What is the risk of Venous Thromboembolism (VTE) with Levonorgestrel (Levonorgestrel) and Drospirenone (Drospirenone)?

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Last updated: May 2, 2025View editorial policy

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From the Guidelines

Levonorgestrel is preferred over drospirenone for patients concerned about venous thromboembolism (VTE) risk due to its lower associated risk.

Key Points

  • Drospirenone-containing contraceptives have a higher VTE risk compared to levonorgestrel formulations, with a relative risk increase of about 50% to 80% 1.
  • The absolute risk of VTE remains low in healthy individuals, but the difference becomes more significant in patients with additional risk factors such as obesity, smoking, family history of VTE, or inherited thrombophilias.
  • For patients requiring hormonal contraception who have VTE risk factors, levonorgestrel options represent safer choices, including Levora, Seasonale, or the Mirena IUD.
  • The increased risk with drospirenone is attributed to its antimineralocorticoid properties, which can promote hypercoagulability.

Considerations

  • The baseline risk of VTE in nonpregnant, nonusers of COCs is 1 to 5 per 10,000 woman-years, while users of drospirenone-containing COCs have a VTE risk of about 10 per 10,000 woman-years 1.
  • Patients with multiple risk factors or a history of VTE may be better suited to non-hormonal contraceptive methods or progestin-only options like the levonorgestrel IUD, which have minimal to no impact on coagulation.
  • It is essential to weigh the risks of COCs against the risks of the condition they are treating or preventing, considering the individual patient's risk factors and medical history.

Recommendations

  • For patients concerned about VTE risk, levonorgestrel-containing contraceptives are the preferred option due to their lower associated risk compared to drospirenone-containing options.
  • Healthcare providers should carefully assess each patient's individual risk factors and medical history to determine the most suitable contraceptive option.

From the FDA Drug Label

COCs containing DRSP may be associated with a higher risk of venous thromboembolism (VTE) than COCs containing levonorgestrel or some other progestins. Before initiating drospirenone and ethinyl estradiol tablets in a new COC user or a woman who is switching from a contraceptive that does not contain DRSP, consider the risks and benefits of a DRSP-containing COC in light of her risk of a VTE.

Drospirenone and VTE Risk: Drospirenone may be associated with a higher risk of VTE compared to levonorgestrel or other progestins.

  • Key Considerations:
    • Consider the risks and benefits of drospirenone in new COC users or those switching from non-DRSP contraceptives.
    • Assess the patient's individual risk of VTE before initiating drospirenone and ethinyl estradiol tablets. 2

From the Research

Venous Thromboembolism Risk with Drospirenone

  • The risk of venous thromboembolism (VTE) with drospirenone-containing oral contraceptives has been studied extensively 3, 4, 5, 6, 7.
  • A study published in 2013 found that drospirenone was associated with a 1.90-fold increased VTE relative risk compared to levonorgestrel 3.
  • Another study published in 2011 found that the risk of VTE with drospirenone-containing oral contraceptives was not significantly increased compared to other oral contraceptives 4.
  • A 2019 study found that older combined oral contraceptives with norethisterone or levonorgestrel have a lower risk for VTE than newer combined oral contraceptives with desogestrel, drospirenone, or gestodene 5.
  • A 2014 study found that the third-generation pill use, including drospirenone, is associated with an increased VTE risk as compared with second-generation pill use 6.
  • A 2010 study found that the crude incidence rate ratio for VTE in women taking a COC containing drospirenone compared to a COC containing other progestins ranged from 0.9 to 1.7 (95% CI 0.5 to 2.4) 7.

Comparison with Levonorgestrel

  • A study published in 2013 found that drospirenone and ethinyl-estradiol 20 μg (DRSP/EE20) had a 2.35-fold VTE relative risk versus levonorgestrel and ethinyl-estradiol 20 μg (LNG/EE20) 3.
  • The same study found that new users of DRSP/EE30 observed an increased relative risk versus LNG/EE30 among women starting to use COCs between 2001 and 2006, but not between 2007 and 2009 3.

Estrogen Dosage

  • A study published in 2013 found that DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41) 3.
  • The same study found that the larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 was unexpected 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Risk of venous thromboembolism with drospirenone-containing oral contraceptives.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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