Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study

Spitzer, Walter O.; Lewis, Michael Alexander Oxenham; Heinemann, L.; Thorogood, Margaret; MacRae, K D

doi:10.1136/bmj.312.7023.83

Cited by 559 publications

(241 citation statements)

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“…During the 1990s, a variety of observational studies provided useful information regarding 'type A' ADRs (known as augmented reactions, which are dose dependent and predictable) of different drugs within a certain drug class (e.g., non-steroid anti-inflammatory drugs and gastrointestinal bleeding [8], selective serotonin reuptake inhibitors and upper gastrointestinal bleeding [9], third-generation oral contraceptives and venous thromboembolism [10][11][12]). During this period, other original articles passed unnoticed by the medical community and the RAs.…”

Section: Example 3: Nifedipine and Fatal Aplastic Anemiamentioning

confidence: 99%

Safety Signal Detection: The Relevance of Literature Review

Pontes¹,

Clément²,

Rollason

2014

Drug Saf

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Adverse drug reactions (ADRs) represent an important risk for patients and have a significant economic impact on health systems. ADRs are the fifth most common cause of hospital death, with a burden estimated at 197,000 deaths per year in the EU. This has a societal cost of €79 billion per year. Because of this strong impact in public health, regulatory authorities (RAs) worldwide are implementing new pharmacovigilance legislation to promote and protect public health by reducing the burden of ADRs through the detection of safety signals. Although, traditionally, signal detection activities have mainly been performed based on spontaneous reporting from healthcare professionals and national health RAs, the new pharmacovigilance legislation underlines the relevance of other sources of information (such as scientific literature) for the evaluation of the benefit-risk balance of a certain product. This review aims to highlight the relevance of periodic scientific literature screening in the safety signal detection process. The authors present four practical examples where a safety signal that was detected from a literature report had an impact on the lifecycle of a drug. In addition, based on practical experience of the screening of medical and scientific literature for safety purposes, this article analyses the requirements of the new pharmacovigilance guidelines on literature screening and highlights the need for the implementation of a literature review procedure and the main challenges encountered when performing literature screening for safety aspects. Key PointsSeveral safety signals detected in literature reports have had a direct impact on the lifecycle of a drugThe reporting culture of healthcare professionals is usually less prevalent than the publishing culture The wide difference in quality, accuracy, and completeness of scientific publications is one of the biggest challenges of literature search and review 1 Introduction

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Section: Example 3: Nifedipine and Fatal Aplastic Anemiamentioning

confidence: 99%

Safety Signal Detection: The Relevance of Literature Review

Pontes¹,

Clément²,

Rollason

2014

Drug Saf

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“…In addition, we sampled serum lipids and the endothelium-derived substance endothelin-1, which is a potent vasoconstrictor and has recently become recognized for its association with vascular risk (21)(22)(23)(24). Owing to the fact that the vaginal ring uses a third-generation progestin, and recent evidence suggests that third-generation progestins may increase coagulation and thrombotic risk (25,26), we also measured baseline fibrinogen levels.…”

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confidence: 99%

Endothelial Function, Endothelin-1, and Fibrinogen in Young Women Using the Vaginal Contraceptive Ring

