Women are more likely to develop Thoracic Outlet Syndrome (TOS) symptoms, according to previous data1,2. While anatomic and mechanical factors, along with variations in pain perception, are suspected to contribute, the precise underlying causes for the difference in incidence between men and women remain uncertain. This article aims to present current data and evidence regarding the specifics of TOS in women.

Neurogenic TOS (nTOS) is the most common form of TOS in women, as in men, in a 3.5:1 proportion1,2. However, the precise incidence remains unknown, and distinguishing it from other painful upper arm conditions can be challenging 3.

NTOS generally comprehend symptoms of pain, weakness, paresthesia, which can occur in the arm, shoulder, back and hand. The social and psychological impact includes sleep disturbances, chronic pain, and work absenteeism due to severe disability4,5.

Several factors can contribute to nTOS, with repetitive trauma being a commonly recognized cause. Very often patients with nTOS are young and active women6. Other causes include automobilist accident and falls3, and this can be often the predisposing factor to a previously asymptomatic patient, as some occupational injuries7.

There are mainly three anatomic points of compression: the costoclavicular space, the interscalene triangle and the space behind the pectoralis minor muscle. Anatomical differences between genders may play a role, with cadaveric studies revealing a smaller interscalene triangle in women 8. Other differences such as heavy breasts in women 8 might possibly narrow the costoclavicular space, however there is no scientific evidence that this can relate do nTOS after extensive literature review8. Predisposing anatomical factors, such as cervical or first rib abnormalities and congenital muscle bands, are more common in women than in men 8,9. Even though these anatomical differences between men and women could play a role in differences in prevalence, there is still no scientific evidence that would explain them.

Diagnosis is difficult due to overlapping symptoms of nTOS and other painful disorders of the upper extremity. The Roos test (elevated arm stress test) stands out as the most valuable individual examination for nTOS10. Scores, such as the Disabilities of the Arm, Shoulder, and Hand (DASH) score, are frequently used to aid in diagnosis 10,11.

Imaging studies are often normal or nonspecific. However, obtaining a plain cervical and chest radiograph is important to rule out cervical rib or elongation of the process of the seventh vertebra12. Magnetic resonance imaging (MRI) is the preferred imaging modality due to its ability to provide a clear view of the thoracic inlet 712. Electrophysiological studies can assist in diagnosing TOS and excluding other possible conditions like carpal tunnel or cubital tunnel syndromes8.

The question of whether surgery is superior to conservative treatment remains a topic of discussion. Conservative treatments, including physiotherapy, posture improvement, and lifestyle adjustments, are often recommended for nTOS patients, and should be tried before considering surgical intervention10. Other modalities of conservative treatment include scalene botulin toxin and local anesthesia injections12,13, which are increasingly used for diagnostic purposes12,14. However, when a clear bony structure, such as a cervical rib, is present, surgery may be necessary12. Recent research suggests better outcomes for patients who undergo surgical treatment after persisting with symptoms despite conservative measures15, but no gender differences where noted This aspect, particularly in relation to women, warrants further analysis. As for better results with primary surgical treatment for men or women, data can be conflicting. While some have reported worse results for women, specifically in post trauma nTOS16, others have found no significative difference among clinical outcomes favoring one gender or the other17.

Multidisciplinary approach to nTOS has been reported with beneficial impact during diagnosis and rehabilitation, whether surgery has been performed or not. No gender differences were reported regarding impact of multidisciplinary approach18.

Venous TOS (vTOS) is a rare condition that affects 3-5% of patients with TOS9. The syndrome is defined by the compression and thrombosis of the axillosubclavian vein through its exit from the thoracic cavity, the costoclavicular junction in the thoracic outlet, associated with repetitive trauma and anatomic predisposition19. The pectoralis minus syndrome, caused by increased compression of the neurovascular structures in the subpectoral tunnel, which can be a cause of vTOS, has been more frequently reported in women20. Women, according to the literature, are more likely to possess predisposing factors for vTOS, although presenting symptoms like men. A few risk factors are more frequent in women such as hypercoagulable acquired states, for example pregnancy and oral contraceptives21.

The disease normally affects young and healthy individuals, and its development may be contributed by muscle hypertrophy of anterior scalene or subclavian muscle, frequently in athletes or in manual labors that require high-resistance upper extremity activities, leading to some of the work-related musculoskeletal disorder. Furthermore, it tends to be unilateral and most often affects the dominant upper limb.

