Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women

Climacteric. 2008 Feb;11(1):63-73. doi: 10.1080/13697130701852390.

Abstract

Objective: To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding.

Methods: A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval and informed consent were obtained prior to initiation and enrollment. Out of 577 postmenopausal women randomized, 575 took E2/NETA 0.1 (n = 194), or E2/NETA 0.25 (n = 181) or placebo (n = 200). Endometrial bleeding was monitored by daily diary cards and endometrial thickness by transvaginal ultrasound at baseline and on completion. An endometrial biopsy was obtained when indicated clinically.

Results: In months 1-6, the amenorrhea rates with E2/NETA 0.1 were 89%, 89%, 86%, 85%, 89% and 89%, respectively and the no-bleeding rates were correspondingly high: 95%, 94%, 93%, 90%, 95% and 95%. The amenorrhea and spotting-only rates were similar with both ultra-low-dose combinations. The withdrawal rates due to bleeding were very low and the same in all three treatment arms (n = 1; 1%). There was a slight increase in the mean endometrial thickness in all three groups, which remained less than 5 mm.

Conclusions: The ultra-low-dose combination of E2/NETA 0.1 or E2/NETA 0.25 resulted in a high incidence of amenorrhea and no bleeding in postmenopausal women, and a corresponding high level of compliance. Overall, there was no significant change in mean endometrial thickness during 6 months of active treatment or placebo.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amenorrhea / chemically induced*
  • Amenorrhea / epidemiology
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endometrium / diagnostic imaging
  • Endometrium / drug effects*
  • Endometrium / pathology
  • Estradiol / pharmacology*
  • Female
  • Humans
  • Middle Aged
  • Norethindrone / analogs & derivatives*
  • Norethindrone / pharmacology
  • Norethindrone Acetate
  • Postmenopause*
  • Prospective Studies
  • Ultrasonography
  • Uterine Hemorrhage / chemically induced*
  • Uterine Hemorrhage / epidemiology

Substances

  • Contraceptives, Oral, Synthetic
  • Estradiol
  • Norethindrone Acetate
  • Norethindrone