Is the timing of withdrawal bleeding a guide to endometrial safety during sequential oestrogen-progestagen replacement therapy? UK Continuous Combined HRT Study Investigators

Lancet. 1994 Oct 8;344(8928):979-82. doi: 10.1016/s0140-6736(94)91640-3.


Current regimens of sequential hormone replacement therapy are based on data that show a protective effect on the endometrium of at least 10 days of progestagen. In clinical practice, onset of bleeding on or after day 11 of the progestagen phase is taken as reassurance of a normal endometrium. 413 postmenopausal women taking oestrogen-progestagen hormone replacement therapy with 10 or 12 days of progestagen per cycle completed bleeding diaries for 3 months before endometrial biopsy. For most women, bleeding started around the 13th day after starting progestagen. There was no correlation between endometrial histology and timing of onset of bleeding. 11 (2.7%) women had complex endometrial hyperplasia. The prevalence of hyperplasia was 2.4% with 10 days of progestagen per cycle and 2.8% with 12 days [corrected]. The timing of onset of withdrawal bleeding during oestrogen-progestagen HRT does not predict endometrial hyperplasia.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Endometrium / drug effects
  • Endometrium / pathology*
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Humans
  • Hyperplasia / chemically induced
  • Middle Aged
  • Uterine Hemorrhage / chemically induced*