Optimal tolerability of ultra-low-dose continuous combined 17beta-estradiol and norethisterone acetate: laboratory and safety results

Climacteric. 2010 Feb;13(1):34-44. doi: 10.3109/13697130903480706.

Abstract

Objective: To evaluate the influence of two ultra-low doses of oral continuous combined hormone therapy and placebo on metabolic parameters, and to assess safety endpoints and overall tolerability in healthy postmenopausal women.

Design: In a subpopulation of the Clinical study on Hormone dose Optimisation In Climacteric symptoms Evaluation (CHOICE) trial, lipids and parameters of glucose metabolism and hemostasis were analyzed in Nordic women (n = 158) at baseline and after 12 and 24 weeks of treatment with 0.5 mg 17beta-estradiol (E2) + 0.25 mg norethisterone acetate (NETA), 0.5 mg E2 + 0.1 mg NETA or placebo. Adverse events occurring from the first trial-related activity, whether related or not related to the study medication, were recorded for the entire population (n = 575) of the trial. The seriousness, relationship to treatment and the reason for withdrawal were reported.

Results: Both ultra-low-dose combinations were neutral to changes in lipid and lipoprotein, hemostasis parameters and carbohydrate metabolism during the trial. The incidence of serious adverse events was only 1% in respective treatment groups. Adverse events were the reason for withdrawal in only 2% and 6% of women in the 0.5 mg E2 + 0.25 mg and 0.1 mg NETA groups, and in 8% in the placebo group. No weight gain or change in blood pressure was reported during the trial in any of the study groups.

Conclusion: The treatments had neutral effects on metabolic parameters in the study population. Excellent tolerability of both ultra-low doses resulted in high completion rates.

Publication types

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

MeSH terms

  • Blood Glucose / analysis
  • Blood Pressure
  • Breast / drug effects
  • Double-Blind Method
  • Estradiol / administration & dosage*
  • Estradiol / adverse effects*
  • Estrogen Replacement Therapy / adverse effects
  • Estrogen Replacement Therapy / methods*
  • Female
  • Hemostasis
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Lipids / blood
  • Mammography
  • Middle Aged
  • Norethindrone / administration & dosage
  • Norethindrone / adverse effects
  • Norethindrone / analogs & derivatives*
  • Norethindrone Acetate
  • Placebos
  • Postmenopause*
  • Sex Hormone-Binding Globulin / analysis
  • Uterine Hemorrhage / epidemiology

Substances

  • Blood Glucose
  • Lipids
  • Placebos
  • Sex Hormone-Binding Globulin
  • Estradiol
  • Insulin-Like Growth Factor I
  • Norethindrone Acetate
  • Norethindrone