Background
Methods
Eligibility criteria
Outcome measures
Data sources and search strategy
Study selection
Data extraction and quality assessment
Data synthesis
Results
Study characteristics
First author, year of publication | Study design | Sample size | Sample size for RRSO | Age at time of studya, mean (range/SD)b
| BRCA status (%) | Menopause status at time of RRSO (%) | Age at RRSO surgery, mean(range/SD)b
| Comparator | Quality rating |
---|---|---|---|---|---|---|---|---|---|
Challberg, 2011 [33] | Cross-sectional survey design | 212 | 212 | 50(36-77) | BRCA1 & BRCA2 (58%) | Premenopausal (100%) | 41.20 (24-48) | Non-exposed and previous users | Low |
Chapman, 2011 [37] | Cross-sectional survey design | 51 | 51 | 49 (36-54) | BRCA1 (63%) & BRCA2 (37%) | Premenopausal (47%) & Postmenopausal (53%) | 46 (31–68) | Non-exposed | Low |
Eisen, 2008 [21] | Matched case control study | 472 | 136 | NS | BRCA1 (100%) | Premenopausal (100%) | 42.45 (28 – 52)c
| Control (no outcome) | High |
Finch, 2011 [38] | Prospective cohort study | 114 | 114 | 53(42-74) | BRCA1 (51%) & BRCA2 (49%) | Premenopausal (66%) & Postmenopausal (34%) | 47.50 (35-69) | Non-exposed, baseline | Low |
Gabriel, 2008 [28] | Retrospective cohort study | 73 | 73 | NS | BRCA1 (64%) & BRCA2 (38%) | Premenopausal (NS) & Postmenopausal (NS) | 42 (29.5-59.2) | Non-exposed | Low |
Garcia, 2015 [30] | Retrospective chart review | 225 | 225 | NS | BRCA1 & 2 (100%) | Premenopausal (NS) & Postmenopausal (NS) | 50 (31-80) | Non-exposed | Low |
Heiniger, 2014 [29] | Matched prospective cohort design | 233 | 38 | NS | BRCA1 & 2 (16.7%) | Premenopausal (NS) & Postmenopausal (NS) | NS | Non-exposed and previous users | Low |
Johansen, 2016 [36] | Retrospective cohort study | 1522 | 294 | 54(33-83) | NSd
| Premenopausal (NS) & Postmenopausal (NS) | 48(31-76) | Non-exposed | Low |
Kotsopoulos, 2016 [31] | Matched case control study | 864 | 210 | NS | BRCA 1 (100%) | Premenopausal (NS) & Postmenopausal (NS) | 42.75(28-53)c
| Control (no outcome) | Low |
Madalinska, 2006 [34] | Cross-sectional survey design | 450 | 450 | 46 ± 6 (range34-59) | BRCA1 & 2 (48%) | Premenopausal (100%) | 43 ± 6 | Non-exposed | High |
Michelsen, 2009 [35] | Cross-sectional survey design | 1956 | 326 | 54.4(8.9) | BRCA1 & 2 (20%) | Premenopausal (NS) & Postmenopausal (NS) | 48 ± 7.8 | Non-exposed | High |
Rebbeck, 2005 [20] | Prospective cohort study | 462 | 155 | 42.7(37-78) | BRCA1 (70%) & BRCA2 (30%) | Premenopausal (NS) & Postmenopausal (NS) | NS | Non-exposed | High |
Tucker, 2016 [32] | Cross-sectional survey design | 119 | 119 | NS | BRCA1 (8.40%) & BRCA2 (11.70%) | Premenopausal (43%) & Postmenopausal (57%) | 50(33-69) | Non-exposed | Low |
