Menopausal hormone therapy and primary liver cancer: long-term follow-up of the women's health initiative randomized trials
In brief
Menopausal hormone therapy showed no overall link to liver cancer over 24 years
In two randomized trials followed for nearly 24 years, neither estrogen alone nor estrogen plus progestin significantly changed liver cancer incidence or deaths; just 74 cancers occurred. Estrogen plus progestin was linked to more cancers in some subgroups, including women aged 50 to 59 and prior oral contraceptive users, but these signals need further study.
- Journal
- British journal of cancer (Q1)
- Published
- 16 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Margaret S Pichardo, Aaron K Aragaki, JoAnn E Manson, Kathy Pan, Su Yon Jung, Thomas E Rohan, et al.
- PMID
- 42749856
- DOI
- 10.1038/s41416-026-03621-9
Why clinicians should know about it
- Picked for Family Practice (top studies of the week, 1 November 2026): Large RCTs show no overall liver cancer risk
- Picked for Breast and Endocrine Surgery (top studies of the week, 20 September 2026): Menopausal hormone therapy and liver cancer, no surgical focus
Abstract
BACKGROUND: Long-term results on liver cancer incidence and mortality are reported from two Women's Health Initiative randomized trials evaluating menopausal hormone therapy. METHODS: 16,608 postmenopausal women with a uterus were randomized to conjugated equine estrogen (CEE) 0.625 mg/d plus medroxyprogesterone acetate (MPA) 2.5 mg/d or placebo and 10,739 women with hysterectomy were randomized to 0.625 mg/d of CEE-alone or placebo. RESULTS: After nearly 24 years follow-up and 74 incident liver cancers, neither CEE-alone nor CEE plus MPA influenced liver cancer development (CEE-alone vs placebo (11 vs 15 cancers; hazard ratio [HR] 0.75; 95% CI, 0.34-1.63; CEE plus MPA vs placebo (30 vs 18 cancers; HR 1.63; 95% CI, 0.91-2.92). CEE plus MPA did not significantly influence liver cancer mortality: 27 vs 22 deaths (HR 1.18; 95% CI, 0.67-2.07). In subgroup analyses, CEE plus MPA vs placebo was associated with more liver cancers among women aged 50-59 years (10 vs 0 cancers (P-trend 0.01) and prior oral contraceptive users (HR 4.30, 95% CI, 1.46-12.72; P-interaction 0.01). CONCLUSIONS: These findings indicate no overall influence of menopausal hormone therapy on liver cancer incidence or mortality although a possible increased risk with CEE plus MPA in select subgroups warrants further investigation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.