Effects of intranasal 17β-estradiol administration on serum bioactive interleukin-6 and C-reactive protein levels in healthy postmenopausal women
Menopause The Journal of The North American Menopause SocietyPublished 9 August 2006
Dominik Rachoń, K Suchecka-Rachoń, Łukasz Hak, Jolanta Myśliwska
Citations229
SJR quartileQ1
SJR score1.14
SNIP1.12
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The results of this study show that intranasal, similarly to transdermal, E2 administration does not increase serum CRP levels in postmenopausal women, and support the hypothesis that CRP increase during oral estrogen treatment is not mediated by the enhancement of interleukin-6 production by the immune cells but is rather caused by the hepatic first-pass metabolism effect.
Abstract
The results of our study show that intranasal, similarly to transdermal, E2 administration does not increase serum CRP levels in postmenopausal women. They also support the hypothesis that CRP increase during oral estrogen treatment is not mediated by the enhancement of interleukin-6 production by the immune cells but is rather caused by the hepatic first-pass metabolism effect.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
JAMARisks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial
15,680 Citations2002Jacques E. Rossouw
Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
JAMARandomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women
6,229 Citations1998Stephen B. Hulley
Treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease and the treatment did increase the rate of thromboembolic events and gallbladder disease.
New England Journal of MedicineC-Reactive Protein and Other Markers of Inflammation in the Prediction of Cardiovascular Disease in Women
5,786 Citations2000Paul M. Ridker, Charles H. Hennekens +2 more
The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.
Immunology TodayThe acute phase response
2,901 Citations1994Heinz Baumann, Jack Gauldie
This review outlines the principal cellular and molecular mechanisms that control initiation of the tissue response at the site of injury, the recruitment of the systemic defense mechanisms, the acute phase response of the liver and the resolution of the acutephase response.
Biochemical JournalInterleukin-6 and the acute phase response
2,746 Citations1990Peter C. Heinrich, José V. Castell +1 more
Systemic reaction characterized by fever, leukocytosis, increase in erythrocyte sedimentation rate, increases in LeucocyTosis secretion of ACTH and glucocorticoids, and by dramatic changes in the concentration of some plasma ,l' proteins.
Arteriosclerosis Thrombosis and Vascular BiologyC-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction
2,463 Citations1999John Yudkin, Coen D.A. Stehouwer +2 more
The data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not.
CirculationPlasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men
2,431 Citations2000Paul M. Ridker, Nader Rifai +2 more
A role for cytokine-mediated inflammation in the early stages of atherogenesis is supported in apparently healthy men, and elevated levels of IL-6 are associated with increased risk of future MI.
CirculationDirect Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells
1,940 Citations2000Vincenzo Pasceri, James T. Willerson +1 more
The hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of Atherosclerosis is supported.
BloodC-reactive protein induces human peripheral blood monocytes to synthesize tissue factor
831 Citations1993Jaroslav Čermák, NS Key +4 more
C-reactive protein (CRP), an acute- phase reactant that markedly increases its serum concentration in response to inflammatory stimuli, induced monocytes to express tissue factor (TF), a potent procoagulant.
HepatologyAcute-phase response of human hepatocytes: Regulation of acute-phase protein synthesis by interleukin-6
756 Citations1990José V. Castell, Marı́a José Gómez-Lechón +4 more
In pulse‐chase experiments it was shown that the time course of the disappearance of the acute‐phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin‐6, suggesting that recombinantinterleuk in‐6 exerts its regulatory effect on acute‐ phase protein synthesis at the pretranslational level.
JAMAInflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease
671 Citations2002Aruna D. Pradhan, JoAnn E. Manson +8 more
These prospective findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP.
CirculationElevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease
671 Citations2000Stephan Fichtlscherer, Gunter Rosenberger +4 more
Normalization of elevated CRP levels over time was associated with a normalization of endothelium-mediated forearm blood flow responses after 3 months, which might provide an important clue to link a systemic marker of inflammation to atherosclerotic disease progression.
CirculationEffect of Postmenopausal Hormones on Inflammation-Sensitive Proteins
668 Citations1999Mary Cushman, Claudine Legault +6 more
The Postmenopausal Estrogen/Progestin Interventions Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors, found postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein.
Annual Review of Public HealthHORMONE REPLACEMENT THERAPY, HEART DISEASE, AND OTHER CONSIDERATIONS
594 Citations1998Elizabeth Barrett‐Connor, Deborah Grady
Until findings from randomized trials confirm and quantitate the benefit of estrogen therapy for prevention of CHD, it is believed it should not be recommended to all postmenopausal women.
Arteriosclerosis Thrombosis and Vascular BiologyC-Reactive Protein Frequently Colocalizes With the Terminal Complement Complex in the Intima of Early Atherosclerotic Lesions of Human Coronary Arteries
564 Citations1998Jan Torzewski, Michael Torzewski +6 more
The data suggest that CRP may promote atherosclerotic lesion formation by activating the complement system and being involved in foam cell formation as well as in the deep fibroelastic layer and in the fibromuscular layer of the intima adjacent to the media.
