Seed M, Godsland I F, Wynn V, Jacobs H S
Clin Endocrinol (Oxf). 1984 Dec;21(6):689-99. doi: 10.1111/j.1365-2265.1984.tb01411.x.
Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as anti-androgen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and women were studied in two groups: the first when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13 to 22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to intravenous tolbutamide was increased by 50% but there was no accompanying change in the glucose nadir as compared with controls. These results show that the combination of CA and EO causes insulin resistance. Plasma C-peptide concentrations following oral glucose were unchanged compared with controls. This shows that the observed hyperinsulinaemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. We propose that these effects are due to a CA-induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C-peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide but this was not significant. We conclude that these results are explained by a reduced but persisting effect of CA.
对一组66名女性进行了碳水化合物代谢研究，她们服用醋酸环丙孕酮（CA）和乙炔雌二醇（EO）作为抗雄激素疗法来治疗多毛症和/或痤疮。采用反向序贯治疗周期，将女性分为两组进行研究：第一组在治疗周期的前12天服用CA和EO的组合，第二组在第13至22天单独服用EO。该组合降低了空腹血糖水平，提高了空腹血浆胰岛素浓度。随着血浆胰岛素浓度升高，葡萄糖耐量恶化，且这些影响随时间逐渐加重。与对照组相比，静脉注射甲苯磺丁脲后血浆胰岛素反应增加了50%，但血糖最低点没有伴随变化。这些结果表明，CA和EO的组合会导致胰岛素抵抗。与对照组相比，口服葡萄糖后血浆C肽浓度没有变化。这表明观察到的高胰岛素血症是由于肝脏对胰岛素的摄取减少，而不是胰岛素分泌增加所致。我们认为，这些影响是由于CA诱导空腹血浆胰岛素升高，导致肝脏胰岛素受体下调，随后诱导胰岛素抵抗并损害肝脏胰岛素摄取。静脉注射甲苯磺丁脲后，CA和EO治疗组的C肽浓度显著高于对照组，表明胰腺胰岛素分泌增加。在患者单独服用EO时进行的测试显示，仅葡萄糖耐量受损，胰岛素水平无变化。对甲苯磺丁脲的反应中血浆胰岛素有所增加，但不显著。我们得出结论，这些结果可以用CA降低但持续存在的作用来解释。
