Long-term effects of oral and transdermal hormone replacement therapy on plasma homocysteine levels

Menopause. 2003 Jul-Aug;10(4):286-91. doi: 10.1097/01.GME.0000054762.94658.B4.


Objective: To compare the long-term effects of oral and transdermal hormone replacement therapy (HRT) on serum homocysteine levels in postmenopausal women.

Design: An open, prospective, controlled study. Seventy-five healthy postmenopausal women were recruited as eligible for the study. Fifty women seeking HRT were randomized to receive continuous 17beta-estradiol, either by oral (2 mg daily; n = 25) or transdermal (50 microg daily; n = 25) administration, plus 10 mg dydrogesterone daily for 14 days of each 28-day cycle. Twenty-five women unwilling to receive hormone treatment received only calcium supplementation, representing the control group. Fasting blood samples were analyzed at baseline and then after 6, 12, and 24 months to determine plasma homocysteine levels.

Results: Fifty-nine women completed the study. After 6 months of therapy, homocysteine concentrations showed a statistically significant reduction in the treated groups versus both baseline and controls, and no further significant variations were found thereafter. The mean reduction in the homocysteine levels throughout the study was 13.6% in the oral and 8.9% in the transdermal group, respectively, without significant difference between the two routes of estradiol administration. Women with the highest baseline levels of homocysteine experienced the greatest reduction. No significant variations in homocysteine concentrations were found in the control group.

Conclusions: Oral and transdermal estradiol sequentially combined with dydrogesterone shows comparable effectiveness in reducing plasma homocysteine levels in postmenopausal women. Women with the highest pretreatment concentrations of homocysteine benefit the most by the lowering effect of HRT.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Drug Therapy, Combination
  • Dydrogesterone / administration & dosage
  • Estradiol / administration & dosage
  • Estradiol / blood*
  • Estrogen Replacement Therapy*
  • Estrone / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Homocysteine / blood*
  • Humans
  • Middle Aged
  • Postmenopause / blood*
  • Progesterone Congeners / administration & dosage
  • Prospective Studies
  • Reference Values


  • Progesterone Congeners
  • Homocysteine
  • Estrone
  • Estradiol
  • Follicle Stimulating Hormone
  • Dydrogesterone