Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives (original) (raw)
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Stress, serotonergic function, and mood in users of oral contraceptives
Psychoneuroendocrinology, 1995
The relationship between stress and changes in insulin levels, plasma ratio of tryptophan to other large neutral amino acids (LNAAs), mood, and food intake was investigated in women taking monophasic oral contraceptives containing progestagens. Subjects experiencing high levels of stress displayed significant decreases of insulin and tryptophan to other LNAAs ratios, before and after the consumption of a standard meal during the pill-free period as compared with the period of pill use. The decline of the tryptophan to other LNAAs ratio was accompanied by worsening of mood. In a control group of subjects experiencing low levels of stress there was no relationship between insulin and tryptophan to other LNAAs ratio, nor between tryptophan to other LNAAs ratio and mood. These results suggest that the combination of stress and alterations in sex hormones may be responsible for mood changes during the pill-free period in women taking oral contraceptives.
The Effects of Hormonal Contraceptives on Cortisol Responders to Psychosocial Stress
Cortisol, an adrenocortical glucocorticoid representing a physiological stress response (Lovell et al., 2011), is frequently instigated by the Trier Social Stress Test (TSST; Kirschbaum et al., 1993), a psychosocial stress inducing procedure, which has proven to be a reliable cortisol inciting protocol (Campbell & Ehlert, 2012). Collection and analysis of salivary cortisol costs >$30 in supplies and >5 work hours/participant. Non-responding participants (identified by <15.5% cortisol increase from baseline; Miller et al., 2013) are not identified until after funds and labor have been spent to collect and analyze the data. Consequently, this data is obsolete and unacceptable for the purposes of the study. For over five years the International Neuroeconomics Institute (INI), at San Jose State University (SJSU) has been analyzing salivary cortisol activity in response to psychosocial stress, instigated by the TSST, and have been faced with 20% of their participants being classified as cortisol non-responders. Hormonal birth control has been demonstrated to be correlated with attenuated cortisol response (Kirschbaum et al., 1995; Kirschaum et al., 1999). However, it had not been determined whether it is related to the proportion of psychosocial stress induced cortisol responders. This study compared the TSST induced salivary cortisol response of 16 females who use hormonal birth control (Mage = 18.9, SD = 1.41) to 18 who do not (Mage = 18.8, SD = 1.14), revealing that females who use hormonal birth control exhibit a lower percentage of responders (56%), compared to non-birth control users (84%), and are more likely to be classified as cortisol non-responders (X2(1, 65) = 5.11, p = .02). Due to this finding, we advocate the exclusion of females who use hormonal birth control in studies that utilize psychosocial stress inducing factors, specifically the TSST.. Doing so will reduce the number of cortisol non-responders and, therefore, retain research funds.
Stress, 2014
Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While the use of hormonal birth control (HBC) is known to exert many physiological effects, including decreasing the salivary cortisol response to stress, it is unknown how HBC influences circulating cortisol levels after exogenous cortisol administration. To determine those effects, we examined the role of HBC on participants' cortisol levels after receiving synthetic cortisol (hydrocortisone) in two separate studies. In Study 1, 24 healthy women taking HBC and 26 healthy men were administered a 0.1 mg/kg body weight intravenous dose of hydrocortisone, and plasma cortisol levels were measured over 3 h. In Study 2, 61 participants (34 women; 16 were on HBC) received a 15 mg hydrocortisone pill, and salivary cortisol levels were measured over 6 h. Taken together, results from these studies suggest that HBC use is associated with a greater cortisol increase following cortisol administration. These data have important methodological implications:
Epigenomics, 2017
Current glucocorticoid replacement regimens, in adrenal insufficiency, fail to mimic the physiological cortisol secretion, thereby fostering serious side effects. Aim: To experimentally evaluate the impact of CpG methylation within the FKBP5 gene as a possible short- and long-term marker for cortisol exposure in humans. Materials & methods: An ACTH-stimulation test was carried out and methylation status of the FKBP5 gene in leukocytes was determined. Results: A negative correlation between basal levels of methylation and serum cortisol was observed. Individual changes in FKBP5 methylation after 24 h correlated with cortisol responses. Conclusion: Considering previous studies conducted with murine leucocytes, FKBP5 methylation may be suitable as a long-term biomarker, rather than acute glucocorticoid exposure, also in humans.
