Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.
Departmental Unit of Thrombosis and Haemostasis, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy.
Semin Thromb Hemost. 2024 Feb;50(1):91-95. doi: 10.1055/s-0043-1764382. Epub 2023 Mar 13.
The development of oral contraceptives (OCs) began in 1921 and continued in the following years until the first regulatory approval from the Food and Drug Administration was granted in 1960. However, it took several years to realize that OCs presented an important but not frequent risk of venous thrombosis. Several reports ignored this dangerous effect and only in 1967 the Medical Research Council clearly stated this as an important risk. Later, research led to the formulation of second-generation OCs containing progestins, which nevertheless presented an increased thrombotic risk. In early 1980s, OCs containing third-generation progestins were introduced into the market. Only in 1995, it became clear that these new compounds induced a higher thrombotic risk than that related to the second-generation progestins. It appeared clear that the modulating action of progestins was against the procoagulant activity of estrogens. Lastly, at the end of the 2000s, OCs containing natural estrogens and a fourth-generation progestin (dienogest) became available. The prothrombotic effect of those natural products was not different from that of preparations containing second-generation progestins. Moreover, research over the years has produced much data on risk factors associated with OCs use such as age, obesity, cigarette smoking, and thrombophilia. These findings allowed us to better assess the individual thrombotic risk (both arterial and thrombotic) of each woman before offering an OC. Furthermore, research has shown that in high-risk people the use of single progestin is not dangerous as far as thrombosis is concerned. In conclusion, the OCs road has been long and difficult but has led to a great and unthinkable scientific and social enrichment since the 1960s.
口服避孕药（OCs）的开发始于 1921 年，并在随后的几年中继续进行，直到 1960 年食品和药物管理局首次批准监管。然而，人们花了几年时间才意识到 OCs 存在重要但不常见的静脉血栓形成风险。有几份报告忽略了这种危险的影响，直到 1967 年，医学研究委员会才明确指出这是一个重要的风险。后来，研究导致了含有孕激素的第二代 OCs 的配方，但它们仍然存在增加的血栓形成风险。20 世纪 80 年代初，含有第三代孕激素的 OCs 被引入市场。直到 1995 年，人们才清楚地认识到这些新化合物引起的血栓形成风险高于与第二代孕激素相关的风险。显然，孕激素的调节作用与雌激素的促凝活性相反。最后，在 2000 年代末，含有天然雌激素和第四代孕激素（地诺孕素）的 OCs 问世。这些天然产品的促血栓形成作用与含有第二代孕激素的制剂没有不同。此外，多年的研究产生了大量与 OCs 使用相关的危险因素的数据，如年龄、肥胖、吸烟和血栓形成倾向。这些发现使我们能够在提供 OCs 之前更好地评估每位女性的个体血栓形成风险（动脉和血栓形成）。此外，研究表明，在高风险人群中，就血栓形成而言，使用单一孕激素并不危险。总之，自 20 世纪 60 年代以来，OCs 的发展道路漫长而艰难，但带来了巨大的、难以想象的科学和社会丰富。
