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Increased VTE Risk in Women: NSAID and Hormonal Contraception Combo

Hormonal Contraception

NSAID and Hormonal Contraception

In a recent study published in The BMJ, the combined use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraception (HC) in women of reproductive age has revealed unexpected insights into their association with venous thromboembolism (VTE).


As both NSAID and HC use becomes increasingly common, concerns about their impact on cardiovascular health have emerged. This study delves into the potential risks associated with their concurrent use, shedding light on their combined effects on VTE risk.

Independent Risk Factors:

Both NSAIDs and HC are recognized as independent risk factors for VTE. HC, in particular, elevates the risk of VTE, with estrogen playing a significant role in promoting coagulation factor gene expression. The risk varies depending on the type of HC, with high-risk options including estrogen-progestin combinations like patches, vaginal rings, and tablets containing specific estrogen and progestin formulations. Medium-risk Hormonal Contraception includes most combined oral contraceptives, while no- or low-risk HC includes progestin-only options and intrauterine devices releasing minute doses of levonorgestrel (LNG-IUDs).

NSAIDs and VTE Risk:

NSAIDs, both older varieties like ibuprofen and diclofenac and newer selective cyclo-oxygenase inhibitors, are also associated with an increased risk of VTE. This risk extends beyond venous thrombosis to arterial thrombosis, potentially leading to strokes and heart attacks.

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Study Findings:

The study was conducted in Denmark on women aged 15-49 who were free of known thrombotic conditions, cancer, thrombophilia, and relevant gynecologic conditions. Over two million women, accumulating 21 million women years, were included in the study. Approximately 530,000 women used both Hormonal Contraception and NSAIDs concurrently, with high-risk HC accounting for nearly 60% of these cases, medium-risk for a quarter, and low-risk or no-risk HC for less than a fifth.

During the study period from 1996 to 2017, over 8,000 VTE events were recorded, with less than 3% proving fatal within a month of occurrence. Researchers analyzed NSAID usage among HC users, focusing on ibuprofen and diclofenac as the most commonly used NSAIDs.

Risk Factors:

The study found that high-risk Hormonal Contraception use, when combined with NSAIDs, increased the risk of VTE by 51 times, with medium-risk HC contributing to a 26-fold higher risk. Conversely, low-risk or no-risk HC did not exhibit this increased risk when combined with NSAIDs.

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Adjusting for Confounding Factors:

Adjusting for potential confounding factors like migraine, inflammatory disorders, hypertension, and diabetes, the study still revealed significantly higher VTE risks with high-risk and medium-risk HC combined with NSAIDs.

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The study’s findings suggest that women of reproductive age using NSAIDs may face an elevated VTE risk, particularly when using high-risk Hormonal Contraception options. However, it’s important to note that the absolute risk of VTE remains relatively low, even with the increased risk observed during the first week of NSAID use.

Further research is needed to explore the potential synergistic effects of these medications on hypercoagulability. The study underscores the importance of studying this association in regular NSAID users, potentially leading to considerations of low- or no-risk hormonal contraceptives for safer reproductive health choices.