Thrombosis Australia

PCOS is a hormonal disorder and is described as having an excess of androgen hormones which can affect the menstrual cycle. PCOS is one of the most common endocrine system and reproductive disorders among women, with the global prevalence in 2020 being 5-20%.

PCOS is not well understood and is multifaceted, affecting not only the reproductive system, but also the metabolic and cardiovascular systems. In 2020, research found that women with PCOS have a 1.5-2.0-fold increased risk of venous thromboembolism (VTE) compared to women without the condition.

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Signs and symptoms

Symptoms of PCOS vary, however a diagnosis is commonly made when there are at least two of the following present:

• Irregular periods – few or irregular periods; or periods which last for many days or longer than is typical. You may also have trouble getting pregnant.
• High levels of androgen resulting in excess facial and/or body hair.
• Polycystic ovaries – ovaries might be bigger and may not work the way they should.

Signs and symptoms are typically more severe in people with obesity.

Research

Being overweight and the use of oral contraceptives (OCP) increases the risk of VTE. However, research findings suggest that PCOS itself is a risk factor for VTE, and the association may not be completely generated by excess weight and OCP use.

It is suggested that the increased risk of VTE in women with PCOS is associated with:

• the level of endogenous estradiol – estradiol is the most potent member of the class of steroid hormones and controls development and maintenance of female sex characteristics referred to the ‘female hormone’; (endogenous means from an internal cause or origin).
• sex -hormone binding globulin (SHBG) – a protein important in transporting sex hormones and regulating their bioavailability.
• free androgen production – androgens are a group of hormones that primarily influence the growth and development of the male reproductive system (mainly testosterone).

Patients with PCOS appear to exhibit a prothrombotic state with altered coagulation and fibrinolysis (normal process which prevents blood clots from growing – breakdown of clots).

Coagulation risk factors for PCOS

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Research has found that women with PCOS have decreased levels of:

• Prothrombin time (PT) – is a test to evaluate blood clotting; prothrombin is a protein which is one of the factors in the blood that helps it to clot properly.
• Thrombin time (TT) – measures fibrin formation caused by the action of thrombin which is the final step in the coagulation cascade; measured in seconds, it is the time it takes for fibrin clot formation.
• Activated partial thrombin time (APTT) – this test measures how long it takes for the blood to form a clot.

and increased levels of:

• Fibrin degradation products (FDP) – substances that remain in your bloodstream after your body dissolves a blood clot; the fibrinolytic or clot-busting system manages and regulates clot dissolving. FDP is found in high concentrations in menstrual blood.
• Fibrinogen (FG) – a protein produced by the liver which helps blood clots to form.
• D-Dimer (DD) – a protein fragment that is made when a blood clot dissolves.

The research found that a combination of PT, TT, and FDP reflected a hypercoagulable state and a disturbance of the haemostatic system (a sequence of responses that stops bleeding).

Oral contraceptive pill (OCP)

OCP has been found to be a treatment option for women with PCOS as it helps to improve hormonal profile, decrease clinical symptoms, and restore the menstrual period cycle. However, research results have shown worsening of metabolic parameters and coagulopathy pathway associated with OCP use, therefore increasing VTE risk among these women.

References

• Gariani, K. et al. (2020). Association between polycystic ovary syndrome and venous thromtoembolism: a systematic review and meta-analysis. Thromb Res. 185: 102-108.
• Machin, N. & Ragni, M.V. (2020). Hormones and thrombosis: risk across the reproductive years and beyond. Translational Research 225: 9-19.
• Manzoor, S. et al. (2021). Analysis of intrinsic and extrinsic coagulation pathway factors
• in OCP treated PCOS women. Ind J Clin Biochem 36(3):278-287.
• Micaily, I. & Bannow, B.T.S. (2021). VTE and anticoagulation in menstruating women. Thrombosis Update.
• Scheres, L.J.J. et al. (2019). Endogenous sex hormones and risk of venous thromboembolism in young women. J Thromb Haemost 17: 1297-1304.
• Sun, Q. et al. (2019). Coagulation parameters predictive of polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biolocy, 240: 36-40.
• Tortora, G.J., & Grabowski, S.R. (2003). Principles of anatomy and physiology, 10th edition. USA: John Wiley & Sons, Inc.
• Wang, Y. (2021). Definition, prevalence, and risk factors of low sex hormone-binding globulin in US adults. J Clin Endocrinol Metab 106.
• Zhu, J. et al. (2019). Sex hormone-binding globulin and polycystic ovary syndrome. Clinica Chimica Acta 499: 142-148.
• Polycystic ovary syndrome (PCOS) – Symptoms and causes – Mayo Clinic
• Androgen | hormone | Britannica
• Estradiol – an overview | ScienceDirect Topics
• Prothrombin time test – Mayo Clinic
• Thrombin Time – an overview | ScienceDirect Topics
• Fibrinogen Degradation Product – an overview | ScienceDirect Topics
• Fibrin Degradation Products (FDP): What Is it? (healthline.com)
• Deep vein thrombosis (DVT) – Symptoms and causes – Mayo Clinic
• Fibrinolysis – primary or secondary: MedlinePlus Medical Encyclopedia
• Activated Partial Thromboplastin Clotting Time – Health Encyclopedia – University of Rochester Medical Center
• Fibrinogen blood test: MedlinePlus Medical Encyclopedia
• D-Dimer Test: MedlinePlus Medical Test

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