Table 2.
Observational studies investigating effects of menopause hormone therapy on Alzheimer’s or dementia risk.
| Reference | Country | Study design | Participants | Age, years* | Therapy | Alzheimer’s disease | Dementia | ||
|---|---|---|---|---|---|---|---|---|---|
| OR/HR/RR | 95% CI | OR/HR/RR | 95% CI | ||||||
| Heyman et al. (1984) | USA | Case–control | 84 | 61 | HT | 2.38 | 0.7–7.8 | ||
| Amaducci et al. (1986) | Italy | Case–control | 213 | >65 | HT | 1.7 | 0.4–5.9 | ||
| Borenstein Graves et al. (1990) | USA | Case–control | 120 | 65 | HT | 1.15 | 0.5–2.6 | ||
| Broe et al. (1990) | Australia | Case–control | 170 | 79 | HT | 0.78 | 0.39–1.56 | ||
| Graves et al. (1990) | USA | Case–control | 260 | 65 | HT | 1.15 | 0.50–2.64 | ||
| Paganini-Hill and Henderson (1994) | USA | Case–control | 688 | 87 | HT | 0.67 | 0.38–1.17 | 0.69 | 0.40–1.20 |
| Lerner et al. (1995) | USA | Case–control | 157 | >60 | HT | 0.41 | 0.30–0.90 | ||
| Mortel and Meyer (1995) | USA | Case–control | 306 | 73 | HT | 0.6 | 0.3–1.2 | 0.48 | 0.20–1.20 |
| Baldereschi et al. (1998) | Italy | Cohort | 2,046 | 65–84 | HT | 0.28 | 0.08–0.98 | ||
| Harwood et al. (1999) | USA | Case–control | 368 | >65 | HT | 0.6 | 0.3–1.0 | ||
| Waring et al. (1999) | USA | Case–control | 444 | 82 | HT | 0.47 | 0.20–1.0 | ||
| Seshadri et al. (2001) | UK | Case–control | 283 | 66 | HT | 1.18 | 0.59–2.37 | ||
| Lindsay et al. (2002) | Canada | Cohort | 2,079 | 73 | HT | 1.37 | 0.48–3.95 | ||
| Zandi et al. (2002) | USA | Cohort | 1,866 | 75 | HT | 0.59 | 0.36–0.96 | ||
| Barnes et al. (2003) | USA | Cohort | 577 | 76 | HT | 0.57 | 0.21–1.6 | ||
| Levine and Hewett (2003) | USA | Case–control | NR | 70 | HT | 1.06 | 0.54–2.05 | 2.2 | 0.9–5.2 |
| Colucci et al. (2006) | Italy | Case–control | 405 | 75 | HT | 0.41 | 0.22–0.79 | ||
| Rippon et al. (2006) | USA | Case–control | 1,498 | 68 | HT | 0.30 | 0.20–0.60 | ||
| Henderson et al. (2007) | USA | Cohort | 7,100 | NR | HT | 0.40 | 0.20–0.85 | ||
| Ryan et al. (2009b) | France | Cohort | 996 | 73 | HT | 1.55 | 0.6–3.97 | ||
| Lau et al. (2010) | USA | Cross-sectional | 4,087 | 77 | HT | 0.96 | 0.64–1.45 | 0.53 | 0.39–0.73 |
| Whitmer et al. (2011) | USA | Cohort | 3,447 | 49–76 | HT | 1.02 | 0.78–1.34 | ||
| Shao et al. (2012) | USA | Cohort | 1,768 | 75 | HT | 0.80 | 0.58–1.09 | ||
| Zucchella et al. (2012) | Italy | Case–control | 551 | 77 | HT | 0.17 | 0.07–0.41 | ||
| Bove et al. (2014) | USA | Cohort | 529 | 78 | HT | 0.91 | 0.74–1.13 | ||
| Imtiaz et al. (2017a) | Finland | Case–control | 230,580 | 72 | HT | 1.10 | 1.06–1.12 | ||
| Imtiaz et al. (2017b) | Finland | Cohort | 8,195 | 72 | HT | 1.10 | 0.83–1.40 | 1.08 | 0.88–1.3 |
| Paganini-Hill et al. (2020) | USA | Cohort | 424 | 69 | HT | 0.94 | 0.69–1.28 | ||
| Song X. et al. (2020) | Singapore | Cohort | 8,222 | 54 | HT | 0.61 | 0.46–0.80 | ||
| Yoo et al. (2020) | Korea | Cohort | 4,696,633 | 61 | HT | 0.77 | 0.70–0.86 | 0.81 | 0.78–0.84 |
| Kim et al. (2021) | USA | Case–control | 379,352 | 68 | HT | 0.43 | 0.41–0.46 | 0.41 | 0.4–0.43 |
| Løkkegaard et al. (2022) | Denmark | Case–control | 16,192 | 83 | HT | 1.05 | 0.93–1.19 | ||
*Mean age, unless stated otherwise.
HT, menopause hormone therapy; NR, not reported.
Most studies provided estimates for overall HT use. For studies reporting estimates for multiple outcomes, we selected the following: (Barnes et al., 2003), HT use for < 10 years; (Ryan et al., 2009b), past use; (Bove et al., 2014), estimates are reported for treatment initiation < 10 years vs. >10 years post-surgery for women who underwent oophorectomy; (Imtiaz et al., 2017a), midlife use; (Yoo et al., 2020), mid-duration of treatment (2–5 years); (Lau et al., 2010) reports on use of PIRx, potentially inappropriate medications with and without HT.