Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen.

Design Observational cohort study.

Setting Data from the French national health insurance database linked with data from the French national hospital discharge database.

Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012.

Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction.

Results The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events.

Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel. For the same type of progestogen, an oestrogen dose of 20 µg versus 30-40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction.

Related collections

Most cited references 31

Record: found
Abstract: not found
Article: not found

CIRCULATION

K Nielsen (1972)

0 comments Cited 157 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Thrombotic stroke and myocardial infarction with hormonal contraception.

Aksel Jensen, Øjvind Lidegaard, Niels Keiding … (2012)

Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting. In this 15-year Danish historical cohort study, we followed nonpregnant women, 15 to 49 years old, with no history of cardiovascular disease or cancer. Data on use of hormonal contraception, clinical end points, and potential confounders were obtained from four national registries. A total of 1,626,158 women contributed 14,251,063 person-years of observation, during which 3311 thrombotic strokes (21.4 per 100,000 person-years) and 1725 myocardial infarctions (10.1 per 100,000 person-years) occurred. As compared with nonuse, current use of oral contraceptives that included ethinyl estradiol at a dose of 30 to 40 μg was associated with the following relative risks (and 95% confidence intervals) for thrombotic stroke and myocardial infarction, according to progestin type: norethindrone, 2.2 (1.5 to 3.2) and 2.3 (1.3 to 3.9); levonorgestrel, 1.7 (1.4 to 2.0) and 2.0 (1.6 to 2.5); norgestimate, 1.5 (1.2 to 1.9) and 1.3 (0.9 to 1.9); desogestrel, 2.2 (1.8 to 2.7) and 2.1 (1.5 to 2.8); gestodene, 1.8 (1.6 to 2.0) and 1.9 (1.6 to 2.3); and drospirenone, 1.6 (1.2 to 2.2) and 1.7 (1.0 to 2.6), respectively. With ethinyl estradiol at a dose of 20 μg, the corresponding relative risks according to progestin type were as follows: desogestrel, 1.5 (1.3 to 1.9) and 1.6 (1.1 to 2.1); gestodene, 1.7 (1.4 to 2.1) and 1.2 (0.8 to 1.9); and drospirenone, 0.9 (0.2 to 3.5) and 0.0. For transdermal patches, the corresponding relative risks were 3.2 (0.8 to 12.6) and 0.0, and for a vaginal ring, 2.5 (1.4 to 4.4) and 2.1 (0.7 to 6.5). Although the absolute risks of thrombotic stroke and myocardial infarction associated with the use of hormonal contraception were low, the risk was increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 μg and by a factor of 1.3 to 2.3 with those that included ethinyl estradiol at a dose of 30 to 40 μg, with relatively small differences in risk according to progestin type. (Funded by the Danish Heart Association.).

0 comments Cited 123 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Hormonal contraception and risk of venous thromboembolism: national follow-up study

Øjvind Lidegaard, Ellen Løkkegaard, Anne Louise Svendsen … (2009)

Objective To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. Design National cohort study. Setting Denmark, 1995-2005. Participants Danish women aged 15-49 with no history of cardiovascular or malignant disease. Main outcome measures Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. Results 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use ( 4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 μg desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). Conclusion The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.

0 comments Cited 118 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Alain Weill: Role: epidemiologist

Marie Dalichampt: Role: statistician

Fanny Raguideau: Role: epidemiologist

Philippe Ricordeau: Role: head

Pierre-Olivier Blotière: Role: statistician

Jérémie Rudant: Role: epidemiologist

François Alla: Role: professor of public health

Mahmoud Zureik: Role: scientific director

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): bmj

Title: The BMJ

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2016

Publication date (Electronic): 10 May 2016

Volume: 353

Electronic Location Identifier: i2002

Affiliations

[1 ]Department of Studies in Public Health, French National Health Insurance, 75986 Paris Cedex 20, France

[2 ]French National Agency for Medicines and Health Products Safety, Saint-Denis, France

Author notes

Correspondence to: A Weill alain.weill@ 123456cnamts.fr

Article

Publisher ID: weia023792

DOI: 10.1136/bmj.i2002

PMC ID: 4862376

PubMed ID: 27164970

SO-VID: 32e74214-87b4-4db4-8e0d-95f918d56451

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study

Read this article at

Abstract

Related collections

Stroke MRI

Most cited references 31

CIRCULATION

Thrombotic stroke and myocardial infarction with hormonal contraception.

Hormonal contraception and risk of venous thromboembolism: national follow-up study

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 179

Cited by 58

Most referenced authors 1,943