The effect of sex hormones on hemostasis and cardiovascular riskfactors in postmenopausal women

University dissertation from Stockholm : Karolinska Institutet, Department of Medicine

Abstract: The influence of cardiac riskfactors and sex hormones on hemostasis were studied in healthy women (n=260) in Study I. Body mass Index (BMI), dyslipidemia, surgical menopause, smoking and years since menopause were associated with an increase of 28% in fibrinogen levels. BMI, total cholesterol (tot. chol.) and Hormone Replacement Therapy (HRT) explained an increase of 5 % on levels of factor VII activity (VIla). Triglycerides (TG), tot. chol., BMI, years since menopause and HRT explained increases in Factor VII antigen (VIIag) levels of 25 %. Low levels of high density lipoprotein (HDL) and years since menopause explained an 8% increase in von Willebrand factor antigen (vWFag) levels. BMI explained 20% and TG 3% of the increase in plasminogen activator inhibitor 1 (PAI-1) levels. In Study II, 21 postmenopausal women with CHD and 42 postmenopausal healthy women were studied for a possible influence of CHD on sex steroids. Estradiol-17 beta (E2) levels were significantly higher in CHD patients. Further, significantly higher ratios between serum E2 and estrone (El) and between serum 4-androstene3.17-dione (A4) and dehydroepiandrosterone (DHEA) were seen in CHD patients. In Study III, sexual hormone binding globuline (SHBG) and corticosteroid binding protein (CBG) as markers for changes in hemostatic factors were studied in postmenopausal women with CHD on oral HRT (n=15) or placebo (n=13). A negative correlation between pretreatment values of PAI-1 and SHBG was found. Oral HRT increased levels of CBG, SHBG, and F VII and decreased levels of PAI-1 and antithrombin ( AT). In Studies IV and V, the effects of HRT on ambulatory blood pressure (ABP), lipids, angina pectoris and quality of life were studied in 60 postmenopausal women with CHD. In Study IV, oral HRT had the most pronounced effects on ABP. A rise in both daytime and night-time systolic ABP was observed after 6 cycles. After 12 cycles, a decrease was observed in night-time ABP. Transdermal HRT did not affect ABP. A decrease in night-time systolic ABP was observed in the placebo group after 12 cycles. In the oral HRT group, moderate beneficial effects on lipids were observed after 12 cycles. The effects were less pronounced in the transdermal group. In Study V, no significant difference between the treatment groups in the occurrence of angina pectoris was observed between baseline and 6 and 12 months. In Study III, sexual hormone binding globuline (SHBG) and corticosteroid binding protein (CBG) as markers for changes in hemostatic factors were studied in postmenopausal women with CHD on oral HRT (n=15) or placebo (n=13). A negative correlation between pretreatment values of PAI-1 and SHBG was found. Oral HRT increased levels of CBG, SHBG, and F VII and decreased levels of PAI-1 and antithrombin (AT). In Studies IV and V, the effects of HRT on ambulatory blood pressure (ABP), lipids, angina pectoris and quality of life were studied in 60 postmenopausal women with CHD. In Study IV, oral HRT had the most pronounced effects on ABP. A rise in both daytime and night-time systolic ABP was observed after 6 cycles. After 12 cycles, a decrease was observed in night-time ABP. Transdermal HRT did not affect ABP. A decrease in night-time systolic ABP was observed in the placebo group after 12 cycles. In the oral HRT group, moderate beneficial effects on lipids were observed after 12 cycles. The effects were less pronounced in the transdermal group. In Study V, no significant difference between the treatment groups in the occurrence of angina pectoris was observed between baseline and 6 and 12 months. Conclusions: BMI, tot. chol., TG och HDL appear to affect the hemostatis more than hormonal status and age in healthy postmenopausal women. The elevated levels of E2 in postmenopausal women with CHD might reflect an increased conversion of El to E2 secondary to inflammation. The correlation found between "steroid sensitive" proteins and hemostatic factors was an increase of SHBG levels and a decrease in PAI-1 levels, which might be a beneficial effect of HRT. Oral hormone therapy has a beneficial effect on lipoprotein levels. HRT has no effect on ABP and seems not to affect symptoms of angina pectoris.

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