INFLUENCE OF ESTROGEN ON PROSTACYCLIN AND THROMBOXANE BALANCE IN POSTMENOPAUSAL WOMEN

Although the cardioprotective effect of estrogen is well recognized, t he mechanism by which this effect occurs is not well understood. One p ossible mechanism may involve an alteration in the local vascular equi librium between prostacyclin (PGI(2)) and thromboxane A(2) (TxA(2)), f avoring PGI(2). To test this hypothesis, we studied the estrogenic eff ect on urinary PGI(2)/TxB(2) balance, both acutely and long term, in p ostmenopausal women. Seven subjects received estradiol (E(2)) during o ne visit and only the vehicle during another visit (control). Both wer e administered intravenously for 8 h. Serum E(2) levels of similar to 200 pg/ml were attained after E(2) treatment. An additional eight subj ects were treated subcutaneously with two 25-mg E(2) pellets for 24 we eks; the serum E(2) levels averaged between 80 and 120 pg/ml. Also, 12 premenopausal women were used for comparison of baseline prostanoid v alues with those of postmenopausal women. A highly specific and sensit ive high-performance liquid chromatography/radioimmunoassay (HPLC-RIA) was used to quantitate PGI(2) and TxA(2) by measuring their stable me tabolites, 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)) and th romboxane B-2 (TxB(2)), respectively, in urine. The 6-keto-PGF(1 alpha ) and TxB(2) levels in postmenopausal women were 35.6 +/- 6.5 and 20.5 +/- 3.8 ng/g of creatinine compared with 32.2 +/- 5.3 and 16.7 +/- 3. 9 ng/g in premenopausal women, respectively. After E(2) infusion, ther e was a significant increase (41%) in mean 6-keto-PGF(1 alpha) levels, a 35% drop in mean TxB(2) levels, and a significantly greater (65%) 6 -keto-PGF(1 alpha)/TxB(2) ratio, compared to the controls. After long- term E(2) treatment, there was a progressive decrease in mean TxB(2) l evels and a transient increase in 6-keto-PGF(1 alpha) levels. The resu lts of our study suggest that the anticipated effects of E(2) treatmen t on PGI(2) and TxA(2) metabolism in postmenopausal women do occur.