Estrogen cardiovascular effects

Estrogens are thought to exert their cardiovascular effects by acting on blood lipoproteins or by direct effects on blood vessels. In studies performed in rats, fulvestrant had no effect on plasma cholesterol levels. When administered along with estradiol, however, it blocked the cholesterol-lowering activity of estradiol (Lundeen et al. 1997). 

Another important point to keep in mind when reviewing the cardiovascular effects of SERMs is that, in the absence of clinical studies of consistency comparable to estrogens, most of the available evidence has been obtained in experimental models. The work has concentrated on the selective areas of vascular physiology that have shown susceptibility to ER activation and, therefore, has followed steps that often overlap with those taken in research with estrogens. 

Herrington DM, Pusser BE, Riley WA, Thuren TY, Brosnihan KB, Brinton EA, MacLean DB (2000) Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women. Arterioscler Thromb Vase Biol 20 1606-1612... 

Raloxifene hydrochloride is a synthetic nonsteroidal drug derived from the benzothiophene and afferent to SERMs. It is known that raloxifene acts on metabolism, the skeleton, and the cardiovascular system as an estrogenic agonist (Khovidhunkit et al. 1999 Ettinger et al. 1999 Walsh et al. 1998), whereas it shows an estrogenic antagonist effect on reproductive organs such as the... 

Estrogens have a number of important metabolic and cardiovascular effects. They seem to be partially responsible for maintenance of the normal structure and function of the skin and blood vessels in women. Estrogens also decrease the rate of resorption of bone by promoting the apoptosis of osteoclasts and by antagonizing the osteoclastogenic and pro-osteoclastic effects of parathyroid hormone and interleukin-... 

Progestins antagonize estrogen s effects on LDL and HDL to a variable extent. However, one large study has shown that the addition of a progestin to estrogen replacement therapy does not influence the cardiovascular risk. 

Other published studies, many of which are of limited scope, do not run closely parallel to the above findings from the Women s Health Initiative, and the data on cardiovascular effects remain particularly confusing. However, Beral and colleagues have pointed out optimistically that substantial new data should soon be available from randomized trials of estrogen-alone hormonal replacement therapy versus placebo, although they added that few additional trial data on combined hormone replacement therapy are expected for about a decade (10). They also pointed out that existing randomized trials are too small to provide reliable evidence on some basic matters, including the relative risks of the various compounds in use. 

Some biochemical natural products have caused cardiotoxicity. Synthetic estrogens and progestins have been linked to cardiovascular disorders in women taking them for contraceptive purposes. Various animal and insect venoms and plant alkaloids may have adverse cardiovascular effects. There is some evidence to suggest that anabolic steroids, commonly linked to scandals involving athletes who take them to enhance performance, have caused cardiovascular disorders. 

The finding that tamoxifen given as adjuvant to surgery improved survival (Fisher et al., 1996) and decreased bone loss (Evans and Turner, 1995 Jordan, 1993) has been a major stimulus to search for other and possibly more potent and specific compounds that would act as antiestrogens in the breast and uterus while having estrogen-like effects in the skeletal and cardiovascular systems. 

Most adverse effects are believed to be due to the estrogen component, but cardiovascular effects reflect the action of both estrogen and progestin. The incidence of side effects with oral contraceptives is relatively low and is determined by the specific compounds and combinations used. 

Cardiovascular System In women, estrogen protects against cardiovascular disease. The protective cardiovascular effects of estrogen include decreased serum LDL cholesterol and increased HDL cholesterol levels, va-sodilatory effect, and antioxidation of LDL cholesterol (Chapter 20). Extensive clinical trials have shown that estrogen replacement therapy of postmenopausal women reduces the risk of heart disease. 

WHI 10,739 apparently Conjugated estrogen No effect on cardiovascular The trial was stopped after... 

Avoid smoking or excessive exposure to secondhand smoke while taking diese dru cigarette smoking during estrogen dierapy may increase die risk of cardiovascular effects. 

P450 2A6 transcriptional regulation has been reviewed by Pitarque et al. [390], Induction has been shown to involve the PXR, along with PPARa [391], P450 2A6 is also induced by estrogen via the ER [392], which may be relevant to a reported influence of the menstrual cycle on P450 2A6 activity (and the cardiovascular effects of nicotine) [393],... 

Prosta.te Ca.ncer, Estrogen has an inhibitory effect on the prostate in addition to its suppression of gonadotropin secretion by the pituitary. The three- and five-year survival rates in prostate cancer patients with metastatic disease improved when treated with DES (7) alone or along with castration. However, DES does not improve the survival rates in patients whose carcinoma is confined to the prostate. Small doses of DES (1 mg/d) appear to retard prostate cancer growth and could reduce the cardiovascular complications associated with larger doses (5 mg/d) (135) (see... 

Aromatase inhibitors are relatively well tolerated however have a number of distinct side effects are observed that stem from the state of estrogen deprivation induced by aromatase inhibitors. Side effects include hot flashes, joint and muscle aches, vasomotor symptoms and vaginal dryness. Variable effects of aromatase inhibitors on lipid levels have been observed. Trials comparing third generation aromatase inhibitors to tamoxifen have also repotted an increased risk of cardiovascular events in the group receiving aromatase inhibitors. 

Bazedoxifene is a third generation SERM that displays estrogenic effects in bone and the cardiovascular system, but functions as an antiestrogen in the breast and uterus. 

Observational studies have suggested possible favourable effects of estrogen replacement therapy (ERT) on the risk of coronary heart disease in postmenopausal women. Since elevated plasma cholesterol has been identified as the primary risk factor for cardiovascular disease, investigations have focused on the inverse association between plasma cholesterol concentration and soy protein consumption. The cholesterol-lowering properties of soy have been demonstrated, and a good correlation has been found in... 

DAVIDSON M H, MAKI K C, MARX P, MAKI A C, CYROWSKI M S, NANAVATI N, ARCE J C (2000) Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women . Archives of Internal Medicine, 160, 3315-25. 

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