Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk?

International Journal of Cancer, 05/04/2012

Trabert B et al. – Our findings support that specific categories of estrogen plus progestin use increases endometrial cancer risk, specifically long durations of sequential progestins; while decreased endometrial cancer risk was observed for users of short duration continuous progestins. Risks were highest among thin-to-normal weight women, presumably reflecting their lower endogenous estrogen levels, suggesting that menopausal hormones and obesity increase endometrial cancer through common etiologic pathways.


  • We evaluated menopausal hormone use and incident endometrial cancer (n=885) in 68,419 postmenopausal women with intact uteri enrolled in the NIH-AARP Diet and Health study.
  • Participants completed a risk factor questionnaire in 1996-1997 and were followed through 2006.


  • Among 19,131 women reporting exclusive estrogen plus progestin use, 176 developed endometrial cancer [RR 0.88; 95% CI: 0.74, 1.06].
  • Long duration (>/=10 years) sequential (<15 days progestin/month) estrogen plus progestin use was positively associated with risk [RR 1.88; 95% CI: 1.36-2.60], whereas continuous (>25 days progestin/month) estrogen plus progestin use was associated with a decreased risk [RR 0.64; 95% CI: 0.49-0.83)].
  • Increased risk for sequential estrogen plus progestin was seen only among thin-to-normal weight women (BMI <25 kg/m2) [RR 2.53].

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