All-cause death,

CVE,stroke,VT

Greenspan et al

2005

373

E/E + P:71.2(5.6)

C:71.3(4.8)

0.625 mg conjugated equine estrogen+ 2.5 mg medroxyprogesterone or 0.625 mg conjugated equine estrogen (hysterectomy)

Placebo

3 y

All-cause death,VT

KEEPS

2014

727

E1 + P:52.8(2.6)

E2 + P:52.7(2.6)

C:52.5(2.5)

0.45 mg conjugated equine estrogen or 50 mcg transdermal 17-estradiol,each with 200 mg progesterone

Placebo

4 y

All-cause death,

stroke,VT

Piret et al.^a

2006

1778

E + P:58.5(3.9)

C:59(3.9)

0.625 mg conjugated equine oestrogen,+ 2.5 mg medroxyprogesterone acetate, or 0.625 mg conjugated equine oestrogens+ 5 mg medroxyprogesterone acetate

Placebo

3.43 y

All-cause death,

stroke

EPAT

2001

222

E:60.9(6.7)

C:62.1(7.1)

1 mg micronized 17-β-estradiol

Placebo

2 y

stroke

WHI

2002

16,608

E + P:63.2(7.1)

C:63.3(7.1)

0.625 mg conjugated equine estrogen+ 2.5 mg medroxyprogesterone acetate

Placebo

5.2 y

All-cause death,

CVE,stroke,VT

WHI II

2004

10,739

E:63.6(7.3)

C:63.6(7.3)

0.625 mg conjugated equine estrogen

Placebo

6.8 y

All-cause death,

CVE,stroke,VT

HERS

1998

2763

E + P:67(7)

C:67(7)

0.625 mg conjugated equine estrogen+ 2.5 mg medroxyprogesterone acetate

Placebo

4.1 y

All-cause death,

CVE,stroke,VT

ESPIRT

2002

1017

E:62.3(5.2)

C:62.9(4.9)

2 mg oestradiol valerate

Placebo

2 y

All-cause death,

CVE,stroke,VT

WELL-HART

2003

226

E:61.8(6.7)

E + P:64.4(6.4)

C:64.2(6.2)

1 mg micronized 17-β-estradiol or 1 mg micronized 17-β-estradiol+ 5 mg of medroxyprogesterone acetate

Placebo

3.3 y

All-cause death

Catherine et al

2001

664

E:72(10)

C:71(10)

1 mg 17-β-estradiol

Placebo

2.8 y

All-cause death,

CVE,stroke,VT

ERT II

1979

168

E + P:55.3

C:54.9

2.5 mg conjugated estrogen+ 10 mg medroxyprogesterone acetate

Placebo

10 y

All-cause death,

CVE

EVTET

2000

140

E + P:55.8(7)

C:55.7(5.9)

2 mg estradiol+ 1 mg norethisterone acetate

Placebo

2 y

VT

STOP^b

2001

489

E/E + P:72(4)

C:71(4)

0.625 mg conjugated estrogen+ 2.5 mg medroxyprogesterone or 0.625 mg conjugated estrogen (hysterectomy)

Placebo

3 y

All-cause death,

stroke,VT

WHISP

2006

100

E/E + P:69.4(8.6)

C:68.3(9)

1 mg 17-β-estradiol+ 0.5 mg norethisterone acetate

Placebo

1 y

All-cause death,

CVE,stroke,VT

WAVE

2002

423

E/E + P:65(9

C:66(9))

0.625 mg conjugated equine estrogen+ 2.5 mg medroxyprogesterone or 0.625 mg conjugated equine estrogen (hysterectomy)

Placebo

2.8 y

All-cause death,

CVE,stroke,VT

WISDOM^c

2007

6026

E + P:63.3(4.7)

C:63.3(4.6)

0.625 mg conjugated equine estrogen+ 2.5 mg medroxyprogesterone

Placebo

10 y

All-cause death,

CVE,VT

EAGAR

2006

83

E/E + P:64(8)

C:64(9)

1 mg 17-β-estradiol + 2.5 mg medroxyprogesterone or 1 mg 17-β-estradiol (hysterectomy)

Placebo

3.5 y

CVE

J.E.B et al

2003

18

E:58.8(4.5)

C:56.6(5)

50 μg estradiol

Placebo

4 w

FMD

Enderle et al

2000

20

E:64.9(7.2)

C:64.9(7.2)

4 mg 17-β-estradiol

Placebo

2 h

FMD,NMD

Claire et al

2007

18

E + P:62(11)

C:62(11)

10 μg ethinyl estradiol+ 1 mg norethisterone acetate

Placebo

3 m

FMD,NMD

Marie et al

1998

17

E:60(48–75)

E + P: (48–75)

C: (48–75)

0.2 mg estradiol or 0.2 mg estradiol+ 300 mg vaginal micronized progesterone

Placebo

14 w

FMD,NMD

Paola et al

2011

40

E + P:52(3.3)

C:51.9(2.4)

1 mg estradiol+ 2 mg drospirenone

Placebo

6 m

FMD,NMD

Akihiko et al

2004

44

Elow:54.1(6.8)

Ehigh:53.4(5.1)

C:52.8(6.9)

0.625 mg conjugated equine estrogen or 0.3125 mg conjugated equine estrogen

NT

3 m

FMD,NMD

B.G et al

2001

51

E + P:55.1(5.3)

C:55.4(6.4)

2 mg oestradiol+ 1 mg norethisterone acetate

Placebo

6 m

FMD,NMD

Antonino et al.^d

2001

90

E + P:56(8)

C:55(6)

1 mg 17-β-estradiol+ 0.5 mg norethisterone acetate

Placebo

6 m

FMD,NMD

Andrew et al

2007

100

CAD:67(8)

H:65(7)

0.05 mg 17-β-estradiol or 0.05 mg 17-β-estradiol+ 0.14 mg norethisterone acetate

Placebo

18 h

FMD,NMD

W.Marchien et al

1999

27

E + P:52.1(0.9)

C:53.2(0.9)

1 mg 17-β-estradiol+ 5 or 10 mg dydrogesterone for the duration of 12 months, 2 mg 17-β-estradiol+ 10 mg dydrogesterone for the final 3 months

Placebo

15 m

FMD,NMD

Mark K et al.^e

2005

61

E + P:64(9)

C:64(9)

0.625 mg conjugated equine estrogen+ 2.5 mg medroxyprogesterone acetate

Placebo

34 m

FMD,NMD

Kerrie L et al.^f

36

Eoral:57(4)

Etrans:57(4)

C:56(7)

1 mg oral estradiol or 0.05 mg transdermal estradiol

Placebo

12 w

FMD

Aris et al

2012

84

E + P:48(4)

C:50(3)

50 mcg 17-β-estradiol+ 200 mg micronized progesterone

NT

3 month

FMD,NMD

PERT

2020

172

E + P:51(3)

C:51(3.2)

0.1 mg transdermal estradiol per day+ 200 mg intermittent micronized progesterone for 12 days per 2 month

Placebo

12 month

FMD,NMD