Horm Metab Res 2010; 42(5): 358-363
DOI: 10.1055/s-0030-1248263
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Effects of Combined Oral Contraceptive Ethinylestradiol (30 μg) and Dienogest (2 mg) on Carbohydrate Metabolism During 1 Year of Conventional or Extended-Cycle Use

I. Wiegratz1 , S. Stahlberg1 , T. Manthey1 , N. Sänger1 , K. Mittmann2 , E. Palombo-Kinne2 , U. Mellinger2 , E. Lange2 , H. Kuhl1
  • 1Center of Obstetrics and Gynecology, University Hospital of Frankfurt, Frankfurt/M, Germany
  • 2Jenapharm GmbH & Co KG, Jena, Germany
Further Information

Publication History

received 02.07.2009

accepted 20.01.2010

Publication Date:
08 March 2010 (online)

Abstract

The effects of extended regimens of combined oral contraceptives (COCs) on carbohydrate metabolism are largely unknown. The present study compared the effects of a COC containing 30 μg ethinylestradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year. Parameters of carbohydrate metabolism were measured in 59 women treated with EE/DNG either conventionally (13 cycles of 21+7 days) or in extended-cycle regimen (4 cycles of 84+7 days). Blood samples were taken in a control cycle, and at 3 and 12 months of treatment. The mean levels of HbA1c and fasting glucose levels remained stable in both conventional and extended-regimen of EE/DNG. The mean levels of fasting insulin and C-peptide underwent comparable increases in both regimens, suggesting a similar readjustment of glucose metabolism via slightly increased insulin secretion. For both regimens, the response to the oral glucose tolerance test (OGTT) showed a slightly impaired glucose tolerance and insulin resistance at 3 months. These changes improved or returned to baseline at 12 months. Accordingly, the mean index for insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) increased and the mean insulin sensitivity index [ISI (composite)] decreased modestly in both groups. The present study demonstrates that there are no statistically significant differences between the effects of conventional and extended-cycle treatment on carbohydrate metabolism over 1 year of treatment. In general, the effects of both regimens were moderate and mostly transient.

