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Dodatak testosterona na hormonsku terapiju žena u menopauzi

Appendices

Appendix 1. Search string

The MEDLINE, Bio Abstract, CINAHL, and PsycINFO databases were searched using the following subject headings and keywords:

1. menopause/ or perimenopause/ or postmenopause/
2. menopaus$.mp.
3. perimenopaus$.mp.
4. postmenopaus$.mp.
5. peri‐menopaus$.mp.
6. post‐menopaus$.mp.
7. climacteric/ or menopause/
8. climacteric.mp.
9. or/1‐8
10. testosterone.mp. or exp Testosterone/
11. androgen$.mp. or exp Androgens/
12. 10 or 11
13. 9 and 12
14. randomised controlled trial.pt.
15. controlled clinical trial.pt.
16. Randomized controlled trials/
17. random allocation/
18. double‐blind method/
19. single‐blind method/
20. or/14‐19
21. clinical trial.pt.
22. exp clinical trials/
23. (clin$ adj25 trial$).ti,ab,sh.
24. ((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or mask$)).ti,ab,sh.
25. placebos/
26. placebo$.ti,ab,sh.
27. random$.ti,ab,sh.
28. Research design/
29. or/21‐28
30. animal/ not (human/ and animal/)
31. 20 or 29
32. 31 not 30
33. 13 and 32
34. limit 33 to yr="2003"
35. limit 33 to yr="2004"
36. limit 33 to yr="2005"
37. limit 33 to yr="2006"
38. limit 33 to yr="2007"

39. limit 33 to yr="2008"

40. or/34‐39
41. from 40 keep 1‐176

The EMBASE database was searched using the following subject headings and keywords:

1. menopause.mp. or exp MENOPAUSE/ or exp MENOPAUSE RELATED DISORDER/ or exp
"MENOPAUSE AND CLIMACTERIUM"/
2. perimenopaus$.mp.
3. peri‐menopaus$.mp.
4. postmenopaus$.mp.
5. post‐menopaus$.mp.
6. menopaus$.mp.
7. or/1‐6
8. exp TESTOSTERONE/ or testosterone.mp.
9. exp ANDROGEN/ or androgen.mp. or exp ANDROGEN THERAPY/
10. androgen$.mp.
11. or/8‐10
12. 7 and 11
13. Controlled study/ or randomised controlled trial/
14. double blind procedure/
15. single blind procedure/
16. crossover procedure/
17. drug comparison/
18. placebo/
19. random$.ti,ab,hw,tn,mf.
20. latin square.ti,ab,hw,tn,mf.
21. crossover.ti,ab,hw,tn,mf.
22. cross‐over.ti,ab,hw,tn,mf.
23. placebo$.ti,ab,hw,tn,mf.
24. ((doubl$ or singl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).ti,ab,hw,tn,mf.
25. (comparative adj5 trial$).ti,ab,hw,tn,mf.
26. (clinical adj5 trial$).ti,ab,hw,tn,mf.
27. or/13‐26
28. nonhuman/
29. animal/ not (human/ and animal/)
30. or/28‐29
31. 27 not 30
32. 12 and 31
33. 32 not men.mp. [mp=title, abstract, subject headings, heading word, drug
trade name, original title, device manufacturer, drug manufacturer name]
34. 33 not male$.mp.
35. 34 not infertil$.mp.
36. 35 not prostat$.mp.
37. 36 not review.mp. [mp=title, abstract, subject headings, heading word, drug
trade name, original title, device manufacturer, drug manufacturer name]
38. 37 not meta‐analysis.mp. [mp=title, abstract, subject headings, heading
word, drug trade name, original title, device manufacturer, drug manufacturer
name]
39. 38 not in vitro.mp. [mp=title, abstract, subject headings, heading word,
drug trade name, original title, device manufacturer, drug manufacturer name]
40. 39 not gene.mp. [mp=title, abstract, subject headings, heading word, drug
trade name, original title, device manufacturer, drug manufacturer name]
41. 40 not cross‐section$.mp.
42. limit 41 to yr="2003"
43. limit 41 to yr="2004"
44. limit 41 to yr="2005"
45. limit 41 to yr="2006"

46. limit 41 to yr="2007"

47. limit 41 to yr="2008"
48. or/43‐47
47. from 48 keep 1‐90

Appendix 2. Central search

1 menopause.mp. or exp MENOPAUSE/ or exp MENOPAUSE RELATED DISORDER/ or exp "MENOPAUSE AND CLIMACTERIUM"/ (3495)
2 perimenopaus$.mp. (211)
3 peri‐menopaus$.mp. (20)
4 postmenopaus$.mp. (5544)
5 post‐menopaus$.mp. (591)
6 menopaus$.mp. (3285)
7 or/1‐6 (7362)
8 exp TESTOSTERONE/ or testosterone.mp. (2137)
9 exp ANDROGEN/ or androgen.mp. or exp ANDROGEN THERAPY/ (1215)
10 androgen$.mp. (1727)
11 or/8‐10 (3151)
12 7 and 11 (381)
13 new.uf. (1538)
14 12 and 13 (3)
15 from 14 keep 1‐3 (3)

Appendix 3. EMBASE

1 menopause.mp. or exp MENOPAUSE/ or exp MENOPAUSE RELATED DISORDER/ or exp "MENOPAUSE AND CLIMACTERIUM"/ (42950)
2 perimenopaus$.mp. (1827)
3 peri‐menopaus$.mp. (142)
4 postmenopaus$.mp. (31390)
5 post‐menopaus$.mp. (3648)
6 menopaus$.mp. (32396)
7 or/1‐6 (56480)
8 exp TESTOSTERONE/ or testosterone.mp. (49813)
9 exp ANDROGEN/ or androgen.mp. or exp ANDROGEN THERAPY/ (76848)
10 androgen$.mp. (38802)
11 or/8‐10 (86212)
12 7 and 11 (5534)
13 Controlled study/ or randomized controlled trial/ (2293356)
14 double blind procedure/ (61834)
15 single blind procedure/ (6177)
16 crossover procedure/ (17992)
17 drug comparison/ (81250)
18 placebo/ (91809)
19 random$.ti,ab,hw,tn,mf. (350155)
20 latin square.ti,ab,hw,tn,mf. (1042)
21 crossover.ti,ab,hw,tn,mf. (31613)
22 cross‐over.ti,ab,hw,tn,mf. (11026)
23 placebo$.ti,ab,hw,tn,mf. (139476)
24 ((doubl$ or singl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).ti,ab,hw,tn,mf. (103309)
25 (comparative adj5 trial$).ti,ab,hw,tn,mf. (5284)
26 (clinical adj5 trial$).ti,ab,hw,tn,mf. (460069)
27 or/13‐26 (2757937)
28 nonhuman/ (2802171)
29 animal/ not (human/ and animal/) (12834)
30 or/28‐29 (2805771)
31 27 not 30 (1615851)
32 12 and 31 (2078)
33 32 not men.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] (1802)
34 33 not male$.mp. (1631)
35 34 not infertil$.mp. (1529)
36 35 not prostat$.mp. (1512)
37 36 not review.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] (1195)
38 37 not meta‐analysis.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] (1183)
39 38 not in vitro.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] (1100)
40 39 not gene.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] (1041)
41 40 not cross‐section$.mp. (997)
42 ("200627" or "200628" or "200629").em. (38660)
43 20063$.em. (133700)
44 ("200640" or "200641" or "200642" or "200643" or "200644" or "200645").em. (76537)
45 or/42‐44 (248897)
46 41 and 45 (36)
47 from 46 keep 1‐36 (36)

Appendix 4. MEDLINE

1 menopause/ or perimenopause/ or postmenopause/ (29597)
2 menopaus$.mp. (32496)
3 perimenopaus$.mp. (2062)
4 postmenopaus$.mp. (31923)
5 peri‐menopaus$.mp. (147)
6 post‐menopaus$.mp. (3659)
7 climacteric/ or menopause/ (21082)
8 climacteric.mp. (4416)
9 or/1‐8 (55288)
10 testosterone.mp. or exp Testosterone/ (63018)
11 androgen$.mp. or exp Androgens/ (85657)
12 10 or 11 (95782)
13 9 and 12 (3736)
14 randomized controlled trial.pt. (242141)
15 controlled clinical trial.pt. (78086)
16 Randomized controlled trials/ (50223)
17 random allocation/ (59871)
18 double‐blind method/ (93163)
19 single‐blind method/ (11128)
20 or/14‐19 (410811)
21 clinical trial.pt. (467703)
22 exp clinical trials/ (199836)
23 (clin$ adj25 trial$).ti,ab,sh. (133967)
24 ((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or mask$)).ti,ab,sh. (91805)
25 placebos/ (26399)
26 placebo$.ti,ab,sh. (116344)
27 random$.ti,ab,sh. (503850)
28 Research design/ (47173)
29 or/21‐28 (897919)
30 animal/ not (human/ and animal/) (3146512)
31 20 or 29 (904514)
32 31 not 30 (831335)
33 13 and 32 (782)
34 200607$.ed. (48685)
35 200608$.ed. (63404)
36 200609$.ed. (55606)
37 200610$.ed. (54157)
38 200611$.ed. (18375)
39 or/34‐38 (240227)
40 33 and 39 (24)
41 from 40 keep 1‐24 (24)

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figuras y tablas -
Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figuras y tablas -
Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Comparison 1 HT plus testosterone versus HT on sense of well being, Outcome 1 Sense of well‐being.
Figuras y tablas -
Analysis 1.1

Comparison 1 HT plus testosterone versus HT on sense of well being, Outcome 1 Sense of well‐being.

