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
Barele, M. van; Heemskerk-Gerritsen, B.A.M.; Doorn, H.C. van; Schmidt, M.K.; Hooning, M.J.; Jager, A. 2020
Introduction: Hormone replacement therapy can diminish hormone depletion -related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Re-... Show moreIntroduction: Hormone replacement therapy can diminish hormone depletion -related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Re- covery of menstruation after chemotherapy -induced amenorrhea in young hormone receptor -negative BC patients however, is accepted. To determine the safety of this strategy, we investigated the effect of recovery of menstruation on disease -free survival (DFS) and overall survival (OS) in young hormone receptor -negative BC patients treated with (neo)adjuvant chemotherapy. Methods: We selected 636 patients from a single -center cohort with early stage hormone receptor - negative BC and under the age of 50 years when treated with chemotherapy. Suf ficient data on course of menstruation in medical records was retrospectively found for 397 patients, of whom 299 patients (75%) had a recovery of menstruation after chemotherapy. We used Cox proportional hazards models to estimate hazard ratios (HR) for the effect of recovery of menstruation on DFS and OS. Results: Patients with recovery of menstruation after chemotherapy less frequently had lymph node involvement at diagnosis (45% vs 66%, p = 0.001). After a median follow-up of 6.7 years, the adjusted hazard ratios were 1.45 (95% CI: 0.83-2.54) for DFS and 1.19 (95% CI: 0.71-1.98) for OS. Conclusion: No signi ficantly increased recurrence risk was found for hormone receptor -negative BC patients with recovery of menstruation after chemotherapy. However, the outcome of the multivariable model is not reassuring and a potentially increased recurrence risk cannot be excluded. The results need to be validated in a larger prospective study for a more de finitive answer. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Hamstra, D.A.; Kloet, E.R. de; Rover, M. de; Does, W. van der 2017
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
