FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2156572025> ?p ?o ?g. }

• W2156572025 endingPage "822" @default.
• W2156572025 startingPage "820" @default.
• W2156572025 abstract "HomeCirculationVol. 115, No. 7Are Some Types of Hormone Therapy Safer Than Others? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBAre Some Types of Hormone Therapy Safer Than Others?Lessons From the Estrogen and Thromboembolism Risk Study Kathryn M. Rexrode, MD, MPH and JoAnn E. Manson, MD, DrPH Kathryn M. RexrodeKathryn M. Rexrode From the Division of Preventive Medicine (K.M.R., J.E.M.), Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston Mass; and Department of Epidemiology (J.E.M.), Harvard School of Public Health, Boston, Mass. Search for more papers by this author and JoAnn E. MansonJoAnn E. Manson From the Division of Preventive Medicine (K.M.R., J.E.M.), Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston Mass; and Department of Epidemiology (J.E.M.), Harvard School of Public Health, Boston, Mass. Search for more papers by this author Originally published20 Feb 2007https://doi.org/10.1161/CIRCULATIONAHA.106.675405Circulation. 2007;115:820–822Despite great strides in hormone therapy (HT) research, clinical trial data on the benefit-to-risk profile of different formulations, doses, and routes administration of HT remain lacking. Most of the large-scale clinical trials1–3 have tested oral conjugated equine estrogens with or without medroxyprogesterone acetate, and data on nonoral routes and different types and doses of estrogens and progestogens have been limited. The evidence is mounting that route of delivery and possibly type and dose of HT are important factors, particularly for venous thromboembolism (VTE). Results of clinical trials4,5 and observational studies6 have been concordant in demonstrating an increased risk of VTE with oral exogenous HT. Recent studies suggest that VTE risk may be lower with transdermal than oral estrogen7 and with estrogen alone than with combined therapy.4 However, in the absence of rigorous evidence from large-scale clinical trials on differential effects by hormone formulation or route of delivery, should these findings influence clinical practice?Article p 840The Estrogen and Thromboembolism Risk (ESTHER) study,7 published in the current issue of Circulation, adds important, relevant data to bolster the case that HT type and route of delivery do indeed make a difference. This well-designed, French, multicenter case-control study of VTE enrolled 271 consecutive cases of VTE in women (age, 45 to 70 years) and matched them to hospital and community controls. Current HT use was present in 46% of the VTE cases compared with 37% of controls. Oral HT users had 4-fold-increased odds of VTE; however, there was no increased risk among transdermal hormone users (odds ratio, 0.9). Previous randomized trials have suggested that the risk of VTE may be higher with combined oral estrogen and progestogen therapy than with estrogen alone.4,5 In ESTHER, type of progestogen also appeared to influence risk of VTE. Neither micronized progesterone nor pregnane derivatives (including medroxyprogesterone acetate) were associated with VTE, whereas norpregnane derivatives were associated with a 4-fold increase in odds of VTE.The present study has several important strengths, including a large number of carefully adjudicated cases, a population with a large percent of transdermal estrogen users, and a wide variety of progestogen types. Similar data on the relationship of clinical end points to route of estrogen and type of progestogen would not be readily obtainable in the United States, where transdermal preparations and alternate types of progestogens constitute a relatively small proportion of total HT use. Because of small numbers, cases and controls using nortestosterone derivatives were excluded from the main analyses, although a significantly increased risk also was observed in this group.As for any observational or case-control study, selection and confounding biases must be considered. Reasons for choosing a particular progestogen in this population are unknown, so it is possible that clinical factors could have contributed to this choice and the observed risks. As the authors point out, norpregnane derivatives often are used for premenopausal women, those with hyperestrogenic symptoms, or those intolerant of estrogens; thus, prescription bias might partially explain the higher risk observed in this group because higher endogenous estrogens may be linked to VTE.8 Transdermal users in