Hormone Replacement Therapy and Cardioprotection

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in women after the age of 50 years in most developed countries. Estrogen deficiency plays a key role in causing CVD in women. Apart from the direct effect of ovarian hormones on the vessel wall, cessation of ovarian function and the consequent reduction of sex steroid hormone levels have important metabolic and pathological implications that negatively influence the cardiovascular system. Therefore, the increased incidence of CVD observed in women after menopause should be considered on a multifactorial basis. Data available for the effects of ERT and HRT in the primary prevention of CVD are mainly observational. However, despite limitations related to this kind of study, it must be noted that their results consistently show a reduction in cardiovascular events in hormone users. Meta-analysis of epidemiological studies found that women who had ever used estrogens had a 34% overall reduction in the relative risk of cardiovascular events compared to those who had never used hormones. Most of the early epidemiological studies were conducted using unopposed estrogen replacement therapy. The number of studies evaluating the effects of estrogen-progestin replacement therapy is limited. Recently, the estrogen-progestin arm of the Women's Health Initiative (WHI) study has been stopped because of an increased incidence of breast cancer, and too early on to give any insight into possible cardiovascular effects. Comments on the cardiovascular effects of HRT from the results of the WHI study are therefore not warranted, as the study did not continue for a duration long enough to enable a calculation of cardiovascular end points. The WHI study included only one single type of estrogen-progestin association; whether different estrogen-progestin combinations, more commonly used outside the United States, may have a different effect is still a matter of speculation. A major difference between observational and randomized studies on the effect of ovarian hormones on cardiovascular function is the time of HRT initiation since menopause, which is significantly shorter in observational studies. In conclusion, the average 35-50% risk reduction in CVD with HRT in primary prevention in postmenopausal women is based on nonrandomized observational data.

Early, But Not Late Onset Estrogen Replacement Therapy Prevents Oxidative Stress and Metabolic Alterations Caused by Ovariectomy

“…Recent studies confirm that the time elapsed after menopause is a relevant factor when taking the decision to recommend hormone replacement therapy (33,37,50). Indeed, a very recent study, showed that ''After 10 years of randomised…”

Effect of Estrogen-Progestin Hormonal Replacement Therapy on Blood Coagulation and Fibrinolysis in Postmenopausal Women

“…15 Rosano et al (2003) suggested that hormone therapy had beneficial cardiovascular effects in early postmenopausal women, while it may have had detrimental effects on coagulative balance and vascular inflammation. 16 The administration route of HT appears to affect the fibrinolytic activity and the coagulation markers. Also, the oral route is associated with changes in the levels of coagulation and fibrinolysis markers, especially during the early period of use.…”

Estrogen in the Paraventricular Nucleus Attenuates l -Glutamate–Induced Increases in Mean Arterial Pressure Through Estrogen Receptor β and NO

“…Key Words: 17␤-estradiol Ⅲ blood pressure Ⅲ estrogen receptor Ⅲ nitric oxide synthase Ⅲ autonomic nervous system T he increased incidence of cardiovascular disease in postmenopausal women has been attributed to the loss of estrogen (E2), 1,2 and it was observed that hormone replacement therapy confers cardiovascular benefits in these women. [1][2][3] In 1993, the Women's Health Initiative trial began recruiting Ͼ16 000 postmenopausal women to assess the benefits and risks of hormone replacement therapy on the incidence of heart disease, cancers, and fractures. 4 Surprisingly, the trial was terminated in 2002 because of increased risks of breast cancer and stroke.…”

“…[1][2][3] In 1993, the Women's Health Initiative trial began recruiting Ͼ16 000 postmenopausal women to assess the benefits and risks of hormone replacement therapy on the incidence of heart disease, cancers, and fractures. 4 Surprisingly, the trial was terminated in 2002 because of increased risks of breast cancer and stroke.…”