Effects of hormone replacement therapy on blood platelets.
BACKGROUND
Hormone replacement therapy (HRT) increases the risk of cardiovascular morbidity in postmenopausal women under certain circumstances. Part of this effect may be the result of the influence of HRT on blood platelets. We studied the effect of short-term oral hormone replacement therapy (unopposed oestradiol or sequentially combined oestradiol and trimegestone or dydrogesterone) on platelet activation parameters in healthy postmenopausal women.


METHODS
We designed a prospective, randomised, placebo-controlled 12-week study. Sixty healthy, normotensive, nonhysterectomised, postmenopausal women received daily micronised oestradiol (E2) 2 mg (n = 16), or 2 mg E2 daily sequentially combined with either trimegestone 0.5 mg daily (n = 14) or dydrogesterone 10 mg daily (n = 14), or placebo (n = 16). Data on platelet activation were collected at baseline and after 12 weeks of treatment using flow cytometry.


RESULTS
Twelve weeks of treatment with combined HRT was associated with an increase in platelet activation parameters P-selectin and glycoprotein 53 (by 17% and 14%, respectively, P = 0.04 vs. the placebo group for both comparisons), suggesting alpha granule and lysosome degranulation. E2 replacement therapy was associated with an increase in P-selectin labelling by 22% (P = 0.04 vs. the placebo group).


CONCLUSIONS
Short-term treatment with oestradiol or combined HRT increases the amount of circulating activated platelets as measured by flow cytometry. This could be a mechanism by which short-term HRT might increase the risk of thrombosis.
Department of General Internal Medicine, VU Academic Medical Center, Amsterdam, the Netherlands. a.thijs@vumc.nl
A
A
Thijs
W M
WM
van Baal
M J
MJ
van der Mooren
P
P
Kenemans
A M
AM
Dräger
P C
PC
Huijgens
C D A
CD
Stehouwer
D015703:Antigens, CD / Q000097:blood; D001161:Arteriosclerosis / Q000139:chemically induced*; D015415:Biomarkers / Q000097:blood; D004394:Dydrogesterone / Q000627:therapeutic use; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D045167:Progesterone Congeners / Q000627:therapeutic use; D011397:Promegestone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D060149:Tetraspanin 30
D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D045167:Progesterone Congeners; D060149:Tetraspanin 30; C050319:trimegestone; D004958:Estradiol; D004394:Dydrogesterone; D011397:Promegestone