|
Table 1:
Hormone replacement therapy (any v. minimal or no use)
|
|
|
Notes |
These reports examine the relationship between postmenopausal use of hormone replacement therapy (HRT) and AD. Use of HRT can refer to use of estrogen alone or estrogen in combination with a progestogen (progestin or progesterone). Most commonly, HRT refers to use of estrogens combined with a progestogen and ERT refers to use of estrogens only. Not all papers provided information about the types of HRT used by their participants. Results here compare AD risk among women who ever used HRT with risk among those who never used HRT.
Some studies in this table compare those with chronic HRT usage with those with "minimal" HRT use. (In other words, some women in the reference group used HRT for a brief interval that investigators considered insufficient to bear meaningfully on AD risk.)
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
Exposure Distribution
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Brenner, 1994
|
ADPR-GHC
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
227
(100%) |
-
(detail) |
No HRT: 52%
HRT - all: 48%
(detail) |
55
52
Total: 107 |
1.00
1.10 |
Ref.
0.60-1.80 |
Ref.
0.73
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Kawas, 1997
|
BLSA
|
Incidence study reporting hazard ratios (HRs) |
472
(100%) |
-
(detail) |
No HRT: 51%
HRT: 49%
(detail) |
25
9
Total: 34 |
1.00
0.46 |
Ref.
0.21-0.99 |
Ref.
0.05
* |
|
|
|
|
Caucasian
|
62
(-)
(28
-
94) |
AD Diagnosis: Brain Imaging, DSM IIIR, NINCDS ADRDA, Neurologic examination
(detail) |
A, E‡
(detail) |
|
Kawas, 1997
|
|
Lindsay, 2002
|
CSHA
|
Cumulative incidence study reporting odds ratios (ORs) |
2079
(100%) |
5.0 y
(detail) |
No HRT: 94%
HRT: 6%
(detail) |
106
4
Total: 110 |
1.00
1.37† |
Ref.
0.48-3.95 |
Ref.
0.56
* |
|
|
|
|
(detail) |
73
(-)
(
-
)
(detail) |
Screening: 3MSE
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E‡
(detail) |
|
Lindsay, 2002
|
|
Roberts, 2006
|
Rochester Epidemiology Project
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
490
(100%) |
-
(detail) |
< 6 mo or never: 89%
≥ 6 mo: 11%
(detail) |
216
28
Total: 244 |
1.00
1.10 |
Ref.
0.63-1.93 |
Ref.
0.73 |
|
|
|
|
Caucasian
(detail) |
84
(-)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IV
(detail) |
A, TM‡
(detail) |
|
Roberts, 2006
|
|
Tang, 1996
|
WHICAP
|
Incidence study reporting hazard ratios (HRs) |
1124
(100%) |
-
(detail) |
No HRT: 86%
HRT: 14%
(detail) |
158
9
Total: 167 |
1.00
0.50 |
Ref.
0.25-0.90 |
Ref.
0.02 |
|
|
|
|
Caucasian, Hispanic, African-American (Black)
|
74
(7)
(
-
)
(detail) |
AD Diagnosis: Brain Imaging, DSM IIIR, Medical History, NINCDS ADRDA, Neuropsychological examination
(detail) |
A, E, APOE4, RE‡
(detail) |
|
Tang, 1996
|
|
Waring, 1999
|
Rochester Epidemiology Project
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
444
(100%) |
-
(detail) |
< 6 mo or never: 93%
≥ 6 mo: 7%
(detail) |
211
11
Total: 222 |
1.00
0.48 |
Ref.
0.22-1.01 |
Ref.
0.05 |
|
|
|
|
Caucasian
(detail) |
-
(-)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A‡
(detail) |
|
Waring, 1999
|
|
Zandi, 2002
|
Cache County Study
|
Incidence study reporting hazard ratios (HRs) |
1866
(100%) |
3.0 y
(detail) |
No HRT: 43%
HRT: 57%
(detail) |
58
26
Total: 84 |
1.00
0.59 |
Ref.
0.36-0.96 |
Ref.
0.03
* |
|
|
|
|
(detail) |
74
(6)
(
-
)
(detail) |
Screening: DQ, Informant interview, 3MSE
AD Diagnosis: Medical History, NINCDS ADRDA, Neurologic examination, Neuropsychological examination
(detail) |
A, E, APOE4‡
(detail) |
|
Zandi, 2002
|
* Derived value.
† Five or fewer cases exist.
