Long-term compliance of continuous combined estrogen and progestogen replacement in postmenopausal women

Maturitas. 1996 Oct;25(2):99-105. doi: 10.1016/0378-5122(96)01048-1.


The occurrence of uterine bleeding usually associated with hormonal replacement therapy is not acceptable for many women. Our objective was to review data on compliance and bleeding patterns in 70 postmenopausal women on oral replacement with estradiol 2 mg, estriol 1 mg, and norethisterone acetate 1 mg daily administered in a continuous combined fashion to avoid withdrawal bleeding. After 1 year, compliance was 97%, after 5 and 9 years 76% and 58%. The most common reason for discontinuation was spotting. Reproductive history, body weight and pretreatment estradiol and FSH concentrations were not different between the subgroups with bleeding-19%- and without bleeding-81%. The probability to maintain amenorrhoe on HRT did not increase with the length of the postmenopausal interval or weight. Endometrial histology revealed one case of a highly differentiated in situ adenocarcinoma of the endometrium. In the women with bleeding, induced serum estradiol levels were significantly and pretreatment SHBG-levels lower compared to the non-bleeders. Whether these findings may be significant for election of patients for continuous combined HRT remains to be determined. In conclusion, we demonstrate that adherence to this treatment regimen apparently provides a choice patients considering long-term HRT should be informed about. However, the lack of parameters to elect patients in conjunction with the problem of uterine bleeding does not permit the recommendation to regard continuous combined HRT as first line therapy for long-term HRT. Criteria need to be developed when to obtain an endometrial histology once uterine bleeding occurs, as the optimal surveillance of this mode of HRT is presently unknown.

MeSH terms

  • Adult
  • Aged
  • Climacteric / drug effects*
  • Climacteric / psychology
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Estradiol / administration & dosage
  • Estriol / administration & dosage
  • Estrogen Replacement Therapy / psychology*
  • Female
  • Follow-Up Studies
  • Gonadal Steroid Hormones / blood
  • Humans
  • Levonorgestrel / administration & dosage
  • Long-Term Care
  • Medroxyprogesterone Acetate / administration & dosage
  • Menstrual Cycle / drug effects
  • Middle Aged
  • Norethindrone / administration & dosage
  • Norethindrone / analogs & derivatives
  • Norethindrone Acetate
  • Patient Compliance / psychology*
  • Progestins / administration & dosage*


  • Gonadal Steroid Hormones
  • Progestins
  • Estradiol
  • Levonorgestrel
  • Norethindrone Acetate
  • Medroxyprogesterone Acetate
  • Estriol
  • Norethindrone