Comparison 2 HT plus testosterone versus HT on sexual function, Outcome 1 Change scores of sexual function.
Figuras y tablas -
Analysis 2.1

Comparison 2 HT plus testosterone versus HT on sexual function, Outcome 1 Change scores of sexual function.

Comparison 2 HT plus testosterone versus HT on sexual function, Outcome 2 Change scores of Personal Distress Scale.
Figuras y tablas -
Analysis 2.2

Comparison 2 HT plus testosterone versus HT on sexual function, Outcome 2 Change scores of Personal Distress Scale.

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 1 Lumbar BMDs at 12 months.
Figuras y tablas -
Analysis 3.1

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 1 Lumbar BMDs at 12 months.

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 2 Lumbar BMDs at 24 months.
Figuras y tablas -
Analysis 3.2

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 2 Lumbar BMDs at 24 months.

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 3 Femur BMDs at 12 months.
Figuras y tablas -
Analysis 3.3

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 3 Femur BMDs at 12 months.

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 4 Femur BMDs at 24 months.
Figuras y tablas -
Analysis 3.4

Comparison 3 HT plus testosterone versus HT on bone mineral density, Outcome 4 Femur BMDs at 24 months.

Comparison 4 HT plus testosterone versus HT on body composition, Outcome 1 Weight.
Figuras y tablas -
Analysis 4.1

Comparison 4 HT plus testosterone versus HT on body composition, Outcome 1 Weight.

Comparison 4 HT plus testosterone versus HT on body composition, Outcome 2 Body mass index.
Figuras y tablas -
Analysis 4.2

Comparison 4 HT plus testosterone versus HT on body composition, Outcome 2 Body mass index.

Comparison 4 HT plus testosterone versus HT on body composition, Outcome 3 Waist:hip ratio.
Figuras y tablas -
Analysis 4.3

Comparison 4 HT plus testosterone versus HT on body composition, Outcome 3 Waist:hip ratio.

Comparison 5 HT plus testosterone versus HT on cognition, Outcome 1 Cognitive performance.
Figuras y tablas -
Analysis 5.1

Comparison 5 HT plus testosterone versus HT on cognition, Outcome 1 Cognitive performance.

Comparison 5 HT plus testosterone versus HT on cognition, Outcome 2 Cognition difficulty.
Figuras y tablas -
Analysis 5.2

Comparison 5 HT plus testosterone versus HT on cognition, Outcome 2 Cognition difficulty.

Comparison 6 HT plus testosterone versus HT on menopausal symptoms, Outcome 1 Vasomotor symptom.
Figuras y tablas -
Analysis 6.1

Comparison 6 HT plus testosterone versus HT on menopausal symptoms, Outcome 1 Vasomotor symptom.

Comparison 7 HT plus testosterone versus HT on facial and body hair growth, Outcome 1 Mean scores of facial and body hair growth.
Figuras y tablas -
Analysis 7.1

Comparison 7 HT plus testosterone versus HT on facial and body hair growth, Outcome 1 Mean scores of facial and body hair growth.

Comparison 7 HT plus testosterone versus HT on facial and body hair growth, Outcome 2 Incidence of facial and body hair growth.
Figuras y tablas -
Analysis 7.2

Comparison 7 HT plus testosterone versus HT on facial and body hair growth, Outcome 2 Incidence of facial and body hair growth.

Comparison 8 HT plus testosterone versus HT on acne, Outcome 1 Mean scores of acne.
Figuras y tablas -
Analysis 8.1

Comparison 8 HT plus testosterone versus HT on acne, Outcome 1 Mean scores of acne.

Comparison 8 HT plus testosterone versus HT on acne, Outcome 2 Incidence of acne.
Figuras y tablas -
Analysis 8.2

Comparison 8 HT plus testosterone versus HT on acne, Outcome 2 Incidence of acne.

Comparison 9 HT plus testosterone versus HT on mammographic findings, Outcome 1 Incidence of increased breast density.
Figuras y tablas -
Analysis 9.1

Comparison 9 HT plus testosterone versus HT on mammographic findings, Outcome 1 Incidence of increased breast density.

Comparison 9 HT plus testosterone versus HT on mammographic findings, Outcome 2 Area of dense breast.
Figuras y tablas -
Analysis 9.2

Comparison 9 HT plus testosterone versus HT on mammographic findings, Outcome 2 Area of dense breast.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 1 Total cholesterol at less than 3 months.
Figuras y tablas -
Analysis 10.1

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 1 Total cholesterol at less than 3 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 2 Triglyceride at less than 3 months.
Figuras y tablas -
Analysis 10.2

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 2 Triglyceride at less than 3 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 3 LDL cholesterol at less than 3 months.
Figuras y tablas -
Analysis 10.3

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 3 LDL cholesterol at less than 3 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 4 HDL cholesterol at less than 3 months.
Figuras y tablas -
Analysis 10.4

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 4 HDL cholesterol at less than 3 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 5 Total cholesterol at 3 ‐ <6 months.
Figuras y tablas -
Analysis 10.5

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 5 Total cholesterol at 3 ‐ <6 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 6 Triglyceride at 3 ‐ <6 months.
Figuras y tablas -
Analysis 10.6

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 6 Triglyceride at 3 ‐ <6 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 7 LDL cholesterol at 3 ‐ <6 months.
Figuras y tablas -
Analysis 10.7

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 7 LDL cholesterol at 3 ‐ <6 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 8 HDL cholesterol at 3 ‐ <6 months.
Figuras y tablas -
Analysis 10.8

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 8 HDL cholesterol at 3 ‐ <6 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 10 Total cholesterol at 6 ‐ <12 months.
Figuras y tablas -
Analysis 10.10

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 10 Total cholesterol at 6 ‐ <12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 11 Triglyceride at 6 ‐ <12 months.
Figuras y tablas -
Analysis 10.11

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 11 Triglyceride at 6 ‐ <12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 12 LDL cholesterol at 6 ‐ <12 months.
Figuras y tablas -
Analysis 10.12

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 12 LDL cholesterol at 6 ‐ <12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 13 HDL cholesterol at 6 ‐ <12 months.
Figuras y tablas -
Analysis 10.13

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 13 HDL cholesterol at 6 ‐ <12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 14 Total cholesterol/HDL at 6 ‐ <12 months.
Figuras y tablas -
Analysis 10.14

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 14 Total cholesterol/HDL at 6 ‐ <12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 15 Total cholesterol at 12 months.
Figuras y tablas -
Analysis 10.15

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 15 Total cholesterol at 12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 16 Triglyceride at 12 months.
Figuras y tablas -
Analysis 10.16

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 16 Triglyceride at 12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 17 LDL cholesterol at 12 months.
Figuras y tablas -
Analysis 10.17

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 17 LDL cholesterol at 12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 18 HDL cholesterol at 12 months.
Figuras y tablas -
Analysis 10.18

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 18 HDL cholesterol at 12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 19 Total cholesterol/HDL at 12 months.
Figuras y tablas -
Analysis 10.19

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 19 Total cholesterol/HDL at 12 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 20 Total cholesterol at 24 months.
Figuras y tablas -
Analysis 10.20

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 20 Total cholesterol at 24 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 21 Triglyceride at 24 months.
Figuras y tablas -
Analysis 10.21

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 21 Triglyceride at 24 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 22 LDL cholesterol at 24 months.
Figuras y tablas -
Analysis 10.22

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 22 LDL cholesterol at 24 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 23 HDL cholesterol at 24 months.
Figuras y tablas -
Analysis 10.23

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 23 HDL cholesterol at 24 months.

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 24 Total cholesterol/HDL at 24 months.
Figuras y tablas -
Analysis 10.24

Comparison 10 HT plus testosterone versus HT on lipid profile, Outcome 24 Total cholesterol/HDL at 24 months.

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 1 Total cholesterol.
Figuras y tablas -
Analysis 11.1

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 1 Total cholesterol.

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 2 HDL cholesterol.
Figuras y tablas -
Analysis 11.2

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 2 HDL cholesterol.

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 3 LDL cholesterol.
Figuras y tablas -
Analysis 11.3

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 3 LDL cholesterol.

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 4 Triglyceride.
Figuras y tablas -
Analysis 11.4

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 4 Triglyceride.

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 5 Total cholesterol/HDL.
Figuras y tablas -
Analysis 11.5

Comparison 11 HT plus testosterone versus HT on lipid profile (subgroup analysis), Outcome 5 Total cholesterol/HDL.

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 1 Discontinuation rate (overall).
Figuras y tablas -
Analysis 12.1

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 1 Discontinuation rate (overall).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 2 Discontinuation rate (type of menopause).
Figuras y tablas -
Analysis 12.2

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 2 Discontinuation rate (type of menopause).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 3 Discontinuation rate (menopausal status).
Figuras y tablas -
Analysis 12.3

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 3 Discontinuation rate (menopausal status).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 4 Discontinuation rate (route of hormone therapy).
Figuras y tablas -
Analysis 12.4

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 4 Discontinuation rate (route of hormone therapy).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 5 Discontinuation rate (type of testosterone).
Figuras y tablas -
Analysis 12.5

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 5 Discontinuation rate (type of testosterone).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 6 Discontinuation rate (duration of treatment).
Figuras y tablas -
Analysis 12.6

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 6 Discontinuation rate (duration of treatment).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 7 Discontinuation rate (blinding).
Figuras y tablas -
Analysis 12.7

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 7 Discontinuation rate (blinding).

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 8 Discontinuation rate (disease status).
Figuras y tablas -
Analysis 12.8

Comparison 12 HT plus testosterone versus HT on discontinuation rate, Outcome 8 Discontinuation rate (disease status).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 1 Discontinuation rate due to adverse events (overall).
Figuras y tablas -
Analysis 13.1

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 1 Discontinuation rate due to adverse events (overall).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 2 Discontinuation rate due to adverse events (type of menopause).
Figuras y tablas -
Analysis 13.2

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 2 Discontinuation rate due to adverse events (type of menopause).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 3 Discontinuation rate due to adverse events (menopausal status).
Figuras y tablas -
Analysis 13.3

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 3 Discontinuation rate due to adverse events (menopausal status).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 4 Discontinuation rate due to adverse events (route of hormone therapy).
Figuras y tablas -
Analysis 13.4

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 4 Discontinuation rate due to adverse events (route of hormone therapy).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 5 Discontinuation rate due to adverse events (type of testosterone).
Figuras y tablas -
Analysis 13.5

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 5 Discontinuation rate due to adverse events (type of testosterone).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 6 Discontinuation rate due to adverse events (duration of treatment).
Figuras y tablas -
Analysis 13.6

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 6 Discontinuation rate due to adverse events (duration of treatment).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 7 Discontinuation rate due to adverse events (blinding).
Figuras y tablas -
Analysis 13.7

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 7 Discontinuation rate due to adverse events (blinding).

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 8 Discontinuation rate due to adverse events (disease status).
Figuras y tablas -
Analysis 13.8

Comparison 13 HT plus testosterone versus HT on discontinuation rate due to adverse events, Outcome 8 Discontinuation rate due to adverse events (disease status).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 1 Discontinuation rate (allocation quality).
Figuras y tablas -
Analysis 14.1

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 1 Discontinuation rate (allocation quality).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 2 Discontinuation rate due to adverse events (allocation quality).
Figuras y tablas -
Analysis 14.2

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 2 Discontinuation rate due to adverse events (allocation quality).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 3 Discontinuation rate (quality of randomisation)).
Figuras y tablas -
Analysis 14.3

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 3 Discontinuation rate (quality of randomisation)).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 4 Discontinuation rate due to adverse events (quality of randomisation).
Figuras y tablas -
Analysis 14.4

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 4 Discontinuation rate due to adverse events (quality of randomisation).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 5 Discontinuation rate (blinding method).
Figuras y tablas -
Analysis 14.5

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 5 Discontinuation rate (blinding method).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 6 Discontinuation rate due to adverse events (blinding method).
Figuras y tablas -
Analysis 14.6

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 6 Discontinuation rate due to adverse events (blinding method).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 7 Discontinuation rate (large studies).
Figuras y tablas -
Analysis 14.7

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 7 Discontinuation rate (large studies).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 8 Discontinuation rate due to adverse events (large studies).
Figuras y tablas -
Analysis 14.8

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 8 Discontinuation rate due to adverse events (large studies).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 9 Discontinuation rate (methyl testosterone doses).
Figuras y tablas -
Analysis 14.9

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 9 Discontinuation rate (methyl testosterone doses).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 10 Discontinuation rate due to adverse events (methyl testosterone doses).
Figuras y tablas -
Analysis 14.10

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 10 Discontinuation rate due to adverse events (methyl testosterone doses).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 11 Discontinuation rate (estrogen doses).
Figuras y tablas -
Analysis 14.11

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 11 Discontinuation rate (estrogen doses).

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 12 Discontinuation rate due to adverse events (estrogen doses).
Figuras y tablas -
Analysis 14.12

Comparison 14 HT‐T versus HT on discontinuation rate (sensitivity analysis), Outcome 12 Discontinuation rate due to adverse events (estrogen doses).

Table 1. Trial outcomes not included in the meta‐analysis

Outcome

Study ID

N

Reason

Conclusion

Acne

Barrett‐Connor 1999

291

The data was not available

Acne of mild or moderate severity was reported by 5 (3%) estrogen‐testosterone treated participants, whereas no participants receiving oestrogen reported acne

Biochemical Markers of bone metabolism

Floter 2002b (Floter 2005)

50

A crossover study with no washout period

Both treatments had similar effects, with a significant decrease in bone resorption (ICTP) and bone turnover (osteocalcin) after 24 weeks.
A 12% reduction in PICP during HT treatment was reversed by the addition of testosterone, and no significant decline was recorded during T‐HT treatment

Biochemical markers of bone metabolism

Miller 2000

57

The data was likely to be skewed because the means were smaller than twice the SDs

There were no between group differences noted in baseline Dpd levels(p=0.111), Dpd% change (P=0.338), baseline NTx levels (P=0.112), or NTx % change (P=0.271)

Biochemical markers of bone metabolism

Raisz 1996

28

The data was not available

The effects of oestrogen‐testosterone and oestrogen alone on markers of bone resorption were generally similar. The increase in bone formation markers after oestrogen‐testosterone treatment was significantly different from the effect of oestrogen for all bone formation parameters.

Bone mineral density of lumbar spine and femur

Barrett‐Connor 1999

199

The data was not available

BMD increased in the estrogen‐testosterone(low dose) were comparable to those in the oestrogen(low dose) group, while the BMD changes at 24 months in the estrogen‐testosterone(high dose) group significantly exceeded those in oestrogen(high dose) group(P=0.014 for lumbar spine, BMD and P=0.009 for total hip BMD)

Bone mineral density

Floter 2002b (Floter 2005)

50

A crossover study with no washout period.

No changes in BMD were noted in the total body, hip, or lumbar spine with either regimen

Bone mineral density

Garnett 1992

50

The data was not available.