VTOS can be composed by intermittent position obstruction, worse with the elevation of the arm (when the vein is still opened) and primary axillosubclavian vein occlusion (effort thrombosis or Paget Schorotter syndrome), distinguished by the secondary thrombosis, usually related to catheter injury or infections22.

VTOS is characterized by symptoms of arm swelling, collateral vein presence on the chest wall and upper extremity and axillosubclavian vein thrombosis. Physical exam may show collateral veins across shoulder, back, chest, arms and neck, pain with the palpation near the clavicle (above and below) areas of pallor, skin discoloration and non-pitting edema. Patients can refer sensation of heaviness of upper limbs and pain of arms ascending to the neck through all this trajectory. Risk factors include post-surgery, cancer, trauma and other hypercoagulable states, radiation therapy and chemotherapy, and placement of catheters, mainly when mispositioned or infected5,22.

Diagnosis of vTOS include symptomatology and imaging studies (such as chest x-ray, duplex ultrasound, MR, CT and venography). In this context, duplex ultrasound of the axillosubclavian venous complex has 97% of sensitive (95 % confidence interval (CI), 90–100 %) and 96% of specify for the diagnosing vTOS (95 % CI, 87–100 %)23. Ultrasound, therefore, has a large importance for vTOS and performs the main role in its diagnosis. Images must include the complete evaluation of axillary and subclavian veins, with their view in transverse and longitudinal section in grayscale and in Doppler spectral with the analysis of the waveform both at rest and stressing positions (abduction of the arm at 90 and 180°).

Ongoing developments in the diagnosis of the condition include dynamic CTa, MRI neurography and Diffusion Tensor Imaging9. Although frequently used, provocative maneuvers for eliciting signs of neurovascular impingement are often inaccurate. One of the most famous for vascular TOS is the Adson's test, which consist in chin elevation, neck extension and rotation of the head toward the affected side. The test would be considered positive with the loss of a palpable radial artery pulse while deep inspiration21.

Management of vTOS depends on the etiology of the condition. However, initial treatment consists of conservative measures, that need to be trialed for at least four to six months to consider surgical intervention24. Modifications of behaviors (avoiding provocative activities and arm positions), individually training programs focusing on strengthening pectoral muscles and restoring normal posture, weight control, relaxation techniques and pharmacologic therapies are some examples of conservative regimens for vTOS with positive results9,25. Nevertheless, definitive treatment of vTOS involves its mechanical decompression. Anticoagulation may also be used, mainly in those cases presented by primary thrombosis. Options include vitamin K inhibitor with warfarin, inhibition of antithrombin III with enoxaparin and new oral anticoagulants (NOACs)5.

Women have the distinct characteristic of the gestational period. During pregnancy and the postpartum period, patients face a four to fivefold increased risk of developing deep vein thrombosis (DVT) compared to non-pregnant patients26. When deemed necessary, heparin has been demonstrated as a safe option for preventing thromboembolism, with minimal associated risks to the developing fetus27. In comparison to men, there have been no studies comparing the efficacy or complications associated with different anticoagulant regimens among male or female patients presenting with vascular TOS5.

Concerning invasive forms of treatment, after failure of conservative measures, surgical options vary from: resection of the first rib, resection (inferior to the vein) of the anterior scalene muscle (lateral to the vein) and endovascular or open revascularization. Regarding the last one, there is no evidence of variations in approach for each sex, although literature shows biases in the decision of treatment of patients with chronic pain, in which nonoperative techniques are more common in women compared to men for some conditions5.

VTOS is by far more common in women. Nevertheless, a notable gap persists in the existing literature and healthcare practices when it comes to understanding and addressing gender-specific variations in vTOS. Thus, sex-related differences in etiology, signs, symptomatology, and treatment of vTOS should be better analyzed to provide high quality assistance for male and female patients with this relatively uncommon yet debilitating disorder.

Arterial thoracic outlet syndrome (aTOS) is defined by the compression of the subclavian artery as it exits the thoracic girdle. It is associated with an anatomic abnormality, generally a cervical rib 28,29. The pathophysiological mechanism is that chronic and repetitive compression on the subclavian artery causes arterial wall damage and may lead to fibrosis, stenosis, post-stenotic dilatation, aneurysm, thrombotic occlusion, or embolization 30. This is the least common form of TOS, with an incidence of 1-5% of all cases. Although cervical ribs and other anatomic abnormalities are twice as common in women than men, there is no body of evidence to suggest that aTOS occurs more frequently in women than men 31,32. Despite being rare, aTOS has severe and potentially debilitating clinical presentations in both sexes, including arm claudication, aneurysm, acute limb ischemia, and distal embolization 33.

