Combined oral contraceptive pills (OCPs) are widely used for pregnancy prevention, but they carry a small, yet significant, risk of venous thromboembolism (VTE). VTE is the formation of a blood clot in a deep vein, which can manifest as deep vein thrombosis (DVT) or a life-threatening pulmonary embolism (PE). While the absolute risk of VTE for OCP users remains low (around 3 to 9 cases per 10,000 women per year), this risk is three to four times higher than in non-users. The risk level is not uniform across all pill formulations and varies based on the specific hormones and dosages used.
How Oral Contraceptives Increase Clotting Risk
The increased risk of blood clots stems primarily from the estrogen component in combined OCPs, specifically ethinyl estradiol. Estrogen influences the liver’s production of clotting factors, leading to hypercoagulability, or increased readiness to clot. This shifts the body’s natural balance toward clot formation. Higher estrogen doses correlate with a greater pro-clotting effect.
The estrogen component increases the plasma concentration of several coagulation factors (including factors II, VII, VIII, and X) and affects inhibitors of the clotting cascade. This process can lead to acquired resistance to activated protein C (APC), a natural anticoagulant. The progestin component plays a secondary modulatory role, either amplifying or mitigating the estrogenic effect. Since VTE risk is absent in progestin-only contraceptives, estrogen is confirmed as the main risk factor.
Comparing Clot Risk Across Different Pill Generations
The combined OCP associated with the lowest VTE risk generally contains the lowest effective dose of estrogen combined with the progestin levonorgestrel. Levonorgestrel is a second-generation progestin. Pills containing 30 micrograms (mcg) of ethinyl estradiol paired with levonorgestrel are considered the baseline for the lowest relative VTE risk. The absolute risk for VTE in users of these OCPs is estimated to be approximately 10 cases per 10,000 women per year.
Newer formulations, including third and fourth-generation pills, typically carry a statistically higher VTE risk compared to levonorgestrel-containing pills. Third-generation progestins (desogestrel and gestodene) and the fourth-generation progestin drospirenone are associated with a relative VTE risk 50% to 80% higher than levonorgestrel. The absolute risk for VTE with these newer progestins is estimated to be around 20 cases per 10,000 women per year.
This difference is thought to be due to how newer progestins interact with estrogen, often having a weaker ability to counteract the estrogen’s effect on coagulation factors. Desogestrel, gestodene, and drospirenone may cause a greater increase in clotting factors, such as factor VII, compared to levonorgestrel. Therefore, formulations containing levonorgestrel and a low estrogen dose (20 to 30 mcg) are generally the preferred choice for minimizing VTE risk among combined OCPs.
Individual Health Factors That Elevate Risk
An individual’s pre-existing health profile plays a significant role in determining total VTE risk, regardless of the pill’s formulation. Hormonal contraceptives are not recommended for women with a personal history of VTE or inherited clotting conditions (thrombophilias). Having a genetic mutation, such as Factor V Leiden, can increase VTE risk up to six times during the first two years of OCP use.
Several acquired factors compound the risk when combined with OCP use. Smoking is a major concern, particularly for women over 35, and is a contraindication for combined hormonal contraception. Obesity (high BMI) independently elevates VTE risk; women under 40 who are obese face a five-fold higher risk compared to non-obese women. Other factors include prolonged immobility (extended bed rest or long-distance travel) and a strong family history of VTE. A thorough medical history review is necessary to assess cumulative risk before starting any combined oral contraceptive.
Recognizing Symptoms of a Blood Clot
Recognizing the signs of a blood clot requires immediate medical attention. A deep vein thrombosis (DVT) commonly occurs in the leg, presenting with specific symptoms that should not be ignored. Signs of a DVT include sudden swelling, usually in only one leg or arm, accompanied by pain or tenderness that may feel like a severe cramp. The affected area may also feel warm to the touch and appear reddish or discolored.
A pulmonary embolism (PE) occurs if the clot travels to the lungs, which is a life-threatening emergency. Symptoms of a PE include the sudden onset of shortness of breath unexplained by exertion. Other warning signs are sharp, stabbing chest pain that often worsens with a deep breath or coughing, and a rapid or irregular heart rate. An unexplained cough (sometimes bringing up bloody mucus), light-headedness, or passing out necessitate calling emergency services immediately.