Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review.
OBJECTIVE
To review the effects of non-oral administration of postmenopausal hormone therapy (HT) on risk markers for atherosclerotic and venous thromboembolic disease.Non-oral postmenopausal HT appears not to increase venous thromboembolic risk, whereas the effect on coronary heart disease risk is less clear.


METHODS
Systematic review of literature obtained from MEDLINE, EMBASE, and CENTRAL databases from 1980 until and including April 2006. Terms for "postmenopausal hormone therapy" and for "non-oral administration" were combined in the search.


METHODS
Randomized clinical trials.


METHODS
Postmenopausal women, both healthy and with established cardiovascular disease or specified cardiovascular risk factors


METHODS
Non-oral HT (e.g., transdermal or intranasal) compared with oral HT or no treatment/placebo.


METHODS
Lipoprotein(a), homocysteine, C-reactive protein (CRP), cell adhesion molecules, markers of endothelial dysfunction, coagulation, and fibrinolysis.


RESULTS
Seventy-two studies investigating either transdermal or intranasal administration were included. For non-oral HT, decreases in lipoprotein(a), cell adhesion molecules, and factor VII generally were significant, resistance to activated protein C (APCr) was slightly increased, and other markers including CRP and homocysteine did not change. Compared with oral HT, changes in CRP and APCr were smaller, changes in cell adhesion molecules and some fibrinolytic parameters tended to be smaller, whereas changes in other factors including lipoprotein(a) and homocysteine did not differ.


CONCLUSIONS
Potentially unfavorable changes seen with oral HT on two important markers, CRP and APCr, are substantially smaller with non-oral HT. Non-oral HT has minor effects on the other cardiovascular risk markers studied. Therefore, compared with oral HT, non-oral HT appears be safer with respect to atherosclerotic and venous thromboembolic disease risk.
Hemelaar
Majoie
M
Project Aging Women and Institute for Cardiovascular Research-Vrije Universiteit, Department of Obstetrics & Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
van der Mooren
Marius J
MJ
Rad
Mandana
M
Kluft
Cornelis
C
Kenemans
Peter
P
D000284:Administration, Oral; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015994:Incidence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000453:epidemiology*
D015415:Biomarkers; D004967:Estrogens