Regulation of Platelet Aggregation and Adenosine Triphosphate Release In Vitro by 17β-Estradiol and Medroxyprogesterone Acetate in Postmenopausal Women

J. Bar; J. Lahav; M. Hod; Z. Ben-Rafael; I. Weinberger; J. Brosens

doi:10.1055/s-0037-1614089

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(04): 695-700
DOI: 10.1055/s-0037-1614089

Review Article

Schattauer GmbH

Regulation of Platelet Aggregation and Adenosine Triphosphate Release In Vitro by 17β-Estradiol and Medroxyprogesterone Acetate in Postmenopausal Women

Authors

J. Bar

¹From the Department of Obstetrics and Gynecology, Tel Aviv University, Tel Aviv, Israel
J. Lahav

²Hemostasis Laboratory, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
M. Hod

¹From the Department of Obstetrics and Gynecology, Tel Aviv University, Tel Aviv, Israel
Z. Ben-Rafael

¹From the Department of Obstetrics and Gynecology, Tel Aviv University, Tel Aviv, Israel
I. Weinberger

²Hemostasis Laboratory, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
J. Brosens

³Department of Reproductive Sciences and Medicine, Division of Paediatrics, Gynaecology and Obstetrics, Imperial College of Science, Technology and Medicine at Hammersmith Hospital, London, United Kingdom

Abstract

Summary

Clinical studies have suggested that hormone replacement therapy (HRT) may reduce the risk of coronary heart disease in postmenopausal women. Although progestins are commonly added to HRT preparations for uteroprotection, the perceived beneficial cardiovascular effects of HRT are thought to be mediated predominantly by the estrogen component. Platelets play a critical role in the pathogenesis of atherosclerosis and cardiovascular disease and, hence, it is possible that the cardiovascular effects of estrogens are mediated, at least in part, through inhibition of illicit platelet activation. The aim of this study was to examine the effects of sex steroids on adenosine diphosphate (ADP)-induced platelet aggregation and adenosine triphosphate (ATP) release in vitro in postmenopausal women. In addition, the effects of antiestrogens [4-hydroxy tamoxifen (4-OHT) and ICI 182780] and antiprogestins (RU 486 and ZK 98299) were also investigated. Preincubation of platelet-rich plasma (PRP) with antiestrogens or antiprogestins did not alter subsequent platelet aggregation or ATP release in response to ADP. However, preincubation with 17β-estradiol (E2) significantly inhibited ADP-mediated platelet aggregation by a mean (±SEM) of 37% ± 6% (p = 0.02) and ATP release by 82% ± 6% (p = 0.03), an effect that was reversed by the addition of ICI 182780 or 4-OHT but not RU 486 and ZK 98299. Although the progestin medroxyprogesterone acetate (MPA) also significantly inhibited platelet aggregation (by 28% ± 5%, p = 0.02) and ATP release (by 63% ± 9%, p = 0.02), this inhibition was not reversed by the addition of antiprogestins or antiestrogens. These data show that sex steroids can modulate platelet function in vitro. Furthermore, as platelets are devoid of nuclear components, these findings indicate that estrogens may regulate platelet function through binding to a non-nuclear receptor with ligand-binding properties similar or identical to the wild-type receptor. By contrast, MPA appears to exert its effect through a mechanism that does not involve binding to the “classical” progesterone receptor.

Key words

Estrogen - progesterone - platelets - menopause - HRT

Full Text

References

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