Published online before print March 11, 2004, doi: 10.1161/01.STR.0000122623.80379.b6
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(Stroke. 2004;35:e71.)
© 2004 American Heart Association, Inc.
Letters to the Editor |
Smoking, Estrogen, and Membrane Microviscosity in Women
Division of Cardiology, Department of Medicine, Wakayama Medical University, Wakayama, Japan
To the Editor:
We read with great interest the recent article by Dr. Kurth et al1 dealing with the relationship between smoking and hemorrhagic stroke in women. The results of their prospective study demonstrated that the risk of total hemorrhagic stroke, such as intracerebral hemorrhage and subarachnoid hemorrhage, was increased in women who are current cigarette smokers. The authors proposed that smoking may cause structural damage to the arterial wall and be a risk factor for both ischemic and hemorrhagic stroke in women.
Numerous studies have shown that estrogen may protect the brain from experimental stroke, such as global brain ischemia and subarachnoidal hemorrhage.2 One of the mechanisms underlying the protective effect of estrogen may be the enhancement of nitric oxide (NO) production. There is evidence showing that vascular endothelial function is markedly influenced by estrogen, and is improved by hormone replacement therapy in postmenopausal women.3 In an in vitro study presented earlier, we demonstrated that 17 ß-estradiol increased membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and improved the rigidity of cell membranes in postmenopausal women via the NO- and cGMP-dependent mechanisms.4 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.5 These findings suggest that, because abnormalities in membrane microviscosity could cause a disturbance in rheological behavior and microcirculation, estrogen-deficiency might be involved in the pathogenesis of vascular complications in women. In this context, it can be speculated that changes in plasma estrogen level might modify the onset and outcome of stroke in women. Mueck and Seeger6 proposed that smoking can reduce the efficacy of orally administered estrogen in women. Although the authors mentioned that use of hormone replacement therapy and postmenopausal status did not substantially change the effect of estimates of the association between smoking and hemorrhagic stroke, we would like to know whether the endogenous sex hormones might be different between smokers and non-smokers in women. It would be important to assess more precisely the relationship between estrogen status and vascular complications in women.
References
1. Kurth T, Kase CS, Berger K, Gaziano JM, Cook NR, Buring JE. Smoking and risk of hemorrhagic stroke in women. Stroke. 2003; 34: 2792–2795.
2. Hurn PD, Brass LM. Estrogen and stroke: a balanced analysis. Stroke. 2003; 34: 338–341.
3. Higashi Y, Sanada M, Sasaki S, Nakagawa K, Goto C, Matsuura H, Ohama K, Chyayama K, Oshima T. Effect of estrogen replacement therapy on endothelial function in peripheral resistance arteries in normotensive and hypertensive postmenopausal women. Hypertension. 2001; 37: 651–657.
4. Tsuda K, Kinoshita Y, Kimura K, Nishio I, Masuyama Y. Electron paramagnetic resonance investigation on modulatory effect of 17ß-estradiol on membrane fluidity of erythrocytes in postmenopausal women. Arterioscler Thromb Vasc Biol. 2001; 21: 1306–1312.
5. Tsuda K, Kinoshita-Shimamoto Y, Mabuchi Y, Nishio I. 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]
6. Mueck AO, Seeger H. Smoking, estradiol metabolism, and hormone replacement therapy. Arzneimittelforschung. 2003; 53: 1–11.[Medline] [Order article via Infotrieve]
Response
Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
Tsuada and Nishio postulate a potential beneficial effect of estradiol on the arterial wall, although the effect of estradiol on the vascular system in the brain remains controversial.1
In addition, recent randomized trial data provided evidence that postmenopausal hormone therapy increases the risk of ischemic stroke.2 Plasma estradiol levels were only measured in a small case-control study3 from participants of the Women’s Health Study. Preliminary results did not show statistically significant differences of plasma estradiol levels according to smoking status among users and non-users of postmenopausal hormone therapy. With respect to exogenous hormones, we showed that current smokers were less likely to utilize postmenopausal hormone therapy (see Table 1 in Reference 4). In our data, although based on a small number of cases, postmenopausal hormone use did not significantly modify the association between smoking and total hemorrhagic stroke.
References
1. Stier CT Jr, Chander PN, Rosenfeld L, Powers CA. Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats. Am J Physiol Endocrinol Metab. 2003; 285: E232–239.
2. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, Kotchen T, Curb JD, Black H, Rossouw JE, Aragaki A, Safford M, Stein E, Laowattana S, Mysiw WJ; WHI Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA. 2003; 289: 2673–2684.
3. Rexrode KM, Manson JE, Lee IM, Ridker PM, Sluss PM, Cook NR, Buring JE. Sex hormone levels and risk of cardiovascular events in postmenopausal women. Circulation. 2003; 108: 1688–1693.
4. Kurth T, Kase CS, Berger K, Gaziano JM, Cook NR, Buring JE. Smoking and risk of hemorrhagic stroke in women. Stroke. 2003; 34: 2792–2795.
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