Table 5.
Risk of breast cancers associated with different categories of HRT formulation or administration.
| Ever use | Duration of use | |||||||
| 1–4 years | 5–9 years | 10+ years | ||||||
| Formulation categories | e-cas/e-ctrl | Adj. OR (95% CI) | e-cas/e-ctrl | Adj. OR (95% CI) | e-cas/e-ctrl | Adj. OR (95% CI) | e-cas/e-ctrl | Adj. OR (95% CI) |
| A. Route of administration | ||||||||
| oral | 1053/2321 | 1.1 (0.99 – 1.3) | 249/769 | 0.9 (0.7 – 1.1) | 405/750 | 1.3 (0.7 – 1.1) | 295/474 | 1.5 (1.2 – 1.9) |
| transdermal | 211/650 | 0.8 (0.6 – 1.1) | 60/212 | 0.7 (0.5 – 1.0) | 81/189 | 1.1 (0.7 – 1.8) | 52/161 | 0.9 (0.5 – 1.4) |
| other | 94/307 | 0.7 (0.5 – 0.98) | 23/98 | 0.5 (0.3 – 1.1) | 24/78 | 0.6 (0.3 – 1.2) | 28/81 | 0.7 (0.4 – 1.3) |
| Only – HRTs | ||||||||
| Estrogen (exclusive) | 368/1168 | 0.8 (0.7 – 1.0) | 82/341 | 0.7 (0.5 – 0.97) | 140/365 | 0.99 (0.7 – 1.4) | 107/311 | 0.8 (0.5 – 1.1) |
| Progestagen (exclusive) | 108/321 | 1.0 (0.7 – 1.4) | 30/104 | 0.8 (0.4 – 1.5) | 29/74 | 1.8 (0.9 – 3.7) | 35/75 | 0.96 (0.5 – 1.8) |
| Combination – HRTs | ||||||||
| Sequential formulations | 546/1370 | 0.9 (0.8–1.1) | 129/453 | 0.8 (0.6–1.1) | 224/489 | 1.0 (0.8–1.3) | 150/266 | 1.3 (0.96 – 1.9) |
| Continuous-combined | 484/802 | 1.5 (1.2–1.8) | 103/257 | 0.96 (0.7 – 1.4) | 197/263 | 1.9 (1.4–2.6) | 141/183 | 1.98 (1.4–2.9) |
| All E+P | 916/1931 | 1.2 (1.0–1.3) | 223/645 | 0.9 (0.7–1.0) | 360/662 | 1.3 (1.0–1.6) | 248/373 | 1.6 (1.2–2.0) |
| CEE/MPA combinations | ||||||||
| CEE + MPA | 87/192 | 1.1 (0.7–1.7) | 26/72 | 0.8 (0.4–1.6) | 37/56 | 1.3 (0.7–2.7) | 14/40 | 1.1 (0.4–3.1) |
| CEE or MPA | 359/890 | 0.9 (0.7–1.2) | 54/263 | 0.6 (0.4–0.99) | 133/305 | 0.9 (0.7–1.3) | 135/222 | 1.2 (0.9–1.8) |
| No CEE, no MPA | 806/1723 | 1.2 (1.0–1.4) | 224/611 | 0.94 (0.8–1.2) | 293/517 | 1.4 (1.1–1.7) | 194/306 | 1.6 (1.2–2.2) |
| B. Formulation content | ||||||||
| Estrogen type | ||||||||
| Estriol (E3) | 12/40 | 0.4 (0.1 – 1.5) | 1/11 | n.d. | 1/9 | n.d. | 6/8 | 0.4 (0.1 – 2.6) |
| Estradiol (E2) | 889/2015 | 1.0 (0.9–1.2) | 218/694 | 0.8 (0.7–1.0) | 346/622 | 1.3 (1.1–1.4) | 241/417 | 1.4 (1.1–1.7) |
| Ethinylestradiol (EE)* | 11/41 | 0.8 (0.3–2.4) | 4/15 | n.d | 4/6 | n.d. | 3/16 | n.d. |
| Conjugated equine estrogens (CEE) | 395/934 | 1.0 (0.8–1.2) | 63/273 | 0.7 (0.5–1.0) | 154/321 | 0.9 (0.7–1.3) | 137/243 | 1.4 (0.98–2.0) |
| Progestin type | ||||||||
| Norethindrone acetate (NETA) | 529/1037 | 1.2 (0.99–1.4) | 114/346 | 0.8 (0.6–1.1) | 209/338 | 1.4 (1.1–1.9) | 157/218 | 1.9 (1.3–2.6) |
| Norgestrel (NG) | 21/67 | 0.9 (0.4–2.2) | 4/13 | n.d. | 7/28 | 0.6 (0.1–2.9) | 6/19 | 0.7 (0.1–4.2) |
| LNG | 290/562 | 1.3 (0.98–1.6) | 69/177 | 1.2 (0.8–1.9) | 131/227 | 1.4 (0.99–2.0) | 69/109 | 1.3 (0.8–2.3) |
| Medroxyprogesterone acetate (MPA) | 138/340 | 0.96 (0.7–1.3) | 43/134 | 0.8 (0.4–1.3) | 53/96 | 1.3 (0.7–2.3) | 26/59 | 0.8 (0.4–1.7) |
| CMA | 33/96 | 0.8 (0.5–1.5) | 13/32 | 1.1 (0.4–3.1) | 3/18 | n.d. | 12/21 | 0.7 (0.2–2.0) |
| CPA | 33/116 | 0.6 (0.4–1.1) | 11/54 | 0.5 (0.2–1.3) | 11/22 | 1.2 (0.4–3.4) | 7/18 | 0.6 (0.1–2.7) |
| Medrogestone | 141/434 | 0.7 (0.5–1.0) | 16/117 | 0.5 (0.2–0.9) | 55/172 | 0.5 (0.3–0.9) | 60/107 | 1.3 (0.8–2.2) |
| Dydrogesterone | 9/51 | 0.5 (0.2–1.2) | 2/20 | n.d. | 3/9 | n.d. | 2/12 | n.d. |
| Progesterone | 7/33 | 1.4 (0.4–4.4) | 4/12 | n.d. | 1/6 | n.d. | 1/5 | n.d. |
| Dienogest | 10/24 | 0.9 (0.2–3.4) | 1/12 | n.d. | 4/5 | n.d. | 3/3 | n.d. |
| Tibolone | 17/61 | 0.8 (0.3–2.1) | 7/21 | 1.8 (0.4–8.3) | 5/16 | 0.98 (0.1–7.9) | 3/19 | n.d. |
The categories are not mutually exclusive – (see text). Conditional logistic regression: Odds ratios (OR) and 95% confidence intervals (95% CI); adjusted for age and residency. No OR was calculated if the frequency of exposed cases or controls was less than 5 women. This applied for use of HRTs containing desogestrel, lynestrenol, hydroxyprogesterone, and raloxifene. Only the index date 0.5 years is depicted in this table.
n.d. = no data.
* = in oral contraceptives used as HRT