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

Area of Science:

• Oncology
• Endocrinology
• Women's Health

Background:

• Hormone therapy, including conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA), has been studied for various health outcomes in postmenopausal women.
• The Women's Health Initiative (WHI) trial investigated the effects of CEE plus MPA on chronic disease incidence and mortality.

Purpose of the Study:

• To report long-term colorectal cancer findings from the WHI trial.
• To evaluate the cumulative effect of CEE plus MPA on colorectal cancer incidence and mortality over 24 years of follow-up.

Main Methods:

• A randomized controlled trial involving 16,608 postmenopausal women with a uterus assigned to CEE plus MPA or placebo.
• Long-term follow-up data were collected for colorectal cancer incidence, mortality, and related adverse events.

Main Results:

• Initially, CEE plus MPA reduced colorectal cancer incidence by 44% (P = .003) but with more lymph node-positive cancers.
• After 24 years, no significant difference in colorectal cancer incidence (HR, 0.95; 95% CI, 0.79 to 1.15) or mortality (P = .26) was observed.
• Increased vaginal bleeding and breast changes were noted with CEE plus MPA, and delayed bowel examinations were linked to intervention, potentially causing diagnostic delays.

Conclusions:

• Five years of CEE plus MPA use in postmenopausal women does not demonstrate a clinically meaningful long-term benefit for colorectal cancer outcomes.
• The initial reduction in colorectal cancer incidence was not sustained, and potential delays in diagnosis due to side effects warrant consideration.