Estrogen + medroxyprogesterone acetate and Breast cancer: is the FAERS signal real?
Estrogen + medroxyprogesterone acetate ↔ Breast cancer
Conjugated equine estrogen plus medroxyprogesterone acetate was the combined hormone-therapy regimen tested in the Women's Health Initiative, the large randomized trial whose 2002 report found an increased risk of invasive breast cancer (as well as cardiovascular events), leading to early termination of that arm and a sharp, worldwide drop in hormone-therapy use (Rossouw et al., JAMA 2002, PMID 12117397). The breast-cancer association is the best-established harm of combined postmenopausal hormone therapy, is duration-dependent, and prompted a boxed warning. Note that this is estrogen plus progestin therapy, not medroxyprogesterone used alone as a contraceptive — the two contexts differ.
Rossouw JE, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333 (PMID 12117397). FDA boxed warning for estrogen+progestin postmenopausal therapy.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Risk emerged during randomized exposure in the WHI |
| Strength | met | PRR 243 here; a modest but real hazard ratio in the randomized trial |
| Consistency | met | Consistent across observational cohorts and the randomized WHI |
| Specificity | partial | Combined therapy; estrogen-alone results differ, so the progestin matters |
| Biological gradient | met | Risk rises with duration of combined therapy |
| Plausibility | met | Hormone-receptor-driven breast tissue growth — named mechanism |
| Coherence | met | Coheres with decades of hormonal-carcinogenesis research |
| Experiment | met | The WHI itself is the randomized experiment — the strongest possible evidence |
| Analogy | met | Similar to other prolonged hormonal exposures |
This page's own qualitative read, not an automated/citation-gated assessment.