Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial

Area of Science:

• Gynecology
• Oncology
• Clinical Trials

Background:

• The risk of endometrial cancer with combined hormone therapy (estrogen plus progestin) requires further clarification regarding incidence, specific histologies, and mortality.
• The Women's Health Initiative (WHI) trial provides a robust dataset to assess these long-term effects.

Purpose of the Study:

• To evaluate the impact of continuous combined estrogen plus progestin therapy on endometrial cancer incidence, histology, and mortality.
• To analyze extended follow-up data from the WHI randomized clinical trial.

Main Methods:

• Analysis of data from 16,608 postmenopausal women in the WHI trial, randomly assigned to conjugated equine estrogen plus medroxyprogesterone acetate or placebo.
• Extended follow-up obtained from 12,788 (83%) surviving participants, with intent-to-treat analyses.

Main Results:

• A statistically significant reduction in endometrial cancer incidence was observed in the combined hormone therapy group compared to placebo (yearly incidence 0.06% vs 0.10%, HR=0.65, P=.007).
• The reduction in endometrial cancer incidence became statistically significant postintervention (HR=0.59, P=.008), with no significant difference in hazard ratios between intervention and postintervention phases.
• A nonsignificant reduction in endometrial cancer deaths was noted in the hormone therapy group (5 vs 11 deaths, HR=0.42).

Conclusions:

• Continuous combined estrogen plus progestin therapy effectively decreases endometrial cancer incidence in postmenopausal women.
• The findings support the use of combined hormone therapy for endometrial cancer risk reduction in appropriate patient populations.