A comparison of hormone therapies on the urinary excretion of prostacyclin and thromboxane A2.
OBJECTIVE
To evaluate the effect of estradiol, estradiol and norethisterone acetate (NETA), raloxifene and tibolone on the prostacyclin (PGI(2))/thromboxane A2 (TxA(2)) ratio in postmenopausal women after 8 weeks of treatment.


METHODS
This was a randomized, double-blind, cross-over study. Each patient took 8-week courses of estradiol 2 mg, estradiol 2 mg + NETA 1 mg, tibolone 2.5 mg, and raloxifene 60 mg; there was an 8-week placebo wash-out between each different intervention. All volunteers took all four treatment options and were randomized to one of three possible sequences. Urine was collected and frozen at each visit. Urinary metabolites of PGI(2) and TxA(2) were then assessed at the end of the study.


RESULTS
The ratio of PGI(2)/TxA(2) was significantly increased for raloxifene. No other treatments showed statistically significant changes.


CONCLUSIONS
The relationship between cardiovascular risk and hormone replacement therapy remains poorly understood. Raloxifene may have additional cardioprotective effects that the other treatments did not demonstrate, and none of the treatments statistically worsened the PGI(2)/TxA(2) ratio. This ratio may be under-utilized as a marker of net effect on cardiovascular health, but more research is needed to link it to health outcomes.
Bruce
D
D
Menopause Research Unit, Kings College School of Medicine, London, UK.
Frick
A
A
Rymer
J
J
Robinson
J
J
Ylikorkala
O
O
D002318:Cardiovascular Diseases / Q000517:prevention & control; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000378:metabolism* / Q000652:urine; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage* / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism* / Q000652:urine
D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D013928:Thromboxane A2; D000077563:Norethindrone Acetate; D011464:Epoprostenol; C027385:tibolone; D009640:Norethindrone