Effects of desogestrel on carbohydrate metabolism
Shoupe, D.
American Journal of Obstetrics and Gynecology 168(3 Part 2): 1041-1047
1993
ISSN/ISBN: 0002-9378 PMID: 8447358 DOI: 10.1016/0002-9378(93)90335-gDocument Number: 335827
Progesterone and the synthetic progestins used in oral contraceptives are associated with a dose-dependent impairment of carbohydrate metabolism. Hyperinsulinemia and alterations in glucose metabolism are significant risk factors for the development of cardiovascular disease. However, long-term use of OCs does not appear to increase the risk of cardiovascular disease. In addition, long-term studies do not indicate any trend toward diabetes in long-term users. Desogestrel, a new progestin derived from 19-nortestosterone, is highly selective for progesterone receptors, with little affinity for androgen receptors. Of the four small studies using 150 mcg monophasic desogestrel and 30 mcg ethinyl estradiol (EE) mild increases in blood glucose were shown in one study after 6 months and after 12 months in another. In addition, plasma insulin decreased in two studies, increased in one, and remained unchanged in one. In a large cross-sectional study, users of OCs for at least 3 months were compared with nonusers. All OC formulations were associated with a deterioration in glucose tolerance. The smallest effect on both glucose tolerance and insulin secretion, as indicated by the C-peptide response, was found with the desogestrel-containing monophasic preparations. In a follow-up study, the metabolic basis of insulin disturbances was investigated as a consequence of the use of combination OCs containing levonorgestrel, norethindrone, or desogestrel as well as progestin-only formulations (norethindrone or ethynodiol diacetate). The levonorgestrel-containing combinations had the greatest effect on intravenous glucose tolerance tests, insulin, and C-peptide concentrations, followed by desogestrel and low-dose norethindrone. The new low-dose OCs show slight decreases in glucose tolerance, usually from 10% to 15% increases in glucose and from 10% to 30% increases in insulin curves compared with base-line. Desogestrel has been demonstrated to have generally less pronounced effects on these parameters of carbohydrate metabolism.