ESTHER also were older and had a longer duration of hormone use than oral users. Bias also could have arisen in the selection of controls.No large-scale randomized trials of transdermal estrogens in relation to VTE have been conducted. Results of observational studies on this subject warrant consideration, however. In addition to an earlier report from ESTHER,9 3 previous case-control studies with small numbers of cases using transdermal estrogen10–12 found no significant differences between oral and transdermal preparations and odds ratios of ≈2 for transdermal users compared with HT nonusers with wide CIs that included null.13 The observed VTE risks for oral estrogen and progestogen in ESTHER were higher than for the Women’s Health Initiative (WHI) randomized trial findings.4,5 Unlike the WHI, the ESTHER study examined only primary or idiopathic VTE; those with predisposing factors (including those with prior history of VTE; recent surgical intervention, immobilization, or bed rest for >8 days; or known cancer, thrombophilia, or systemic inflammatory disease) were excluded. If hormone use is a particularly strong risk factor for primary VTE, this might explain the higher risk observed for ESTHER, although selection biases are an alternate explanation and indicate the need for caution in interpreting the findings.Route of AdministrationThe data from ESTHER lend additional support to the evidence that route of estrogen administration matters. Transdermal preparations avoid the induction of hepatic protein synthesis associated with the first-pass effect of oral estrogens. Hypercoagulant effects (higher prothrombin fragment 1+2 and factor VII levels) and increased synthesis of C-reactive protein are observed after oral but not transdermal estrogen.14 Transdermal estradiol also avoids peaks and nadirs in circulating concentrations. Although the differences in rates of VTE with route of estrogen are intriguing, any extrapolation of these findings to other forms of cardiovascular disease should be undertaken with caution given the increased risk of cardiovascular disease events observed in the Papworth trial, a trial of transdermal estrogen for the secondary prevention of cardiovascular disease.15Type of ProgestogenWhy would the type of progestogen influence the risk of VTE? Although all progestogens share a protective effect on estrogen-primed endometrium, many other biological effects differ between formulations. The parent compounds differ for progestins and may determine many of the biological effects through differing activity on progesterone, androgen, glucocorticoid, and antimineralocorticoid receptors.16 Progestogen types may have different effects on lipids, markers of inflammation, coagulation, and thrombosis,16 but few direct comparisons exist. In a small study comparing medroxyprogesterone acetate and micronized progesterone, both significantly decreased tissue factor antigen and increased tissue factor activity, suggesting activation of coagulation pathways, and both lowered plasminogen activator-1 levels, demonstrating enhanced fibrinolysis.17 In the oral contraceptive literature, type of progestogen has been related to risk of VTE, with 19-nortestosterone derivatives particularly associated with higher risk of VTE.18 Thus, although not definitive, the ESTHER results should focus more attention on the particular properties of different progestogen formulations and their impact on clinical outcomes.DoseAlthough the authors did not specifically examine dose, this also should be considered in clinical practice. In observational studies, higher-dose oral contraceptives and higher-dose HT have been associated with significantly higher risk of VTE.18 Low-dose HT (0.3 mg conjugated equine estrogen) had significantly fewer effects on coagulation and inflammatory markers (prothrombin fragment 1+2, antithrombin III, and C-reactive protein) than conventional dose therapy.19 Thus, dose should remain a consideration when hormonal therapies are prescribed.Clinical Implications and Avenues for Future ResearchThe ESTHER study suggests that, at least for risk of VTE, both the route of estrogen administration and the choice of progestogen make a difference. The lower risk of VTE associated with transdermal compared with oral estradiol for postmenopausal HT raises the question of whether transdermal routes for contraceptives might also minimize the excess risk of VTE, although estrogen dosing and progestogen formulation also would have to be considered. For perimenopausal and postmenopausal HT, the present study suggests