Study

Comparator

Outcome measure

Information available

Notes

Results for meta‐analysis

SMD

Al‐Azzawi 1999

HT

Presence of vasomotor symptoms, severity measured by Greene menopausal symptoms scale

6 HRT and 9 tibolone patients were without symptoms at baseline. 67 HRT and 58 tibolone patients were free at month 3

Contacted study authors, no reply

Baracat 2002

HT

Total score: mean number of hot flushes per day multiplied by severity score

Means plotted as bar chart in Figure 1.

Baseline, 11 for tibolone (n = 40), 12 for control (n = 45).

At 3 months, 1.8 for tibolone and 1.5 for control. At 13 months,

0.2 for both

Would have to impute SDs – ‘no significant difference’

Unclear how to do this, given the available info

Unable to find contact details

Benedeck‐Jaszmann 1987

Placebo

0 to 3 severity score

12 months

From Fig 1:

Mean

P: 1.6

T: 0.6

SD

P: 1

T: 0.9

N

P: 19

T: 24 (assuming 30 per arm to start, not explicitly stated)

Extracted from figure

Mean

P: 1.6

T: 0.6

SD

P: 1

T: 0.9

N

P: 19

T: 24

SMD: ‐1.0384784 SE: 0.3268612

Bouchard 2012

Placebo

Severity score

Calculate 12 week values

P: 1.59

T: 1.16

Sample sizes of 150 (P) and 164 (T)

Wk 12

Use SD from sample size calc, which is in line with other studies

P: Mean 1.59

SD 0.9

N = 150

T: Mean 1.16

SD: 0.9

N = 164

SMD: ‐0.4766282

SE: 0.1145686

Egarter 1996

HT

Severity of hot flushes (modified Kupperman Index)

Baseline mean

C: 2.1

T: 2.2

6 months

C: 0.4

T: 0.4

‘N/S’

N = 34 (C)

N = 62 (T)

Impute SD ‐ unclear how to

Contacted study authors: no reply

Hammar 2007

HT

Number of hot flushes

Week 48, baseline mean of both groups 6, follow‐up mean ≤ 1

Baseline SD

C: 4.40

T: 4.37

N = 241 (C)

N = 222 (T)

Use baseline SDs (these appear reasonable, given Landgren 2002)

C: mean 1, SD 4.40;

N = 241

T: mean 1, SD 4.37

N = 222

SMD: 0.00

SE: 0.09302624

Hudita 2003

Placebo (3 –arm study)

5‐point severity scale for hot flushes

Week 24

P: 3

T: 1.25 mg: 0.2

T: 2.5mg: 0.1

N = 34

N = 45

N = 41

P < 0.01 for both compared with placebo

Split control group size between 2 arms

Used P value to calculate SD

Get implausible answers. Used known value instead (e.g. Hammar 1998)

Mean

P: 3

T: 1.25 mg: 0.2

T: 2.5 mg: 0.1

N

N = 34/2 = 17

N = 45

N = 41

SD

P: 0.63

T: 1.25: 0.87

T: 2.5: 0.87

1.25

SMD: ‐3.4009511

SE: 0.4175209

2.5

SMD: ‐3.5375963

SE: 0.4371477

Kokcu 2000

HT

Occurrence of hot flushes

OR: 4.16 (0.75 to 22.9)

2/19 have symptoms in C

12/19 have symptoms in T

SMD: 1.6236743

SE: 0.5369759

Landgren 2002

Placebo (5‐arm study)

Frequency of hot flushes

Read means and SEs at 12 weeks from Figure 1

Mean

P = 5.2

T 0.625 = 5

T 1.25 = 2.1

T 2.5 = 1.8

T 5.0 = 1.6

Standard error

P = 0.37

T 0.625 = 0.37

T 1.25 = 0.40

T 2.5 = 0.43

T 5.0 = 0.37

Ns (calculated as all evaluable – dropouts ‐this assumes dropout occurred after 1st measurement at week 4)

