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(Circulation. 2004;109:e218.)
© 2004 American Heart Association, Inc.

Correspondence

Sex Hormones and Membrane Microviscosity in Elderly Women

Kazushi Tsuda, MD; Ichiro Nishio, MD

Division of Cardiology, Department of Medicine, Wakayama Medical University, Kimiidera 811–1, Wakayama 641–8509, Japan, tsudak{at}mail.wakayama-med.ac.jp

To the Editor:

We read with great interest the recent article by Dr Vaccarino and colleagues¹ dealing with the gender differences in health status after coronary artery bypass (CABG) surgery. The results of their study demonstrated that at 6 months, the physical function and mental health improved in men (mean age, 64.2 years old) significantly more than in women (mean age, 69.6 years old). In addition, it was demonstrated that the absolute rate of adverse outcomes, such as hospital readmission, worsening functional status, and worsening mental health were significantly higher in women than in men. The authors proposed that CABG surgery is associated with lower functional gains and higher readmission rates in women compared with men.

Evidence indicates that vascular endothelial function is markedly influenced by estrogen, and is improved by hormone replacement therapy in postmenopausal women.² In an in vitro study presented earlier, we demonstrated that 17ß-estradiol increased membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and improved the rigidity of cell membranes in postmenopausal women via a nitric oxide (NO)- and cGMP-dependent mechanism.³ In a separate series of experiments, we showed that hormone replacement therapy restored the membrane microviscosity in elderly women with a concomitant increase in plasma NO metabolite level.⁴ These findings suggest that, because abnormalities in membrane microviscosity could cause a disturbance in the rheological behavior and the microcirculation, estrogen-deficiency might be involved in the pathogenesis of vascular complications in elderly women. Recently, the role of estrogen in male physiology has also become evident, and normal physiological estrogen, which is converted from testosterone by aromatase, may confer cardiovascular benefits for elderly men.⁵ In this context, we speculate that changes in sex hormones might modify the course of cardiovascular diseases both in men and women. Therefore, we would like to know whether the endogenous sex hormones might be different between men and women after CABG surgery. It would be important to assess more precisely the relationship between sex hormone status and vascular complications after CABG surgery in the elderly.

References

1. Vaccarino V, Lin ZQ, Kasl SV, et al. Sex differences in health status after coronary artery bypass surgery. Circulation. 2003; 108: 2642–2647.[Abstract/Free Full Text]
   
2. Higashi Y, Sanada M, Sasaki S, et al. Effect of estrogen replacement therapy on endothelial function in peripheral resistance arteries in normotensive and hypertensive postmenopausal women. Hypertension. 2001; 37: 651–657.[Abstract/Free Full Text]
   
3. Tsuda K, Kinoshita Y, Kimura K, et al. Electron paramagnetic resonance investigation on modulatory effect of 17ß-estradiol on membrane fluidity of erythrocytes in postmenopausal women. Arterioscler Thromb Vas Biol. 2001; 21: 1306–1312.[Abstract/Free Full Text]
   
4. Tsuda K, Kinoshita-Shimamoto Y, Mabuchi Y, et al. Hormone replacement therapy improves membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation. Am J Hypertens. 2003; 16: 502–507.[CrossRef][Medline] [Order article via Infotrieve]
   
5. Cho JJ, Cadet P, Salamon E, et al. The nongenomic protective effects of estrogen on the male cardiovascular system: clinical and therapeutic implications in aging men. Med Sci Monit. 2003; 9: RA63–RA68.[Medline] [Order article via Infotrieve]
   

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Response

Viola Vaccarino, MD, PhD

Department of Medicine, Division of Cardiology, Emory University School of Medicine and, Department of Epidemiology, Rollins School of Public Health, Atlanta, Ga, lvaccar{at}emory.edu

Zhen Qiu Lin, PhD; Jennifer A. Mattera, MPH; Sarah A. Roumanis, RN

Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Conn

Stanislav V. Kasl, PhD

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn

Jerome L. Abramson, PhD

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Ga

Harlan M. Krumholz, MD

Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine and, Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Conn

We appreciate the comments from Drs Tsuda and Nishio. We did not have information on menopausal status or on endogenous sex hormone levels in our study.¹ Although numerous favorable effects of estrogen on the vasculature have been described,² including the findings that Drs Tsuda and Nishio report in their letter, potentially adverse effects have also been noted, such as proinflammatory properties of exogenous estrogen replacement therapy.³ Importantly, the role of estrogen as a protective factor toward cardiovascular events in women with⁴ and without⁵ established coronary atherosclerosis has been questioned by recent randomized trials. The endogenous estrogen molecule, 17ß-estradiol, has also failed to show a protective effect in a recent trial examining progression of coronary atherosclerosis in postmenopausal women with coronary artery disease.⁶ Therefore, there is little evidence currently that estrogen deficiency is a major factor in patients’ clinical course and health status after coronary artery bypass graft surgery.

References

1. Vaccarino V, Lin ZQ, Kasl SV, et al. Sex differences in health status after coronary artery bypass surgery. Circulation. 2003; 108: 2642–2647.[Abstract/Free Full Text]
   
2. Mendelsohn ME, Karas RH. The protective effect of estrogen on the cardiovascular system. N Engl J Med. 1999; 340: 1801–1811.[Free Full Text]
   
3. Cushman M, Legault C, Barrett-Connor E, et al. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation. 1999; 100: 717–722.[Abstract/Free Full Text]
   
4. Hulley S, Grady D, Bush T. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998; 280: 605–613.[Abstract/Free Full Text]
   
5. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003; 349: 523–534.[Abstract/Free Full Text]
   
6. Hodis HN, Mack WJ, Azen SP, et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med. 2003; 349: 535–545.[Abstract/Free Full Text]
   

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tsuda, K. Articles by Krumholz, H. M. Search for Related Content PubMed PubMed Citation Articles by Tsuda, K. Articles by Krumholz, H. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Coronary Artery Bypass Surgery Hazardous Substances DB NITRIC OXIDE Related Collections Health policy and outcome research Epidemiology Endothelium/vascular type/nitric oxide Behavioral/psychosocial - CV surgery CV surgery: coronary artery disease