CirculationHormone Replacement Therapy and Increased Plasma Concentration of C-Reactive Protein
446 Citations1999Paul M. Ridker, Charles H. Hennekens +3 more
In this cross-sectional survey, CRP levels were increased among apparently healthy postmenopausal women taking HRT, and the potential impact of HRT on inflammatory parameters should be investigated in ongoing clinical trials.
The Journal of Clinical Endocrinology & MetabolismThe Effects of Hormone Replacement Therapy and Raloxifene on C-Reactive Protein and Homocysteine in Healthy Postmenopausal Women: A Randomized, Controlled Trial1
331 Citations2000Brian W. Walsh, Sofia Paul +5 more
HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women, and the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.
Thrombosis and HaemostasisEffects of Oral and Transdermal Estrogen Replacement Therapy on Markers of Coagulation, Fibrinolysis, Inflammation and Serum Lipids and Lipoproteins in Postmenopausal Women
270 Citations2001Satu Vehkavaara, Angela Silveira +6 more
Oral estradiol increased markers of fibrinolytic activity, decreased serum soluble E-selectin levels and induced potentially antiatherogenic changes in lipids and lipoproteins, and changed markers of coagulation towards hypercoagulability, and increased serum CRP concentrations.
The Journal of ImmunologyCRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes
232 Citations1996Gertjan Wolbink, Mieke C. Brouwer +3 more
Measurement of complement-CRP complexes provides a suitable tool to study CRP-mediated activation of complement in vivo, and increased levels of these complexes occur in clinical samples, indicating that CRP may induce activation of complementary protein in vivo.
CirculationInterferon-γ and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by C-Reactive Protein
180 Citations2000Akihiro Nakagomi, Ben Freedman +1 more
There was a striking positive correlation between age and monocyte TF induction, with a dramatic rise on monocytes from postmenopausal women that was not apparent on cells from women taking HRT, which may contribute to age and sex differences in coronary events and to the protective effects of HRT.
The Journal of Clinical Endocrinology & MetabolismHormone Replacement Therapy and Interrelation between Serum Interleukin-6 and Body Mass Index in Postmenopausal Women: A Population-Based Study
163 Citations2000Rainer H. Straub, H. W. Hense +4 more
Journal of the American College of CardiologyDifferential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women
152 Citations2003Wanpen Vongpatanasin, Meryem Tuncel +4 more
In postmenopausal women, oral but not transdermal ET increased CRP by a first-pass hepatic effect, and the route of administration may be an important consideration in minimizing the adverse effects of ET on cardiovascular outcomes.
Thrombosis and HaemostasisIncreased C-reactive Protein Levels during Short-term Hormone Replacement Therapy in Healthy Postmenopausal Women
143 Citations1999Marchien van Baal, Peter Kenemans +4 more
In healthy postmenopausal women, short-term treatment with E2 or E2+P was associated with a rapid rise in CRP concentrations, raising the possibility that the increased risk of cardiovascular events is related to an initial increase inCRP levels after starting hormone replacement therapy.
CirculationIncreased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response
129 Citations2003Antonello Silvestri, Otávio Gebara +7 more
The discrepancy between increased Plasma levels of CRP and reduced plasma levels of all other markers of inflammation suggests that the increased CRP levels after oral HRT may be related to metabolic hepatic activation and not to an acute-phase response.
CirculationEffect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women
121 Citations2002Andrea DeCensi, U. Omodei +10 more
In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment, and the implications for early risk of coronary heart disease require further studies.
Journal of EndocrinologyEffects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women
113 Citations2002Dominik Rachoń, Jolanta Myśliwska +3 more
It is suspected that the late complications of oestrogen deficiency, such as osteoporosis, coronary heart disease and Alzheimer's disease, may be mediated by an exaggerated production of IL-6 - a cytokine which seems to play a pivotal role in the pathogenesis of these age-related diseases.
Journal of Leukocyte BiologyC-reactive protein increases production of IL-1α, IL-1β, and TNF-α, and expression of mRNA by human alveolar macrophages
107 Citations1993Béatrice Galve-de Rochemonteix, Krzysztof Wiktorowicz +2 more
It is suggested that one of the fimctions of CRP may be to stimulate the production of IL‐1 and TNF by macrophages at inflammatory sites where alterations of capillary permeability combined with an increased serum level lead to enhanced local concentrations of this acute‐phase protein.
CirculationEffect of Medroxyprogesterone Acetate on Vascular Inflammatory Markers in Postmenopausal Women Receiving Estrogen
98 Citations2002Akihiko Wakatsuki, Yuji Okatani +2 more
The LancetEfficacy and acceptability of intranasal 17 β-oestradiol for menopausal symptoms: randomised dose-response study
93 Citations1999John Studd, Bruno Pornel +5 more
S21400 dose-dependently decreased KI is significantly better than placebo; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated.
