Oral contraceptives and venous thromboembolic disease: The findings from database studies in the United Kingdom and Germany

• Published in: American journal of obstetrics and gynecology Vol. 179; no. 3; pp. s78 - s86
• Main Authors: Farmer, R.D.T, Lawrenson, R.A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-1998
• Subjects: Adult; Age Distribution; Case-control studies; Contraceptives, Oral, Hormonal - administration & dosage; Contraceptives, Oral, Hormonal - adverse effects; desogestrel; Dose-Response Relationship, Drug; Female; Germany - epidemiology; gestodene; Humans; Logistic Models; Odds Ratio; oral contraceptives; Registries; Risk; Thrombophlebitis - chemically induced; Thrombophlebitis - epidemiology; United Kingdom - epidemiology; venous thromboembolism; gestodene; oral contraceptives; Case-control studies; desogestrel; venous thromboembolism; Measurement; Contraceptive Agents > pharmacodynamics; Biology; Research Methodology; Incidence; Vascular Diseases; Research Report; Retrospective Studies; Levonorgestrel > pharmacodynamics; Thromboembolism; Contraceptive Agents, Female > pharmacodynamics; Northern Europe; Europe; Oral Contraceptives > side effects; Risk Factors; United Kingdom; Contraception; Contraceptive Methods > side effects; Family Planning; Oral Contraceptives, Combined > side effects; Desogestrel > pharmacodynamics; Embolism; Diseases; Western Europe; Studies; Contraceptive Agents, Progestin > pharmacodynamics; Developed Countries; Gestodene > pharmacodynamics; Epidemiologic Methods; Germany
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1053/ob.1998.v179.a92634

Objective: Three research articles published in late 1995 and early 1996 suggested that oral contraceptives containing either of the newer progestogens (gestodene or desogestrel) could be associated with an increased risk of venous thromboembolism. During the months after the initial publications, the results have been scrutinized with great care and further studies have been published. The findings of 2 recent database studies, 1 in the United Kingdom and 1 in Germany, are presented in this article.
PATTERNS OF USE: The average age of users of combined oral contraceptives in Germany was 27 years, compared with 26 years in the United Kingdom. In Germany the use of gestodene-based products was lower than that in the United Kingdom. In the United Kingdom the users of desogestrel with 20 μg ethinyl estradiol (Mercilon) were older than the users of desogestrel with 30 μg ethinyl estradiol (Marvelon).
CRUDE INCIDENCE: The crude incidence of venous thromboembolism in the UK study was 4.1 cases/10,000 woman-y exposure to combined oral contraceptives. In Germany it was 4.2 cases/10,000 woman-y. In Germany the rates among users of second-generation combined oral contraceptives were higher than those among users of third-generation products. The reverse was the case in the United Kingdom. In the United Kingdom the crude incidence rates were higher for the 20 μg estrogen desogestrel product than for the 30 μg product.
CASE-CONTROL ANALYSIS: The adjusted odds ratios in the UK study did not show significant increases for desogestrel or gestodene compared with levonorgestrel products. There were inconsistencies in the results among centers in the 2 international studies (the World Health Organization and Transnational studies). In both there was a consistent inverse dose-response relationship with estrogen in all centers.
CONCLUSION: The limitations of the observational studies are such that the hypothesis that the newer progestogens are more likely to cause venous thromboembolism cannot be proved. (Am J Obstet Gynecol 1998;179:S78-86.)