Torgrimson

Kaplan

Minson

2008

Fertility and Sterility

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Objective-To assess the effects of the vaginal contraceptive ring cycle on indices of cardiovascular health and risk by studying healthy women during the active hormone phase compared with the ring-free phase of a standard 21/7-day cycle.Design-Observational prospective cohort; 4 weeks' duration. Setting-Department of Human Physiology, University of Oregon. Patient(s)-Twenty healthy women.Intervention(s)-Endothelial function testing using standard flow-mediated vasodilation of the brachial artery and sublingual nitroglycerin administration. All participants underwent venous blood collection.Main Outcome Measure(s)-Endothelium-dependent and endothelium-independent vasodilation of the brachial artery using Doppler ultrasound imaging. Baseline levels of highdensity lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, endothelin-1, and fibrinogen. Result(s)-The active hormone phase of thevaginal ringcycle showed significantly higher vasodilation compared with the ring-free phase. The active hormone phase also showed increased fibrinogen levels compared with the ring-free phase. Low-density lipoprotein lipid levels also fluctuated and were significantly higher during the ring-free phase. Conclusion(s)-Preliminarystudy observations of improved endothelial function and lowered low-density lipoprotein levels during the active hormone phase versus the ring-free phase suggest that the vaginal contraceptive ring has beneficial effects on vascular health in women. KeywordsEstradiol; etonorgestrel; hormone delivery; vascular health; hormonal contraception; flowmediated dilation; progestin; estrogen Reprint requests to: Christopher T. Minson, Human Physiology, University of Oregon, 122 C Esslinger Hall, Eugene, OR 97403 (FAX: 541-346-7841; minson@uoregon.edu). B.T. has nothing to disclose. J.M. has nothing to disclose. N.M. has nothing to disclose. P.K. has nothing to disclose. C.M. has nothing to disclose.Presented at the 56th Annual Meeting, Pacific Coast Reproductive Society, Rancho Las Palmas Resort and Spa, Palm Springs, Florida, April 9-13, 2008. NIH Public Access Although decades of research have consistently shown that oral contraceptives increase the relative risk for vascular thromboembolic events (1-3), we know much less about nonoral hormonal contraceptives and cardiovascular risk. Historically, vascular thrombosis risk in oral contraceptive pills users has been associated with high oral estrogen dosing (3) and the subsequent effects of oral estrogen on coagulation pathways in the vasculature (4-8). To date, there are few data on coagulation factors and vascular function in women using nonoral hormonal contraceptives.The combination ethinyl estradiol/etonorgestrel monthly vaginal contraceptive ring is considered to be an advantageous route for hormone delivery compared with oral contraceptive pills (OCPs), because it avoids first-pass hepatic metabolism, allows for lower hormone doses, provides steady serum hormone levels, and requires less frequent administration. Compared with oral...

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“…In the third generation new progestin-formulas like desogestrel and gestoden were introduced (Speroff and DeCherney, 1993). Even though the latter preparations have less negative in¯uence on lipoproteins, new studies showed that the incidence of venous thromboembolism is even higher in women taking these new OC than in women using second generation OC (WHO, 1995;Jick et al, 1995;Spitzer et al, 1996). Therefore, other mechanisms for the impact of OC on cardiovascular disease require further investigation.…”

Section: Introductionmentioning

confidence: 99%

Use of oral contraceptives and serum beta-carotene

Berg

Kohlmeier²,

Brenner

1997

Eur J Clin Nutr

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Objective: Antioxidants, in particular carotenoids, may in¯uence the risk for cardiovascular disease. This study investigates the in¯uence of oral contraceptives (OC) on the serum concentration of beta-carotene, which may in turn affect the risk of cardiovascular diseases due to its antioxidative impact. Design: Cross-sectional epidemiologic study. Examinations included a detailed questionnaire on medical history and lifestyle factors, a 7 day food record, and blood samples. Setting: National health and nutrition survey among healthy people living in private homes in West Germany in 1987±1988. Subjects: Nonpregnant and nonlactating women aged 18±44 (n 610). Results: Overall, the use of OC was negatively associated with serum beta-carotene concentration in bi-and multivariable analyses after adjustment for age, smoking, alcohol consumption, dietary intake of beta-carotene, use of vitamin supplements, body mass index, pregnancies, and serum concentrations of total triglyceride and cholesterol. A strong interaction between OC use and age on beta-carotene concentration was observed. While no relationship between OC use and serum beta-carotene was seen in the youngest age-group (18±24 y), there was a modest but signi®cant negative association between OC use and beta-carotene levels among 25±34 y old women. The use of OC was associated with a strong decrease in beta-carotene levels among 35±44 y old women. The interaction between OC use and age could partly be explained by age dependent use of OC with higher estrogen content. Conclusions: OC use seems to be strongly related to serum beta-carotene levels, particularly among women above the age of 35. Further studies are needed to clarify the underlying mechanisms of this association and its implications for health risks of OC use. Sponsorship: The national health and nutrition survey was founded by the German Ministry of Research and Technology.

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Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study

Abstract: Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Cited by 559 publications

References 10 publications

Safety Signal Detection: The Relevance of Literature Review

Safety Signal Detection: The Relevance of Literature Review

Endothelial Function, Endothelin-1, and Fibrinogen in Young Women Using the Vaginal Contraceptive Ring

Use of oral contraceptives and serum beta-carotene

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