Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Diabetologia
Erschienen in: Diabetologia 10/2007

01.10.2007 | Article

Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study

verfasst von: E. L. Ding, Y. Song, J. E. Manson, N. Rifai, J. E. Buring, S. Liu

Erschienen in: Diabetologia | Ausgabe 10/2007

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Prospective data directly investigating the role of endogenous sex hormones in diabetes risk have been scant, particularly in women. We aimed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes in postmenopausal women.

Methods

We conducted a prospective, nested case–control study of plasma oestradiol, testosterone and dehydroepiandrosterone sulfate and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause. Among women not using hormone therapy and free of baseline cardiovascular disease, cancer and diabetes, 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years.

Results

Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes. After adjustment for BMI, family history, lifestyle and reproductive variables, the multivariable relative risks (95% CI) comparing the highest vs lowest quintile were 12.6 (2.83–56.3) for total oestradiol (p = 0.002 for trend), 13.1 (4.18–40.8) for free oestradiol (p < 0.001 for trend), 4.15 (1.21–14.2) for total testosterone (p = 0.019 for trend) and 14.8 (4.44–49.2) for free testosterone (p < 0.001 for trend). These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA1c levels.

Conclusions/interpretation

In postmenopausal women, higher plasma levels of oestradiol and testosterone were strongly and prospectively related to increased risk of developing type 2 diabetes. These prospective data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes.
ClinicalTrials.gov ID no.: NCT00000479.
Literatur
1.
Ding EL, Song Y, Malik VS, Liu S (2006) Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295:1288–1299PubMedCrossRef
2.
Golden SH, Dobs AS, Vaidya D, et al (2007) Endogenous sex hormones and glucose tolerance status in postmenopausal women. J Clin Endocrinol Metab 92:1289–1295PubMedCrossRef
3.
Joffe HV, Ridker PM, Manson JE, Cook NR, Buring JE, Rexrode KM (2006) Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease. Ann Epidemiol 16:105–112PubMedCrossRef
4.
Sowers MR, Jannausch M, Randolph JF, et al (2005) Androgens are associated with hemostatic and inflammatory factors among women at the mid-life. J Clin Endocrinol Metab
5.
Dhatariya K, Bigelow ML, Nair KS (2005) Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes 54:765–769PubMedCrossRef
6.
Villareal DT, Holloszy JO (2004) Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. Jama 292:2243–2248PubMedCrossRef
7.
Nair KS, Rizza RA, O’Brien P, et al (2006) DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 355:1647–1659PubMedCrossRef
8.
Basu R, Man CD, Campioni M, et al (2007) Two years of treatment with dehydroepiandrosterone does not improve insulin secretion, insulin action, or postprandial glucose turnover in elderly men or women. Diabetes 56:753–766PubMedCrossRef
9.
Liu S, Lee IM, Song Y, et al (2006) Vitamin E and risk of type 2 diabetes in the women’s health study randomized controlled trial. Diabetes 55:2856–2862PubMedCrossRef
10.
Wacholder S, Silverman DT, McLaughlin JK, Mandel JS (1992) Selection of controls in case-control studies. Parts I–III. Am J Epidemiol 135:1019–1050PubMed
11.
Ding EL, Song Y, Manson JE, Pradhan AD, Buring JE, Liu S (2007) Accuracy of administrative coding for type 2 diabetes in children, adolescents, and young adults–response to Rhodes et al. Diabetes Care 30 (in press)
12.
Kley HK, Schlaghecke R, Kruskemper HL (1985) Stability of steroids in plasma over a 10-year period. J Clin Chem Clin Biochem 23:875–878PubMed
13.
Bolelli G, Muti P, Micheli A, et al (1995) Validity for epidemiological studies of long-term cryoconservation of steroid and protein hormones in serum and plasma. Cancer Epidemiol Biomarkers Prev 4:509–513PubMed
14.
Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, Speizer FE (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2–3-year period. Cancer Epidemiol Biomarkers Prev 4:649PubMed
15.
Sanchez-Carbayo M, Mauri M, Alfayate R, Miralles C, Soria F (1998) Elecsys testosterone assay evaluated. Clin Chem 44:1744–1746PubMed
16.
Yang DT, Owen WE, Ramsay CS, Xie H, Roberts WL (2004) Performance characteristics of eight estradiol immunoassays. Am J Clin Pathol 122:332–337PubMedCrossRef
17.
Blake GJ, Pradhan AD, Manson JE, et al (2004) Hemoglobin A1c level and future cardiovascular events among women. Arch Intern Med 164:757–761PubMedCrossRef
18.
Ridker PM, Rifai N, Rose L, Buring JE, Cook NR (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347:1557–1565PubMedCrossRef
19.
Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810PubMedCrossRef
20.
Rinaldi S, Geay A, Dechaud H, et al (2002) Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. Cancer Epidemiol Biomarkers Prev 11:1065–1071PubMed
21.
Endogenous Hormones and Breast Cancer Collaborative Group (2003) Free estradiol and breast cancer risk in postmenopausal women: comparison of measured and calculated values. Cancer Epidemiol Biomarkers Prev 12:1457–1461
22.
Oh JY, Barrett-Connor E, Wedick NM, Wingard DL (2002) Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care 25:55–60PubMedCrossRef
23.
Rincon J, Holmang A, Wahlstrom EO, et al (1996) Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes 45:615–621PubMedCrossRef
24.
Bjorntorp P (1996) The regulation of adipose tissue distribution in humans. Int J Obes Relat Metab Disord 20:291–302PubMed
25.
