Different effects of oral and transdermal hormonal replacement on prostacyclin and thromboxane A2.
OBJECTIVE
To elucidate the mechanism of cardiovascular protection of hormone replacement therapy (HRT) by comparing the effect of oral and transdermal HRTs on the production of antiaggregatory, vasodilatory prostacyclin, and its endogenous antagonist, thromboxane A2.


METHODS
Oral estradiol (2.0 mg/d) plus norethisterone acetate (1.0 mg/d) (n = 13) or transdermal estradiol (50 micrograms/d) plus medroxyprogesterone acetate (10 mg/d) as 12-day courses at 4-week intervals (n = 13) were given to postmenopausal women. Urinary excretion of the metabolites of prostacyclin, ie, 6-ketoprostaglandinF1 alpha and 2,3-dinor-6-ketoprostaglandinF1 alpha, as well as those of thromboxane A2, ie, thromboxane B2 and 2,3-dinor-thromboxane B2, were measured by radioimmunoassays, after purification by extraction and high performance liquid chromatography, before and during the sixth and the 12th treatment cycles.


RESULTS
Oral HRT stimulated excretion of thromboxane B2 from 3.4 +/- 0.7 ng/mmol creatinine to 4.5 +/- 1.5 (mean +/- standard deviation, P < .05) and that of 2,3-dinor-thromboxane B2 from 16.6 +/- 8.0 ng/mmol creatinine to 26.2 +/- 10.7 (P < .01), and thus led to the dominance of thromboxane A2. No changes in prostanoids occurred during transdermal HRT.


CONCLUSIONS
The effects of various HRTs on prostanoids may significantly differ.
Viinikka
L
L
Department of Clinical Chemistry, University of Helsinki, Finland.
Orpana
A
A
Puolakka
J
J
Pyörälä
T
T
Ylikorkala
O
O
D000279:Administration, Cutaneous; D000284:Administration, Oral; D011464:Epoprostenol / Q000096:biosynthesis* / Q000652:urine; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000008:administration & dosage*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D045167:Progesterone Congeners / Q000008:administration & dosage*; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000652:urine
D045167:Progesterone Congeners; D004958:Estradiol; D013928:Thromboxane A2; D000077563:Norethindrone Acetate; D011464:Epoprostenol; D008525:Medroxyprogesterone; D009640:Norethindrone