The LancetHormone replacement therapy and sensitive C-reactive protein concentrations in women with type-2 diabetes
86 Citations1999Naveed Sattar, Mahesh Perera +2 more
A combination of transdermal oestradiol 80 microg with continuous oral norethisterone 1 mg significantly reduced C-reactive protein concentrations in postmenopausal women with type-2 diabetes.
CirculationStatin Attenuates Increase in C-Reactive Protein During Estrogen Replacement Therapy in Postmenopausal Women
79 Citations2002Kwang Kon Koh, William H. Schenke +3 more
The combination of statin with estrogen may attenuate the potential harmful effects of estrogen therapy in postmenopausal women and maximize any benefit to cardiovascular risk.
The American Journal of CardiologyRole of tumor necrosis factor-α and interleukin-6 in the effects of hormone replacement therapy and raloxifene on C-reactive protein in postmenopausal women
71 Citations2001Brian W. Walsh, David A. Cox +4 more
Journal of Toxicology and Environmental HealthComparative metabolism of 17α‐ethynyl steroids used in oral contraceptives
59 Citations1977R. E. Ranney
The metabolism of mestranol, ethyl moiety at the C-13 position appears to slow the metabolism of this steroid so that biotransformation to more polar metabolites and conjugation of these steroids does not proceed as rapidly as that of the other progestins.
American Journal of Obstetrics and GynecologyHormone replacement therapy: Estrogen and progestin effects on plasma C-reactive protein concentrations
57 Citations2002Sven O. Skouby, Jørgen Gram +4 more
HRT resulted in a significant increase in CRP concentrations in the women receiving the continuous combination of E2V plus norethindrone acetate and the continuous regimen of E 2V plus local delivery of levonorgestrel, and both the estrogen and the progestin component are of importance for the change.
Thrombosis and HaemostasisEffects of Transdermal and Oral Oestrogen Replacement Therapy on C-Reactive Protein Levels in Postmenopausal Women: A Randomised, Placebo-Controlled Trial
45 Citations2002Marinka S. Post, Coen D.A. Stehouwer +5 more
Oral E2 significantly increased CRP levels, which was larger than the increase found during oral E2 + G, and did not affect transdermal E2 levels.
MaturitasHormone replacement therapy, C-reactive protein, and fibrinogen in healthy postmenopausal women
39 Citations2003Mehmet Yılmazer, Veysel Fenkçi +5 more
These elevated levels of CRP, which appears very recently as a crucial marker for cardiovascular disease, may be responsible for the early increased cardiovascular risk after starting oral combined HRT, but this increased risk in the early period seems to decrease with long-term use.
The American Journal of CardiologyDiffering effects of oral and transdermal hormone replacement therapy on cardiovascular risk factors in healthy postmenopausal women
38 Citations2003Timo Strandberg, Olavi Ylikorkala +1 more
The aim of the present investigation was to compare the effects of oral and transdermal HRT on serum lipids, glucose, and insulin as well as the novel cardiovascular risk factor serum highly sensitive C-reactive protein (hs-CRP7) in healthy postmenopausal women.
Thrombosis and HaemostasisOral Ethinyl Estradiol, but not Transdermal 17β-estradiol, Increases Plasma C-reactive Protein Levels in Men
33 Citations2000Erik J. Giltay, Louis Gooren +3 more
The American Journal of CardiologyEffect of hormonal replacement therapy on C-reactive protein and cell-adhesion molecules in postmenopausal women
27 Citations2003Stefania Lamon‐Fava, Borbala Posfai +1 more
A randomized, double-blind, placebo-controlled, crossover study comparing the effects of conjugated equine estrogen (CEE) and the combination of CEE and MPA in postmenopausal women, the most frequently prescribed progestin, on the regulation of cell-adhesion molecules and CRP levels is performed.
MetabolismDoes the type of hormone replacement therapy affect lipoprotein (a), homocysteine, and C-reactive protein levels in postmenopausal women?
27 Citations2004H. Bukowska, Stanisław Stanosz +5 more
In women in the early postmenopausal stage with normal initial concentrations of Lp(a) and homocysteine, the form of therapy used has no influence on values of these parameters, and a tendency to increase CRP values when using oral HRT is observed, while such an effect is not observed in case of transdermal therapy after 3 months.
The Journal of Clinical Endocrinology & MetabolismLevels of Serum C-Reactive Protein during Oral and Transdermal Estradiol in Postmenopausal Women with and without a History of Intrahepatic Cholestasis of Pregnancy
19 Citations2005Anne Ropponen, Kristiina Aittomäki +2 more
The synthesis of CRP is readily and dose dependently stimulated by oral but not by transdermal E2 in as soon as 2 wk, and this response was unaffected by a history of ICP or the use of MPA.
MaturitasPrevention of postmenopausal bone loss by pulsed estrogen therapy: comparison with transdermal route
9 Citations2004Pierre D. Delmas, L Marianowski +5 more
Pulsed estrogen therapy was as effective in normalizing bone turnover and preventing postmenopausal bone loss as a reservoir patch.