Association of Hormone Replacement Therapy With Hemostatic and Other Cardiovascular Risk Factors

Abstract

Abstract The risk of cardiovascular diseases in women is small until menopause but increases considerably afterwards. When all age groups are considered, cardiovascular diseases are responsible for approximately half of the total mortality in women. It has been suggested that hormone replacement therapy (HRT) in perimenopausal and postmenopausal women could be useful in the prevention of cardiovascular diseases, but its effects are insufficiently known. We performed a cross-sectional study on the associations of menopause and HRT with cardiovascular risk factors, in particular with hemostatic factors, on female participants of the FINRISK Hemostasis Study. The participants, aged 45 to 64 years, were recruited from the Finnish population register by random sampling from three geographically defined areas. The participation rate of women was 83.2%. Of the 1202 women included in the study, 29.2% were current users of HRT. Differences in cardiovascular risk factors by menopausal status and by HRT use were examined after adjustment for age, study area, current smoking, body mass index, self-reported diabetes, and years of education. Postmenopausal women not using exogenous sex hormones had on average a total cholesterol level 0.5 mmol/L (8.9%) higher and an LDL cholesterol level 0.4 mmol/L (11.4%) higher than premenopausal women. Women reporting irregular menstruation (presumably due to perimenopause) had higher adjusted plasma fibrinogen, factor VII coagulant activity, and factor VII antigen than women with regular menstruation or no menstrual periods. HRT users had an adjusted total cholesterol level 0.28 mmol/L (5%) lower ( P <.0001) and an adjusted LDL cholesterol level 0.3 mmol/L (7%) ( P <.0001) lower than nonusers. The data also suggested that HRT attenuated the age-dependent difference in total and LDL cholesterol ( P =.01 for age by HRT interaction). HRT users had lower adjusted insulin and glucose values than nonusers. When the hemostatic factors were studied, the users were seen to have lower adjusted fibrinogen ( P <.0001) but higher factor VII antigen ( P =.007) and plasminogen levels ( P <.0001) than nonusers. No difference was found in factor VII coagulant activity or in Lp(a). In conclusion, HRT users have clearly more favorable lipid profiles as well as insulin and glucose values compared with nonusers. Accordingly, HRT can be a potentially useful adjunct to the prevention of cardiovascular disease. Its effects on hemostatic factors are, however, mixed and of unclear clinical significance at the moment. More prospective studies on the effects of HRT on hemostasis are therefore needed before it can be recommended for the prevention of cardiovascular diseases.