Results of the clinical studies of menopausal hormone therapy and the risks of breast cancer
| Study | Year | Design | Population, n | Mean age (range) | Medications | Follow-up years (mean, range) | HR (95% CI) | RR (95% CI) | OR (95% CI) |
|---|---|---|---|---|---|---|---|---|---|
| Rossouw et al.9, WHI† | 2002 | RCT | 16,608 | 63.2 (50–79) | EPT (CEE 0.625 mg + MPA 2.5 mg) | 5.2 (3.5–8.5) | 1.26 (1.00–1.59) | NA | NA |
| Anderson et al.19, WHI | 2004 | RCT | 10,739 | 63.6 (50–79) | ET (CEE 0.625 mg) | 6.8 (5.7–10.7) | 0.77 (0.59–1.01) | NA | NA |
| LaCroix et al.20, WHI | 2011 | RCT | 10,739 | 63.6 (50–79) | ET (CEE 0.625 mg) | 10.7 | 0.77 (0.62–0.95) | NA | NA |
| Manson et al.21, WHI | 2013 | RCT | 10,739 16,608 | 63.6 (50–79) 63.2 (50–79) | ET (CEE 0.625 mg) EPT (CEE 0.625 mg + MPA 2.5 mg) | 13.0 (IQR, 9.1–14.1) 13.2 (IQR, 10.5–14.2) | 0.79 (0.65–0.97) 1.28 (1.11–1.48) | NA | NA |
| Manson et al.22, WHI | 2017 | RCT | 10,739 16,608 | 63.6 (50–79) 63.2 (50–79) | ET (CEE 0.625 mg) EPT (CEE 0.625 mg + MPA 2.5 mg) | 18 | 0.55 (0.33–0.92) 1.44 (0.97–2.15) | NA | NA |
| Schierbeck et al.23, DOPS† | 2012 | RCT | 1,006 | 49.5 (45–58) | ET (E2 2 mg)/EPT (E2 2 mg + norethisterone acetate 1 mg) | 10 16 | 0.58 (0.27–1.27) 0.90 (0.52–1.57) | NA | NA |
| Beral et al.10, MWS† | 2003 | OCS | 1,084,110 | 55.9 (50–64) | ET EPT Tibolone | 2.6 | NA | 1.30 (1.21–1.40) 2.00 (1.88–2.12) 1.45 (1.25–1.68) | NA |
| Fournier et al.11, EPIC-E3N† | 2005 | OCS | 54,548 | 52.8 (40–66.1) | ET EPT (estrogen + progesterone) EPT (estrogen + synthetic progestins) | 5.8 (0.1–10.6) | NA | 1.1 (0.8–1.6) 0.9 (0.7–1.2) 1.4 (1.2–1.7) | NA |
| Fournier et al.12, E3N† | 2008 | OCS | 80,377 | 53.1 (40–66.1) | ET EPT (estrogen+ progesterone) EPT (estrogen+ dydrogesterone) EPT (estrogen+ other progestogens) | 8.1(2–12) | NA | 1.29 (1.02–1.65) 1.00 (0.83–1.22) 1.16 (0.94–1.43) 1.69 (1.50–1.91) | NA |
| Bakken et al.24, EPIC† | 2011 | OCS | 133,744 | 58.1 (52.1–61.5) | ET EPT | 8.6 | NA | 1.42 (1.23–1.64) 1.77 (1.40–2.24) | NA |
| Fournier et al.25, EPIC-E3N | 2014 | OCS | 78,353 | 50.2 | ET Current use Past use EPT(Estrogen + progesterone/dydrogesterone) Current use Past use EPT (Estrogen + other progestogen†) Current use Past use | 11.2 | 1.17 (0.99–1.38) 1.06 (0.95–1.19) 1.22 (1.11–1.35) 0.96 (0.87–1.06) 1.87 (1.71–2.04) 1.12 (1.02–1.23) | NA | NA |
| Holm et al.26, Diet, Cancer and Health Cohort | 2019 | OCS | 29,243 | 56 (50–64) | ET EPT, sequential regimens EPT, continuous regimens | 17 | 1.37 (0.95–1.98) 1.27 (0.88–1.83) 1.56 (1.05–2.31) | NA | NA |
| Vinogradova et al.27 | 2020 | OCS | 556,109 | About 63.3(50–79) | ET Recent users (< 5 years) with longterm use (≥ 5 years) EPT Recent users (< 5 years) with longterm use (≥ 5 years) | 20 | NA | NA | 1.06 (1.03–1.10) 1.15 (1.09–1.21) 1.26 (1.24–1.29) 1.79 (1.73–1.85) |
For convenience, we denoted estrogen treatment as ET and estrogen plus progestogens treatment as EPT. RCT, randomized controlled trial; OCS, observational cohort study; WHI, The Women’s Health Initiative; MWS, Million Women Study; EPIC, European Prospective Investigation into Cancer and Nutrition; E3N, Etude Epidémiologique de femmes de la Mutuelle Générale de l’Education Nationale; DOPS, Danish Osteoporosis Prevention Study; Other progestogen†: chlormadinone acetate, demegestone, dienogest, drospirenone, ethynodiol acetate, gestodene, levonorgestrel, lynestrenol, medrogestone, medroxyprogesterone acetate, megestrol acetate, nomegestrol acetate, norethisterone acetate, and promegestone. HR, Hazard ratio; RR, relative risk; OR, odds ratio.