‡ Covariates: "A" (age), "E" (education), "AAMr" (age at menarche), "AAMp" (age at menopause), "ALC" (alcohol intake), "APOE4" (APOE e4 genotype), "BW50" (body weight at age 50), "HYS" (history of hysterectomy), "CH" (number of children), "PS" (propensity score), "RE" (race/ethnicity), "SM" (smoking status), "TM" (type of menopause)
|
|
|
|
Table 2:
Hormone replacement therapy, duration of use (categorical)
|
|
Notes |
These reports examine the relationship between the duration of use of hormone replacement therapy (HRT; either in years or number of prescriptions filled) and AD. The risk among women in each category of duration of use is compared with the risk among never users. As in Table 1, use of HRT can refer to use of estrogen alone or estrogen in combination with a progestogen (progestin or progesterone), although some studies are not explicit about which types of HRT are represented.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
Exposure Distribution
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Brenner, 1994
|
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
227
(100%) |
5.0 y
*
(detail) |
All estrogens
No HRT: 52%
1 - 2 prescriptions: 17%
3 - 10 prescriptions: 15%
11 - 50 prescriptions: 16%
(detail) |
55
22
15
50
Total: 142 |
1.00
1.50
0.90
0.80 |
Ref.
0.70-3.00
0.40-2.10
0.30-1.80 |
Ref.
0.27
0.8
0.63
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Brenner, 1994
|
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
175
(100%) |
5.0 y
*
(detail) |
Oral estrogens
No HRT: 67%
1 - 4 prescriptions: 10%
5 - 16 prescriptions: 13%
17 - 50 prescriptions: 10%
(detail) |
55
7
12
6
Total: 80 |
1.00
0.70
1.40
0.40 |
Ref.
0.20-2.00
0.50-3.80
0.10-1.50 |
Ref.
0.54
0.52
0.18
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Brenner, 1994
|
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
194
(100%) |
5.0 y
*
(detail) |
Vaginal estrogens
No HRT: 60%
1 prescription: 13%
2-4 prescriptions: 15%
5 - 27 presciptions: 12%
(detail) |
55
15
15
8
Total: 93 |
1.00
1.70
1.40
0.70 |
Ref.
0.70-4.00
0.60-3.10
0.30-1.90 |
Ref.
0.23
0.42
0.45
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Kawas, 1997
|
BLSA
|
Incidence study reporting hazard ratios (HRs) |
472
(100%) |
-
(detail) |
No HRT:
> 0 - 5 years:
> 5 - 10 years:
> 10 years:
(detail) |
-
-
-
-
Total: 34 |
1.00
0.44
0.34
0.50 |
Ref.
0.13-1.51
0.05-2.52
0.17-1.47 |
Ref.
0.19
0.29
0.21 |
|
|
|
|
Caucasian
|
62
(-)
(28
-
94) |
AD Diagnosis: Brain Imaging, DSM IIIR, NINCDS ADRDA, Neurologic examination
(detail) |
A, E‡
(detail) |
|
Kawas, 1997
|
|
Roberts, 2006
|
Rochester Epidemiology Project
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
490
(100%) |
-
(detail) |
< 0.5 years or never: 89%
0.5 - 3 years: 5%
> 3 years: 6%
(detail) |
216
14
14
Total: 244 |
1.00
1.22
1.01 |
Ref.
0.55-2.69
0.47-2.20 |
Ref.
0.63
0.97 |
|
|
|
|
Caucasian
(detail) |
84
(-)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IV
(detail) |
A, TM‡
(detail) |
|
Roberts, 2006
|
|
Seshadri, 2001
|
GPRD
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
280
(100%) |
5.3 y
(detail) |
No HRT: 75%
12-35 months: 7%
36-59 months: 9%
≥ 60 months: 9%
(detail) |
44
6
5
4
Total: 59 |
1.00
1.68
0.89†
1.05† |
Ref.
0.60-4.69
0.29-2.69
0.32-3.44 |
Ref.
0.32
0.84
0.94
* |
|
|
|
|
(detail) |
66
(-)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: NINCDS ADRDA
(detail) |
BMI, SM‡
(detail) |
|
Seshadri, 2001
|
|
Tang, 1996
|
WHICAP
|
Incidence study reporting hazard ratios (HRs) |
1124
(100%) |
-
(detail) |
No HRT: 86%
Unknown: 3%
≤ 1 year: 6%
> 1 year: 5%
(detail) |
158
3
5
1
Total: 167 |
1.00
1.30†
0.47†
0.13† |
Ref.
0.40-4.20
0.20-1.10
0.02-0.92 |
Ref.
0.66
0.06
0.01
* |
|
|
|
|
Caucasian, Hispanic, African-American (Black)
|
74
(7)
(
-
) |
AD Diagnosis: Brain Imaging, DSM IIIR, Medical History, NINCDS ADRDA, Neuropsychological examination
(detail) |
A, E, APOE4, RE‡
(detail) |
|
Tang, 1996
|
|
Waring, 1999
|
Rochester Epidemiology Project
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
444
(100%) |
-
(detail) |
No HRT: 82%
< 6 months: 11%
≥ 6 months: 7%
(detail) |
189
22
11
Total: 222 |
1.00
0.85
0.42 |
Ref.
0.44-1.62
0.18-0.96 |
Ref.
0.62
0.04 |
|
|
|
|
Caucasian
(detail) |
-
(-)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A‡
(detail) |
|
Waring, 1999
|
* Derived value.
