Esterified Estrogen and Conjugated Equine Estrogen and the Risk of Incident Myocardial Infarction and Stroke

Lemaitre, R. N.

doi:10.1001/.399

Cited by 11 publications

(10 citation statements)

References 20 publications

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“…21-27 We previously described the comparative safety of oral esterified estrogen compared with oral CEE and found that compared with oral esterified estrogen, oral CEE was associated with an increased risk of VT and possibly MI and ischemic stroke; findings were validated in controls, where oral CEE users had greater resistance to APC than oral esterified estrogen users. 3, 4, 28 Further, recent publications suggest that estrogen and progestogen drug type may be differentially associated with cardiovascular event risk although primary analyses compared HT use with non-use. 26, 27 …”

Section: Discussionmentioning

confidence: 99%

Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens

et al. 2014

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“…Post-MW treated with esterified estrogen alone have lower risk of ischemic stroke and myocardial infarction, and no increase in venous thrombosis risk compared to Post-MW treated with CEE [117, 141]. Also, experimental studies demonstrated that treatment of ovariectomized hypertensive rats with estradiol valerate causes an increase in serum vascular endothelial growth factor (VEGF), which accelerates endothelial cell growth both in vitro and in vivo [142].…”

Section: Introductionmentioning

confidence: 99%

Vascular Effects of Estrogenic Menopausal Hormone Therapy

Reslan

Khalil²

2012

RRCT

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Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post-MW) than premenopausal women (Pre-MW). Despite recent advances in preventive measures, the incidence of CVD in women has shown a rise that matched the increase in the Post-MW population. The increased incidence of CVD in Post-MW has been related to the decline in estrogen levels, and hence suggested vascular benefits of endogenous estrogen. Experimental studies have identified estrogen receptor ERα, ERβ and a novel estrogen binding membrane protein GPR30 (GPER) in blood vessels of humans and experimental animals. The interaction of estrogen with vascular ERs mediates both genomic and non-genomic effects. Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide, prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton, extracellular matrix, lipid profile and the vascular inflammatory response have been reported. In addition to the experimental evidence in animal models and vascular cells, initial observational studies in women using menopausal hormonal therapy (MHT) have suggested that estrogen may protect against CVD. However, randomized clinical trials (RCTs) such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), which examined the effects of conjugated equine estrogens (CEE) in older women with established CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular effects of estrogen treatment. Despite the initial set-back from the results of MHT RCTs, growing evidence now supports the ‘timing hypothesis’, which suggests that MHT could increase the risk of CVD if started late after menopause, but may produce beneficial cardiovascular effects in younger women during the perimenopausal period. The choice of an appropriate MHT dose, route of administration, and estrogen/progestin combination could maximize the vascular benefits of MHT and minimize other adverse effects, especially if given within a reasonably short time after menopause to women that seek MHT for the relief of menopausal symptoms.

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“…23 A meta-analysis of nine cohort studies published in 2002 also points toward a significant increase in ischaemic but not haemorrhagic stroke with MHT ever-use compared with never-use. 24 Of the largest recent observational studies evaluating the risk of stroke in relation to MHT use, three are concordant with these conclusions, [25][26][27] whereas both Lemaitre et al 29 and Prentice et al 28 found no evidence of an elevation in the risk of stroke with MHT use.…”

Section: Cerebrovascular Diseasementioning

confidence: 75%

Should transdermal rather than oral estrogens be used in menopausal hormone therapy?: a review

Fournier

2010

Menopause International

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The current evaluation of the benefit/risk ratio associated with menopausal hormone therapy (MHT) use is largely based on clinical trials which investigated the effects of oral treatments. Would MHT with transdermal estrogens be associated with a more favourable benefit/risk ratio? We reviewed the available epidemiologic evidence on that question. Epidemiologic studies were considered if they provided risk estimates of conditions which carry an important weight among menopausal women, and for which epidemiologic evidence of a possible link with MHT use is convincing: cardiovascular diseases, breast cancer, diabetes, colorectal cancer and hip fracture. We did not include studies with only surrogate measures. We found that the available information on the potential impact of the route of administration of MHT on the risk of our selected outcomes is limited. To date, epidemiologic data suggest that it has no impact on the risk of breast cancer and hip fracture. Results on the risk of coronary heart disease and colorectal cancer are inconsistent. Studies on stroke and diabetes risk are too few to allow meaningful conclusions. There is a suggestion that transdermal MHT may be less deleterious than oral MHT regarding venous thromboembolism which needs to be confirmed. The issue of the route of administration of MHT should remain an active area of research as part of an attempt to identify treatment modalities that would have the least potential for exerting adverse effects.

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Esterified Estrogen and Conjugated Equine Estrogen and the Risk of Incident Myocardial Infarction and Stroke

Abstract: Background: Clinical trials of conjugated equine estrogen (CEE) or estradiol vs placebo in postmenopausal women have found no effect or an elevated risk of myocardial infarction (MI) and stroke. The association of these end points with the use of esterified estrogen (EE) is unknown.

Cited by 11 publications

References 20 publications

Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens

Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens

Vascular Effects of Estrogenic Menopausal Hormone Therapy

Should transdermal rather than oral estrogens be used in menopausal hormone therapy?: a review

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