There was no significant differences in bone density at any of the sites measured between women receiving oestrogen alone and those receiving estrogen‐testosterone. No treated subjects had a significant bone loss(more than twice the measurement precision) at either spine or femoral neck at 1 year, but three in each treated group showed a small but non significant decrease at both sites

Bone mineral density of L1‐L4, femur and forearm

Watts 1995

48

The data was not available

The estrogen‐testosterone showed significant increases in spinal BMD at 12 and 24 months(P<0.01). The estrogen group demonstrated a non significant increase in spinal BMD. The difference between groups was not significant at 12 or 24 months. There were no significant changes in BMD from baseline in either group at the radius, femoral neck, Ward triangle, or greater trochanter

Body composition

Dobs 2002

40

It was unclear with regard to the standard deviation (SD) of the data

‐ When compared with oestrogen alone, estrogen‐testosterone treatment significantly increased lean body mass in the arms, legs, and trunk. Body fat percentage decreased significantly from baseline in the same arms, legs, and trunk in the oestrogen‐testosterone group but not the oestrogen alone group. When changes in arms, legs, and trunk in each participant were analysed simultaneously, the difference between treatments was significant for lean body mass(P=0.007) and percentage of fat tissue(P=0.077)

Body composition

Floter 2002b (Floter 2005)

50

A crossover study with no washout period

There was no significant differences in total body fat, total lean body mass, trunk fat, and trunk lean mass between the two treatments

Body composition

Leao 2006

37

The data was likely to be skewed

When compared to HT alone, T‐HT treatment significantly increased visceral fat area (P = 0.009). However there was no significant difference in subcutaneous fat area between the two groups

Cognition and psychological well being

Regestein 2001

42

A crossover study with no washout period

Switching Attention Test that mean reaction time in the switching condition was faster in the estrogen‐testosterone group than in the estrogen group(t=3.25, df=37, P<0.002, effect size = 0.53 SD). For other conditions of the same test, such as side condition and direction condition, they did not differ between two groups.
There were no other effects of added methyltestosterone found on psychological, sleep, and exercise measures

Cognition

Sherwin 1988

49

The data was not available

There was no comparative effects between oestrogen‐testosterone and oestrogen alone group.
The women treated with all hormone preparations were higher during both treatment phases compared to scores of women who received placebo (P<0.01)

Cognition

Shepanek 1999

30

The data was likely to be skewed

No significant interactions were found showing an advantage for oestrogen‐testosterone treated group as contrasted to oestrogen‐treated group

Cognition (Cube Comparisons and Building Memory)

Dobs 2002(Wisniewski 2002)

26

The data was likely to be skewed

Differences in task performance between women receiving E or E‐T treatment were assessed with a 2‐factor(treatment group x test session), mixed analysis of variance for each cognitive task. Post hoc comparisons were conducted using Tukey's method of multiple comparisons. With regard to Cube Comparisons, performance improved for both groups across test sessions, however this improvement only approached statistical significance (P=0.09). No other effects were significant. Regarding Building Memory, a main effect of test session was observed, with performance declining across sessions for both groups(P<0.01). A treatment x test session interaction was observed(P<0.05). Post hoc comparison revealed that this effect was due to a decrease in the E group(P<0.05) but not The E‐T group(P>0.1) across sessions.

Hematocrit

Barrett‐Connor 1999

199

The data was not available.

There was no clinically significant difference in haematology

Hematocrit

Floter 2002b

50

A cross‐over study with no washout period

They reported that there was no change in blood counts during the study

Hematocrit

Hickok 1993

26

The data was not available.

‐ At 6 months, statistically significant between‐group differences were seen for hematocrit. The difference was small in magnitude, remained within the normal ranges, and was not considered clinically significant.

Hematocrit

Shifren 2000

67

A cross‐over study with no washout period

Transdermal testosterone treatment had no significant effects on blood counts

Hematocrit

Watts 1995

48

The data were not available

No clinically significant changes in hematologic indices

Hirsutism

Barrett‐Connor 1999

199

The data was not available

Changes in hair growth in the oestrogen‐testosterone(low dose) group were similar to those in the oestrogen(low dose) group, and there were no statistically significant differences in the hirsutism scores between the treatment groups. In the high‐dose groups only four participants treated with oestrogen‐testosterone and two treated with oestrogen reported hirsutism as an adverse event at month 12. At 24 months, 10 oestrogen‐testosterone‐treated and 3 oestrogen‐treated participants reported hirsutism as an adverse event

Hirsutism and acne

Floter 2002b

50

A crossover study with no washout period

Incidences of hirsutism and acne were similar in two treatment groups

Hirsutism and acne

Shifren 2000

67

A crossover study with no washout period

The hirsutism and acne scores did not change significantly during treatment. The mean facial depilation rate increased slightly during treatment with estrogen‐testosterone 300 microgram

Lipid profile

Dobs 2002

40

The data was not available.

After 16 weeks of treatment, significant decreases in total cholesterol, HDL, and triglycerides occurred in the estrogen‐testosterone group. LDL values were virtually unchanged. The oestrogen group demonstrated the opposite effect on lipids, with a significant decrease in LDL and no meaningful change in the other lipid parameters

Lipid profile

Dobs 2002 (Floter 2005)

50

A crossover study with no washout period

Serum levels of total testosterone increased markedly from a baseline mean of 0.8–4.9 mmol/l during testosterone addition. Total and LDL‐cholesterol levels were significantly reduced by both treatments as also were those of Lp‐(a) although the difference was not significant. A 13% reduction in HDL‐cholesterol levels was found when testosterone was added, but no change with oestrogen alone. Triglyceride levels were increased by oestrogen treatment, but not affected by the combination of oestrogen plus testosterone

Lipid profile

Miller 2000 (Luciano 1998a)

56

The data was not available

There were significant reductions in total cholesterol and LDL cholesterol in all groups. In estrogen‐testosterone‐treated group triglyceride levels increased 26.0% and HDL cholesterol levels decreased 9.0%. In contrast, with oestrogen therapy triglyceride levels decreased 9.0% and HDL cholesterol levels increased 9.0%

Lipid profile

Miller 2000

57

The data was likely to be skewed because the means were smaller than twice the SDs

The study found significant reductions in total cholesterol and LDL cholesterol in all groups. Triglyceride levels increased 26.0% and HDL cholesterol levels decreased 9.0% in estrogen‐testosterone‐treated group. In contrast, with oestrogens therapy triglyceride levels decreased 9.0% and HDL cholesterol levels increased 9.0%

Lipid profile

Nathrost‐Boos 2006

60

A crossover study with no washout period

Total cholesterol, triglycerides, HDL and LDL revealed no significant differences between any of the periods or groups

Menopausal symptoms, sense of well being and sexual function

Barrett‐Connor 1999

199

The data were not available

Women in all treatment groups reported an improvement in menopausal symptoms and quality of life measures at 24 months. There was a non significant trend toward greater improvement in well being and sexual interest and higher scores on the modified menopausal rating scale in the oestrogen‐testosterone groups

Menopausal symptoms and sexual function

Dow 1983

40

The data were non‐normal distribution

There were no significant differences between treatments on any variable at either 2 months or 6 months after treatment

Menopausal symptoms

Hickok 1993

26

The data were non‐normal distribution

There was no statistically significant difference between two treatments in menopausal symptoms

Menopausal symptoms

Miller 2000 (Luciano 1999)

51

The data were not available

Vasomotor symptoms were reduced by at least 75% after treatment in all groups

Menopausal symptoms

Raisz 1996

28

The data was likely to be skewed

Both treatments significantly decreased somatic symptom scores, but only estrogen‐testosterone treatment provided significant relief of psychosomatic and psychological symptoms

Menopausal symptoms

Sarrel 1998

20

The data was not available

There was no statistical difference between the estrogen‐testosterone groups versus the oestrogen group

Menopausal symptoms

Sherwin 1988 (Sherwin 1984)

49

The data was not available

There was no result for the comparative effect on hot flushes between estrogen‐testosterone and oestrogen alone

Menopausal symptoms

Sherwin 1988 (Sherwin 1985a)

43

The data were not available

Menopausal index:
1. Somatic symptoms: The scores of the oestrogen‐testosterone, androgen alone groups were lower than those of the oestrogen alone and placebo groups (P<0.01).
2. Psychosomatic symptoms: There were no significant changes in any of the groups across time.
3. Psychological symptoms: The scores of the estrogen‐alone and placebo groups were significantly higher than those of the oestrogen‐testosterone, androgen‐alone groups during both treatment phases (p<0.01).
4. Total scores: The E‐T, androgen‐alone groups attained lower total scores during treatment phases than the E‐alone and P groups

Menopausal symptoms

Simon 1999

92

The data was not available

In general, estrogen‐testosterone therapy provided greater relief from these symptoms than oestrogen therapy. This was most apparent in the finding that the degree of vasomotor symptom relief with low dose estrogen‐testosterone preparation was similar to relief experienced with higher dose estrogen therapy alone.

