Table Of ContentSchering Foundation Workshop 5
Sex Steroids and the Cardiovascular System
Schering Foundation Workshop
Editors: Gunter Stock
Ursula-F. Habenicht
Vol. 1
Bioscience'" Society
Workshop Report
Editors: D. J. Roy, B. E. Wynne, R. W. Old
Vol. 2
Round Table Discussion on Bioscience'" Society
Editor: J. J. Cherfas
Vol. 3
Excitatory Amino Acids and Second Messenger Systems
Editors: V. I. Teichberg, L. Turski
Vol. 4
Spermatogenesis - Fertilization - Contraception
Editors: E. Nieschlag, U.-F. Habenicht
Vol. 5
Sex Steroids and the Cardiovascular System
Editors: P. Ramwell, G. Rubanyi, E. Schillinger
Schering Foundation Workshop 5
Sex Steroids and
the Cardiovascular System
P. Ramwell, G. Rubanyi, E. Schillinger,
Editors
With 56 Figures
Springer-Verlag Berlin Heidelberg GmbH
ISBN 978-3-662-02766-0 ISBN 978-3-662-02764-6 (eBook)
DOI 10.1007/978-3-662-02764-6
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© Springer-Verlag Berlin Heidelberg 1992
Originally published by Springer-Verlag Berlin Heidelberg New York in 1992
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Preface
Evidence accumulated over the past decade show that gonadal steroid
hormones participate in an important way in the physiological and pa
thophysiological regulation of the cardiovascular system. The hor
monal profile appears to put males at a disadvantage biologically in
terms of cardiovascular diseases. The incidence of hypertension is
higher in men than in pre-monopausal women indicating an influence
of gender on the hypertensive disease process. Males and females have
equivalent cholesterol levels until puberty but males suffer an ex
ponential increase in heart disease in their forties, while the female rise
does not start until a decade later, after menopause. Animal and human
studies provided ample evidence, that estrogens lower the levels of low
density lipoproteins and keep high density lipoproteins elevated. These
changes may be advantageous in the prevention of heart diesease. Co
ronary artery atherosclerosis has been shown to be more pronounced in
ovarectomized female monkeys as in intact females. Androgen, con
versely, lowers the high density lipoproteins and elevates low density
lipoproteins. Regarding blood pressure, it is well established that
hypertension is more severe or develops more rapidly in male than fe
male rats in several genetic forms of hypertension, and that gonadal
steroid hormones are probably playing an important role in explaining
this observation. Risk factors of human hypertension and coronary
heart dies ease include menopause and ovarectomy.
Despite these convincing evidences from epidemiological and animal
studies, there are presently few data to link menopause to the increased
rate of hypertension or coronary heart disease. For example, studies on
cellular mechanisms of atherosclerosis have been conducted predomi-
VI Preface
nantly in male animals. The mechanisms by which steroids may in
fluence the proliferation of smooth muscle cells and plaque formation
is unclear. Although endothelial injury, activation and consequent dys
function is an important feature in both hypertension and atherogen
esis, data are not available on gender differences in vascular wall re
sponse to injury, endothelial integrity or the proliferative response.
The Schering Foundation Workshop on "Sex Steroids and the Car
diovascular System", which took place in Berlin on February 5-7,
1992, was organized to discuss the present knowledge and future re
search directions in this important, but still poorly understood field.
Leading basic scientists, epidemiologists and clinicians reviewed and
discussed three main themes: Firstly, sexual dimorphism and the role
of sex steroids (estrogen, progesterone and testosterone) in the control
of the cardiovascular system and physiological (e.g. pregnancy) and
pathological (e.g. hypertension) conditions; secondly, sex steroids and
vascular wall biology and pathology, and thirdly, oral contraceptive
steroids and hemostasis.
This book contains the proceedings of the workshop. The excellent
chapters by the leading experts give an overview of the methodologies
(from transgenic techniques to classical physiology methods) and the
multidisciplinary approaches utilized to analyze some of the scientific
questions.
In addition to the comprehensive summary of the present state of the
art in these three areas, this book also points out basic questions where fu
ture research is needed. The organizers of the workshop and editors of this
volume consider the latter as one of the major achievements of the meet
ing and hope that this book will stimulate scientists and clinicians alike to
continue or initiate research in these and related areas.
Peter Ramwell
Gabor M. Rubanyi
Ekkehard Schillinger
Contents
Cardiovascular Sexual Dimorphism
Peter W. Ramwell and Estelle Ramey .................. .