First author | Type of HT | Dose of HT | Route of HT | Duration of HTa-mean (range/SD)b
|
---|---|---|---|---|
Challberg [33] | ET, EPT and tibolone | NS | NS | 3.4 (0.1-19) |
Chapman [37] | NS | NS | NS | 6 (0.75-9) |
Eisen [21] | ET and EPT | NS | NS | 3.85c (NS) |
Finch [38] | ET and EPT | NS | NS | NS |
Gabriel [28] | ET and EPT | NS | NS | 2.79 ± 3.22 |
Garcia [30] | NS | NS | Systemic HT (60%) | NS |
Heiniger [29] | NS | NS | NS | NS |
Johansen [36] | ET, EPT and tibolone | NS | Systemic HT (39.28%) & local/vaginal HT (6.54%) | NS |
Kotsopoulos [31] | ET and EPT | NS | NS | 4.35(0.05-25)c
|
Madalinska [34] | EPT and tibolone | NS (standard) | Systemic HT (Oral/transdermal) | 3 ± 2.3 |
Michelsen [35] | NS | NS | Systemic (Oral/transdermal) | NS |
Rebbeck [20] | ET and EPT | NS | NS | NS |
Tucker [32] | ET | NS | Systemic HT (20% - oral and transdermal) & local/vaginal HT (8%) | NS |
Synthesis of results
Outcome | First author | Tool of assessment | N of analysis | Mean differenceab
| Measure of association (95% CI)c
|
P value | Duration of follow-up |
---|---|---|---|---|---|---|---|
General QOL | Tucker [32] | SF-36 – total | 108 | Systemic HT = 1.76 | - | 0.57 | NA |
93 | Local HT = 3.3 | - | 0.86 | ||||
SF-36 – pain | 108 | Systemic HT = 14.64 | - |
<0.01
| |||
93 | Local HT = 4.85 | - | 0.75 | ||||
SF-36 – physical | 108 | Systemic HT = 7.15 | - | 0.38 | |||
93 | Local HT = 5.34 | - | 0.52 | ||||
SF-36 – emotional | 108 | Systemic HT = -0.50 | - | 0.50 | |||
93 | Local HT = -5.5 | - | 0.27 | ||||
SF-36 – social | 108 | Systemic HT = -3.67 | - | 0.82 | |||
93 | Local HT = 3.66 | - | 0.92 | ||||
SF-36 – energy | 108 | Systemic HT = 0.6 | - | 0.42 | |||
93 | Local HT = 3.66 | - | 0.87 | ||||
SF-36 – general health | 108 | Systemic HT = 4.55 | - | 0.55 | |||
93 | Local HT = 3.37 | - | 0.96 | ||||
Menopause specific QOL | Challberg [33] | FACT-ESd – total | 141 | 3.1 | - | 0.09 | NA |
Chapman [37] | MSLe – total | 51 | -1.1 | - | 0.06 | NA | |
Finch [38] | MENQOL Interventione – total | 73 | -3.37f
| - |
<0.01
| 13.6 months (10.8–21.8) | |
MENQOL – vasomotor | 73 | -3.4 | - |
<0.01
| |||
MENQOL – physical | 73 | -0.38 | - | 0.28 | |||
MENQOL – psychosocial | 73 | -0.07 | - | 0.89 | |||
MENQOL – sexual | 73 | -1.22 | - |
0.02
| |||
Heiniger [29] | MRSe
| 38 | NS | - | >0.05 | 3 yearsg
| |
Madalinska [34] | FACT-ESd – total | 164 | 3.4 | - |
0.03
| NA | |
Tucker [32] | MENQOLe – total | 108 | Systemic HT = -2.76f
| - |
<0.01
| ||
93 | Local HT = -2.23f
| - |
<0.01
| ||||
MENQOL – vasomotor | 108 | Systemic HT = -1.08 | - |
0.02
| |||
