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Published on: August 13, 2019
The risk for cardiovascular disease in women: from estrogens to selective estrogen receptor modulators
Antonio Cano1, Carlos Hermenegildo, Pilar Oviedo
1Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain. Antonio.Cano@uv.es
Insights
Selective estrogen receptor modulators (SERMs) show a neutral effect on heart attack and stroke risk but may increase the risk of venous thromboembolic disease (VTED), similar to estrogens. Further research is needed to clarify their cardiovascular disease (CVD) impact.
Area of Science:
- Endocrinology and Cardiovascular Science
Background:
- Cardiovascular disease (CVD) encompasses coronary heart disease (CHD), stroke, and venous thromboembolic disease (VTED).
- Estrogen's role in CVD is debated due to conflicting evidence from clinical trials regarding its risk/benefit ratio.
- Selective estrogen receptor modulators (SERMs) are being investigated as potential alternatives to estrogen therapy.
Purpose of the Study:
- To evaluate the current clinical data on the effects of SERMs in cardiovascular disease (CVD).
- To compare the cardiovascular effects of SERMs with those of estrogens.
- To explore the pathogenetic mechanisms underlying SERM action in arterial and venous diseases.
Main Methods:
- Review of available clinical data on SERMs and CVD.
- Analysis of experimental models investigating atherogenesis and hypercoagulability.
- Comparison of SERM effects against estrogen effects in various CVD contexts.
Main Results:
- Available data suggest a neutral effect of SERMs on coronary heart disease (CHD) and stroke.
- SERMs appear to increase the risk of venous thromboembolic disease (VTED), similar to estrogens.
- Experimental models indicate SERMs offer less protection against atherogenesis than estrogens but do not increase plaque vulnerability.
Conclusions:
- Definitive clinical data on SERMs in CVD remain limited.
- SERMs present a similar risk profile for VTED as estrogens.
- Mechanisms underlying SERM-induced VTED risk require further investigation.
Abstract:
Cardiovascular disease, a generic denomination including coronary heart disease (CHD), stroke, and venous thromboembolic disease (VTED), has shown sensitivity to estrogens. The relative protection of women as compared with men has nourished a debate about a possible protective role for estrogens, but the prejudicial effects detected in clinical trials has created confusion on the risk/benefit ratio induced by hormone administration. The hypothesis that agonists distinct to estrogens might improve the effects associated with estrogens is at the base of the increasing interest on the role of selective estrogen receptor modulators (SERMs). There is a lack of definitive clearcut clinical data on the effects of SERMs in CVD, although the available information suggests a neutral balance on CHD and stroke and an increase in risk similar to estrogens for VTED. Research on pathogenetic mechanisms concentrates in atherosclerosis as the main determinant of the arterial forms of the disease and in hypercoagulability as the counterpart for venous disease. The different experimental models used up to the present moment suggest that, compared with estrogens, SERMs play a less active protection against atherogenesis but do not increase vulnerability of unstable plaques. There is not a clear notion on the mechanisms promoted by SERMs to increase risk for VTED.
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