This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duncan, A. C. Articles by Lumsden, M. A. Search for Related Content PubMed PubMed Citation Articles by Duncan, A. C. Articles by Lumsden, M. A.

The Effect of Estradiol and a Combined Estradiol/Progestagen Preparation on Insulin Sensitivity in Healthy Postmenopausal Women

Department of Obstetrics and Gynecology, Queen Mother’s Hospital (A.C.D., H.L., R.N.R., M.J.P., S.M., D.M.H., M.A.L.), Yorkhill, Glasgow, United Kingdom G3 8SJ; and the Department of Medicine and Therapeutics, Western Infirmary (J.R.P., J.M.C.C.), Glasgow, United Kingdom G11 8NT

Address all correspondence and requests for reprints to: Dr. M. A. Lumsden, Department of Obstetrics and Gynecology, The Queen Mother’s Hospital, Yorkhill, Glasgow, United Kingdom G3 8SJ.

Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result in an improvement in these parameters, although progestagens may antagonize these effects. We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause. After baseline measurements, subjects were randomized to receive either transdermal 17ß-estradiol (50 µg) or matching placebo patches for 6 weeks. The subjects were then further randomized to receive either estradiol in combination with oral norethisterone (1 mg) or a matching oral placebo preparation, crossing over after 6 weeks, with assessment of insulin sensitivity at the end of each treatment. No significant increase in insulin sensitivity was observed after 6 weeks of transdermal 17ß-estradiol treatment (95% confidence interval, -0.54, 1.86; P = 0.27). Addition of norethisterone for a further 6 weeks had no detectable effect on insulin sensitivity (95% confidence interval, -1.65, 1.10; P = 0.65). The results of this study using transdermal estradiol do not support previous reports that unopposed estrogens exert potentially beneficial effects on insulin sensitivity and suggest that the addition of an oral progestagen confers no clinically important risk or benefit. It is therefore unlikely that effects on insulin sensitivity contribute appreciably to the cardioprotective benefits attributed to hormone replacement therapy.

This article has been cited by other articles:

				M. J. Toth, B. C. Cooper, R. E. Pratley, A. Mari, D. E. Matthews, and P. R. Casson Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1035 - E1045. [Abstract] [Full Text] [PDF]

				R. E. van Genugten, K. M. Utzschneider, J. Tong, F. Gerchman, S. Zraika, J. Udayasankar, E. J. Boyko, W. Y. Fujimoto, S. E. Kahn, and and the American Diabetes Association GENNID Study Effects of Sex and Hormone Replacement Therapy Use on the Prevalence of Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance in Subjects With a Family History of Type 2 Diabetes Diabetes, December 1, 2006; 55(12): 3529 - 3535. [Abstract] [Full Text] [PDF]

				H. Gao, G. Bryzgalova, E. Hedman, A. Khan, S. Efendic, J.-A. Gustafsson, and K. Dahlman-Wright Long-Term Administration of Estradiol Decreases Expression of Hepatic Lipogenic Genes and Improves Insulin Sensitivity in ob/ob Mice: A Possible Mechanism Is through Direct Regulation of Signal Transducer and Activator of Transcription 3 Mol. Endocrinol., June 1, 2006; 20(6): 1287 - 1299. [Abstract] [Full Text] [PDF]

				D.-J. Kim and E. Barrett-Connor Association of serum proinsulin with hormone replacement therapy in nondiabetic older women: the rancho bernardo study. Diabetes Care, March 1, 2006; 29(3): 618 - 624. [Abstract] [Full Text] [PDF]

				L. M C. S M Leao, M. P. C Duarte, D. M. B Silva, P. R. V Bahia, C. M. Coeli, and M. L. F. de Farias Influence of methyltestosterone postmenopausal therapy on plasma lipids, inflammatory factors, glucose metabolism and visceral fat: a randomized study Eur. J. Endocrinol., January 1, 2006; 154(1): 131 - 139. [Abstract] [Full Text] [PDF]

				C. K. Sites, G. D. L'Hommedieu, M. J. Toth, M. Brochu, B. C. Cooper, and P. A. Fairhurst The Effect of Hormone Replacement Therapy on Body Composition, Body Fat Distribution, and Insulin Sensitivity in Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2701 - 2707. [Abstract] [Full Text] [PDF]

				R. Rossi, G. Origliani, and M. G. Modena Transdermal 17-{beta}-Estradiol and Risk of Developing Type 2 Diabetes in a Population of Healthy, Nonobese Postmenopausal Women Diabetes Care, March 1, 2004; 27(3): 645 - 649. [Abstract] [Full Text] [PDF]

				R. E. Van Pelt, W. S. Gozansky, R. S. Schwartz, and W. M. Kohrt Intravenous estrogens increase insulin clearance and action in postmenopausal women Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E311 - E317. [Abstract] [Full Text] [PDF]

				S. Fenkci, V. Fenkci, M. Yilmazer, M. Serteser, and T. Koken Effects of short-term transdermal hormone replacement therapy on glycaemic control, lipid metabolism, C-reactive protein and proteinuria in postmenopausal women with type 2 diabetes or hypertension Hum. Reprod., April 1, 2003; 18(4): 866 - 870. [Abstract] [Full Text] [PDF]

				B. Andersson, G. Johannsson, G. Holm, B.-A. Bengtsson, A. Sashegyi, I. Pavo, T. Mason, and P. W. Anderson Raloxifene Does Not Affect Insulin Sensitivity or Glycemic Control in Postmenopausal Women with Type 2 Diabetes Mellitus: A Randomized Clinical Trial J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 122 - 128. [Abstract] [Full Text] [PDF]

				A. S. Ryan, B. J. Nicklas, and D. M. Berman Hormone Replacement Therapy, Insulin Sensitivity, and Abdominal Obesity in Postmenopausal Women Diabetes Care, January 1, 2002; 25(1): 127 - 133. [Abstract] [Full Text] [PDF]

				R. J. Saad, B. S. Keenan, K. Danadian, V. D. Lewy, and S. A. Arslanian Dihydrotestosterone Treatment in Adolescents with Delayed Puberty: Does it Explain Insulin Resistance of Puberty? J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4881 - 4886. [Abstract] [Full Text] [PDF]

				E. M. Evans, R. E. Van Pelt, E. F. Binder, D. B. Williams, A. A. Ehsani, and W. M. Kohrt Effects of HRT and exercise training on insulin action, glucose tolerance, and body composition in older women J Appl Physiol, June 1, 2001; 90(6): 2033 - 2040. [Abstract] [Full Text] [PDF]

				A. M. Oleksik, T. Duong, N. Pliester, G. Asma, C. Popp-Snijders, and P. Lips Effects of the Selective Estrogen Receptor Modulator, Raloxifene, on the Somatotropic Axis and Insulin-Glucose Homeostasis J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2763 - 2768. [Abstract] [Full Text] [PDF]

				S. Vehkavaara, J. Westerbacka, T. Hakala-Ala-Pietilä, A. Virkamäki, O. Hovatta, and H. Yki-Järvinen Effect of Estrogen Replacement Therapy on Insulin Sensitivity of Glucose Metabolism and Preresistance and Resistance Vessel Function in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4663 - 4670. [Abstract] [Full Text]