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Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
Lancet. 1995 Dec 16; 346(8990):1582-8.Lct

Abstract

A multinational hospital-based case-control study of the risk of venous thromboembolic disease associated with combined oral contraceptives (OCs) done in 1989-93 prompted a separate inquiry comparing the risk of venous thromboembolism (VTE) associated with low oestrogen (< 35 micrograms ethinyloestradiol) OCs containing levonorgestrel with risks in low oestrogen preparations containing the third-generation progestagens desogestrel or gestodene. This analysis of data from 9 countries, involved 769 cases and 1979 age matched hospital controls and, in one centre, 246 community controls matched on age and general practice. 137 cases and 203 controls were current users of levonorgestrel (odds ratio [OR with 95% confidence interval] 3.5 [2.6-4.7]), with non-users as the reference; 35 cases and 28 controls were current users of desogestrel (9.1 [4.9-17.0]), and 36 cases and 28 controls were current users of gestodene (9.1 [4.9-16.7]). The ratios of these risks, compared with levonorgestrel, were 2.6 (1.4-4.8) for both products separately. Risk estimates adjusted for body mass index (BMI) were 3.4, 7.3, and 10.2 for levonorgestrel, desogestrel, and gestodene, respectively, compared with non-users, and 2.2 and 3.0 for desogestrel and gestodene, respectively, compared with levonorgestrel. 48 (68%) cases and 48 (86%) controls exposed to desogestrel or gestodene were from the UK (Oxford region). In this centre risk estimates compared with non-users, adjusted for BMI, were 2.6, 5.3, and 5.7 for levonorgestrel, desogestrel, and gestodene, respectively. Current users of low oestrogen dose combined OCs containing desogestrel or gestodene appear to be at higher risk of VTE than users of combined OCs containing levonorgestrel. The possibility that these unexpected results on a secondary study objective are due to chance, bias, or residual confounding cannot be excluded entirely and the results need to be confirmed by independent studies. They are at variance with the apparently more favourable metabolic effects of the newer progestagens. Whether the new progestagens are associated with lower risk of arterial disease (stroke and myocardial infarction) must be evaluated further.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7500749

Citation

"Effect of Different Progestagens in Low Oestrogen Oral Contraceptives On Venous Thromboembolic Disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception." Lancet (London, England), vol. 346, no. 8990, 1995, pp. 1582-8.
Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995;346(8990):1582-8.
(1995). Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet (London, England), 346(8990), 1582-8.
Effect of Different Progestagens in Low Oestrogen Oral Contraceptives On Venous Thromboembolic Disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995 Dec 16;346(8990):1582-8. PubMed PMID: 7500749.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. PY - 1995/12/16/pubmed PY - 1995/12/16/medline PY - 1995/12/16/entrez SP - 1582 EP - 8 JF - Lancet (London, England) JO - Lancet VL - 346 IS - 8990 N2 - A multinational hospital-based case-control study of the risk of venous thromboembolic disease associated with combined oral contraceptives (OCs) done in 1989-93 prompted a separate inquiry comparing the risk of venous thromboembolism (VTE) associated with low oestrogen (< 35 micrograms ethinyloestradiol) OCs containing levonorgestrel with risks in low oestrogen preparations containing the third-generation progestagens desogestrel or gestodene. This analysis of data from 9 countries, involved 769 cases and 1979 age matched hospital controls and, in one centre, 246 community controls matched on age and general practice. 137 cases and 203 controls were current users of levonorgestrel (odds ratio [OR with 95% confidence interval] 3.5 [2.6-4.7]), with non-users as the reference; 35 cases and 28 controls were current users of desogestrel (9.1 [4.9-17.0]), and 36 cases and 28 controls were current users of gestodene (9.1 [4.9-16.7]). The ratios of these risks, compared with levonorgestrel, were 2.6 (1.4-4.8) for both products separately. Risk estimates adjusted for body mass index (BMI) were 3.4, 7.3, and 10.2 for levonorgestrel, desogestrel, and gestodene, respectively, compared with non-users, and 2.2 and 3.0 for desogestrel and gestodene, respectively, compared with levonorgestrel. 48 (68%) cases and 48 (86%) controls exposed to desogestrel or gestodene were from the UK (Oxford region). In this centre risk estimates compared with non-users, adjusted for BMI, were 2.6, 5.3, and 5.7 for levonorgestrel, desogestrel, and gestodene, respectively. Current users of low oestrogen dose combined OCs containing desogestrel or gestodene appear to be at higher risk of VTE than users of combined OCs containing levonorgestrel. The possibility that these unexpected results on a secondary study objective are due to chance, bias, or residual confounding cannot be excluded entirely and the results need to be confirmed by independent studies. They are at variance with the apparently more favourable metabolic effects of the newer progestagens. Whether the new progestagens are associated with lower risk of arterial disease (stroke and myocardial infarction) must be evaluated further. SN - 0140-6736 UR - https://www.unboundmedicine.com/medline/citation/7500749/Effect_of_different_progestagens_in_low_oestrogen_oral_contraceptives_on_venous_thromboembolic_disease__World_Health_Organization_Collaborative_Study_of_Cardiovascular_Disease_and_Steroid_Hormone_Contraception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(95)91927-9 DB - PRIME DP - Unbound Medicine ER -