† Five or fewer cases exist.
‡ Covariates: "A" (age), "E" (education), "APOE4" (APOE e4 genotype), "BMI" (body mass index), "HYS" (history of hysterectomy), "RE" (race/ethnicity), "SM" (smoking status), "TM" (type of menopause)
|
|
|
‡ Covariates: "A" (age), "TM" (type of menopause)
|
|
|
|
Table 4:
Hormone replacement therapy, current/past/never (categorical)
|
|
Notes |
These reports examine the relationship between the timing of HRT use and AD. As in Table 1, use of HRT can refer to use of estrogen alone or estrogen in combination with a progestogen (progestin or progesterone), although some studies are not explicit about which types of HRT are represented.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
Exposure Distribution
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Brenner, 1994
|
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
227
(100%) |
5.0 y
*
(detail) |
All estrogens
No HRT: 52%
Former use: 24%
Current Use: 23%
(detail) |
55
33
19
Total: 107 |
1.00
1.70
0.60 |
Ref.
0.90-3.20
0.30-1.20 |
Ref.
0.1
0.15
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Brenner, 1994
|
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
175
(100%) |
5.0 y
*
(detail) |
Oral estrogens
No HRT: 67%
Former use: 14%
Current Use: 19%
(detail) |
55
13
12
Total: 80 |
1.00
1.40
0.40 |
Ref.
0.60-3.50
0.20-1.10 |
Ref.
0.45
0.07
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Brenner, 1994
|
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
194
(100%) |
5.0 y
*
(detail) |
Vaginal estrogens
No HRT: 60%
Former use: 29%
Current Use: 11%
(detail) |
55
31
7
Total: 93 |
1.00
1.60
0.60 |
Ref.
0.80-3.00
0.20-1.70 |
Ref.
0.16
0.35
* |
|
|
|
|
Caucasian
|
74
(7)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: DSM IIIR, NINCDS ADRDA
(detail) |
A, HYS‡
(detail) |
|
Brenner, 1994
|
|
Ryan, 2009
|
3C
|
Incidence study reporting hazard ratios (HRs) |
3130
(100%) |
4.0 y
(detail) |
No HRT: 69%
Former use: 16%
Current Use: 15%
(detail) |
-
-
-
Total: 53 |
1.00
0.39
1.36 |
Ref.
0.39-2.23
0.44-4.20 |
Ref.
0.86
0.59 |
-
-
-
Total: 79 |
1.00
0.74
0.83 |
Ref.
0.35-1.55
0.32-2.17 |
Ref.
0.42
0.7 |
Caucasian
(detail) |
74
(5)
(65
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV
(detail) |
A, E, AAMp, ANTCH, BMI, CI, DEP, HICAF, MS, O, PP‡
(detail) |
|
Ryan, 2009
|
|
Seshadri, 2001
|
GPRD
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
280
(100%) |
5.3 y
(detail) |
No HRT: 76%
Current Use: 24%
(detail) |
44
15
Total: 59 |
1.00
1.18 |
Ref.
0.59-2.37 |
Ref.
0.64
* |
|
|
|
|
(detail) |
66
(-)
(
-
)
(detail) |
Screening: Other
AD Diagnosis: NINCDS ADRDA
(detail) |
BMI, SM‡
(detail) |
|
Seshadri, 2001
|
|
Zandi, 2002
|
Cache County Study
|
Incidence study reporting hazard ratios (HRs) |
1866
(100%) |
3.0 y
(detail) |
No HRT: 43%
Former use: 26%
Current Use: 31%
(detail) |
58
9
17
Total: 84 |
1.00
0.33
1.08 |
Ref.
0.15-0.65
0.59-1.91 |
Ref.
0.003
0.8
* |
|
|
|
|
(detail) |
74
(6)
(
-
)
(detail) |
Screening: DQ, Informant interview, 3MSE
AD Diagnosis: Medical History, NINCDS ADRDA, Neurologic examination, Neuropsychological examination
(detail) |
A, E, APOE4‡
(detail) |
|
Zandi, 2002
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "AAMp" (age at menopause), "ANTCH" (anticholingergic drugs), "APOE4" (APOE e4 genotype), "BMI" (body mass index), "CI" (comorbidity index), "DEP" (depression), "HICAF" (high caffeine intake), "HYS" (history of hysterectomy), "MS" (marital status), "O" (other), "PP" (physical performance), "SM" (smoking status)
|
|
|
‡ Covariates: "A" (age), "TM" (type of menopause)
|
|
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "APOE4" (APOE e4 genotype), "PS" (propensity score), "TM" (type of menopause)
|
|
|
* Derived value.
† Five or fewer cases exist.
‡ Covariates: "A" (age), "E" (education), "APOE4" (APOE e4 genotype), "BMI" (body mass index), "PS" (propensity score), "SM" (smoking status)
|
|
|
* Derived value.
‡ Covariates: "A" (age), "HYS" (history of hysterectomy)
|