differences in VTE risk with route of estrogen administration and possibly progestogen type. Whether differences in other cardiovascular disease end points also might be affected by route of estrogen administration and type of progestogen should be tested in clinical trials, but such large-scale clinical trials are unlikely to be conducted in the near future. In the meantime, studies should look at biological intermediaries associated with different hormone regimens. The Kronos Early Estrogen Prevention Study (KEEPS) will offer one look at these differences. KEEPS is randomizing recently menopausal women to conjugated equine estrogens (0.45 mg) and micronized progesterone (200 mg) daily or to transdermal estradiol (50 μg) and micronized progesterone (200 mg) daily and evaluating changes in carotid intimal medial thickness, coronary artery calcium, and thrombotic, inflammatory, and other biomarkers.20 At present, the totality of evidence appears compelling enough to suggest that transdermal preparations be considered, among other factors relevant to decision making, when choosing an HT regimen. The findings from ESTHER remind us that HT is not a singular entity; we need to consider route, type, and dose of these complex agents in practice and in future research.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.DisclosuresNone.FootnotesCorrespondence to Kathryn M. Rexrode, MD, MPH, 900 Commonwealth Ave, 3rd Floor, Boston, MA 02215. E-mail [email protected] References 1 Women’s Health Initiative Steering Committee Writing Group for the Women’s Health Initiative Investigators. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004; 291: 1701–1712.CrossrefMedlineGoogle Scholar2 Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288: 321–333.CrossrefMedlineGoogle Scholar3 Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women: Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. JAMA. 1998; 280: 605–613.CrossrefMedlineGoogle Scholar4 Curb JD, Prentice RL, Bray PF, Langer RD, Van Horn L, Barnabei VM, Bloch MJ, Cyr MG, Gass M, Lepine L, Rodabough RJ, Sidney S, Uwaifo GI, Rosendaal FR. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch Intern Med. 2006; 166: 772–780.CrossrefMedlineGoogle Scholar5 Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, Rosendaal FR. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004; 292: 1573–1580.CrossrefMedlineGoogle Scholar6 Grodstein F, Stampfer MJ, Goldhaber SZ, Manson JE, Colditz GA, Speizer FE, Willett WC, Hennekens CH. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet. 1996; 348: 983–987.CrossrefMedlineGoogle Scholar7 Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Lévesque H, Trillot N, Barrellier M-T, Wahl D, Emmerich J, Scarabin P-Y; for the Estrogen and Thromboembolism Risk (ESTHER) Study. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007; 115: 840–845.LinkGoogle Scholar8 Simon T, Beau Yon de Jonage-Canonico M, Oger E, Wahl D, Conard J, Meyer G, Emmerich J, Barrellier MT, Guiraud A, Scarabin PY. Indicators of lifetime endogenous estrogen exposure and risk of venous thromboembolism. J Thromb Haemost. 2006; 4: 71–76.MedlineGoogle Scholar9 Scarabin PY, Oger E, Plu-Bureau G. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003; 362: 428–432.CrossrefMedlineGoogle Scholar10 Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet. 1996; 348: 977–980.CrossrefMedlineGoogle Scholar11 Perez Gutthann S, Garcia Rodriguez LA, Castellsague J, Duque Oliart A. Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. BMJ. 1997; 314: 796–800.CrossrefMedlineGoogle Scholar12 Varas-Lorenzo C, Garcia-Rodriguez LA, Cattaruzzi C, Troncon MG, Agostinis L, Perez-Gutthann S. Hormone replacement therapy and the risk of hospitalization for venous thromboembolism: a population-based study in southern Europe. Am J Epidemiol. 1998; 147: 387–390.CrossrefMedlineGoogle Scholar13 Douketis J. Hormone replacement therapy and risk for venous thromboembolism: what’s new and how do these findings influence clinical practice? Curr Opin Hematol. 2005; 12: 395–400.MedlineGoogle Scholar14 Vehkavaara S, Silveira A, Hakala-Ala-Pietila T, Virkamaki A, Hovatta O, Hamsten A, Taskinen MR, Yki-Jarvinen H. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost. 2001; 85: 619–625.CrossrefMedlineGoogle Scholar15 Clarke SC, Kelleher J, Lloyd-Jones H, Slack M, Schofiel PM. A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. BJOG. 2002; 109: 1056–1062.CrossrefMedlineGoogle Scholar16 Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Classification and pharmacology of progestins. Maturitas. 