Effects of menopausal hormone treatments on prostanoid levels and platelet sensitivity to cyclic AMP activation in healthy, recently menopausal women

Abstract

Estrogen modulates the prostanoids prostacyclin (PGI2) and thromboxane A2 (TXA2) which contribute to vascular hemostasis in endothelium and platelets. Estrogen decreases in women at menopause, and menopausal hormone therapy (MHT) may increase risk of thrombosis. This study aimed to determine effects of MHT on serum prostanoid levels and on prostanoid‐related platelet functions in healthy, recently‐menopausal women. Women (age 52.3±2.3 yrs; n=115) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) were randomized to either: 1) oral conjugated equine estrogen, 2) transdermal 17β estradiol each with intermittent oral progesterone or 3) placebo, for 48 months. Serum PGI2 and TXA2 levels were assessed by quantification (ng/ml) of their stable metabolites 6‐k‐PGF1α and TXB2, respectively. Initial TXB2 levels (46.9±7.5) were unchanged (P>; 0.05) after 48 months in each treatment group. However, 6‐k‐PGF1α decreased from 2.1±0.2 to 1.4±0.1 at 48 months in combined groups, but was statistically significant (1.5±0.3) only in the transdermal group. Inhibition of platelet ATP secretion by PGE1 did not correlate with serum 6‐k‐PGF1α levels. These results suggest that serum PGI2 levels decrease with age in menopausal women and are unaffected by MHT. Factors other than changes in serum prostanoids may impose thrombotic risk associated with MHT. (Supported by the Aurora Fnd, NIH HL88988 and Mayo Clinic).