Masters Degrees (Physiological Sciences)

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Browsing Masters Degrees (Physiological Sciences) by Author "Booyens, Renata"

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    Effects of various hormone therapies on the coagulation system
    (Stellenbosch : Stellenbosch University, 2022-12) Booyens, Renata; Pretorius, Resia; Engelbrecth, Anna-Mart; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Introduction: Untreated menopause may have serious health implications, but treatments can have dangerous side effects. Many hormone replacement therapies (HRT) are available to relieve these symptoms, such as conjugated equine estrogen (CEE) and bioidentical hormone therapy (BHT). The routes of administration include oral and transdermal. Hormones that are administered orally undergo hepatic first-pass metabolism. The by- products have lower efficacy and possibly enhanced side effects. Furthermore, hormone treatments influence the coagulation cascade through coagulation factors or their regulators, where increased coagulation poses a risk for venous thromboembolism (VTE). A definite conclusion on whether the side effects from hormone treatments exceed the risk of untreated menopause cannot be made due to insufficient research. However, a more individualised approach to hormone treatments may be the most feasible solution to this dilemma. Aims/Objectives: Firstly, we aimed to evaluate the changes in blood coagulation due to the addition of different estrogens. Thromboelastography (TEG) analysis was utilised to investigate whether estrogenic effects influence clot formation and -strength and, consequently, coagulation. furthermore, fluorescence microscopy (FM) was used to analyse platelet morphology and -activation and fibrinaloid formation. Secondly, we aimed to evaluate the changes in blood coagulation due to the use of transdermal BHT. Blood samples were collected before and three months into transdermal compounded BHT (cBHT). TEG and FM were used to evaluate the properties of clots and platelets, as mentioned for the first aim. A serum-amyloid A (SAA) enzyme linked immunoabsorbent assay (ELISA) was also conducted with these samples. Thirdly, we investigated the possibility of a more individualised approach to HRT by utilising genetic screening, amongst other tests. Results: At high concentrations, estradiol/17β-estradiol (E2) and estrone sulfate (ES) influenced the coagulability of blood samples, and these changes were seen within reaction time (R), kinetic time (K), maximal amplitude (MA), time to maximum rate of thrombus generation (TMRTG) and total thrombus generation (TTG) parameters of a TEG analysis. The addition of E2 and ES changed the platelet spreading in whole blood (WB) samples compared to the control, but no changes were seen in platelet clumping and fibrinaloid formation. ES seemed to have no effect in the platelet-rich plasma (PRP) model, but E2 increased platelet clumping and activation. No statistically significant differences existed between controls and treatments within the measured TEG parameters. However, even though not significant, R, K, and TMRTG increased slightly after treatment, indicating the possible anticoagulation properties of these treatments. The FM results showed that both the control and treatment groups resulted in moderate platelet spreading, mild platelet clumping, and moderate areas of plasma protein misfolding visible as fibrinaloids. Overall, the control group, as well as the treatment group, were ‘mildly’ coagulable. SAA levels showed a statistically significant increase for the treatment group. Genetic tests can provide insights into how a person regulates coagulation and the impact on coagulation due to variations of certain genes. Conclusion: The use of hormone treatments might promote coagulation through platelet activation, but it exhibits anticoagulation properties at high concentrations. To eliminate or decrease the effects of HRT on the risk of VTE, an individualised approach might be the most feasible at this stage.