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.
Key words
combined oral contraceptives - extended-cycle regimen - glucose metabolism - insulin - C-peptide - glucose tolerance
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