Raedler Thomas J, Jahn Holger, Goedeken Birgit, Gescher Dorothee M, Kellner Michael, Wiedemann Klaus
Department of Psychiatry and Psychotherapy, University of Hamburg Medical Center, Martinistr. 52, 20246, Hamburg, Germany.
Cancer Chemother Pharmacol. 2003 Dec;52(6):482-6. doi: 10.1007/s00280-003-0697-6. Epub 2003 Sep 16.
Clinical observations suggest that prolonged treatment with megestrol can lead to Cushing-like symptoms, while withdrawal of prolonged treatment with megestrol may result in adrenal insufficiency. However, only little is known about the acute effects of megestrol on the hypothalamic-pituitary-adrenal (HPA) axis. As part of an endocrine study, we evaluated the acute effects of megestrol, hydrocortisone and placebo on morning cortisol and ACTH levels.
. Using a balanced double-blind design, ten healthy male subjects were treated at 11:00 p.m. and 8:00 a.m. with megestrol (total dose 320 mg), hydrocortisone (total dose 30 mg) or placebo. After 1 h of rest, blood was drawn at 10:00 a.m. and 10:30 a.m. for determination of cortisol and ACTH levels.
. Compared to placebo, acute administration of megestrol resulted in a significant decrease in morning ACTH and cortisol levels. The suppression of ACTH after pretreatment with megestrol was less pronounced than after pretreatment with hydrocortisone.
Our results suggest that megestrol exerts glucocorticoid-like effects and has an acute depressing effect on the HPA axis. Therefore alterations in the steroid system should be included in the differential diagnosis of all subjects under treatment with megestrol.
临床观察表明，甲地孕酮长期治疗可导致库欣样症状，而甲地孕酮长期治疗停药可能导致肾上腺功能不全。然而，关于甲地孕酮对下丘脑-垂体-肾上腺（HPA）轴的急性影响知之甚少。作为一项内分泌研究的一部分，我们评估了甲地孕酮、氢化可的松和安慰剂对早晨皮质醇和促肾上腺皮质激素（ACTH）水平的急性影响。
采用平衡双盲设计，10名健康男性受试者于晚上11:00和上午8:00接受甲地孕酮（总剂量320mg）、氢化可的松（总剂量30mg）或安慰剂治疗。休息1小时后，于上午10:00和10:30采集血液，测定皮质醇和ACTH水平。
与安慰剂相比，甲地孕酮急性给药导致早晨ACTH和皮质醇水平显著降低。甲地孕酮预处理后对ACTH的抑制作用不如氢化可的松预处理后明显。
我们的结果表明，甲地孕酮具有糖皮质激素样作用，对HPA轴有急性抑制作用。因此，在对所有接受甲地孕酮治疗的受试者进行鉴别诊断时，应考虑类固醇系统的改变。
