Randomized trial of effect of transdermal continuous combined hormone replacement therapy on cardiovascular risk markers

J C Stevenson, A Oladipo, N Manassiev, M I Whitehead, S Guilford, A J Proudler

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69 Citations (Scopus)


Whether hormone replacement therapy (HRT) is beneficial for coronary heart disease (CHD) is controversial. We hypothesized that continuous combined transdermal HRT may have benefits on CHD risk markers without the potential adverse effects seen with certain other HRT regimens. Sixty apparently healthy postmenopausal women, aged 40-65 years, entered a prospective, double-blind, randomized, placebo-controlled clinical trial; 55 women completed the 6-month study. Women received either transdermal oestradiol 17beta 0.05 mg and norethisterone acetate 0.125 mg daily, or identical placebo. Circulating markers of vascular function and remodelling, forearm blood flow, lipids and lipoproteins, glucose and insulin, and haemostatic safety parameters were measured at baseline and after treatment. Compared with placebo after 6 months, HRT administration resulted in decreased E-selectin (P <0.01), and angiotensin-converting-enzyme (ACE; P = 0.05). Cholesterol (P <0.05), low-density lipoproteins (LDL; P <0.05), high-density lipoprotein(3) (HDL3; P <0.05) and apolipoproteins AII (P <0.05) and B (P <0.05), and fasting insulin (P <0.05) also decreased in the HRT group. Factor VII coagulation activity decreased (P <0.01) and plasminogen activator inhibitor-1 and fibrin D-dimer increased (P <0.05) in the HRT group, whilst prothrombin fragment 1 + 2 (P <0.05) decreased, more so in the placebo group. There were no changes in matrix metalloproteinase (MMP)-2, or in LDL particle size. This transdermal HRT had beneficial effects on vascular function and CHD risk markers.
Original languageEnglish
Pages (from-to)802 - 808
Number of pages7
JournalBritish Journal of Haematology
Issue number6
Publication statusPublished - Mar 2004


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