Menopausal symptoms

Watts 1995

66

The data were not available

There were no significant differences in somatic symptoms between the oestrogen and estrogen‐testosterone groups at baseline or after treatment. Psychosomatic and psychologic symptom values are not presented because of the small number of evaluable symptomatic participants

Mood (hostility)

Sherwin 1988 (Sherwin 1985c)

36

The data were not available

Hostility scores did not differ significantly in the two groups (testosterone‐oestrogen or oestrogen alone)

Sense of well being

Dobs 2002

40

The data were not available.

With regard to QUALMS questionnaire, the oestrogen‐testosterone group showed significant improvement from baseline in somatic symptoms(week 10, P=0.003; week 16, P=0.073). The oestrogen group showed significant improvement from baseline in well being (week 16, P= 0.049) and cognition (week 10, P=0.054)

Sense of well being

Floter 2002b

50

A crossover study with no washout period

There were no significant differences between the treatments in any of the sub scores or total PGWB index

Sense of well being

Montgomery 1987

84

The data were likely to be skewed

There was no difference in SRD 30 scores between the two active treatment groups at either 2 or 4 months

Sense of well being

Penotti 2001

40

The data were not available.

No conclusion on psycho‐physical well being.

Sense of well being

Regestein 2001

35

A cross‐over study with no washout period

No significant effects of adding testosterone into hormone therapy

Sense of well being

Sherwin 1988 (Sherwin 1985c)

43

The data was not available.

Anxiety: There was no differences among any of the groups across time.
Depression: Mean group scores fell within the normal range. Depression scores in the placebo group were significantly higher than those in oestrogen‐testosterone(P<0.05), A(P<0.01), E(P<0.05) groups during both treatment phases.
Hostility: hostility scores did not differ significantly in the two groups (testosterone‐oestrogen versus oestrogen alone)

Sense of well being

Shifren 2000

65

A crossover study with no washout period

Adding 300 microgram patch into oral oestrogen has a significant improvement in general well being by means of PGWB (P=0.04). There also were significant increases with oestrogen‐testosterone 300 microgram treatment for sub scales of positive well being and depressed mood.

Sexual function

Burger 1987

20

The data was not available.

After six weeks the loss of libido in the single implant group remained, while the combined group showed significant symptomatic relief(P<0.01). Eight in the single implant group chose to have a testosterone implant at the first follow up visit at 6 weeks; the other two stopped coming because of dissatisfaction with the treatment

Sexual function

Dobs 2002

40

The data was not available.

The sample size was not powered, nor was entry criteria designed to assess sexual dysfunction parameters; however, there were significant results. In the oestrogen‐testosterone group, BISF‐W mean increases at each visit were statistically significant for frequency/psychosexual(P=0.05) and pleasure/orgasm(P=0.041) domains. The mean composite BISF‐W score increased in the oestrogen‐testosterone group, whereas the mean score in the estrogen group decreased. Although it appeared that the two treatment groups were not well balanced at baseline(the estrogen group seemed to have healthier sexual function at baseline than the estrogen‐testosterone group), the estrogen‐testosterone group showed significant improvement in sexual function compared with the estrogen group.
The SRS total score in the estrogen‐testosterone group improved significantly at each visit, whereas scores in the estrogen group did not change significantly. The SIQ score for the estrogen‐testosterone group also increased significantly for interest in sex at weeks 10(P=0.031) and 16(P=0.014) when compared with before menopause. The oestrogen group showed no significant change from baseline

Sexual function (total McCoy score)

Floter 2002b

44

A crossover study with no washout period

After 24 weeks of treatment, the addition of testosterone had a significantly better effect on the variables 'enjoyment of sex', 'satisfaction with frequency of sexual activity' and 'interest in sex'. The total McCoy score was significantly increased by both treatments, but the addition of testosterone exerted a stronger effect (P<0.05)

Sexual function

Miller 2000 (Luciano 1999)

51

The data was not available

Improvement (P<0.05) in sexual interest, sexual satisfaction, frequency of sexual intercourse and intensity and frequency of orgasm during sexual intercourse were reported in all groups except the estrogen alone group

Sexual function

Nathrost‐Boos 2006

60

A cross‐over study with no washout period

The scores concerning frequency of sexual activity, orgasm and intercourse, sexual arousal, fantasies and enjoyment, satisfaction with orgasms, and interest in sex were all significantly improved for testosterone addition as compared to placebo both before and after crossover

Sexual function(desire and satisfaction)

Penotti 2001

33

The data was not available

No difference between two groups was observed at any of the considered time points.

Sexual function

Shepanek 1999

30

The data was likely to be skewed

Oestrogen‐testosterone‐treated participants reported significantly less lack of sexual desire or interest to engage in sexual activity, compared to participants receiving oestrogen alone

Sexual function

Sherwin 1988 (Sherwin 1985b)

43

The data was not available

Women who received either of the androgen‐containing preparations had significantly higher scores than women in the estrogen and placebo groups(P<0.01) in association with their higher levels of plasma testosterone. Women in the estrogen‐testosterone and testosterone‐only group experienced a greater number of fantasies during every treatment than did women in the oestrogen and placebo group (P<0.01). During treatment phases, both androgen groups attained higher levels of sexual arousal than did the estrogen and placebo groups(P<0.01)

Sexual function (scores)

Shifren 2000

65

A cross‐over study with no washout period

The mean composite score expressed as a percentage of the mean value for normal women, increased from 52(27) percent at baseline to 72(38) percent during estrogen treatment, 74(37) percent during treatment with estrogen plus 150 microgram of testosterone per day, and 81(37) percent during treatment with estrogen plus 300 microgram of testosterone per day(P=0.05 for the comparison with estrogen‐alone). The scores for thoughts‐desire, frequency of sexual activity, and pleasure‐orgasm were lowest at baseline and increased in a dose‐dependent fashion. With the estrogen plus testosterone 300 microgram, the increases in scores for frequency of sexual activity and pleasure‐orgasm were significantly greater than those with estrogen‐alone (P=0.03 for both comparisons). The score for problems affecting sexual function was 116%(48) of the normative mean at baseline and decreased to 98%(49) during treatment with estrogen plus 300 microgram of testosterone(P=0.07 for the comparison with oestrogen‐alone)

Sexual function (the prevalence of particular types of sexual behavior)

Shifren 2000

65

A crossover study with no washout period

The percentage of women who reported having sexual fantasies at least once a week was 12% at baseline, 10% during oestrogen treatment, 18 percent during estrogen plus testosterone 150 microgram, and 24% during treatment with estrogen plus 300 microgram of testosterone. The percentage of women who reported masturbating at least once a week was 3%, 5% and 10% at baseline, estrogen treatment and estrogen plus testosterone treatment, respectively. Finally, the percentage of women who engaged in sexual intercourse at least once a week was 23% at baseline, 35% during treatment with either oestrogen‐alone or oestrogen plus 150 microgram of testosterone, and 41% during treatment with oestrogen plus 300 microgram of testosterone

Unexplained fatigue (vitality)

Floter 2002b

50

A crossover study with no washout period

There was no significant difference between the treatments in vitality

Unexplained fatigue (vitality)

Shifren 2000

67

A crossover study with no washout period

Vitality improved in women treated with testosterone patch combined with oral conjugated equine oestrogen

Unexplained fatigue and sense of well being

Sherwin 1988 (Sherwin 1985a)

43

The data was not available

Women in estrogen alone and placebo groups reported significantly lower ratings of energy level and well being than did those who received either of the androgen‐containing preparations (P<0.01)

Figuras y tablas -
Table 1. Trial outcomes not included in the meta‐analysis
Comparison 1. HT plus testosterone versus HT on sense of well being

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Sense of well‐being Show forest plot

2

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 sexual function

2

160

Std. Mean Difference (IV, Fixed, 95% CI)

0.47 [0.15, 0.80]

1.2 Cognitive difficulty

1

95

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.40, 0.40]

1.3 Somatic or physical symptoms

2

164

Std. Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.11, 0.54]

1.4 Anxiety or fear

1

95

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.70, 0.11]

1.5 Depressed mood

1

95

Std. Mean Difference (IV, Fixed, 95% CI)

0.26 [‐0.14, 0.67]

1.6 Vasomotor symptoms

2

166

Std. Mean Difference (IV, Fixed, 95% CI)

0.24 [‐0.08, 0.56]

1.7 Sleep problems

1

95

Std. Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.35, 0.45]

1.8 Menstrual symptoms

1

95

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.11 [‐0.52, 0.29]

1.9 Attractiveness

1

95

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.23, 0.58]

1.10 Psychosocial

1

70

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.05 [‐0.57, 0.47]

Figuras y tablas -
Comparison 1. HT plus testosterone versus HT on sense of well being
Comparison 2. HT plus testosterone versus HT on sexual function

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change scores of sexual function Show forest plot

9

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Number of satisfying

5

1893

Std. Mean Difference (IV, Fixed, 95% CI)

0.29 [0.20, 0.38]

1.2 Number of activity

7

1946

Std. Mean Difference (IV, Fixed, 95% CI)

0.25 [0.17, 0.34]

1.3 Number of orgasms

5

1893

Std. Mean Difference (IV, Fixed, 95% CI)

0.30 [0.21, 0.39]

1.4 Libido, desire or interest in sex

9

2215

Std. Mean Difference (IV, Fixed, 95% CI)

0.35 [0.26, 0.43]

1.5 Orgasm

6

1872

Std. Mean Difference (IV, Fixed, 95% CI)

0.28 [0.19, 0.37]

1.6 Arousal

5

1845

Std. Mean Difference (IV, Fixed, 95% CI)

0.36 [0.27, 0.45]

1.7 Pleasure or enjoyment of sex

6

1641

Std. Mean Difference (IV, Fixed, 95% CI)

0.33 [0.22, 0.43]

1.8 Sexual concerns

5

1852

Std. Mean Difference (IV, Fixed, 95% CI)

0.32 [0.22, 0.41]

1.9 Responsiveness

8

2171

Std. Mean Difference (IV, Fixed, 95% CI)

0.32 [0.23, 0.40]

1.10 Sexual self‐image

5

1839

Std. Mean Difference (IV, Fixed, 95% CI)

0.26 [0.16, 0.35]

1.11 Satisfaction

1

32

Std. Mean Difference (IV, Fixed, 95% CI)

0.98 [0.24, 1.72]

1.12 Fantasy

1

32

Std. Mean Difference (IV, Fixed, 95% CI)

1.37 [0.59, 2.15]

1.13 Frequency of desire

1

96

Std. Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.19, 0.61]

1.14 Composite score

3

330

Std. Mean Difference (IV, Fixed, 95% CI)

0.41 [0.19, 0.63]

2 Change scores of Personal Distress Scale Show forest plot

5

1845

Mean Difference (IV, Fixed, 95% CI)

‐8.13 [‐10.59, ‐5.67]

2.1 Personal Distress Scale

5

1845

Mean Difference (IV, Fixed, 95% CI)

‐8.13 [‐10.59, ‐5.67]

Figuras y tablas -
Comparison 2. HT plus testosterone versus HT on sexual function
Comparison 3. HT plus testosterone versus HT on bone mineral density

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Lumbar BMDs at 12 months Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Mean score

2

90

Mean Difference (IV, Fixed, 95% CI)

‐0.05 [‐0.11, 0.00]

1.2 Change score

1

57

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐1.93, 1.13]

2 Lumbar BMDs at 24 months Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 Mean score

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Change score

1

32

Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.19, 0.03]

3 Femur BMDs at 12 months Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 Mean score

2

90

Mean Difference (IV, Fixed, 95% CI)

‐0.05 [‐0.09, ‐0.01]

3.2 Change score

1

57

Mean Difference (IV, Fixed, 95% CI)

1.4 [0.14, 2.66]

4 Femur BMDs at 24 months Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 Mean score

1

32

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.16, 0.02]

4.2 Change score

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figuras y tablas -
Comparison 3. HT plus testosterone versus HT on bone mineral density
Comparison 4. HT plus testosterone versus HT on body composition

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Weight Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Mean weight at the endpoint (3 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

1.30 [‐3.86, 6.46]

1.2 Mean weight at the endpoint (6 months)

1

37

Mean Difference (IV, Fixed, 95% CI)

5.40 [‐4.79, 15.59]

1.3 Mean weight at the endpoint (12 months)

1

37

Mean Difference (IV, Fixed, 95% CI)

6.30 [‐3.83, 16.43]

1.4 Weight gain

1

37

Mean Difference (IV, Fixed, 95% CI)

1.18 [‐0.25, 2.61]

2 Body mass index Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 Body mass index at 3 months

1

42

Mean Difference (IV, Fixed, 95% CI)

1.0 [‐0.64, 2.64]

2.2 Body mass index at 6 months

1

37

Mean Difference (IV, Fixed, 95% CI)

1.60 [‐2.31, 5.51]

2.3 Body mass index at 12 months

1

37

Mean Difference (IV, Fixed, 95% CI)

2.10 [‐1.83, 6.03]

3 Waist:hip ratio Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 At 6 months

1

37

Mean Difference (IV, Fixed, 95% CI)

‐0.05 [‐0.08, ‐0.02]

3.2 At 12 months

1

37

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.06, 0.00]

Figuras y tablas -
Comparison 4. HT plus testosterone versus HT on body composition
Comparison 5. HT plus testosterone versus HT on cognition

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cognitive performance Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Identical Pictures

1

26

Mean Difference (IV, Fixed, 95% CI)

‐2.40 [‐6.67, 1.87]

1.2 Shape Memory

1

26

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐2.19, 2.39]

2 Cognition difficulty Show forest plot

1

95

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.21, 0.21]

Figuras y tablas -
Comparison 5. HT plus testosterone versus HT on cognition
Comparison 6. HT plus testosterone versus HT on menopausal symptoms

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Vasomotor symptom Show forest plot

2

166

Mean Difference (IV, Fixed, 95% CI)

0.09 [‐0.18, 0.37]

Figuras y tablas -
Comparison 6. HT plus testosterone versus HT on menopausal symptoms
Comparison 7. HT plus testosterone versus HT on facial and body hair growth

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean scores of facial and body hair growth Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2 Incidence of facial and body hair growth Show forest plot

7

2127

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.52 [1.07, 2.17]

Figuras y tablas -
Comparison 7. HT plus testosterone versus HT on facial and body hair growth
Comparison 8. HT plus testosterone versus HT on acne

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean scores of acne Show forest plot

1

216

Mean Difference (IV, Fixed, 95% CI)

0.1 [‐0.03, 0.23]

2 Incidence of acne Show forest plot

7

2127

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.51 [1.07, 2.14]

Figuras y tablas -
Comparison 8. HT plus testosterone versus HT on acne
Comparison 9. HT plus testosterone versus HT on mammographic findings

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Incidence of increased breast density Show forest plot

1

87

Odds Ratio (M‐H, Fixed, 95% CI)

1.35 [0.46, 3.95]

2 Area of dense breast Show forest plot

1

87

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐7.62, 7.62]

Figuras y tablas -
Comparison 9. HT plus testosterone versus HT on mammographic findings
Comparison 10. HT plus testosterone versus HT on lipid profile

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Total cholesterol at less than 3 months Show forest plot

4

231

Mean Difference (IV, Random, 95% CI)

‐14.92 [‐27.81, ‐2.03]

2 Triglyceride at less than 3 months Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 LDL cholesterol at less than 3 months Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Totals not selected

4 HDL cholesterol at less than 3 months Show forest plot

4

231

Mean Difference (IV, Random, 95% CI)

‐17.11 [‐23.47, ‐10.75]

5 Total cholesterol at 3 ‐ <6 months Show forest plot

2

256

Mean Difference (IV, Random, 95% CI)

‐9.42 [‐31.76, 12.93]

5.1 Mean score

1

40

Mean Difference (IV, Random, 95% CI)

3.87 [‐15.08, 22.82]

5.2 Change score

1

216

Mean Difference (IV, Random, 95% CI)

‐19.2 [‐26.16, ‐12.24]

6 Triglyceride at 3 ‐ <6 months Show forest plot

2

256

Mean Difference (IV, Fixed, 95% CI)

‐25.62 [‐38.53, ‐12.72]

6.1 Mean score

1

40

Mean Difference (IV, Fixed, 95% CI)

‐44.29 [‐85.55, ‐3.03]

6.2 Change score

1

216

Mean Difference (IV, Fixed, 95% CI)

‐23.6 [‐37.18, ‐10.02]

7 LDL cholesterol at 3 ‐ <6 months Show forest plot

2

256

Mean Difference (IV, Random, 95% CI)

18.78 [‐18.39, 55.94]

7.1 Mean score

1

40

Mean Difference (IV, Random, 95% CI)

38.67 [21.22, 56.12]

7.2 Change score

1

216

Mean Difference (IV, Random, 95% CI)

0.7 [‐5.58, 6.98]

8 HDL cholesterol at 3 ‐ <6 months Show forest plot

2

256

Mean Difference (IV, Random, 95% CI)

‐18.72 [‐26.04, ‐11.39]

