Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis

Abstract

Background: Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT. Objectives: To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers. Search methods: PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews. Selection criteria: We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers. Data collection: The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies. Results: 1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79-4.07, while other oral hormonal preparations increased risk by 4.0-48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold. Conclusion: Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300-400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning. Summary: HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between three-and ninefold for blood clots for healthy women. The risks found would project 300-400 women dying from using HC each year in the United States.

ST-Elevation Myocardial Infarction in a 23-Year-Old Female: The Mystery of Thrombus Formation

“…Cardiovascular risk factors for our patient included obesity and phentermine use for weight loss. Another possible risk would be oral contraceptives, however, our patient had a levonorgestrel IUD, which has been shown to not have an increased risk for venous or arterial thrombosis [ 18 - 19 ]. Another uncommon but frequently seen condition in young females presenting with STEMI is spontaneous coronary artery dissection (SCAD) [ 20 ], however, our patient did not have evidence of dissection on coronary artery angiography or IVUS.…”

Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial

“…With regard to serious AEs, death, typically from thrombotic events, is the most severe AE reported in association with female contraception. A 2019 systematic review suggests at least 300–400 women die annually from venous thrombosis due to hormonal contraception 23. Death has not been reported as a correlated event in any male contraceptive efficacy studies.…”

Hormonally Active Contraceptives Part I: Risks Acknowledged and Unacknowledged

“…A genetic screening should until further also be restricted to women with a family disposition. (1356)In a 2018 systematic review (Keenan et al 2018) of the most evidenced-based articles from the 1960s to 2018 comparing users of COCs to nonusers, with a confirmed diagnosis of VTE, and including more than 17 million woman-years of observation, women on hormonal contraceptives (HC) increase their risk by three- to ninefold. However, the first year of use has the highest risk for clot formation, and if a woman is younger than thirty, her risk is increased thirteenfold in the first year.…”

“…This systematic review of the literature concludes that 136-260 women die from VTE a year in the United States from hormonal contraception. Combined with the added risk of stroke and heart attack from the COCs, 300-400 women die each year in the United States simply due to their choice of using HC for family planning (Keenan et al 2018). To give some perspective, meningitis killed forty-five people (of all ages) in 2017: most US states mandate meningitis vaccination for college and university students.…”

“…An effort was made to perform a series of comprehensive literature surveys to better understand immediate and long-term side effects of these agents. Some of these have been previously published (Peck and Norris 2012; Williams 2017; Keenan et al 2018; Williams et al 2018), while others are included here for the first time. Comparison of the scientific literature with the current prescribing information revealed that many of these risks, although well documented in the peer-reviewed literature, are not included in the prescribing information.…”