The clinical presentation of aTOS varies greatly 28. However, the correct definitions should be used, so that this syndrome may not be confused with other forms of TOS 34. The 2016 Reporting standards of the Society for Vascular Surgery for thoracic outlet syndrome 35 defined it as the existence of symptomatic ischemia or objective arterial damage (stenosis, post-stenotic dilatation, aneurysm, occlusion, or embolizing ulceration) in the presence of an anatomic abnormality within the thoracic outlet. 3634 aTOS primarily affects active young adults 37–39. Eventually, it can also affect patients in their fifties and sixties after a long and delayed history13. In most cases, a cervical rib is the anatomic abnormality that causes compression11,12,14.

A recent study reported the authors’ experience 40. In a total of 278 cases of TOS, 13 patients (13 / 278 = 4.7%) had aTOS. Eleven (85%) were women. Most patients presented in a chronic stage, with arm claudication (stenosis or occlusion) or neck mass (aneurysm). Previous metanalysis on prevalence of cervical ribs also showed a higher prevalence in women, even in a healthy population. When aTOS is diagnosed women will get more surgery than men41.

A combination of clinical history, physical examination, and imaging exams makes the diagnosis of aTOS 42. Provocative maneuvers can help diagnose the condition, but they are not pathognomonic 43,44. Plain X-rays of the cervical region can reveal a cervical rib (Figure 1), an elongated C7 transverse process, or a clavicle callus 45. Duplex ultrasound can also image the subclavian artery, although the clavicle may limit adequate visualization 46.

Computed tomography angiography (CTa) and magnetic resonance imaging angiography (MRIa) can demonstrate the subclavian artery pathology and determine the anatomic abnormalities.47Digital subtraction angiography may not provide adequate imaging in aneurysms, as the contrast fills the lumen, not the vessel wall. However, it can be a valuable tool in cases where more detail about the arterial outflow in the arm is necessary. This information is essential in planning surgical reconstruction 45.

The treatment of aTOS is surgical 29. Conservative measures should not be used to treat aTOS, as this is associated with complications such as thrombosis and distal embolization. These complications can cause significant disability and even limb loss 30,38. There are no data to suggest sex-based differences in prognosis or treatment outcomes for aTOS 32.

Three principles guide the surgical strategy: decompression, arterial resection, and vascular reconstruction. Decompression involves the resection of the cervical rib, ligamentous bands, the anterior and the middle scalene muscles, and other associated abnormalities (Figure 2). Some authors advocate that the first rib should be routinely removed in aTOS 48. Others propose that the first rib must be selectively removed when it is abnormal or causing compression 38. This “rib-sparing approach” results in less morbidity, lower risk of pleural or plexus injury, and shorter hospital stay 30,40,49.

After adequate decompression, the need for arterial resection and vascular reconstruction is determined by the damage the subclavian artery, based on imaging and intraoperative findings 50. 3034

Aneurysms, thrombotic occlusions, or embolizing ulcerations require resection and vascular reconstruction. Removal of the affected arterial segment is mandatory. The appropriate vascular reconstruction depends on the extent of subclavian artery resection 29,30. The preferred conduit for the graft is the thigh great saphenous vein due to its availability, resistance to infection, and flexibility. These characteristics are desirable in an area that is subjected to high levels of motion, such as the thoracic outlet 40. 34

The preferred approach for surgical treatment of aTOS is the supraclavicular 29,34,40,46. This approach provides a broad exposure of the thoracic outlet structures, enabling the removal of the anterior and middle scalene muscles, the cervical rib, and the first rib. It also permits the aneurysm resection and the appropriate vascular reconstruction (Figure 2). When a bypass or an interposition graft is necessary, an infraclavicular incision is usually added to obtain distal axillary artery control.

The transaxillary approach can decompress the thoracic outlet by removing the first rib without manipulating neurovascular structures 51. This approach can be facilitated by videothoracoscopy 52. However, since this approach does not allow for adequate arterial and reconstruction, its value in aTOS is limited.

Endovascular techniques are not recommended as the primary treatment for aTOS 34,46,53. The bony compression often results in the fracture of endovascular devices and concomitant arterial thrombosis. The mechanical forces present at the thoracic outlet can easily break even the strongest stent or stent-graft 28,29. Although some recent studies have reported subclavian stenting in conjunction with surgical decompression, there is still a higher risk of stent fracture and thrombosis 54.

Although cervical ribs are more prevalent in women, and the majority of operated patients for this condition are women, there is no data suggesting differences in outcomes between sexes. Nor should the indications for intervention be different in patients with aTOS.