2003; 46 (suppl 1): S7–S16.MedlineGoogle Scholar17 Koh KK, Jin DK, Yang SH, Lee SK, Hwang HY, Kang MH, Kim W, Kim DS, Choi IS, Shin EK. Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women. Circulation. 2001; 103: 1961–1966.CrossrefMedlineGoogle Scholar18 Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med. 2004; 164: 1965–1976.CrossrefMedlineGoogle Scholar19 Koh KK, Shin MS, Sakuma I, Ahn JY, Jin DK, Kim HS, Kim DS, Han SH, Chung WJ, Shin EK. Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women. Arterioscler Thromb Vasc Biol. 2004; 24: 1516–1521.LinkGoogle Scholar20 Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N. KEEPS: The Kronos Early Estrogen Prevention Study. Climacteric. 2005; 8: 3–12.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Fitzgerald K and Glynn R (2013) Venous Thromboembolism Women and Health, 10.1016/B978-0-12-384978-6.00067-4, (1021-1037), . Miller V and Manson J (2013) Women’s Health Initiative Hormone Therapy Trials: New Insights on Cardiovascular Disease from Additional Years of Follow up, Current Cardiovascular Risk Reports, 10.1007/s12170-013-0305-1, 7:3, (196-202), Online publication date: 1-Jun-2013. Tremollieres F, Brincat M, Erel C, Gambacciani M, Lambrinoudaki I, Moen M, Schenck-Gustafsson K, Vujovic S, Rozenberg S and Rees M (2011) EMAS position statement: Managing menopausal women with a personal or family history of VTE, Maturitas, 10.1016/j.maturitas.2011.03.011, 69:2, (195-198), Online publication date: 1-Jun-2011. Jayachandran M, Preston C, Hunter L, Jahangir A, Owen W, Korach K and Miller V (2009) Loss of estrogen receptor β decreases mitochondrial energetic potential and increases thrombogenicity of platelets in aged female mice, AGE, 10.1007/s11357-009-9119-y, 32:1, (109-121), Online publication date: 1-Mar-2010. Miller V, Black D, Brinton E, Budoff M, Cedars M, Hodis H, Lobo R, Manson J, Merriam G, Naftolin F, Santoro N, Taylor H and Harman S (2009) Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS), Journal of Cardiovascular Translational Research, 10.1007/s12265-009-9104-y, 2:3, (228-239), Online publication date: 1-Sep-2009. Canonico M and Scarabin P (2009) Hormone therapy and risk of venous thromboembolism among postmenopausal women, Climacteric, 10.1080/13697130903006837, 12:sup1, (76-80), Online publication date: 1-Jan-2009. Vitale C, Mercuro G, Cerquetani E, Marazzi G, Patrizi R, Pelliccia F, Volterrani M, Fini M, Collins P and Rosano G (2007) Time Since Menopause Influences the Acute and Chronic Effect of Estrogens on Endothelial Function, Arteriosclerosis, Thrombosis, and Vascular Biology, 28:2, (348-352), Online publication date: 1-Feb-2008. Chalhoub V, Edelman P, Staiti G and Benhamou D (2008) Contraception orale, traitement hormonal de la ménopause : risque thromboembolique et implications périopératoires, Annales Françaises d'Anesthésie et de Réanimation, 10.1016/j.annfar.2008.04.002, 27:5, (405-415), Online publication date: 1-May-2008. Rathbun S (2008) Venous thromboembolism in women, Vascular Medicine, 10.1177/1358863X07085404, 13:3, (255-266), Online publication date: 1-Aug-2008. Canonico M and Scarabin P (2008) Traitement hormonal de la ménopause et risque de thrombose veineuse, médecine/sciences, 10.1051/medsci/2008243228, 24:3, (228-231), Online publication date: 1-Mar-2008. Podmore S, Botha J, Gray A and Esterhuizen T (2014) Impact of recent evidence on the use of hormone therapy in the South African private sector (2001–2005), South African Family Practice, 10.1080/20786204.2008.10873780, 50:6, (42-42d), Online publication date: 1-Nov-2008. Haas E, Meyer M, Schurr U, Bhattacharya I, Minotti R, Nguyen H, Heigl A, Lachat M, Genoni M and Barton M (2007) Differential Effects of 17β-Estradiol on Function and Expression of Estrogen Receptor α, Estrogen Receptor β, and GPR30 in Arteries and Veins of Patients With Atherosclerosis, Hypertension, 49:6, (1358-1363), Online publication date: 1-Jun-2007. Caufriez A (2007) Hormonal replacement therapy (HRT) in postmenopause: a reappraisal, Annales d'Endocrinologie, 10.1016/j.ando.2007.06.015, 68:4, (241-250), Online publication date: 1-Sep-2007. Grey A (2007) Emerging pharmacologic therapies for osteoporosis, Expert Opinion on Emerging Drugs, 10.1517/14728214.12.3.493, 12:3, (493-508), Online publication date: 1-Sep-2007. February 20, 2007Vol 115, Issue 7 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.106.675405PMID: 17309929 Originally publishedFebruary 20, 2007 Keywordswomenhormonesvenous thrombosisEditorialsPDF download Advertisement SubjectsEpidemiology" @default.
