Raloxifene, tamoxifen and vascular tone.
1. Oestrogen deficiency causes progressive reduction in endothelial function. Despite the benefits of hormone-replacement therapy (HRT) evident in earlier epidemiological studies, recent randomized trials of HRT for the prevention of heart disease found no overall benefit. Instead, HRT users had higher incidences of stroke and heart attack. Most women discontinue HRT because of its many side-effects and/or the increased risk of breast and uterine cancer. This has contributed to the development of selective oestrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, as alternative oestrogenic agents. 2. A SERM is a molecule that binds with high affinity to oestrogen receptors but has tissue-specific effects distinct from oestrogen, acting as an oestrogen agonist in some tissues and as an antagonist in others. Clinical and animal studies suggest multiple cardiovascular effects of SERMs. For example, raloxifene lowers serum levels of cholesterol and homocysteine, attenuates oxidation of low-density lipoprotein, inhibits endothelial-leucocyte interaction, improves endothelial function and reduces vascular smooth muscle tone. 3. Available evidence suggests that raloxifene and tamoxifen are capable of acting directly on both endothelial cells and the underlying vascular smooth muscle cells and cause a multitude of favourable modifications of the vascular wall, which jointly contribute to improved local blood flow. The outcome of the Raloxifene Use for the Heart (RUTH) trial will determine whether raloxifene, currently approved for the treatment of post-menopausal osteoporosis, could substitute for HRT in alleviating cardiovascular symptoms in post-menopausal women.
Leung
Fung Ping
FP
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Tsang
Suk Ying
SY
Wong
Chi Ming
CM
Yung
Lai Ming
LM
Chan
Yau Chi
YC
Leung
Hok Sum
HS
Yao
Xiaoqiang
X
Huang
Yu
Y
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects*
D002317:Cardiovascular Agents; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride