Objective:Decreased insulin sensitivity and deterioration in oral glucose tolerance curves habe been reported with oral contraceptive use, particularly with those containing levonorgestrel. However, the subdermal levonorgestrel systems release a lower dosage of steriod and avoid the first pass through the liver that occurs with oral administration. We hypothesized, therefore, that continuous subdermal levonorgestrel has no significant effect on insulin sensitivity and other indices of glucose metabolism.
Methods:Nine women desiring a subdermal hormonal contraceptive system were recruited for this longitudinal prospective study. Each subject underwent a 3-hour frequently sampled intravenous glucose tolerance test immediately before insertion and after 6 months of continuous ues. Insulin sensitivity and glucose effectiveness were determined using a mathematical minimal modeling approach. Glucose clearance and fasting and peak levels of glucose and insulin were examined as well. The matched-pair data were analzed using paired t tests.
Results:There was no significant change in insulin sensitivity, glucose effectiveness, glucose clearance, or fasting or peak insulin levels. Fasting glucose levels remained within a normal range.
Conclusions:Subdermal levonorgestrel appears to have no significant effects on tissue insulin sensitivity or glucose metabolism after 6 months of continuous use.
1. Waine H, Frieden EH, Caplan HZ, et al. Metabolic effects of Enovid or rheumatoid patients. Arthritis Rheum1963;6:796-796.
2.
2. Spellacy WN, Buhi WC, Birk SA. The effect of estrogens on carbohydrate metabolism: Glucose, insulin and growth hormone studies on one hundred and sevenry-one women ingesting Premarin, mestranol, and ethinyl estradiol for six months. Am J Obstet Gynecol1972;114:378-392.
3.
3. Kalkoff RK. Effects of oral contraceptive agents on carbohydrate metabolism. J Steroid Biochem1975;6:949-956.
4.
4. Spellacy WN, Buhi WC, Birk SA. The effects of norgestrel on carbohydrate and lipid metabolism over one year. Am J Obster Gynecol1976;125:984-986.
5.
5. Spellacy WN, Buhi WC, Birk SA. Carbodhydrate metabolism prosepectively studied in women using a low-estrogen oral contraceptive for six months. Contraception1979;20:137-148.
6.
6. Wynn V, Adams PW, Godsland I, et al. Comparison of effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism. Lancet1979;1:1049-1049.
7.
7. Spellacy WN, Buhi WC, Birk SA. Prospective studies of carbohydrate metabolism in “normal” women using norgestrel for eighteen months. Fertil Steril1981;35:167-171.
8.
8. Spellacy WN. Carbohydrate metabolism during treatment with estrogen, progestogen, and low-dose oral contraceptives. Am J Obstet Gynecol1982;142:732-734.
9.
9. Spellacy WN, Buhi WC, Birk SA. The effects of two years of mestranol tretment on carbohydrate metabolism. Metabolism1982;31:1006-1008.
10.
10. Briggs MH, Briggs M.Randomized prospective studies on metabolic effects of oral contraceptives. Acta Obstet Gynecol Scand Suppl1982;105:25-31.
11.
11. Kung AWC, Ma JTC, Wong VCW, et al. Glucose and lipid metabolism with triphasic oral contraceptives in women with history of gestational diabetes. Contraception1987;35:257-259.
12.
12. Spellacy WN, Ellingson AB, Kotilk A, Tsibris JCM. Plasma glucose and isulin levels in women using a levonorgestrelcontaining triphsic oral contraceptive for three months. Contraception1988;38:27-35.
13.
13. Godsland IF, Crook D, Simpson R, et al. The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med1990;323:1375-1381.
14.
14. Srivastava MC, Oakely NW, Tompkins CV, Sonksen PH, Wynn V.Insulin metabolism, insulin sensitivity and hormonal responses to insulin infusion in patients taking oral contraceptive steroids. Eur J Clin Invest1975;5:425-433.
15.
15. Kasdorf G, Kalkhoff RK. Prospective studies of insulin sensitivity in normal women receiving oral contraceptive agents. J Clin Endocrinol Metab1988;66:846-852.
16.
16. Godsland IF, Walton C, Falton C, Proudler S, Patel A, Wynn V.Insulin resistance, secretion, and metabolism in users of oral contraceptives. J Clin Endocrinol Metab1991;74:64-70.
17.
17. Olsson SE, Odlind V, Johansson EDB, Nordstrom ML. Plasma levels of levonorgestrel and free levonorgestrel index in women using Norplant implants or two covered rods (Norplant-2). Contraception1987;35:215-228.
18.
18. Shoup D, Mischell DR. Norplant: Subdermal implant system for long-term contraception. Am J Obstet Gynecol1989;160:1286-1292.
19.
19. Yang YJ, Youn JH, Bergman RN. Modified protocols improve insulin sensitivity estimation using the minimal model. Am J Physiol1987;253:E595-E602.
20.
20. Bergman RN, Phillips LS, Cobelle C.Physiologic evaluation of factors controlling glucose tolerance in man. Measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest1981;68:1456-1467.
21.
21. Bergman RN, Finegood DT, Ader M.Assessment of insulin sensitivity in vivo. Endocr Rev1985;6:45-86.
22.
22. Beard JC, Bergman RN, Ward WK, Porte D Jr.The insulin sensitivity index in nondiabetic man. Correlation between clamp-derived and IVGTT-derived valures. Diabetes1986;35:362-369.
23.
23. Pacini G, Bergman RN. Minmod: A computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Comput Methods Programs Biomed1986;23:113-122.
24.
24. Konje JC, Otolorin EO, Ladipo OA. The effect of continuous subdermal levonorgestrel (Norplant) on carbohydrate metabolism. Am J Obstet Gynecol1992;166:15-19.
25.
25. Bergman RN, Prager R, Volund A, Olefsky, JM, Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest1987;79:790-800.
26.
26. Shamma FN, Rosse G, HajHassan L, et al. The effect of Norplant on glucose metabolism under hyperglycemic conditions. Fertil Steril1995;63:767-772.
