Meade T W, Greenberg G, Thompson S G
Br Med J. 1980 May 10;280(6224):1157-61. doi: 10.1136/bmj.280.6224.1157.
Progestogens probably have metabolic effects that may contribute to the increased risk of cardiovascular reactions associated with combined oestrogen-progestogen oral contraceptives. This possibility was investigated by a study of nearly 2000 reports to the Committee on Safety of Medicines from 1964 to 1977. The reports concerned preparations in which norethisterone acetate in doses of 1.0, 2.5, 3.0, or 4.0 mg was combined with 50 microgram of ethinyloestradiol and those in which levonorgestrel in doses of 150 or 250 microgram was combined with 30 microgram of ethinyloestradiol. Observed and expected numbers of reports were compared, using retail pharmacy purchase figures as a measure of the use of different preparations. There was a significant positive association between the dose of norethisterone acetate and deaths from stroke and ischaemic heart disease (IHD); this association was also found for all cases of these two conditions, fatal plus non-fatal. There were no associations of dose of norethisterone acetate with hypertension or venous thrombosis. The higher dose of levonorgestrel was associated with a possible excess of deaths, non-venous plus venous, and an excess of strokes. There was no association between dose of levonorgestrel and hypertension or venous thrombosis. The reports were also used to assess the relative safety of 30-microgram and 50-microgram oestrogen preparations. Those with 30 microgram of oestrogen were associated with significantly fewer reports of death and IHD (both fatal, and fatal plus non-fatal) than those with 50 microgram of oestrogen. In view of the large-scale move towards preparations with progressively lower oestrogen doses, there are no grounds for major changes in oral contraceptive practice. Within the range of preparations currently in use, however, there is a case for minimising the dose of progestogen to reduce the chances of thromboembolism.
孕激素可能具有代谢作用，这可能会增加与雌激素 - 孕激素复方口服避孕药相关的心血管反应风险。1964年至1977年向药品安全委员会提交的近2000份报告对这一可能性进行了研究。这些报告涉及以下制剂：醋酸炔诺酮剂量为1.0、2.5、3.0或4.0毫克与50微克炔雌醇联合使用的制剂，以及左炔诺孕酮剂量为150或250微克与30微克炔雌醇联合使用的制剂。以零售药店购买数据作为不同制剂使用情况的衡量标准，比较了观察到的报告数量和预期报告数量。醋酸炔诺酮剂量与中风和缺血性心脏病（IHD）死亡之间存在显著正相关；在这两种疾病的所有病例（致命和非致命）中也发现了这种关联。醋酸炔诺酮剂量与高血压或静脉血栓形成无关联。较高剂量的左炔诺孕酮与可能的死亡过量（非静脉和静脉）以及中风过量有关。左炔诺孕酮剂量与高血压或静脉血栓形成无关联。这些报告还用于评估30微克和50微克雌激素制剂的相对安全性。与含50微克雌激素的制剂相比，含30微克雌激素的制剂与死亡和IHD报告（包括致命和致命加非致命）显著减少相关。鉴于向雌激素剂量逐渐降低的制剂大规模转变，口服避孕药的使用没有理由发生重大变化。然而，在目前使用的制剂范围内，有理由尽量减少孕激素剂量以降低血栓栓塞的风险。
