Vein 2 Worlds Collide: May–Thurner Syndrome and Oral Contraceptive Pill Use Precipitating Deep Vein Thrombosis in an Otherwise Healthy Patient

Abstract

May–Thurner syndrome (MTS) is a developmental anatomical variant in which the right common iliac artery compresses the left common iliac vein against the underlying lumbar vertebral body. This compression leads to endothelial injury, venous stasis, and progressive luminal narrowing, significantly increasing the risk of left-sided iliofemoral deep vein thrombosis (DVT). Combined oral contraceptives containing ethinyl estradiol are known to increase the risk of DVT, particularly during the initial months of use or during dose changes, with thrombotic risk persisting for up to 10 to 12 weeks after discontinuation. We present the case of a 34-year-old previously healthy female with no significant past medical history who presented with left leg swelling and lower abdominal discomfort. She had intermittently used a combined estrogen-containing oral contraceptive pill, discontinued 2 weeks prior to presentation. Imaging confirmed extensive DVT, and computed tomography venography revealed classic features of MTS, with compression of the left common iliac vein by the right common iliac artery. This case underscores the importance of evaluating structural etiologies in young patients and emphasizes the synergistic risk between hormonal and anatomical factors in precipitating a DVT. Timely diagnosis and targeted management were essential to achieving a favorable outcome.

Introduction

May–Thurner syndrome (MTS), also referred to as iliac vein compression syndrome or Cockett’s syndrome, is an anatomical variant characterized by compression of the left common iliac vein by the overlying right common iliac artery against the lumbar vertebrae. This mechanical compression predisposes affected individuals to deep vein thrombosis (DVT).^1,2 While this anatomical configuration is present in ~20% to 25% of the general population, as demonstrated by autopsy and imaging studies,^3,4 the development of symptomatic MTS remains relatively uncommon. Only 1% to 5% of individuals with the anatomical variant progress to exhibit clinical symptoms.^4,5 Among patients diagnosed with lower-extremity DVT, MTS is estimated to account for 2% to 3% of cases. MTS is most frequently observed in young to middle-aged women. ³

The clinical presentation of MTS is variable, ranging from asymptomatic venous compression to severe, recurrent thrombotic events.^6,7 Symptom onset can be gradual or abrupt, particularly in the setting of acute thrombosis. In the present case, the patient experienced sudden onset of left lower extremity swelling, tenderness, and difficulty ambulating, accompanied by mild shortness of breath and lower abdominal discomfort. Importantly, she lacked typical risk factors for venous thromboembolism (VTE), including recent surgery, trauma, or prolonged immobilization. Her only identifiable risk factor was intermittent use of estrogen-containing oral contraceptive pills (OCPs) over the preceding 2 years. In patients presenting with unprovoked DVT, especially in the absence of conventional risk factors, underlying anatomical anomalies such as MTS or inherited thrombophilias should be considered. Prompt diagnostic imaging is essential for definitive diagnosis. Referral to a vascular specialist ensures tailored management.

Case Presentation

A 34-year-old woman with no significant past medical history presented to the emergency department with new-onset left leg swelling and pain. She reported progressive swelling and discomfort over the preceding 3 days, first noticing tightness behind her left knee while bending down at home. The symptoms gradually worsened, prompting an emergency hospital visit on the fourth day due to severe pain (rated 8/10) and difficulty ambulating. On arrival, vital signs were stable (blood pressure of 106/73 mmHg, heart rate of 103 bpm, respiratory rate of oxygen saturation of 18, 100% on room air, T 98.1 °F). Body mass index of was 27.2 kg/m². The patient denied tobacco or supplement use, reported occasional alcohol use, and had no other regular medications. She denied shortness of breath, chest pain, recent immobilization, trauma, previous thromboembolic events, recent hospitalization, or any known personal or family history of clotting disorders. The patient reported intermittent use of a combined estrogen-containing OCP for ~2 years, which she discontinued 2 weeks prior to symptom onset. The specific formulation and dosage were unknown.

Lower extremity Doppler ultrasound revealed acute DVT involving the left common femoral and superficial femoral veins. No thrombus was identified in the right lower extremity. Computed tomography (CT) angiography of the abdomen and pelvis demonstrated an occlusive thrombus in the left common, internal, and external iliac veins, extending proximally to the inferior vena cava (IVC) as visualized in Figure 1. Imaging findings were consistent with MTS, characterized by compression of the inferior vena cava by the overlying right common iliac artery. Figure 2 shows an additional CT IVC narrowed to 12.32 mm, when the normal range is 20 to 30 mm. Criteria for MTS is compression of >50% of standard (25 mm). Laboratory results were within normal limits (WBC 8.3 × 10³/μL, Hgb 12.4 g/dL, Plt 269 × 10³/μL, Na 140 mmol/L, K 4.0 mmol/L, creatinine 0.59 mg/dL, prothrombin time of 10.3 s, international normalized ratio of 0.95, partial thromboplastin time of 38.9 s). A thrombophilia panel including factor V Leiden, prothrombin gene mutation, and antiphospholipid antibodies was ordered, but unavailable at the time of discharge, although later all resulted as negative or within normal limits. The patient was initiated on intravenous heparin per institutional protocol. Given the extent of thrombus burden and imaging evidence of iliac vein compression, interventional radiology was consulted. She underwent a left lower extremity venogram, mechanical thrombectomy, angioplasty, and stent placement in the left common iliac vein using a 16 × 80 mm Abre (Medtronic; Abre) stent. Postprocedure, the patient received a loading dose of clopidogrel and was resumed on heparin.

