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• W2312988788 abstract "Letters to the EditorReply to “Letter to the Editor: ‘Understanding the WHI gap’”Angela S. Pechenino, Alison R. Lee, Li Lin, Fiona N. Mbai, John N. Stallone, and A. A. KnowltonAngela S. PecheninoCellular and Molecular Cardiology, Department of Medicine, , Alison R. LeeCellular and Molecular Cardiology, Department of Medicine, , Li LinDepartment of Physiology, Second Military Medical University, Shanghai, China; , Fiona N. MbaiCellular and Molecular Cardiology, Department of Medicine, Institute of Tropical Medicine and Infectious Diseases, University of Nairobi, Nairobi, Kenya; and , John N. StalloneDepartment of Physiology, and Pharmacology, School of Veterinary Medicine, Texas A&M, College Station, Texas, and A. A. KnowltonCellular and Molecular Cardiology, Department of Medicine, Department of Medical Pharmacology, University of California, Davis; VA Northern California Health Care System, Mather, California; Published Online:01 Mar 2012https://doi.org/10.1152/physiolgenomics.00188.2011MoreSectionsPDF (34 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat reply: This is a reply in response to Drs. Kerber's and Turner's commentary about our article (10) in Physiological Genomics. We thank Kerber and Turner for their enthusiastic response to our article and are pleased that they found it useful in their practice (10). However, we would like to point out that the link between estrogen therapy postmenopause and a decrease in dementia in older women is tenuous at best. Few studies indicate definitively that hormone replacement therapy (HRT) results in a decrease in dementia, and most only point toward a possibility that has yet to be realized (5). Basic studies in rodent models suggest that estrogen replacement can reduce brain injury in models of stroke, but more work is needed before taking these findings to the clinical setting (1). Additionally, the Women's Health Initiative (WHI) and the Million Woman Study indicate that breast cancer risk increases significantly when women are put on HRT, specifically with estrogen and progesterone taken in combination, a finding that should limit the use of HRT to those women who do not already manifest a high risk for breast cancer (2, 9).In contrast to chronic estrogen replacement, there is a small, but growing, literature supporting a role for a protective role of estrogen in acute injury (11–13). We and others have found that treatment with a high concentration of 17β-estradiol at the time of injury can greatly reduce inflammation and apoptosis (3, 4, 6, 14). Such limited use of E2 will not increase the risk of cancer but does have the possibility of greatly reducing tissue injury.We feel that a more promising area for the treatment of postmenopausal symptoms comes from the selective estrogen receptor modulators (SERMs). For example, raloxifene improved verbal memory in postmenopausal women when given over a period of 5 yr.(7) In contrast tamoxifen, a SERM that is primarily an estrogen antagonist, was associated with poorer performance on letter fluency and manual dexterity in women with breast cancer compared with untreated controls (8). Many SERMs have been synthesized, and some may have the positive, protective effects of estrogen without promoting cell proliferation and cancer. More work will be needed identifying the specific effects of these compounds before this type of treatment can be applied in the clinic to ameliorate aging-associated changes such as cardiovascular disease and dementia.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author(s).AUTHOR CONTRIBUTIONSAuthor contributions: A.S.P. drafted manuscript; A.S.P., A.R.L., L.L., F.N.M., J.N.S., and A.A.K. approved final version of manuscript; A.R.L., L.L., F.N.M., J.N.S., and A.A.K. edited and revised manuscript.REFERENCES1. Brown CM , Suzuki S , Jelks KAB , Wise PM . Estradiol is a potent protective, restorative, and trophic factor after brain injury. Semin Reprod Med 27: 240–249, 2009.Crossref | PubMed | ISI | Google Scholar2. Cuzick J . Hormone replacement therapy and the risk of breast cancer. Eur J Cancer 44: 2344–2349, 2008.Crossref | PubMed | ISI | Google Scholar3. Hamilton KL , Gupta S , Knowlton AA . Estrogen and regulation of heat shock protein expression in female cardiomyocytes: cross-talk with NFκB signaling. J Mol Cell Cardiol 36: 579–586, 2004.Crossref | ISI | Google Scholar4. Hamilton KL , Mbai FN , Gupta S , Knowlton AA . Estrogen, heat shock proteins, and NFkappaB in human vascular endothelium. Arterioscler Thromb Vasc Biol 24: 1628–1633, 2004.Crossref | PubMed | ISI | Google Scholar5. Hogervorst E , Bandelow S . Sex steroids to maintain cognitive function in women after the menopause: a meta-analyses of treatment trials. Maturitas 66: 56–71, 2010.Crossref | PubMed | ISI | Google Scholar6. Hsieh YC , Yang S , Choudhry MA , Yu HP , Rue LW , Bland KI , Chaudry IH . PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage. Am J Physiol Heart Circ Physiol 289: H2665–H2672, 2005.Link | ISI | Google Scholar7. Jacobsen DE , Samson MM , Emmelot-Vonk MH , Verhaar HJJ . Raloxifene improves verbal memory in late postmenopausal women: a randomized, double-blind, placebo-controlled trial. Menopause 17: 309–314, 2010.Crossref | PubMed | ISI | Google Scholar8. Lejbak L , Vrbancic M , Crossley M . Endocrine therapy is associated with low performance on some estrogen-sensitive cognitive tasks in postmenopausal women with breast cancer. J Clin Exp Neuropsychol 32: 836–846, 2010.Crossref | PubMed | ISI | Google Scholar9. Narod SA . Hormone replacement therapy and the risk of breast cancer. Nature Review: Clin Oncol 8: 669–676, 2011.Crossref | PubMed | ISI | Google Scholar10. Pechenino AS , Lin L , Mbai FN , Lee AR , He XM , Stallone JN , Knowlton AA . Impact of aging vs. estrogen loss on cardiac gene expression: late estrogen replacement and inflammation. Physiol Genomics 43: 1065–1073, 2011.Link | ISI | Google Scholar11. Stice JP , Chen L , Kim SC , Chen L , Tran AL , Liu TT , Knowlton AA . 17β-Estradiol, aging, inflammation and the stress response in the female heart. Endocrinology 152: 1589–1598, 2011.Crossref | PubMed | ISI | Google Scholar12. Stice JP , Lee JS , Pechenino AS , Knowlton AA . Estrogen, aging and the cardiovascular system. Future Cardiol 5: 93–103, 2009.Crossref | PubMed | Google Scholar13. Yu HP , Chaudry IH . The role of estrogen and receptor agonists in maintaining organ function after trauma-hemorrhage. Shock 31: 1–20, 2009.Crossref | PubMed | ISI | Google Scholar14. Yu HP , Shimizu T , Hsieh YC , Suzuki T , Choudhry MA , Schwacha MG , Chaudry IH . Tissue-specific expression of estrogen receptors and their role in the regulation of neutrophil infiltration in various organs following trauma-hemorrhage. J Leukoc Biol 79: 963–970, 2006.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: A. A. Knowlton, Molecular and Cellular Cardiology Genomics and Biomedical Sciences Facility, Univ. of California, Davis, 451 Health Sciences Way, Davis, CA 95616 (e-mail: [email protected]edu). Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesTranslational Physiology: Understanding the WHI gap 01 Mar 2012Physiological Genomics More from this issue > Volume 44Issue 5March 2012Pages 330-330 https://doi.org/10.1152/physiolgenomics.00188.2011History Published online 1 March 2012 Published in print 1 March 2012 Metrics" @default.
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