93 | Local HT = -1.04 | - | 0.22 | ||||
MENQOL – physical | 108 | Systemic HT = -0.74 | - |
0.03
| |||
93 | Local HT = -0.54 | - | 0.38 | ||||
MENQOL – psychosocial | 108 | Systemic HT = -0.1 | - | 0.36 | |||
93 | Local HT = -0.1 | - | 0.91 | ||||
MENQOL – sexual | 108 | Systemic HT = -0.84 | - |
0.03
| |||
93 | Local HT = -0.55 | - | 0.74 | ||||
Breast cancer | Eisen [21] | Self-reportedh
| 124 | - | OR = 0.48(0.19-1.21) | 0.12 | NA |
Kotsopoulos [31] Same study as Eisen but an updated analysis
| Self-reported | 210 | - | OR = 1.06(0.58-1.96) | 0.85 | NA | |
OR = 1.06(0.52-2.18) - Breast cancer risk with HT use of ≤3 years vs. never use
| 0.87 | ||||||
OR = 1.06 (0.41-2.71) - Breast cancer risk with HT use of >3 years vs. never use
| 0.91 | ||||||
Gabriel [28] | Self-reportedh
| 60 | - | OR = 0.31(0.09-1.04)f
| >0.05 | NS | |
OR = 0.48(0.1-2.1) - Breast cancer risk with ET only (no cases with EPT)
| >0.05 | ||||||
Rebbeck [20] | Medical records, operative notes, and pathology reports | 155 | - | HR = 3.93(0.51-30.50)i
| >0.05 | 2.6 years (0.1-19.1) | |
HR = 2.56(0.08-78.13) Breast cancer risk with EPT vs. ET
| >0.05 | ||||||
Vasomotor symptoms | Challberg [33] | FACT-ESj
| 141 | - | Hot flashes OR = 0.55(0.23-1.28)f
| >0.05 | NA |
Night sweats OR = 0.28(0.11-0.76)f
|
<0.05
| ||||||
Finch [38] | Self-reported | 73 | - | Hot flashes OR = 0.27(0.09-0.80)f
|
0.03
| 13.6 months (10.8–21.8) | |
Madalinska [34] | FACT-ESj
| 164 | - | Hot flashes OR = 0.34(0.17-0.70)f
|
<0.01
| NA | |
Night sweats OR = 0.51(0.26-1.00)f
|
0.04
| ||||||
Sexual function | Finchk [38] | SAQd
| 61 | Pleasure = 1.22 | 0.50 | 13.6 months (10.8–21.8) | |
Discomfort = 1.92 |
0.03
| ||||||
Habit = 0.19 | 0.10 | ||||||
Heiniger [29] | SAQd
| 38 | NS for all 3 dimensions | - | >0.05 | ||
Johansen [36] | SAQl
| 157 | Pleasure systemic HT (both ET and EPT) = 0.9 | - | >0.05 | ||
102 | Pleasure local HT = -1.5 | - | >0.05 | ||||
116 | Pleasure systemic ET = 0.8 | >0.05 | |||||
111 | Pleasure systemic EPT = 0.5 | >0.05 | |||||
112 | Pleasure systemic tibolone = 1.5 | >0.05 | |||||
157 | Discomfort systemic HT (both ET and EPT) = -1.2 |
<0.01
| |||||
102 | Discomfort local HT = -0.7 | 0.2 | |||||
116 | Discomfort systemic ET = -1.1 |
0.04
| |||||
111 | Discomfort systemic EPT = -1.2 |
0.02
| |||||
112 | Discomfort systemic tibolone = -1.39 |
<0.01
| |||||
Madalinska [34] | SAQd
| 164 | Pleasure = 0.4 | 0.70 | NA | ||
Discomfort = 0.4 | 0.17 | ||||||
Habit = 0.1 | 0.45 | ||||||
Tucker [32] | FSFIdm – total | 108 | Systemic HT 5.36 | OR = 0.40(0.12-1.31); P = 0.130 Risk of FSD with systemic HT
| 0.14 | NA | |
93 | Local HT 7.61 | OR = 0.22(0.05-0.95);
P = 0.043