Figure 1.

CT demonstrates inferior vena cava compressed by overlying right iliac artery with yellow line demonstrating the length of impact. CT, computed tomography.

Figure 2.

CT image showing a collapsed IVC, with yellow line measuring 12.32 mm. CT, computed tomography.

A follow-up venous Doppler ultrasound the next day showed no evidence of recurrent thrombosis. The procedural site was monitored postoperatively, with suture removal on hospital day 2. The patient was discharged on apixaban 5 mg twice daily and clopidogrel 75 mg once daily, both to be continued for 6 months. She was counseled extensively regarding her new diagnosis of MTS, the associated risk of recurrence, and the critical importance of follow-up. Although a 6-month duration of therapy was prescribed, she was advised that the need for long-term anticoagulation would be reassessed based on outpatient hypercoagulability workup results. Her postoperative course was favorable, with notable improvement in leg swelling, no bleeding or new thrombotic complications, and successful wound healing. Due to the diagnosis of MTS and recent extensive thrombosis, she was advised to discontinue estrogen-containing contraceptives and was referred to gynecology for safer alternatives, including progesterone-only pills, hormonal intrauterine devices, or nonhormonal methods. This preventive approach aims to reduce the risk of recurrence and improve long-term vascular outcomes.

Discussion

Compression of the left common iliac vein against the lumbar vertebrae by the overlying right common iliac artery leads to chronic venous irritation, stasis, and luminal narrowing, thereby increasing the risk of DVT.^1,2 The repetitive pulsatile force of the overlying artery induces intimal hyperplasia and fibrosis of the vein wall, further compromising venous return. ⁸ While asymptomatic compression is relatively common, clinical symptoms typically manifest when thrombosis develops or when venous outflow becomes significantly obstructed. ⁸ MTS most commonly affects women in their third to fifth decades of life and may present with unilateral leg swelling, a sensation of heaviness, or venous claudication. In some cases, signs of chronic venous insufficiency, such as varicose veins, skin hyperpigmentation, or venous ulcers, may also be observed. ⁶ The prothrombotic effects of estrogen-containing oral contraceptives are most pronounced during the first few months of use, especially after initiating or restarting therapy, and can persist for up to 10 to 12 weeks following discontinuation due to lingering effects on hepatic synthesis of clotting factors and suppression of protein S. ⁹ Although the specific formulation of birth control for our patient was unknown, the timing of discontinuation supports a causal role in this event. ⁹ The coexistence of May–Thurner anatomy and recent estrogen exposure highlights a dual mechanism of venous thrombosis, both mechanical and biochemical. Awareness of this interaction is crucial for prompt diagnosis, comprehensive management, and preventive counseling in reproductive-age women presenting with unilateral DVT.

The initial diagnostic modality often employed is duplex ultrasonography, which is effective in detecting thrombi within the femoral and popliteal veins. However, its utility diminishes when assessing iliac vein involvement, particularly when the thrombus extends proximally beyond the inguinal ligament. ¹⁰ CT venography is preferred for visualization in such cases. ¹ Magnetic resonance venography and intravascular ultrasound are also highly sensitive in specialized settings. ⁷ Unlike standard DVT treatment, which often involves anticoagulation alone, MTS typically requires procedures to relieve the mechanical obstruction and restore flow. ²

Although the ATTRACT trial ¹¹ demonstrated that catheter-directed thrombolysis was not superior to systemic anticoagulation in the general population of patients with acute lower extremity DVT, a distinct approach is warranted in patients with MTS. In this subgroup, effective thrombus removal and restoration of venous outflow remain central to management strategies. ¹² Eligible patients should be strongly considered for pharmacomechanical thrombolysis to maximize clot clearance and allow for evaluation of underlying iliac vein stenosis. This is typically followed by angioplasty and stent placement to address the anatomical obstruction. The duration of anticoagulation and, when applicable, antiplatelet therapy after stenting is determined on a case-by-case basis, factoring in patient-specific considerations and clinical judgment. Regular follow-up is essential to reassess the need for and duration of ongoing pharmacologic therapy. Management of modifiable risk factors is also essential. In this case, the patient had a history of intermittent use of estrogen-containing OCPs, which are well-established risk factors for VTE due to their prothrombotic effects on both the coagulation cascade and endothelial function. ³ This case underscores the importance of evaluating for underlying thrombophilias even when an anatomic etiology such as MTS is evident. Identifying inherited or acquired coagulation abnormalities can inform the duration and intensity of anticoagulation therapy and guide counseling regarding recurrence risk. Although the thrombophilia work-up was pending at discharge, evaluation for inherited or acquired hypercoagulable disorders is recommended in young patients presenting with extensive DVT to inform anticoagulation duration and recurrence risk.

Conclusion

This case highlights the intersection between anatomical and hormonal risk factors in the development of DVT. While MTS is often underdiagnosed due to its subtle and chronic nature, its presence can be unmasked or exacerbated by additional prothrombotic conditions, such as estrogen-containing OCP use. Early recognition of MTS, along with prompt multidisciplinary intervention and risk modification, can prevent potentially life-threatening complications and guide long-term preventive strategies. This case underscores the importance of individualized evaluation in VTE and serves as a reminder to consider the synergistic impact of modifiable and anatomical risks in clinical decision-making. While this was the appropriate approach in this case, treatment decisions should be individualized based on thrombosis extent, symptoms, and contributing risk factors.