8.1 Mean score

1

40

Mean Difference (IV, Random, 95% CI)

‐23.2 [‐30.19, ‐16.21]

8.2 Change score

1

216

Mean Difference (IV, Random, 95% CI)

‐15.60 [‐18.59, ‐12.61]

9 Total cholesterol/HDL cholesterol at 3 ‐ <6 months

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Total cholesterol at 6 ‐ <12 months Show forest plot

10

1910

Mean Difference (IV, Random, 95% CI)

‐2.93 [‐7.18, 1.32]

10.1 Mean score

3

101

Mean Difference (IV, Random, 95% CI)

‐6.27 [‐20.41, 7.88]

10.2 Change score

7

1809

Mean Difference (IV, Random, 95% CI)

‐2.74 [‐7.47, 2.00]

11 Triglyceride at 6 ‐ <12 months Show forest plot

10

1909

Mean Difference (IV, Random, 95% CI)

‐5.79 [‐14.25, 2.67]

11.1 Mean score

3

101

Mean Difference (IV, Random, 95% CI)

7.00 [‐8.74, 22.74]

11.2 Change score

7

1808

Mean Difference (IV, Random, 95% CI)

‐8.64 [‐18.40, 1.11]

12 LDL cholesterol at 6 ‐ <12 months Show forest plot

10

1906

Mean Difference (IV, Fixed, 95% CI)

1.86 [‐0.15, 3.87]

12.1 Mean score

3

101

Mean Difference (IV, Fixed, 95% CI)

3.24 [‐10.76, 17.23]

12.2 Change score

7

1805

Mean Difference (IV, Fixed, 95% CI)

1.83 [‐0.20, 3.86]

13 HDL cholesterol at 6 ‐ <12 months Show forest plot

10

1907

Mean Difference (IV, Random, 95% CI)

‐5.84 [‐9.10, ‐2.58]

13.1 Mean score

3

101

Mean Difference (IV, Random, 95% CI)

‐9.38 [‐13.64, ‐5.12]

13.2 Change score

7

1806

Mean Difference (IV, Random, 95% CI)

‐4.74 [‐8.42, ‐1.07]

14 Total cholesterol/HDL at 6 ‐ <12 months Show forest plot

1

45

Mean Difference (IV, Fixed, 95% CI)

20.6 [12.76, 28.44]

14.1 Change score

1

45

Mean Difference (IV, Fixed, 95% CI)

20.6 [12.76, 28.44]

15 Total cholesterol at 12 months Show forest plot

4

231

Mean Difference (IV, Random, 95% CI)

‐7.99 [‐23.45, 7.48]

15.1 Mean score

2

70

Mean Difference (IV, Random, 95% CI)

1.75 [‐15.03, 18.52]

15.2 Change score

2

161

Mean Difference (IV, Random, 95% CI)

‐14.35 [‐38.05, 9.35]

16 Triglyceride at 12 months Show forest plot

4

231

Mean Difference (IV, Random, 95% CI)

‐23.38 [‐55.53, 8.76]

16.1 Mean score

2

70

Mean Difference (IV, Random, 95% CI)

3.92 [‐21.60, 29.43]

16.2 Change score

2

161

Mean Difference (IV, Random, 95% CI)

‐45.29 [‐80.17, ‐10.40]

17 LDL cholesterol at 12 months Show forest plot

4

231

Mean Difference (IV, Fixed, 95% CI)

8.84 [2.13, 15.54]

17.1 Mean score

2

70

Mean Difference (IV, Fixed, 95% CI)

5.81 [‐10.02, 21.64]

17.2 Change score

2

161

Mean Difference (IV, Fixed, 95% CI)

9.50 [2.10, 16.90]

18 HDL cholesterol at 12 months Show forest plot

4

231

Mean Difference (IV, Random, 95% CI)

‐14.49 [‐25.28, ‐3.70]

18.1 Mean score

2

70

Mean Difference (IV, Random, 95% CI)

‐7.22 [‐13.99, ‐0.45]

18.2 Change score

2

161

Mean Difference (IV, Random, 95% CI)

‐23.64 [‐28.95, ‐18.33]

19 Total cholesterol/HDL at 12 months Show forest plot

1

45

Mean Difference (IV, Fixed, 95% CI)

15.40 [4.40, 26.40]

19.1 Mean score

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

19.2 Change score

1

45

Mean Difference (IV, Fixed, 95% CI)

15.40 [4.40, 26.40]

20 Total cholesterol at 24 months Show forest plot

3

167

Mean Difference (IV, Random, 95% CI)

‐11.69 [‐32.36, 8.97]

20.1 Mean change

1

32

Mean Difference (IV, Random, 95% CI)

3.87 [‐24.74, 32.48]

20.2 Change score

2

135

Mean Difference (IV, Random, 95% CI)

‐16.63 [‐42.67, 9.42]

21 Triglyceride at 24 months Show forest plot

3

167

Mean Difference (IV, Fixed, 95% CI)

‐52.46 [‐69.58, ‐35.35]

21.1 Mean change

1

32

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐54.94, 54.94]

21.2 Change score

2

135

Mean Difference (IV, Fixed, 95% CI)

‐58.11 [‐76.12, ‐40.09]

22 LDL cholesterol at 24 months Show forest plot

3

167

Mean Difference (IV, Fixed, 95% CI)

9.15 [1.09, 17.20]

22.1 Mean change

1

32

Mean Difference (IV, Fixed, 95% CI)

3.87 [‐20.94, 28.68]

22.2 Change score

2

135

Mean Difference (IV, Fixed, 95% CI)

9.77 [1.26, 18.29]

23 HDL cholesterol at 24 months Show forest plot

3

167

Mean Difference (IV, Random, 95% CI)

‐17.63 [‐31.45, ‐3.80]

23.1 Mean change

1

32

Mean Difference (IV, Random, 95% CI)

0.0 [‐11.76, 11.76]

23.2 Change score

2

135

Mean Difference (IV, Random, 95% CI)

‐26.34 [‐28.00, ‐22.69]

24 Total cholesterol/HDL at 24 months Show forest plot

1

45

Mean Difference (IV, Fixed, 95% CI)

20.80 [11.00, 30.60]

24.1 Mean change

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

24.2 Change score

1

45

Mean Difference (IV, Fixed, 95% CI)

20.80 [11.00, 30.60]

Figuras y tablas -
Comparison 10. HT plus testosterone versus HT on lipid profile
Comparison 11. HT plus testosterone versus HT on lipid profile (subgroup analysis)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Total cholesterol Show forest plot

17

2488

Mean Difference (IV, Random, 95% CI)

‐7.59 [‐13.08, ‐2.10]

1.1 Testosterone patch

5

1738

Mean Difference (IV, Random, 95% CI)

0.08 [‐2.37, 2.52]

1.2 Testosterone implant

2

63

Mean Difference (IV, Random, 95% CI)

‐2.34 [‐23.12, 18.45]

1.3 Oral testosterone

10

687

Mean Difference (IV, Random, 95% CI)

‐14.02 [‐21.63, ‐6.40]

2 HDL cholesterol Show forest plot

17

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 Testosterone patch

5

1735

Mean Difference (IV, Random, 95% CI)

‐1.09 [‐1.98, ‐0.19]

2.2 Testosterone implant

2

63

Mean Difference (IV, Random, 95% CI)

‐5.01 [‐11.72, 1.70]

2.3 Oral testosterone

10

687

Mean Difference (IV, Random, 95% CI)

‐18.63 [‐22.18, ‐15.08]

3 LDL cholesterol Show forest plot

16

2406

Mean Difference (IV, Random, 95% CI)

4.41 [0.76, 8.07]

3.1 Testosterone patch

5

1734

Mean Difference (IV, Random, 95% CI)

1.77 [‐0.34, 3.87]

3.2 Testosterone implant

2

64

Mean Difference (IV, Random, 95% CI)

3.37 [‐13.92, 20.66]

3.3 Oral testosterone

9

608

Mean Difference (IV, Random, 95% CI)

10.39 [1.46, 19.32]

4 Triglyceride Show forest plot

17

2487

Mean Difference (IV, Random, 95% CI)

‐14.80 [‐23.24, ‐6.36]

4.1 Testosterone patch

5

1737

Mean Difference (IV, Random, 95% CI)

‐3.64 [‐8.73, 1.44]

4.2 Testosterone implant

2

63

Mean Difference (IV, Random, 95% CI)

9.10 [‐16.04, 34.24]