References

  • 1 Wynn V, Godsland I, Niththyananthan R, Adams PW, Melrose J, Oakley NW, Seed M. Comparison of effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism.  Lancet. 1979;  19 1045-1049
  • 2 Godsland IF. The influence of female sex steroids on glucose metabolism and insulin action.  J Intern Med. 1996;  240 (S 738) 1-65
  • 3 Gaspard UJ. Metabolic effects of oral contraceptives.  Am J Obstet Gynecol. 1987;  157 1029-1041
  • 4 Crook D, Godsland I. Safety evaluation of modern oral contraceptives.  Contraception. 1998;  57 189-201
  • 5 Godsland IF, Crook D, Stevenson J, Wynn V. Estrogen/progestin combinations and carbohydrate metabolism.  Int Proc J. 1989;  1 74-80
  • 6 Wiegratz I, Kuhl H. Long-cycle treatment with oral contraceptives.  Drugs. 2004;  64 2447-2462
  • 7 Sulak PJ, Kuehl TJ, Ortiz M, Shull BL. Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms.  Am J Obstet Gynecol. 2002;  186 1142-1149
  • 8 Jung-Hoffmann C, Kuhl H. Pharmacokinetics and pharmacodynamics of oral contraceptive steroids: factors influencing steroid metabolism.  Am J Obstet Gynecol. 1990;  163 2183-2197
  • 9 Wiegratz I, Hommel HH, Zimmermann T, Kuhl H. Attitudes of German women and gynecologists towards long-cycle treatment with oral contraceptives.  Contraception. 2004;  69 37-42
  • 10 Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling.  Diabetes Care. 2004;  27 1487-1495
  • 11 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing.  Diabetes Care. 1999;  22 1462-1470
  • 12 Song S, Chen JK, Yang PJ, He ML, Li LM, Fan BC, Rekers H, Fotherby K. A cross-over study of three oral contraceptives containing ethinyloestradiol and either desogestrel or levonorgestrel.  Contraception. 1992;  45 523-532
  • 13 Oelkers W, Foidart JM, Dombrovicz N, Welter A, Heithecker R. Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism.  J Clin Endocrinol Metab. 1995;  80 1816-1821
  • 14 Rubeck Petersen K, Skouby SO, Gronholt Pedersen R. Desogestrel and gestodene in oral contraceptives: 12 months’ assessment of carbohydrate and lipoprotein metabolism.  Obstet Gynecol. 1991;  78 666-672
  • 15 Kuhl H, Jung-Hoffmann C, Weber J, Boehm BO. The effect of a biphasic desogestrel-containing oral contraceptive on carbohydrate metabolism and various hormonal parameters.  Contraception. 1993;  47 55-68
  • 16 Knopp RH, Broyles FE, Cheung M, Moore K, Marcovina S, Chandler WL. Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel.  Contraception. 2001;  63 1-11
  • 17 Gaspard U, Scheen A, Endrikat J, Buicu C, Lefebvre P, Gerlinger C, Heithecker R. A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism.  Contraception. 2003;  67 423-429
  • 18 Troisi RJ, Cowie CC, Harris MI. Oral contraceptive use and glucose metabolism in a national sample of women in the United states.  Am J Obstet Gynecol. 2000;  183 389-395
  • 19 Godsland IF, Crook D, Simpson R, Proudler T, Felton C, Lees B, Anyaoku V, Devenport M, Wynn V. The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.  N Engl J Med. 1990;  323 1375-1381
  • 20 Endrikat J, Klipping C, Cronin M, Gerlinger C, Ruebig A, Schmidt W, Düsterberg B. An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 μg ethinyl estradiol and 100 μg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables.  Contraception. 2002;  65 215-221
  • 21 Lüdicke F, Gaspard UJ, Demeyer F, Scheen A, Lefebvre P. Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism.  Contraception. 2002;  66 411-415
  • 22 Kuhl H, Gahn G, Romberg G, Althoff PH, Taubert HD. A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic serum parameters: II. Effects upon thyroid function, gastrin, STH, and glucose tolerance.  Contraception. 1985;  32 97-107
  • 23 Skouby SO, Endrikat J, Düsterberg B, Schmidt W, Gerlinger C, Wessel J, Goldstein H, Jespersen J. A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 μg ethinyl estradiol combined with 100 μg levonorgestrel.  Contraception. 2005;  71 111-117
  • 24 Bonassi Machado R, Fabrini P, Machado Cruz A, Maia E, da Cunha Bastos A. Clinical and metabolic aspects of the continuous use of contraceptive association of ethinyl estradiol (30 μg) and gestodene (75 μg).  Contraception. 2004;  70 365-370
  • 25 The Expert Committee on the diagnosis and classification of diabetes mellitus . Report of the expert committee on the diagnosis and classification of diabetes mellitus.  Diabetes Care. 2002;  25 (S 01) S5-S20
  • 26 Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage.  Am J Physiol Endocrinol Metab. 2008;  294 E15-E26
  • 27 Jarret RJ, Graver HJ. Changes in oral glucose tolerance during the menstrual cycle.  BMJ. 1968;  2 528-529
  • 28 Cagnacci A, Paoletti AM, Renzi A, Orru M, Pilloni M, Melis GB, Volpe A. Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel.  J Clin Endocrinol Metab. 2003;  88 3621-3625
  • 29 Godsland IF, Walton C, Felton C, Proudler A, Patel A, Wynn V. Insulin resistance, secretion, and metabolism in users of oral contraceptives.  J Clin Endocrinol Metab. 1991;  74 64-70

Correspondence

PD Dr. I. Wiegratz

Department of Obstetrics and Gynecology

J. W. Goethe University

Theodor-Stern-Kai 7

60590 Frankfurt am Main

Germany

Phone: +49/69/6301 5708

Fax: + 49/69/6301 5522

Email: inkawiegratz@hotmail.com

    >