Glucose Metabolism and Insulin Resistance in Women with Polycystic Ovary Syndrome during Therapy with Oral Contraceptives Containing Cyproterone Acetate or Desogestrel

Abstract

Oral contraceptives slightly deteriorate insulin sensitivity. The present study investigated whether they may further unbalance the glucose metabolism of lean women with polycystic ovary syndrome (PCOS). Women with PCOS were assigned to receive for 6 months the biphasic association of 40/30 micro g ethinyl estradiol (EE) and 25/125 micro g desogestrel (DSG; n = 10) or the monophasic association of 35 micro g EE and 2 mg cyproterone acetate (CPA; n = 10). Glucose tolerance was investigated by an oral glucose tolerance test (OGTT). Glucose utilization dependent [insulin sensitivity (SI)] or independent (Sg) of insulin was investigated by the minimal model method applied to a frequently sampled iv glucose tolerance test. EE/DSG increased the response of C peptide to OGTT (1413 +/- 113 vs. 2053 +/- 213 area under the curve; P < 0.009) and the C peptide/insulin ratio (0.085 +/- 0.01 vs. 0.134 +/- 0.01 area under the curve; P < 0.003). It also increased the Sg (0.026 +/- 0.002 vs. 0.034 +/- 0.003; P < 0.04) and decreased the SI (2.40 +/- 0.26 vs. 1.68 +/- 0.27; P < 0.01). EE/CPA did not modify responses to OGTT of glucose, insulin, C peptide, or C peptide/insulin ratio. It did not modify Sg and significantly increased SI (1.47 +/- 0.38 vs. 3.27 +/- 0.48; P < 0.04). The present study indicates that EE/CPA improves SI, whereas EE/DSG impairs SI, but improves insulin clearance. The long-term metabolic effects of these two compounds on women with PCOS require further investigations.

Comparison of effects of 3 mg drospirenone plus 20 μg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome

“…Oral contraceptives containing 30 mg or more of EE associated with second-generation progestins, such as levonorgestrel, decrease peripheral insulin receptors (25) and induce subclinical abnormalities in carbohydrate metabolism (26,27). Oral contraceptives with third-generation progestins (desogestrel and gestodene, norgestimate) are considered more neutral (28)(29)(30), but in some studies a decrease in insulin sensitivity has been reported (31)(32)(33). The androgenic properties of all 19 nortestosterone derivatives may play a role in reducing insulin sensitivity (20,34).…”

“…The androgenic properties of all 19 nortestosterone derivatives may play a role in reducing insulin sensitivity (20,34). No negative changes or an improvement in insulin sensitivity with progestins with antiandrogenic activity have been documented by some investigators (31,33). Drospirenone is a unique progestin, being related to 17a-spironolactone rather than derived from 19-nortestosterone.…”

“…a P< .01 vs. baseline value in the DRP/EE20 þ CPA group; b P< .05 vs. baseline value in the DRP/EE20 þ metformin group; c P< .005 vs. baseline value in the DRP/EE20 þ CPA group; d P< .001 vs. baseline value in the DRP/EE20 þ CPA group; e P< .05 vs. baseline value in the DRP/EE20 group; f P< .01 vs. baseline value in the DRP/EE20 group; g P< .001 vs. baseline value in the DRP/EE20 group; h P< .001 vs. baseline value in the DRP/EE20 þ metformin group. in women with PCOS treated with EE plus CPA (14,33,37,38). In studies involving 2 mg CPA, no changes in insulin concentrations and sensitivity or an improvement of insulin sensitivity has been reported in nonobese women with PCOS.…”

Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study

“…Furthermore, pills with different E 2 dosages and type of progestins have been used. The outcome of these studies was extremely variable and showed improvements, no changes, development of glucose intolerance, or type 2 diabetes (28)(29)(30)(31). In common with other OCs, the pill containing EE and drospirenone seems to impair insulin resistance (26,32).…”

Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome

“…There are many studies where two pills (containing different antiandrogenic progestogens) have been compared (6,7). Our objective was to compare the therapeutic effects of three types of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone, in patients with PCOS, at 6 and 12 months of therapy.…”