Hormone replacement therapy and stroke

  • A.M.R. B
  • M. P
  • V. C
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Abstract

Stroke is the third most common cause of death in women and a major cause of disability. Stroke occurs in older age in women compared with men. High premenopausal estrogen concentrations in women are thought to be protective against stroke and cardiovascular disease. Estrogens are essential for normal reproductive function and they exert complex and diverse non reproductive actions on multiple tissues such as neuroprotective effects, vasodilatation, improved vascular reactivity, antithrombotic effects and lipid lowering effects. After menopause estrogen concentrations are depleted and in the past estrogen replacement therapy was considered at a potential protective agent against both cardiovascular disease and stroke. Although the use of hormone therapy was originally associated with a reduction in the risk of heart disease by about 50% in observational studies, the results regarding stroke have been less clear. In order to investigate the effect of hormone therapy on stroke risk, randomized controlled trials of cardio-and/or cerebrovascular-disease prevention in women with established heart disease have been designed. The Heart Estrogen-Progestin Replacement Study included stroke as secondary outcome. This study did not show any differences in myocardial infarction (MI) or coronary death (HR 0.99; 95%CI 0.80-1.22) and in stroke rate. In another study, the Women Estrogen Stroke Trial, 17 beta estradiol 1 mg/placebo was administered to women with previous ischemic stroke or transient ischaemic attack (TIA) having a mean age 71. No differences in stroke rate (RR 1.1; 95% CI 0.8-1.4) and in mortality rate (RR 1.2; 95% CI 0.8-1.8) were found, while a trend showing an increased rate of fatal strokes (RR 2.9; 95% CI 0.9-9.0) and for more severe non-fatal strokes (% patients with final National Institutes of Health Stroke Scale (NIHSS) 0-1: 19% vs. 33%; p = 0.12) was observed. The Women's Health Initiative, a primary prevention study, where conjugated equine estrogen (CEE) plus medroxyprogesterone acetate/ placebo was utilized, was stopped because of an excess in breast cancer and increased stroke rates (RR 1.4; 95% CI 1.1-1.8). Recently, a meta-analysis including 39,769 women participating in 28 trials has been published. Twelve studies were of secondary prevention and the overall stroke rate was 2%. In the hormone replacement therapy (HRT) arm there was a 29% increased rate of ischemic stroke (Number Needed to Harm, NNH:147). Furthermore, a 56% increased rate of death or dependency after stroke and a tendency of more fatal stroke were observed. Additionally, a higher stroke risk was reported in the first year of treatment. Conclusions: There seems to be no indication for hormone replacement therapy in the prevention of stroke in women. Further studies are needed to discover why estrogens have different effects on the heart and brain. Conventional risk-factors which could increase the risk of estrogen therapy need to be identified and as well as more restrictive inclusion and exclusion criteria such as coagulation parameters and intimal thickness should be adopted before new randomized trials are started. © 2008 Bentham Science Publishers Ltd.

