Endometrial histology and bleeding patterns after 8 years of continuous combined estrogen and progestogen therapy in postmenopausal women

Obstet Gynecol. 1991 Dec;78(6):1008-10.


Continuous combined estrogen and progestogen preparations enable the postmenopausal woman to enjoy the benefits of estrogen replacement without the inconvenience of regular progestogen-induced withdrawal bleeding. The endometrium appears to be adequately protected in the short term, but no published data are available on the bleeding patterns or endometrial response after more than 18 months of therapy. Therefore, we reviewed 41 patients who continued on such preparations for up to 10 years (mean duration of use 8.0 years). Six women had experienced episodes of breakthrough bleeding after achieving amenorrhea, two of whom had benign endometrial polyps and two with adenocarcinoma of the endometrium. The remaining 35 women each had prolonged amenorrhea and were found to have an atrophic inactive endometrium. It is too early to comment on the long-term endometrial effects of these preparations because the numbers are too small; however, any breakthrough bleeding occurring after a period of prolonged amenorrhea must be investigated by means of endometrial biopsy.

MeSH terms

  • Drug Therapy, Combination
  • Endometrium / pathology*
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens, Conjugated (USP) / adverse effects
  • Female
  • Humans
  • Menopause*
  • Norethindrone / adverse effects
  • Progesterone / adverse effects
  • Time Factors
  • Uterine Hemorrhage / chemically induced*


  • Estrogens, Conjugated (USP)
  • Progesterone
  • Norethindrone