Risk of FSD with local HT
| 0.07 | ||||
FSFI – desiren
| 108 | Systemic HT 0.09 | OR = 0.77(0.23-2.52) P = 0.66 Risk of HSDD with systemic HT
| 0.83 | |||
93 | Local HT 0.52 | OR = 0.29(0.07-1.28); P = 0.10 Risk of HSDD with local HT
| 0.25 | ||||
FSFI – arousal | 108 | Systemic HT 0.57 | - | 0.63 | |||
93 | Local HT 1.35 | - | 0.09 | ||||
FSFI – lubricationo
| 108 | Systemic HT 1.39 | OR = 0.38(0.12-1.19); P = 0.10 Risk of lubrication difficulty with systemic HT
|
0.04
| |||
93 | Local HT 1.84 | OR = 0.29(0.05-1.53); P = 0.14 Risk of lubrication difficulty with local HT
|
0.03
| ||||
FSFI – paino
| 108 | Systemic HT 1.97 | OR = 0.16(0.03-0.81);
P = 0.03
Risk of dyspareunia with systemic HT
|
<0.01
| |||
93 | Local HT 1.55 | OR = 0.99(0.22-4.47); P = 0.99 Risk of dyspareunia with local HT
| 0.05 | ||||
FSFI – orgasmo
| 108 | Systemic HT 0.71 | OR = 0.35(0.10-1.21); P = 0.10 Risk of orgasm difficulty with systemic HT
| 0.40 | |||
93 | Local HT 1.47 | OR = 0.57(0.10-3.15); P = 0.52 Risk of orgasm difficulty with local HT
| 0.13 | ||||
FSFI – satisfactiono
| 108 | Systemic HT 0.62 | OR = 0.36(0.11-1.14); P = 0.08 Risk of dissatisfaction with sex life with systemic HT
| 0.25 | |||
93 | Local HT 0.86 | OR = 0.88(0.19-4.06); P = 0.87 Risk of dissatisfaction of sex life with local HT
| 0.36 | ||||
FSDS-Rp
| 108 | Systemic HT -4.07 | OR = 0.36(0.16-1.13); P = 0.08 Risk of sexual distress with systemic HT
| 0.07 | |||
93 | Local HT -2.34 | OR = 1.28(0.30-5.41); P = 0.74 Risk of sexual distress with local HT
| 0.94 | ||||
Loss of interest in sex | Challberg [33] | FACT-ESj
| 141 | OR = 0.68(0.34-1.37)f
| >0.05 | NA | |
Madalinska [34] | FACT-ESj
| 164 | OR = 0.66(0.30-1.47)f
| 0.35 | NA | ||
Vaginal dryness | Challberg [33] | FACT-ESj
| 141 | OR = 0.48(0.20-1.16)f
| >0.05 | NA | |
Finch [38] | MENQOL Interventione
| 73 | -1.22 |
0.02
| 13.6 months (10.8–21.8) | ||
Madalinska [34] | FACT-ESj
| 164 | - | OR = 0.47(0.21-1.07)f
| >0.05 | NA | |
Tucker24
| MENQOL – sexual | 108 | Systemic HT = -0.84 | - |
0.03
| ||
93 | Local HT = -0.55 | - | 0.74 | ||||
FSFI – lubricationo
| 108 | Systemic HT 1.39 | OR = 0.38(0.12-1.19); P = 0.10 Risk of lubrication difficulty with systemic HT
|
0.04
| |||
Bone loss prevention | Challberg[33] | 93 | Local HT 1.84 | OR = 0.29(0.05-1.53); P = 0.14 Risk of lubrication difficulty with local HT
|
0.03
| NA | |
Chapman [37] | DXA scan | 31 | - | OR = 0.41(0.07-2.41)fi
| >0.05 | NA | |
Garcia [30] | DXA scan | 198 | OR = 0.84(0.26-2.74) | >0.05 | NA | ||
Cardiovasc-ular disease | Michelsen [35] | Physical measurements, blood samples and self-administered questionnaire | 326 | - | NS | >0.05 | NA |