4.3 Oral testosterone

10

687

Mean Difference (IV, Random, 95% CI)

‐27.07 [‐41.44, ‐12.70]

5 Total cholesterol/HDL Show forest plot

1

45

Mean Difference (IV, Fixed, 95% CI)

20.80 [11.00, 30.60]

5.1 Testosterone patch

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.2 Testosterone implant

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.3 Oral testosterone

1

45

Mean Difference (IV, Fixed, 95% CI)

20.80 [11.00, 30.60]

Figuras y tablas -
Comparison 11. HT plus testosterone versus HT on lipid profile (subgroup analysis)
Comparison 12. HT plus testosterone versus HT on discontinuation rate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Discontinuation rate (overall) Show forest plot

21

3124

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.99 [0.83, 1.19]

2 Discontinuation rate (type of menopause) Show forest plot

20

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2.1 Surgical menopause

8

1942

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.09 [0.87, 1.36]

2.2 Natural menopause

5

764

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.88 [0.60, 1.29]

2.3 Both

7

419

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.44 [0.79, 2.63]

3 Discontinuation rate (menopausal status) Show forest plot

22

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

3.1 Perimenopausal

0

0

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Postmenopausal

19

3076

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.04 [0.86, 1.25]

3.3 Both

3

148

Peto Odds Ratio (Peto, Fixed, 95% CI)

3.26 [0.85, 12.47]

4 Discontinuation rate (route of hormone therapy) Show forest plot

22

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

4.1 Oral HT

13

1840

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.01 [0.79, 1.30]

4.2 Non‐oral HT

7

289

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.32 [0.62, 2.82]

4.3 Oral and non‐oral HT

2

1095

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.09 [0.82, 1.46]

5 Discontinuation rate (type of testosterone) Show forest plot

22

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

5.1 Methyl testosterone

10

955

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.33 [0.89, 1.98]

5.2 Testosterone

9

2087

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.98 [0.79, 1.21]

5.3 Other

3

182

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.68 [0.53, 5.29]

6 Discontinuation rate (duration of treatment) Show forest plot

22

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

6.1 Less than 3 months

3

195

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.20 [0.46, 3.10]

6.2 3 ‐ <6 months

5

428

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.61 [0.87, 2.99]

6.3 6 ‐ < 12 months

10

2164

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.98 [0.80, 1.21]

6.4 12 ‐ < 24 months

2

92

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.93 [0.12, 6.98]

6.5 24 months

2

345

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.31 [0.71, 2.42]

7 Discontinuation rate (blinding) Show forest plot

22

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

7.1 Double‐blind

18

3088

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.05 [0.87, 1.26]

7.2 Open or single‐blind

4

136

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.85 [0.53, 6.49]

8 Discontinuation rate (disease status) Show forest plot

21

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

8.1 Inadequate symptom control

9

2048

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.00 [0.80, 1.25]

8.2 Low T plus inadequate symptom control

2

303

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.02 [0.62, 1.67]

8.3 No symptom

10

771

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.49 [0.90, 2.46]

Figuras y tablas -
Comparison 12. HT plus testosterone versus HT on discontinuation rate
Comparison 13. HT plus testosterone versus HT on discontinuation rate due to adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Discontinuation rate due to adverse events (overall) Show forest plot

20

3096

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.24 [0.95, 1.62]

2 Discontinuation rate due to adverse events (type of menopause) Show forest plot

19

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2.1 Surgical menopause

8

1942

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.16 [0.85, 1.59]

2.2 Natural menopause

4

704

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.31 [0.72, 2.39]

2.3 Both

7

424

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.94 [0.79, 4.78]

3 Discontinuation rate due to adverse events (menopausal status) Show forest plot

20

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

3.1 Perimenopausal

0

0

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Postmenopausal

17

2948

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.24 [0.95, 1.61]

3.3 Both

3

148

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.99 [0.20, 19.45]

4 Discontinuation rate due to adverse events (route of hormone therapy) Show forest plot

19

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

4.1 Oral HT

11

1707

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.31 [0.92, 1.86]

4.2 Non‐oral HT

7

294

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.42 [0.48, 4.20]

4.3 Oral and non‐oral HT

2

606

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.04 [0.57, 1.92]

5 Discontinuation rate due to adverse events (type of testosterone) Show forest plot

20

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

5.1 Methyl testosterone

8

827

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.56 [0.94, 2.57]

5.2 Testosterone

9

2087

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.13 [0.82, 1.55]

5.3 Other

3

182

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.53 [0.25, 9.35]

6 Discontinuation rate due to adverse events (duration of treatment) Show forest plot

20

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

6.1 Less than 3 months

2

122

Peto Odds Ratio (Peto, Fixed, 95% CI)

3.90 [0.76, 20.16]

6.2 3 ‐ < 6 months

5

428

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.94 [0.79, 4.77]

6.3 6 ‐ < 12 months

10

2164

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.13 [0.82, 1.54]

6.4 12 ‐ <24 months

1

37

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.5 24 months

2

345

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.25 [0.67, 2.33]

7 Discontinuation rate due to adverse events (blinding) Show forest plot

20

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

7.1 Double‐blind

16

2960

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.21 [0.93, 1.59]

7.2 Open or single‐blind

4

136

Peto Odds Ratio (Peto, Fixed, 95% CI)

3.59 [0.59, 21.94]

8 Discontinuation rate due to adverse events (disease status) Show forest plot

19

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

8.1 Inadequate symptom control

8

1988

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.19 [0.85, 1.67]

8.2 Low T plus inadequate symptom control

2

303

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.05 [0.52, 2.12]

8.3 No symptom

9

703

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.36 [0.77, 2.39]

Figuras y tablas -
Comparison 13. HT plus testosterone versus HT on discontinuation rate due to adverse events
Comparison 14. HT‐T versus HT on discontinuation rate (sensitivity analysis)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Discontinuation rate (allocation quality) Show forest plot

14

2773

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.98 [0.81, 1.17]

2 Discontinuation rate due to adverse events (allocation quality) Show forest plot

14

2778

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.20 [0.91, 1.57]

3 Discontinuation rate (quality of randomisation)) Show forest plot

17

2902

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.97 [0.81, 1.16]

4 Discontinuation rate due to adverse events (quality of randomisation) Show forest plot

17

2931

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.24 [0.95, 1.61]

5 Discontinuation rate (blinding method) Show forest plot

17

3057

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.97 [0.81, 1.17]

6 Discontinuation rate due to adverse events (blinding method) Show forest plot

15

2929

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.21 [0.93, 1.59]

7 Discontinuation rate (large studies) Show forest plot

15

723

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.38 [0.77, 2.49]

8 Discontinuation rate due to adverse events (large studies) Show forest plot

13

595

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.44 [0.57, 3.64]

9 Discontinuation rate (methyl testosterone doses) Show forest plot

10

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

9.1 Methyl testosterone, all doses

10

955

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.96 [0.68, 1.35]

9.2 Methyl testosterone 1.25mg

5

473

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.89 [0.55, 1.43]

9.3 Methyl testosterone 2 mg

1

60

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.93 [0.12, 6.98]

9.4 Methyl testosterone 2.5mg

6

431

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.95 [0.57, 1.58]

10 Discontinuation rate due to adverse events (methyl testosterone doses) Show forest plot

8

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

10.1 Methyl testosterone, all doses

8

827

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.43 [0.92, 2.22]

10.2 Methyl testosterone 1.25mg

5

477

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.26 [0.71, 2.23]

10.3 Methyl testosterone 2.5mg

5

358

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.60 [0.80, 3.23]

11 Discontinuation rate (estrogen doses) Show forest plot

24

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

11.1 Estrogen, all doses

24

3394

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.98 [0.82, 1.17]

11.2 Conjugated estrogen 0.625mg or equivalent doses of other estrogens

7

766

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.00 [0.70, 1.41]

11.3 Conjugated estrogen 1.25mg or equivalent doses of other estrogens

15

907

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.01 [0.68, 1.52]

12 Discontinuation rate due to adverse events (estrogen doses) Show forest plot

22

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

12.1 Estrogen, all doses

22

3266

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.22 [0.93, 1.58]

12.2 Conjugated estrogen 0.625mg or equivalent doses of other estrogens

6

706

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.34 [0.80, 2.24]

12.3 Conjugated estrogen 1.25mg or equivalent doses of other estrogens

14

839

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.42 [0.76, 2.65]

Figuras y tablas -
Comparison 14. HT‐T versus HT on discontinuation rate (sensitivity analysis)