• estrogen;
  • progestin;
  • endometrial carcinoma;
  • uterine cancer;
  • epidemiology



Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen-plus-progestin regimens remain unclear.


The National Institutes of Health-AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995–1996 and 1996–1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never-use of hormone therapy.


In 51,312 women who never used hormones or only used estrogen-plus-progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10–14 days per cycle: RR, 0.74; 95% CI, 0.39–1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for ≥20 days per cycle: RR, 0.80; 95% CI, 0.55–1.15) had any statistically significant association with endometrial cancer. Long durations (≥5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38–1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53–1.36) were not associated with endometrial cancer.


Confirmation that these estrogen-plus-progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen-plus-progestin therapy. Cancer 2007. Published 2007 by The American Cancer Society.