Cortisol Reactivity and Emotional Memory After Psychosocial Stress in Oral Contraceptive Users
Journal of Neuroscience Research, 2017
Oral contraceptive (OC) users typically show a blunted or no cortisol response to psychosocial stress. Although most OC regimens include both an inactive (dummy) and active pill phase, studies have not systematically investigated cortisol responses during these pill phases. Further, high levels of cortisol following a stressor diminish retrieval of emotional material, but the effects of stress on memory among OC users are poorly understood. We examined the effects of a psychosocial stressor, the Trier Social Stress Test, vs. a control condition on cortisol responsivity and emotional memory retrieval in women tested either during their active (n 5 18) or inactive pill phase (n 5 21). In secondary analyses, we quantitatively compared OC users with normally cycling women and showed a significant lack of cortisol response during both active and inactive pill phase. Emotional recall did not differ between active and inactive pill phases. Stress differentially diminished recall of negative words compared with positive or neutral words, but cortisol levels were unrelated to memory performance. These findings indicate that OC users have distinct cortisol and memory responses to stress that are similar between the active and inactive pill phases. V C 2016 Wiley Periodicals, Inc.
Psychoneuroendocrinology, 2018
Chronic exposure to cortisol is associated with cardiovascular, metabolic, and psychiatric disorders. Although cortisol can be readily measured from peripheral sources such as blood, urine, or saliva, multiple samplings spanning several days to weeks are necessary to reliably assess chronic cortisol exposure levels (referred to as cortisol load). Although cortisol levels in hair have been proposed as a measure of cortisol load, measurement is cumbersome and many people are not candidates due to short hair length and use of hair dyes. To date, there are no blood biomarkers that capture cortisol load. To identify a blood biomarker capable of integrating one-month cortisol exposure levels, 75 healthy participants provided 30+ days of awakening and bedtime saliva cortisol and completed psychosocial measures of anxiety, depression, and stress. Mean daily awakening and bedtime cortisol levels were then compared to CpG methylation levels, gene expression, and genotypes of the stress respon...
Frontiers in Medicine, 2020
Introduction: Hypertensive disorders are of interest in obstetrics and gynecology because they are the second place among causes of maternal mortality and a source of complications in the short, mid, and long term. Even if the pathophysiological process behind preeclampsia (PE) is still unknown, stress factors have been revealed to play an important role in the genesis of this pathologic process. Methods: A case-control study was designed with the purpose of determining if there is a differential methylation in NR3C1, HSD11B2, CYP11A1, CRHBP, TEAD3, and HSP90AA1 genes, related to signaling of the hypothalamic-pituitary-adrenal axis, and its regulation on early-onset PE (EOPE). Results: A total of 20 cases and 20 controls were studied by DNA methylation analysis, demonstrating differences among groups in the percentage of methylation of the NR3C1 gene. After a contingency analysis, an odds ratio (OR) for PE of 12.25 was identified for NR3C1 and 9.9 for HSP90AA1 genes. NR3C1, TEAD3, and HSP90AA1 genes showed a positive correlation with the systolic and diastolic blood pressure levels with a p ≤ 0.05. Conclusion: This study found a differential methylation in the glucocorticoid receptor (GR) NR3C1 and its co-chaperone HSP90AA1 in women with PE, with a possible regulatory role in the response to stress in pregnancy and is a likely physiopathological mechanism in PE.
Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study in healthy women
Acta Psychiatrica Scandinavica
VG. Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study in healthy women. Objective: Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent registerbased studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging. Methods: [ 11 C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions. Results: We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate regionbased analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (À12.8% (95% CI [À21.0; À3.9], P corrected = 0.03). Conclusion: We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.