Author-supplied keywords

  • *cerebrovascular accident/dt [Drug Therapy]
  • *cerebrovascular accident/ep [Epidemiology]
  • *cerebrovascular accident/pc [Prevention]
  • *cerebrovascular accident/si [Side Effect]
  • *cerebrovascular accident/th [Therapy]
  • *hormone substitution
  • antiinflammatory activity
  • antioxidant activity
  • arterial wall thickness
  • breakthrough bleeding/si [Side Effect]
  • breast cancer/si [Side Effect]
  • cardiovascular disease/pc [Prevention]
  • cardiovascular risk
  • cerebrovascular accident/si [Side Effect]
  • chronic kidney failure/co [Complication]
  • clinical trial
  • combination chemotherapy
  • conjugated estrogen plus medroxyprogesterone aceta
  • conjugated estrogen/ae [Adverse Drug Reaction]
  • conjugated estrogen/an [Drug Analysis]
  • conjugated estrogen/cb [Drug Combination]
  • conjugated estrogen/cm [Drug Comparison]
  • conjugated estrogen/ct [Clinical Trial]
  • conjugated estrogen/dt [Drug Therapy]
  • conjugated estrogen/pa [Parenteral Drug Administra
  • conjugated estrogen/pk [Pharmacokinetics]
  • conjugated estrogen/po [Oral Drug Administration]
  • conjugated estrogen/pr [Pharmaceutics]
  • conjugated estrogen/tp [Topical Drug Administratio
  • conjugated estrogen/va [Intravaginal Drug Administ
  • diabetes mellitus
  • drug absorption
  • drug administration route
  • drug bioavailability
  • drug blood level
  • drug dosage form comparison
  • drug efficacy
  • drug formulation
  • drug mechanism
  • drug withdrawal
  • esclim
  • estradiol/ad [Drug Administration]
  • estradiol/ae [Adverse Drug Reaction]
  • estradiol/cr [Drug Concentration]
  • estradiol/ct [Clinical Trial]
  • estradiol/do [Drug Dose]
  • estradiol/dt [Drug Therapy]
  • estradiol/pk [Pharmacokinetics]
  • estradiol/po [Oral Drug Administration]
  • estradiol/pr [Pharmaceutics]
  • estradiol/td [Transdermal Drug Administration]
  • estradiol/va [Intravaginal Drug Administration]
  • estragel
  • estrogen blood level
  • estrogen derivative/po [Oral Drug Administration]
  • estrogen derivative/pr [Pharmaceutics]
  • estrogen/ad [Drug Administration]
  • estrogen/ae [Adverse Drug Reaction]
  • estrogen/cb [Drug Combination]
  • estrogen/cm [Drug Comparison]
  • estrogen/do [Drug Dose]
  • estrogen/dt [Drug Therapy]
  • estrogen/pd [Pharmacology]
  • estrogen/pk [Pharmacokinetics]
  • estrogen/po [Oral Drug Administration]
  • estrogen/td [Transdermal Drug Administration]
  • gestagen/ae [Adverse Drug Reaction]
  • gestagen/cb [Drug Combination]
  • gestagen/cm [Drug Comparison]
  • gestagen/ct [Clinical Trial]
  • gestagen/dt [Drug Therapy]
  • hormonal therapy
  • human
  • hydroxymethylglutaryl coenzyme A reductase inhibit
  • hyperplasia/si [Side Effect]
  • insulin release
  • insulin sensitivity
  • low drug dose
  • mastalgia/si [Side Effect]
  • menopausal syndrome/dt [Drug Therapy]
  • monotherapy
  • mortality
  • neuroprotection
  • nonhuman
  • oral contraceptive agent/po [Oral Drug Administrat
  • piperazine estrone sulfate/po [Oral Drug Administr
  • placebo
  • postmenopause
  • postmenopause osteoporosis/dt [Drug Therapy]
  • progesterone/cb [Drug Combination]
  • progesterone/ct [Clinical Trial]
  • progesterone/dt [Drug Therapy]
  • review
  • risk assessment
  • risk benefit analysis
  • risk reduction
  • secondary prevention
  • sex difference
  • side effect/si [Side Effect]
  • single drug dose
  • stroke/dt [Drug Therapy]
  • stroke/ep [Epidemiology]
  • stroke/pc [Prevention]
  • stroke/si [Side Effect]
  • stroke/th [Therapy]
  • synthetic conjugated estrogen/ad [Drug Administrat
  • synthetic conjugated estrogen/pk [Pharmacokinetics
  • synthetic conjugated estrogen/po [Oral Drug Admini
  • synthetic conjugated estrogen/pr [Pharmaceutics]
  • synthetic conjugated estrogen/td [Transdermal Drug
  • synthetic conjugated estrogen/va [Intravaginal Dru
  • tibolone/ae [Adverse Drug Reaction]
  • tibolone/cm [Drug Comparison]
  • tibolone/dt [Drug Therapy]
  • tibolone/pd [Pharmacology]
  • transdermal patch
  • treatment indication
  • unclassified drug
  • vagina ring
  • venous thromboembolism/pc [Prevention]
  • venous thromboembolism/si [Side Effect]
  • women's health

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Authors

  • Billeci A.M.R.

  • Paciaroni M.

  • Caso V.

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