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Menopausal hormone therapy and primary liver cancer: long-term follow-up of the women's health initiative randomized trials.

Created on 17 Sep 2026

Authors

Margaret S Pichardo, Aaron K Aragaki, JoAnn E Manson, Kathy Pan, Su Yon Jung, Thomas E Rohan, Reed Mszar, Rowan T Chlebowski

Published in

British journal of cancer. Sep 16, 2026. Epub Sep 16, 2026.

Abstract

Long-term results on liver cancer incidence and mortality are reported from two Women's Health Initiative randomized trials evaluating menopausal hormone therapy.
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.
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).
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.
clinicaltrials.gov Identifier: NCT00000611.

PMID:
42749856
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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