This PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological... Show moreThis PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological research. Furthermore, incorporation of these variables in models of emotional information processing may be of help in understanding and treating mood disorders in women. Namely, even small biases may affect information processing and may contribute to the resilience or proneness to mood-disorders.Our research was among the first to show that the genetic makeup of healthy women may play a role in the influence of the female hormonal status on emotional information processing. Healthy female MR-haplotype 1/3 carriers may be more prone to distress, and may also be more sensitive to (pharmacological) changes which may counteract or sustain their vulnerability. Consistently, we observed subtle markers of depressogenic side-effects of OC only in MR-haplotype 1/3 carriers. Our findings regarding the MR-haplotypes 2 carriers are generally in line with earlier observations. We observed that MR-haplotype 2 carriers – especially homozygotes – are the less susceptible, more optimistic and more rational individuals, also in ‘unstressed’ conditions. However, stress-related psychopathology is very heterogeneous by nature and proteins from multiple genes are likely to interact in the stress-susceptibility phenotype. Last but not least, we should not ignore that the increased vulnerability of women to mood disorders is the result of a plethora of biological, psychological and sociological factors.OC-users had lower affect variability and reduced sensitivity to interpersonal emotional cues. This may be experienced as either a stabilizing or a blunting effect of OC, perhaps depending on the individual’s appraisal. The lower depression scores of OC-users in our longitudinal study suggests a protective effect of monophasic OC on symptoms of reproductive depression. Future studies should investigate (former) OC-users in larger cohorts including novel users, satisfied users and ‘brand-switchers’ in order to control for the survivor effect. Show less
Hamstra, D.A.; Kloet, E.R. de; Rover, M. de; Does, W. van der 2017
Non-oral delivery of ethinyl estradiol (EE) does not reduce its biochemical impact compared to oral treatment. This is in contrast to non-EE oestrogens for which differential effects of route of... Show moreNon-oral delivery of ethinyl estradiol (EE) does not reduce its biochemical impact compared to oral treatment. This is in contrast to non-EE oestrogens for which differential effects of route of delivery have been described in the literature. Furthermore, non-oral non-EE oestrogens seem to have less unfavourable impact on haemostasis parameters and SHBG than non-oral EE, as do oral non-EE oestrogens compared to oral EE. Although these conclusions follow from an indirect comparison of results, they are in line with findings on oral and non-oral hormone replacement therapy and that the risk of venous thrombo-embolism is not reduced by non-oral routes of administration of EE-containing combined hormonal contraceptives. So far, no gold standard exists for estimating the risk of cardiovascular disease during the course of development of hormonal contraceptives. This is mainly due to the lack of data on the exact mechanism of steroid-induced disease. This has resulted in a lack of consensus on which biomarkers or biomarker fractions to study. The solution would be to investigate biomarkers and the relevant clinical outcome prospectively in one study. Such a study will entail a great deal of expense, but will provide with reliable information and prove more efficient in the long term. Show less
Hamstra, D.A.; Rover, M. de; Rijk, R.H. de; Does, W. van der 2014
Since the introduction of the first contraceptive pill in 1959, the development of new hormonal contraceptives has focused on maintaining the benefits of oral contraceptives while reducing their... Show moreSince the introduction of the first contraceptive pill in 1959, the development of new hormonal contraceptives has focused on maintaining the benefits of oral contraceptives while reducing their adverse effects. Four approaches have been used to optimize the risk-benefit profile: (i) lowering of the steroid dose; (ii) development of new formulas and schedules of administration; (iii) development of new steroids and (iv) development of new routes of administration. The first objective of this thesis was to compare the multiphasic schedule of administration of oral contraceptives with the classic monophasic schedule of administration in terms of contraceptive effectiveness, bleeding pattern and discontinuation. The second objective was to predict the thrombotic risk of oral contraceptives containing the new steroid drospirenone by comparing the thrombin generation-based APC-resistance in users of pills containing drospirenone with the APC-resistance in users of pills containing other progestogens. We also focused on the biological basis of acquired APC-resistance in oral contraceptive users by studying the two main determinants of the thrombin generation-based APC-resistance test, free protein S and tissue factor pathway inhibitor free antigen. In addition, we tested the usefulness of sex hormone binding globulin as a new marker for the thrombotic risk of a hormonal contraceptive. The third objective was to estimate the thrombotic risk of contraceptives which administer steroids vaginally, transdermally or intrauterine by assessing the effect of these contraceptives on thrombin generation-based APC-resistance. At last we evaluated whether varying levels of estradiol and progesterone during a natural menstrual cycle are associated with differences in APC-resistance. Show less
Air travel has become a well-known risk factor for venous thrombosis with an absolute risk of 1 in 4600 long-haul flights and a dose-response relationship with duration and number of flights. In... Show moreAir travel has become a well-known risk factor for venous thrombosis with an absolute risk of 1 in 4600 long-haul flights and a dose-response relationship with duration and number of flights. In this thesis we studied the pathophysiology that underlies the risk as well as the effect of behaviour of passengers on the risk of thrombosis after air travel. To study the pathophysiology, we conducted a case-crossover study in which we investigated the effect on the coagulation system of 8 hours of air travel, 8 hours of immobilisation in a cinema and 8 hours of daily activities in 71 volunteers. Behaviour of passengers was studied in the MEGA study, a large case-control study on risk factors of venous thrombosis. The main conclusion of this thesis is that immobilisation alone does not explain coagulation activation after air travel. A factor that seems to contribute is hypoxia. The results of this thesis do not support the theories that fluid loss, air pollution, infection or stress play a role in coagulation activation after air travel. Certain kinds of behaviour during air travel affect the risk of venous thrombosis. Lastly, harmless prevention methods possibly counter the effect of immobilisation. Show less