2 Sexual Dimorphism of Cardiovascular Function:
The Role of Androgens
Jurgen Bachmann. Ursula Ganten. Gunter Stock.
and Detlev Ganten . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3 Sexual Dimorphism in the Cardiovascular Actions
of Vasopressin
Leonard Share and Joan T. Crofton . . . . . . . . . . . . . . . . . . .. 31
4 Cardiovascular Adaptation to Pregnancy
Mark J. Morton .................................... 53
5 Oral Contraceptives and Thrombotic Risk:
A Critical Overview
Eberhard F. Mammen.. . . . . . . . . . . . . .. . . . . . . .. . . . . . .. 65
6 Studies on the Mechanisms of Action of Steroids
on Coagulation and Fibrinolysis
Cees Kluft, Jan A. Gevers Leuven,
and Frans M. Helmerhorst . . . . . . . . . . . . . . . . . . . . . . . . . .. 95
VIII Contents
7 Can Animal Models Be Used to Predict
the Hemostasiologic Effect of Steroid Hormones in Man?
Andreas Siij3milch, Rupprecht Zierz, Karsten Parczyk,
KrzystoJ Chwalisz, Karl-Heinrich Fritzemeier,
and Berthold Baldus ................................ 111
8 Estradiol and Myointimal Proliferation
Marie L. Foegh .................................... 129
9 Modulation of the Extracellular Matrix by Sex Steroids
Hermann GraJ ..................................... 139
10 Vascular Non-genomic Effects of Estrogen
Michel Farhat, Sylvie Abi-Younes, Roberto Vargas,
Raymond M. Wolfe, Robert Clarke,
and Peter W. Ramwell ............................... 145
11 Effects of Estrogens and Progestins
on Atherosclerosis in Primates
Michael R. Adams, Janice D. Wagner,
and Thomas B. Clarkson ............................. 161
12 A Review of the Epidemiology of Postmenopausal Estrogens
and the Risk of Coronary Heart Disease
Meir J. StampJer ................................... 177
Subject Index ......................................... 199
List of Contributors
Abi-Younes, Sylvie
Department of Physiology and Biophysics, Georgetown University
Medical Center, 3800 Reservoir Road NW, Washington DC 20007,
USA
Adams, Michael R.
Comparative Medicine Clinical Research Center, Bowman Gray
School of Medicine of Wake Forest University, Medical Center Blvd.,
Winston-Salem, NC 27157
Bachmann, liirgen
Gennan Institute for High Blood Pressure Research, 1m Neuenheimer
Feld 366, 6900 Heidelberg, FRG
Baldus, Berthold
Research Center of Schering AG, Miillerstr., 1000 Berlin 65, FRG
Chwalisz, Krzystof
Research Center of Schering AG, Miillerstr., 1000 Berlin 65, FRG
Clarkson, Thomas B.
Comparative Medicine Clinical Research Center, Bowman Gray
School of Medicine of Wake Forest University, Medical Center Blvd.,
Winston-Salem, NC 27157
x
List of Contributors
Crofton, Joan T,
Department of Physiology and Biophysics, University of Tennessee,
894 Union Avenue, Memphis, TN 38163, USA
Farhat, Michel
Department of Physiology and Biophysics, Georgetown University
Medical Center, 3800 Reservoir Road NW, Washington DC 20007,
USA
Foegh, Marie L.
Department of Surgery, Georgetown University Medical Center, 3800 Re
servoir Road NW, Washington DC 20007, USA
Fritzemeier, Karl-Heinrich
Research Center of Schering AG, Miillerstr., 1000 Berlin 65, FRG
Ganten, Detlef
Max Delbriick Center for Molecular Medicine (MDC), Robert-Rossle
Str. 10, 1115 Berlin Buch, FRG
Ganten, Ursula
Max Delbriick Center for Molecular Medicine (MDC), Robert-Rossle
Str. 10, 1115 Berlin Buch, FRG
Gevers Leuven, Jan A.
IVVO-TNO, Gaubius Laboratory, P.O. Box 430, 2300 AK Leiden,
The Netherlands
Graf, Hermann
Institute of Pharmacology, Schering AG, Muellerstrasse 170-178,
1000 Berlin 65, FRG
Helmerhorst, Frans M.
University Hospital, 2300 AK Leiden, The Netherlands