P = 113

T 0.625 = 129

T 1.25 = 124

T 2.5 = 139

T 5.0 = 136

Read means and SEs from Figure 1

Calculated SDs using SEs and sample sizes

Split placebo group size in 4

113/4 = 28.25

Mean

P = 5.2

T 0.625 = 5

T 1.25 = 2.1

T 2.5 = 1.8

T 5.0 = 1.6

SD

P = 3.93

T 0.625 = 4.20

T 1.25 = 4.45

T 2.5 = 5.07

T 5.0 = 4.31

N (calculated as all evaluable – dropouts – this assumes dropout occurred after 1st measurement at week 4)

P = 28.25

T 0.625 = 129

T 1.25 = 124

T 2.5 = 139

T 5.0 = 136

0.625

SMD: ‐0.04792794

SE: 0.20552850

1.25

SMD: ‐0.7077526

SE: 0.2102005

2.5

SMD: ‐0.6912512

SE: 0.2076033

5.0

SMD: ‐0.8437215

SE: 0.2097448

Mendoza 2002

HT

Flushes subscore of the Modified Kupperman Index, 0 to 2 score

Number (%) reduced

Have number and percentage that improved in terms of vasomotor symptoms after 1 year

Have 2 possible control groups – choose the best performing to give a conservative estimate

25/26 reduced in control group

27/29 reduced in T groups

Calculate odds ratio for reduced vasomotor symptoms. Turn this into an SMD for combination

(27/2)/(25/1) = 0.54

SE log(OR) =

Sqrt(1/27+1/2+1/25+1/1)

= 1.26

OR for improvement: OR = 0.54

SE(log(OR)) = 1.26

(so T worse)

SMD: 0.3734461

SE: 0.7610917

Nappi 2006a

HT

Vasomotor symptoms (0 to 3 severity score)

At 6 months

Means from Figure 4

C: 1.75

T: 1.5

P value for treatment term in ANOVA given as ‘P < 0.4’

N = 20 in both groups

Assume ANOVA P value is 0.4 and work out SDs as though this was a t‐test

Gives SD of 0.657, assuming same in both groups

SMD: ‐0.3729492

SE: 0.3189649

Ross 1999

HT

Greene Climacteric Scale subscore

Nothing usable. Only present 1 of 6 relevant comparisons because it is almost significant. Do not present 3 month score

Siseles 1995

HT

Kupperman Index

No information given for vasomotor subscale

Have contacted study authors, no reply

Swanson 2006

Placebo (3‐arm study)

Number of hot flushes per day

Median change from baseline at week 12

‐5.5 P

‐9.7 T 2.5

‐8.3 T 1.25

P < 0.001 for T 2.5 vs P

P < 0.003 for T 125 vs P

N

P: 133

T 2.5: 125

T 1.25: 133

Actually, mean changes at week 12 and P values given in abstract

T 2.5 vs P

‐10.14 vs ‐5.85, P < 0.001

T 1.25 vs P, week12

‐8.32

P < 0.003

Use reported values and calculate as for t‐tests. Split placebo group in half.

Will have to impute SDs and final scores, as changes cannot be pooled with final scores if SMDs are used.

For baseline, take median of values from Hammar 2007 and Landgren 2002

6,6,8,8,8,9,9.7

Mean 7.8. Too low – Figure 2 shows large changes. Say, 10

P: 10 ‐ 5.85 = 4.15

T 2.5: 10 ‐ 10 = 0

T 1.25: 10 ‐ 8.32 = 1.68

SDs too large when calculated from t‐test. Use values from Langren:

P: 3.93

T 2.5: 5.07

T 1.25: 4.45

Mean

P: 10 ‐ 5.85 = 4.15

T 2.5: 10 ‐ 10 = 0

T 1.25: 10 ‐ 8.32 = 1.68

SD

P: 3.93

T 2.5: 5.07

T 1.25: 4.45

N

P: 66

T 2.5: 125

T 1.25: 133

1.25

SMD: ‐0.5741771133

SE: 0.1532927

2.5

SMD: ‐0.9661562

SE: 0.1599848

Vieira 2009

Placebo

Kupperman Index

Only overall Kupperman Index shown

Have contacted study authors, no reply

Volpe 1986

Placebo

HT

0 to 9 score, with

0 = absent, 3 = mild, 6 = moderate, 9 = severe

Unclear whether intermediate scores are possible

Can extract means for 24 weeks for tibolone arm, placebo arm and each of several HT arms, which have been partially combined, from Figure 1 in the paper