• W2156572025 created "2016-06-24" @default.
• W2156572025 creator A5049411008 @default.
• W2156572025 creator A5079743437 @default.
• W2156572025 date "2007-02-20" @default.
• W2156572025 modified "2023-10-17" @default.
• W2156572025 title "Are Some Types of Hormone Therapy Safer Than Others?" @default.
• W2156572025 cites W1586699954 @default.
• W2156572025 cites W1593442063 @default.
• W2156572025 cites W1841210688 @default.
• W2156572025 cites W2000836832 @default.
• W2156572025 cites W2021062942 @default.
• W2156572025 cites W2024947181 @default.
• W2156572025 cites W2070500804 @default.
• W2156572025 cites W2090177155 @default.
• W2156572025 cites W2091232445 @default.
• W2156572025 cites W2107766028 @default.
• W2156572025 cites W2113264115 @default.
• W2156572025 cites W2118379947 @default.
• W2156572025 cites W2126595069 @default.
• W2156572025 cites W2149877121 @default.
• W2156572025 cites W2154151283 @default.
• W2156572025 cites W2169148439 @default.
• W2156572025 doi "https://doi.org/10.1161/circulationaha.106.675405" @default.
• W2156572025 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17309929" @default.
• W2156572025 hasPublicationYear "2007" @default.
• W2156572025 type Work @default.
• W2156572025 sameAs 2156572025 @default.
• W2156572025 citedByCount "17" @default.
• W2156572025 countsByYear W21565720252013 @default.
• W2156572025 crossrefType "journal-article" @default.
• W2156572025 hasAuthorship W2156572025A5049411008 @default.
• W2156572025 hasAuthorship W2156572025A5079743437 @default.
• W2156572025 hasBestOaLocation W21565720251 @default.
• W2156572025 hasConcept C121608353 @default.
• W2156572025 hasConcept C126322002 @default.
• W2156572025 hasConcept C177713679 @default.
• W2156572025 hasConcept C2776654903 @default.
• W2156572025 hasConcept C2780275930 @default.
• W2156572025 hasConcept C38652104 @default.
• W2156572025 hasConcept C41008148 @default.
• W2156572025 hasConcept C530470458 @default.
• W2156572025 hasConcept C71924100 @default.
• W2156572025 hasConcept C98274493 @default.
• W2156572025 hasConceptScore W2156572025C121608353 @default.
• W2156572025 hasConceptScore W2156572025C126322002 @default.
• W2156572025 hasConceptScore W2156572025C177713679 @default.
• W2156572025 hasConceptScore W2156572025C2776654903 @default.
• W2156572025 hasConceptScore W2156572025C2780275930 @default.
• W2156572025 hasConceptScore W2156572025C38652104 @default.
• W2156572025 hasConceptScore W2156572025C41008148 @default.
• W2156572025 hasConceptScore W2156572025C530470458 @default.
• W2156572025 hasConceptScore W2156572025C71924100 @default.
• W2156572025 hasConceptScore W2156572025C98274493 @default.
• W2156572025 hasIssue "7" @default.
• W2156572025 hasLocation W21565720251 @default.
• W2156572025 hasLocation W21565720252 @default.
• W2156572025 hasLocation W21565720253 @default.
• W2156572025 hasOpenAccess W2156572025 @default.
• W2156572025 hasPrimaryLocation W21565720251 @default.
• W2156572025 hasRelatedWork W1994962682 @default.
• W2156572025 hasRelatedWork W2040325131 @default.
• W2156572025 hasRelatedWork W2089013277 @default.
• W2156572025 hasRelatedWork W2156572025 @default.
• W2156572025 hasRelatedWork W2426745713 @default.
• W2156572025 hasRelatedWork W2748952813 @default.
• W2156572025 hasRelatedWork W2899084033 @default.
• W2156572025 hasRelatedWork W2970019813 @default.
• W2156572025 hasRelatedWork W3131607753 @default.
• W2156572025 hasRelatedWork W4250188085 @default.
• W2156572025 hasVolume "115" @default.
• W2156572025 isParatext "false" @default.
• W2156572025 isRetracted "false" @default.
• W2156572025 magId "2156572025" @default.
• W2156572025 workType "article" @default.