Table 2.
Summary of Results—Any Use of Hormone Therapy and Alzheimer's Disease/Dementia Risk
| Author, Year (Reference No.) | Study | Study Design | No. of Persons | Covariates | Exposure Distribution |
Alzheimer's Disease |
Dementia |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Description | % | No. of Cases | RRa | 95% CI | P Value | No. of Cases | RR | 95% CI | P Value | |||||
| Brenner, 1994 (33) | Alzheimer Disease Patient Registry-Group Health Cooperative | Nested case-control | 227 | Age, history of hysterectomyb | No hormone therapy | 52 | 55 | 1.00 | Referent | |||||
| Hormone therapy | 48 | 52 | 1.10 | 0.60, 1.80 | 0.73 | |||||||||
| Kawas, 1997 (34) | Baltimore Longitudinal Study of Aging | Prospective cohort | 472 | Age, educationc | No hormone therapy | 51 | 25 | 1.00 | Referent | |||||
| Hormone therapy | 49 | 9 | 0.46 | 0.21, 1.00 | 0.05 | |||||||||
| Lindsay, 2002 (35) | Canadian Study of Health and Aging | Prospective cohort | 2,079 | Age, education | No hormone therapy | 94 | 106 | 1.00 | Referent | |||||
| Hormone therapy | 6 | 4 | 1.37 | 0.48, 3.95 | 0.56 | |||||||||
| Roberts, 2006 (37) | Rochester Epidemiology Project | Nested case-control | 486 | Type of menopause, matched on age | <6 months, never | 89 | 216 | 1.00 | Referent | |||||
| ≥6 months of hormone therapy | 11 | 28 | 1.10 | 0.63, 1.93 | 0.73 | |||||||||
| Ryan, 2009 (39) | Enquête de Santé Psychologique-Risques Incidence et Traitement Study | Prospective cohort | 996 | Age, education | No hormone therapy | 66 | 19 | 1.00 | Referent | |||||
| Hormone therapy | 34d | 8 | 1.41 | 0.59, 3.34 | 0.44 | |||||||||
| Seshadri, 2001 (40) | General Practice Research Database | Nested case-control | 283 | Body mass index, smoking. Matched on age, physician's practice, case index date, date of first prescription in database | <1 year, never | 25 | 44 | 1.00 | Referent | |||||
| Hormone therapy | 75 | 18 | 1.19 | 0.62, 2.27 | 0.60 | |||||||||
| Shao, 2012 (41) | Cache County Study | Prospective cohort | 1,768 | Age, APOE status, education, propensity score for any hormone therapy use | No hormone therapy | 38 | 89 | 1.00 | Referent | NR | 1.00 | Referent | ||
| Hormone therapy | 62 | 87 | 0.80 | 0.58, 1.09 | 0.17 | NR | 0.84 | 0.65, 1.09 | 0.19 | |||||
| Shumaker, 2004 (11) | Women's Health Initiative Memory Study | Randomized placebo-controlled trial | 7,479 | None | Placebo | 51 | 21 | 1.00 | Referent | 40 | 1.00 | Referent | ||
| E or E+P | 49 | 33 | 1.62e | 0.91, 2.96 | 0.08 | 68 | 1.76 | 1.19, 2.60 | 0.005 | |||||
| Tang, 1996 (42) | Washington Heights–Inwood Columbia Aging Project | Prospective cohort | 1,124 | Ethnicity, education, participation group (senior center vs. Medicare sample) | No hormone therapy | 86 | 158 | 1.00 | Referent | |||||
| Hormone therapy | 14 | 9 | 0.50 | 0.25, 0.90 | 0.02 | |||||||||
| Waring, 1999 (43) | Rochester Epidemiology Project | Nested case-control | 444 | Controls matched by age and length of time in record linkage systemf | <6 months, never | 93 | 211 | 1.00 | Referent | |||||
| ≥6 months | 7 | 11 | 0.48 | 0.22, 1.01 | 0.05 | |||||||||
| Zandi, 2002 (45)g | Cache County Study | Prospective case-control | 1,866 | Age, education, APOEh | No hormone therapy | 43 | 58 | 1.00 | Referent | |||||
| Hormone therapy | 57 | 26 | 0.59 | 0.36, 0.96 | 0.03 | |||||||||
Abbreviations: APOE, apolipoprotein E; CI, confidence interval; E, estrogen; E+P, estrogen and progestin combined; NR, not reported; RR, relative risk.
a RR, or the relative risk, can be an odds ratio or a hazard ratio depending on the study design and sampling scheme; refer to Table 1 for the specific effect measure reported in each study.
b The investigators did not include the following variables in their final model because they determined that further adjustment for them did not appreciably change their findings: education, marital status, ethnicity, and history of either smoking or progestin use.
c The investigators examined other variables that did not affect the results of this study, including age at menopause, age at menarche, years of natural cyclic estrogen exposure, menopause duration, and surgical menopause.
d In contrast to many of the studies based in the United States, in this study women used predominantly transdermal estradiol (with or without progesterone), with less than 20% taking oral estradiol. None of the women took conjugated equine estrogens.
e Hazard ratios for Alzheimer's disease were not provided in the paper. We derived incidence rate ratios by using available data on Alzheimer's disease (number of cases, number of noncases, person-time).
f It is unclear which covariates (if any) were included in the final models, but authors reported that the odds ratio did not change noticeably after adjusting for education, age at menopause, and parity, and it was not different in the stratum of women who had undergone natural menopause or in the stratum of women who used estrogen for more than 1 year.
g This study was not included in our meta-analyses of any versus minimal or no hormone therapy use, as the Shao paper (41) from the same cohort provided updated results from the same study population.
h Authors reported that results did not change appreciably when terms were added separately for diabetes mellitus, cardiovascular disease, depression, or use of nonsteroidal antiinflammatory drugs.