No real way to calculate SD from info in the paper, and the scale is different from those used in other studies (so not reasonable to use one from another study)

Wender 2004

Placebo

Kupperman Index

Only overall Kupperman Index shown

Have contacted study authors, no reply

Study

Comparator

Outcome measure

Information available

Method used

Results for meta‐analysis

SMD

Hudita 2003

Placebo (3‐arm study)

0 to 4 scale

From figure

Week 24

P: 2.6

T 1.25 mg: 1

T 2.5 mg: 0.9

N = 34/2 = 17

N = 45

N = 41

Split control group size between 2 arms

Use known value from other study for SD

Use those from Nappi 2006a

SD

T: 0.89

HT: 0.89

Mean

P: 2.6

T 1.25 mg: 1

T 2.5 mg: 0.9

N

N = 34/2 = 17

N = 45

N = 41

SD

P: 0.89

T 1.25: 0.89

T 2.5: 0.89

1.25mg

SMD: ‐1.7751711

SE: 0.3262804

2.5mg

SMD: ‐1.8843965

SE: 0.3373802

Kenemans 2009

Placebo

Vaginal dryness as binary

P: 33/1558

T: 19/1575

Convert OR to SMD

P: 33/1558

T: 19/1575

Swanson 2006

Placebo (3‐arm study)

0 to 3 score

Mean change from baseline at week 12

P: ‐0.2

T 2.5: ‐0.26

T 1.25: ‐0.39

N

P: 133

T 2.5: 125

T 1.25: 133

Split control group size between 2 arms

Calculate final means using baseline and change – but no baseline values given

Would also need to use SDs from another study

Cannot use

Huber 2002

HT

Vaginal dryness as binary

HT: 7/166

T: 6/158

Convert OR to SMD

HT: 7/166

T: 6/158

SMD: ‐0.06613757

SE: 0.34411866

Kokcu 2000

HT

Vaginal dryness as binary

HT: 0/21

T: 1/23

Convert OR to SMD

HT: 0/21

T: 1/23

SMD: 0.6382727

SE: 1.0064298

Ziaei 2010

HT and placebo

Vaginal dryness as binary

Also, lubrication scores 1 to 5, higher is better – can reverse signs of mean differences

HT: 20/42

T: 33/47

P: 37/48

Mean

HT: 4.93

T: 4.58

P: 3.65

SD

HT: 1.95

T: 1.26

P: 1.81

Use the continuous data

Calculate and reverse sign, so that greater = increased vaginal dryness

HT: 20/42

T: 33/47

P: 37/48

Using OR to SMD

vs HT

SMD: 0.5774306 0.2691251

vs placebo

SMD ‐0.5904427

SE: 0.2096301

Using lubrication scores

vs HT:

SMD after switching sign:

0.2138954

SE: 0.2129393

vs placebo: SMD after switching sign: ‐0.1313959 SE: 0.2185150

Nappi 2006a

HT

Vaginal dryness 0 to 3 score

From Figure 4, mean at 6 months

Mean

T: 0.7

HC: 0.6

SD: can read SE off Figure 4 and calculate SD

N = 20 both groups

SD: can read SE off Figure 4 and calculate SD

T: 0.89

HT: 0.89

Mean

T: 0.7

HC: 0.6

SD

T: 0.89

HT: 0.89

N = 20

SMD: 0.1101248

SE: 0.3164674

Uygur 2005

HT

7‐point scale with ‐3 as worsened a lot and 3 as improved a lot

6 months

Mean (higher is better)

HT: 0

T: 0.56

N

HT: 34

T: 38

P < 0.05 given. Assume P = 0.05 and calculate SD, assuming equal in 2 groups:

Gives SD = 1.7

Mean (higher is better)

HT: 0

T: 0.56

N

HT: 34

T: 38

Sd=1.7 for both

SMD after sign change: ‐0.3258676 0.2376236