Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism

Abstract

This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 µg ethinyl estradiol (EE) and 75 µg gestodene (GSD) or 20 µg ethinyl estradiol and 150 µg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-µg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel.

Sex Hormones, Insulin Sensitivity, and Diabetes Mellitus

“…In general, studies of women indicate that the use of newer oral contraceptive formulations have minimal deleterious effects on glucose tolerance and insulin sensitivity and are not associated with an increased risk for development of DM2 (Adams et al 1980;Chasan-Taber et al 1997;Godsland and Crook 1994;Kim et al 2002;Rimm et al 1992;Vela and Yen 1969). As lower doses of estrogen and newer progestins with less androgenic activity and more specificity are coming into use, the side effects of oral contraceptives are further reduced (Godsland et al 1990;Ludicke et al 2002). Although oral, low-dose, progestin-only contraceptives have minimal metabolic effects (Godsland et al 1990(Godsland et al , 1992, parenteral administration of medroxyprogesterone is associated with worsening glucoregulation (Amatayakul et al 1980), particularly with longer duration of use (Liew et al 1985).…”

The Management of Polycystic Ovary Syndrome

“…Several studies have recorded a modest increase in insulin and glucose in response to OGT38 during the course of treatment with OCs containing gestodene (75 mcg) and EE (30 mcg) observed in women over the age of 26 and not in younger patients 39. A modest increase in the response to the glucose tolerance test and of glycemia in fasting, but not of insulinemia in fasting or under stimulus, was also encountered with preparations featuring a low estrogen dosage with gestodene and desogestrel 40. Other reports have not recorded modifications in insulinemia and glycemia after 6 months assumption of the triphasic combination containing gestodene and of other combinations containing levonorgestrel, desogestrel, and noretisterone;41 nor were variations in insulin sensitivity recorded after 6 months of treatment with low dosage estro‐progestins 42.…”

“…39 A modest increase in the response to the glucose tolerance test and of glycemia in fasting, but not of insulinemia in fasting or under stimulus, was also encountered with preparations featuring a low estrogen dosage with gestodene and desogestrel. 40 Other reports have not recorded modifications in insulinemia and glycemia after 6 months assumption of the triphasic combination containing gestodene and of other combinations containing levonorgestrel, desogestrel, and noretisterone; 41 nor were variations in insulin sensitivity recorded after 6 months of treatment with low dosage estro-progestins. 42 Even considering patients with previous gestational diabetes, no modifications in the glucose, insulin, and glucagon response to the OGTT were observed during treatment with levonorgestrel; 43 on the other hand, using the euglycemic clamp technique, a greater reduction in the peripheral sensitivity to insulin was observed in comparison to the control samples treated with the same combination.…”

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

“…The present results are comparable with those of previous studies showing no or modest eff ects on fasting glucose levels during treatment with 20 -35 μ g EE in combination with diff erent types and doses of progestogens [12 -20] . A modest but signifi cant increase in fasting glucose (approximately 10 % ), in contrast, has been reported with COCs containing EE and desogestrel (DG) or gestodene (GSD) [21,22] , while a decrease was observed after 1 year of treatment with low-dose EE / levonorgestrel (LNG) [23] .…”