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Oral administration of 17beta-estradiol over 3 months without progestin co-administration does not improve coronary flow reserve in post-menopausal women: a randomized placebo-controlled cross-over CMR study


Schwitter, Juerg; Kozerke, Sebastian; Bremerich, Jens; Baltes, Christof; Attenhofer Jost, Christine; Birkhäuser, Martin; Boesiger, Peter; Buser, Peter (2007). Oral administration of 17beta-estradiol over 3 months without progestin co-administration does not improve coronary flow reserve in post-menopausal women: a randomized placebo-controlled cross-over CMR study. Journal of Cardiovascular Magnetic Resonance, 9(4):665-72.

Abstract

BACKGROUND: Several large epidemiological outcome studies did not demonstrate a benefit of combined estrogen-progestin replacement treatment (HRT) on cardiovascular events in elderly postmenopausal women. Whether progestin antagonism is responsible for these negative results or the natural estrogen 17ss-estradial (E2) itself is not effective in the coronary circulation is unknown.
AIM: To assess the effect of 3 months of E2 treatment on the coronary circulation, i.e., on coronary flow reserve (CFR), in postmenopausal women without established coronary artery disease (CAD).
METHODS: In a double-blind placebo-controlled cross-over design postmenopausal women (60 +/- 5 years, n = 14) were randomized to either start with placebo or E2 (Estrofem, Novo Nordisk, Copenhagen, Denmark) 2 mg/d given orally over 3 months and to switch thereafter for another 3 months of therapy. At baseline, a stress echocardiography was performed to exclude CAD. CFR was determined by coronary sinus CMR flow measurements (with motion-adapted gating and interactive acquisition window control; spatial/temporal resolution of 0.8 x 0.9 mm2/25-30 ms) which were performed at rest and during vasodilation (dipyridamole 0.56 mg/kg over 4 minutes IV) at baseline, and after 3 and 6 months of therapy, respectively.
RESULTS: Hemodynamics such as heart rate and systolic and diastolic blood pressure were not different for the control and E2 group. For CFR and for resting and hyperemic coronary sinus blood flow, no differences between the placebo and E2 group were found (2-way ANOVA for repeated measurements). Reproducibility of phase-contrast CMR measurements of CFR was -1.1 +/- 4.9%.
CONCLUSIONS: In elderly postmenopausal women without significant CAD, oral administration of E2 over 3 months without a progestin co-administration does not improve CFR. This finding yields partly explanation for some large epidemiological trials which could not demonstrate a clinical cardiovascular benefit of HRT in elderly women.

BACKGROUND: Several large epidemiological outcome studies did not demonstrate a benefit of combined estrogen-progestin replacement treatment (HRT) on cardiovascular events in elderly postmenopausal women. Whether progestin antagonism is responsible for these negative results or the natural estrogen 17ss-estradial (E2) itself is not effective in the coronary circulation is unknown.
AIM: To assess the effect of 3 months of E2 treatment on the coronary circulation, i.e., on coronary flow reserve (CFR), in postmenopausal women without established coronary artery disease (CAD).
METHODS: In a double-blind placebo-controlled cross-over design postmenopausal women (60 +/- 5 years, n = 14) were randomized to either start with placebo or E2 (Estrofem, Novo Nordisk, Copenhagen, Denmark) 2 mg/d given orally over 3 months and to switch thereafter for another 3 months of therapy. At baseline, a stress echocardiography was performed to exclude CAD. CFR was determined by coronary sinus CMR flow measurements (with motion-adapted gating and interactive acquisition window control; spatial/temporal resolution of 0.8 x 0.9 mm2/25-30 ms) which were performed at rest and during vasodilation (dipyridamole 0.56 mg/kg over 4 minutes IV) at baseline, and after 3 and 6 months of therapy, respectively.
RESULTS: Hemodynamics such as heart rate and systolic and diastolic blood pressure were not different for the control and E2 group. For CFR and for resting and hyperemic coronary sinus blood flow, no differences between the placebo and E2 group were found (2-way ANOVA for repeated measurements). Reproducibility of phase-contrast CMR measurements of CFR was -1.1 +/- 4.9%.
CONCLUSIONS: In elderly postmenopausal women without significant CAD, oral administration of E2 over 3 months without a progestin co-administration does not improve CFR. This finding yields partly explanation for some large epidemiological trials which could not demonstrate a clinical cardiovascular benefit of HRT in elderly women.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Language:English
Date:2007
Deposited On:24 Apr 2014 14:07
Last Modified:05 Apr 2016 17:51
Publisher:BioMed Central
ISSN:1097-6647
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1080/10976640601138730
PubMed ID:17578722
Permanent URL: https://doi.org/10.5167/uzh-95560

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