Effect of hormone replacement
The physiological effects of exogenous estrogens are consistent with the cardioprotective effect. Estrogens reduce the level of LDL cholesterol and increase the level of HDL cholesterol, reduce the content of lipoprotein (a), plasminogen activator inhibitor 1, insulin levels, inhibit the process of LDL oxidation and improve endothelial function.
The effect of estrogen on inflammation is complex, since fibrinogen level is reduced, and the level of NRW is increased. Many of these effects are expressed when taking estrogen per os and are minimal when transdermally applied, which indicates the effect of the first pass. Estrogens can also improve glucose tolerance.
Despite the results of observational and physiological studies that suggested the favorable effect of hormone replacement therapy (HRT), the results of 7 recently completed randomized studies (5 – for secondary prevention and 2 – for primary prevention) not only failed to confirm the beneficial effect of HRT on the CHD, but showed that combination estrogen and progestin therapy may increase the risk of CHD. This dramatic change in perspective on the effects of HRT illustrates the problems of uncontrolled interference in cohort observational studies and the importance of randomized controlled clinical trials.
Evidence also indicates that age and time from the onset of menopause may alter the effect of estrogen on cardiovascular risk (CCP).
The first HERS study on secondary prophylaxis did not reveal a positive effect of adding estrogen and progestin on the cardiovascular system even with an increase in the observation period. Subsequent studies did not find a favorable effect of HRT or an increase in the risk of KBS events.
One branch of the large-scale WHI study was planned to assess the relative benefit and risk of estrogen plus progestin for 8.5 years in 16,608 women aged 50 to 79 years with an intact uterus at the start of the study. However, after 5.2 years of observation, the study was stopped because the number of cases of invasive breast cancer exceeded the limits of this PE, i.e. risk exceeded the benefit. At that time, the estimated total risk (RR) for coronary heart disease (CHD) was 1.29 (95% CI 1.02-1.63), for MI – 1.41 (95% CI 1.07-1.85 ) and for pulmonary embolism – 2.13 (95% CI 1.39-3.25).
The overall risk (RR) for all cardiovascular diseases (CVD) was 1.22 (95% CI 1.09-1.36). The absolute excess of SSR per 10 thousand person-years associated with taking estrogen and progestin was equal to 7 cases of CHD, 8 cases of MI and 8 cases of pulmonary embolism. The benefit was to reduce the number of fractures and colorectal cancers.
Later, the estrogen branch of the WHI study involving 10,739 healthy women aged 50–79 years without a uterus was also stopped due to a slight increase in the risk of MI, especially in women aged> 60 years. After 6.8 years of follow-up, the use of estrogens was associated with a 39% increase in the risk of MI, an unreliable 9% decrease in the CHD and a 30-39% decrease in the number of fractures. A more thorough study showed that women with recent menopause had a reduced risk of KBS (MI and coronary revascularization) and a more favorable overall index when taking estrogen compared with placebo.
Although menopause clearly increases the risk of coronary heart disease (CHD), a recent study shows that HRT with estrogens and progestins does not protect the cardiovascular system, especially in older women. Will be able to or pet other regimens or drugs HRT to protect the cardiovascular system, will show the results of other studies.
Recommendations. HRT for the prevention of CVDs is no longer recommended by the USPSTF, the North American Menopause Society, AHA or other scientific organizations. Moreover, in 2003, the FDA revised the labels of all drugs for hormone therapy containing only estrogens or their combination with progestins, and obliged to include warning labels about an increased risk of heart disease, MI, MI and breast cancer. Nevertheless, HRT continues to be used in clinical practice for the treatment of moderate and severe symptoms of menopause.