Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial

Authors

Rowan T Chlebowski
Aaron K Aragaki
Kathy Pan
Juhua Luo
Thomas E Rohan
Karen C Johnson
Jean Wactawski-Wende
Su Yon Jung
Qian Xiao
Sayeh Lavasani
JoAnn E Manson
Michael S Simon

Language

English

Publication Date

10-20-2024

Journal

Journal of Clinical Oncology

DOI

10.1200/JCO.23.02092

PMID

39028918

PMCID

PMC11748022

PubMedCentral® Posted Date

10-20-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

We report long-term colorectal cancer findings from the Women’s Health Initiative trial where 16,608 postmenopausal women with a uterus were randomized to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. When intervention ended after 5.6-years, while there were 44% fewer colorectal cancers in the intervention group (43 vs 72, P = 0.003), the cancers more commonly were lymph node positive (59.0% vs 29.4%, P = 0.003). Now after cumulative 24-year follow-up, with 431 breast cancers, CEE plus MPA no longer influenced colorectal cancer incidence (215 [0.15, annualized rate %] vs 216 [0.15], HR 0.95 95% CI 0.79–1.15). Although not statistically significant, there were more colorectal cancer deaths with CEE plus MPA (87 [0.049] vs 69 [0.041] deaths, HR 1.20 95% CI 0.87 to 1.65, P = 0.26). Vaginal bleeding (54.1% vs 5.2% at 6-months) and breast changes were more frequent in the intervention group. After adjusting for post-randomization vaginal bleeding and breast changes, bowel examinations were significantly delayed in intervention group participants (P = 0.005) potentially contributing to diagnostic delay. Taken together, the findings suggest no clinically meaningful benefit for about 5-years CEE plus MPA use on colorectal cancer outcome.

Keywords

Aged, Female, Humans, Middle Aged, Colorectal Neoplasms, Estrogen Replacement Therapy, Estrogens, Conjugated (USP), Medroxyprogesterone Acetate, Postmenopause, Women's Health

Published Open-Access

yes

Recommended Citation

Chlebowski, Rowan T; Aragaki, Aaron K; Pan, Kathy; et al., "Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial" (2024). Faculty, Staff and Student Publications. 619.
https://digitalcommons.library.tmc.edu/uthsph_docs/619