Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies
Judith L. Turgeon,
Molly C. Carr,
Pauline M. Maki,
Michael E. Mendelsohn and
Phyllis M. Wise
Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, Department of Internal Medicine (J.L.T.), University of California, Davis, Davis, California 95616; Division of Endocrinology, Metabolism, and Molecular Medicine (M.C.C.), Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611; Department of Psychiatry and Psychology (P.M.M.), University of Illinois at Chicago, Chicago, Illinois 60612; Molecular Cardiology Research Institute, Department of Medicine, and Division of Cardiology (M.E.M.), New England Medical Center Hospitals and Tufts University School of Medicine, Boston, Massachusetts 02111; and Departments of Physiology and Biophysics, and Biology (P.M.W.), University of Washington, Seattle, Washington 98195
Correspondence: Address all correspondence and requests for reprints to: Judith Turgeon, Ph.D., Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, University of California Davis, Davis, California 95616. E-mail: jlturgeon{at}ucdavis.edu
Recent publications describing the results of the Women’sHealth Initiative (WHI) and other studies reporting the impactof hormone therapy on aging women have spurred reexaminationof the broad use of estrogens and progestins during the postmenopausalyears. Here, we review the complex pharmacology of these hormones,the diverse and sometimes opposite effects that result fromthe use of different estrogenic and progestinic compounds, givenvia different delivery routes in different concentrations andtreatment sequence, and to women of different ages and healthstatus. We examine our new and growing appreciation of the roleof estrogens in the immune system and the inflammatory response,and we pose the concept that estrogen’s interface withthis system may be at the core of some of the effects on multiplephysiological systems, such as the adipose/metabolic system,the cardiovascular system, and the central nervous system. Wecompare and contrast clinical and basic science studies as wefocus on the actions of estrogens in these systems because theuntoward effects of hormone therapy reported in the WHI werenot expected. The broad interpretation and publicity of theresults of the WHI have resulted in a general condemnation ofall hormone replacement in postmenopausal women. In fact, carefulreview of the extensive literature suggests that data resultingfrom the WHI and other recent studies should be interpretedwithin the narrow context of the study design. We argue thatthese results should encourage us to perform new studies thattake advantage of a dialogue between basic scientists and clinicianscientists to ensure appropriate design, incorporation of currentknowledge, and proper interpretation of results. Only then willwe have a better understanding of what hormonal compounds shouldbe used in which populations of women and at what stages ofmenopausal/postmenopausal life.
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