Polderman KH, Gooren LJ, Asscheman H, Bakker A, Heine RJ (1994) Induction of insulin resistance by androgens and estrogens. J Clin Endocrinol Metab 79:265–271PubMedCrossRef
26.
Lovejoy JC, Bray GA, Bourgeois MO, et al (1996) Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women—a clinical research center study. J Clin Endocrinol Metab 81:2198–2203PubMedCrossRef
27.
Gambineri A, Pagotto U, Tschop M, et al (2003) Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome. J Endocrinol Invest 26:629–634PubMed
28.
Ibanez L, Valls C, Ferrer A, Ong K, Dunger DB, De Zegher F (2002) Additive effects of insulin-sensitizing and anti-androgen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. J Clin Endocrinol Metab 87:2870–2874PubMedCrossRef
29.
Kalish GM, Barrett-Connor E, Laughlin GA, Gulanski BI (2003) Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial. J Clin Endocrinol Metab 88:1646–1652PubMedCrossRef
30.
Kanaya AM, Herrington D, Vittinghoff E, et al (2003) Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 138:1–9PubMed
31.
Margolis KL, Bonds DE, Rodabough RJ, et al (2004) Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women’s Health Initiative Hormone Trial. Diabetologia 47:1175–1187PubMedCrossRef
32.
Bonds DE, Lasser N, Qi L, et al (2006) The effect of conjugated equine oestrogen on diabetes incidence: the Women’s Health Initiative randomised trial. Diabetologia 49:459–468PubMedCrossRef
33.
O’Sullivan AJ, Crampton LJ, Freund J, Ho KK (1998) The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women. J Clin Invest 102:1035–1040PubMedCrossRef
34.
Strandberg TE, Ylikorkala O, Tikkanen MJ (2003) Differing effects of oral and transdermal hormone replacement therapy on cardiovascular risk factors in healthy postmenopausal women. Am J Cardiol 92:212–214PubMedCrossRef
35.
Vehkavaara S, Silveira A, Hakala-Ala-Pietila T et al (2001) Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost 85:619–625PubMed
36.
Selby P, McGarrigle HH, Peacock M (1989) Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women. Clin Endocrinol (Oxf) 30:241–249
37.
Vehkavaara S, Hakala-Ala-Pietila T, Virkamaki A et al (2000). Differential effects of oral and transdermal estrogen replacement therapy on endothelial function in postmenopausal women. Circulation 102:2687–2693PubMed
38.
Decensi A, Omodei U, Robertson C et al (2002) Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women. Circulation 106:1224–1228PubMedCrossRef
39.
Ding EL, Song Y, Liu S (2006) Testosterone, Estradiol and Type 2 Diabetes—Reply. JAMA 296:169–170CrossRef
40.
Espeland MA, Hogan PE, Fineberg SE et al (1998) Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Diabetes Care 21:1589–1595PubMedCrossRef
41.
Hemelaar M, van der Mooren MJ, van Baal WM, Schalkwijk CG, Kenemans P, Stehouwer CD (2005) Effects of transdermal and oral postmenopausal hormone therapy on vascular function: a randomized, placebo-controlled study in healthy postmenopausal women. Menopause 12:526–535PubMedCrossRef
42.
Song Y, Manson JE, Tinker L et al (2007) Circulating levels of endothelial adhesion molecules and risk of diabetes mellitus in an ethnically diverse cohort of women. Diabetes 56:1898–1904PubMedCrossRef
43.
Cagnacci A, Soldani R, Carriero PL, Paoletti AM, Fioretti P, Melis GB (1992) Effects of low doses of transdermal 17 beta-estradiol on carbohydrate metabolism in postmenopausal women. J Clin Endocrinol Metab 74:1396–1400PubMedCrossRef
44.
Matute ML, Kalkhoff RK (1971) Sex steroid influence on hepatic gluconeogenesis and glycogen formation. J Lab Clin Med 78:997–998PubMed
45.
Larsson-Cohn U, Wallentin L (1977) Metabolic and hormonal effects of post-menopausal oestrogen replacement treatment. I. Glucose, insulin and human growth hormone levels during oral glucose tolerance tests. Acta Endocrinol (Copenh) 86:583–596
46.
De Cleyn K, Buytaert P, Coppens M (1989) Carbohydrate metabolism during hormonal substitution therapy. Maturitas 11:235–242PubMedCrossRef
47.
Lindheim SR, Presser SC, Ditkoff EC, Vijod MA, Stanczyk FZ, Lobo RA (1993) A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin. Fertil Steril 60:664–667PubMed
48.
Kojima T, Lindheim SR, Duffy DM, Vijod MA, Stanczyk FZ, Lobo RA (1993) Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives. Am J Obstet Gynecol 169:1540–1544PubMed
49.
Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A (2006) The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect 114:106–112PubMedCrossRef
50.
Mahabir S, Baer DJ, Johnson LL et al (2006) Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women. Cancer Epidemiol Biomarkers Prev 15:2502–2507PubMedCrossRef
Metadaten
Titel
Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study
verfasst von
E. L. Ding
Y. Song
J. E. Manson
N. Rifai
J. E. Buring
S. Liu
Publikationsdatum
01.10.2007
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 10/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0785-y

Weitere Artikel der Ausgabe 10/2007

Diabetologia 10/2007 Zur Ausgabe

Article

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

Short Communication

Adiponectin levels do not predict clinical onset of type 1 diabetes in antibody-positive relatives

Article

An adenylate kinase is involved in KATP channel regulation of mouse pancreatic beta cells

Research Letter

Regulation of retinol binding protein 4 production in primary human adipocytes by adiponectin, troglitazone and TNF-α

Erratum

The BioBreeding rat diabetes model is infected with Ljungan virus

Research Letter

Analysis of the obesity gene FTO in 14,803 type 1 diabetes cases and controls

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise