Brain correlates of hormonal contraceptive effects on emotion and cognition
|Zusammenfassung der Sitzung|
Oral contraceptives just celebrated their 60th anniversary and are used by 150 million women worldwide. First reports that the use of combined oral contraceptives may result in altered mood date back to the 1960s. Yet, the neurobiological correlates of these side effects remain yet to be uncovered. Cognitive effects of oral contraceptives have only been investigated by a handful of studies and came up with inconsistent results due to small sample sizes and a lack of control for the contraceptive formulation used. While most combined oral contraceptives contain the same estrogen (ethinylestradiol), various different progestins are on the market. Some of these progestins act as androgen receptor agonists (androgenic progestins), while others act as androgen receptor antagonists (anti-androgenic progestins). Accordingly, these progestins might elicit different effects in those emotional and cognitive functions, which are influenced by testosterone. Thus, well-powered neuroimaging studies differentiating different contraceptive formulations are needed to understand the neurobiological underpinnings of contraceptive effects on emotion and cognition. Comparing the effects of androgenic and anti-androgenic contraceptives can also help to disentangle those effects that result from the estrogenic actions of contraceptives and those effects that result from the progestin component. In that respect, some light may also be shed by investigating the effects of selective progesterone receptor antagonists on the brain, as these likely oppose the progestagenic effects of hormonal contraceptives. In this symposium, we present current data from various labs involved in contraceptive research aiming to disentangle the various effects of different contraceptive components on the brain.
Progesterone antagonism beneficial for premenstrual dysphoric disorder
Uppsala University, Sweden
Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by late luteal phase affective, cognitive, and physical symptoms, causing significant distress in about 3-5% of women of reproductive age. Progesterone is posited to be implicated in the symptomatology, thus we tested the efficacy of a selective progesterone modulator (SPRM) for PMDD. In a multicentre, double-blind, placebo-controlled clinical trial, we demonstrated that half of the women receiving the treatment improved completely, while the corresponding proportion of women receiving placebo was 21 per cent. Furthermore, SPRM treatment was associated with enhanced reactivity in the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex during aggressive response to provocation stimuli, as assessed by functional magnetic resonance imaging. The mechanism of action of the study drug provides insights into the potential molecular mechanisms underlying this psychiatric disorder and its treatment, suggesting a beneficial effect of progesterone receptor antagonism on top-down emotion regulation.
The predictive role of (synthetic) sex hormones in hippocampal and amygdala grey matter volumes
1Psychiatry and Psychotherapy, University of Tübingen, Germany; 2University of Amsterdam, Netherlands; 3Women’s and Children’s Health, University of Uppsala, Sweden
Worldwide oral contraceptives (OC) are one of the most prescribed medication with millions of female users. OC use suppresses endogenous hormone levels (i.e., estradiol (E2) and progesterone (P)) by creating a negative feedback loop with the addition of synthetic hormones. Endogenous and synthetic sex hormones can pass the blood brain barrier and bind to brain regions with high densities of E2 and P receptors such as the hippocampus and the amygdala. Previous studies reported a generally reduced grey matter (GM) volume in these areas in OC users. However, findings are mixed. The aim of our study was to test the potential predictive role of endogenous and synthetic sex hormones, as well as of intake duration and OC androgenicity in GM volume of hippocampus and amygdala.
The GM volumes of hippocampus and amygdala of 48 OC users were compared to 66 naturally cycling (NC) women (i.e., early follicular: n = 36, peri-ovulatory: n = 30) using Freesurfer software on the collected MP2Rage images. OC women had a significantly smaller hippocampal GM volume compared to NC women, but there was no difference for the amygdala. Interestingly, preliminary regression analyses showed that for the hippocampus OC intake duration was a positive predictor for GM volume, whereas for the amygdala there was a significant interaction between intake duration and OC androgenicity. Potential implications of these results for previously found mixed findings regarding the influence of OCs on hippocampal and amygdala GM volumes will be discussed.
Women's ability to regulate emotions: relationship with personality, sex steroids and hormonal contraceptives
1Department of Neurobiology and Biophysics, Vilnius University, Lithuania; 2University of Würzburg, Germany; 3Institute of Psychology, University of Tartu, Estonia; 4Department of Psychiatry and Psychotherapy, University of Tübingen, Germany
Emotion regulation plays a key role in everyday life: it can impact our health, personal relationships and psychological well-being. How people experience and regulate emotions is strongly connected with various psychological and biological factors, such as personality traits, emotion regulation strategies, hormones. In this study we examined how use of hormonal contraceptives is related to emotion regulation as a trait and a state.
57 women (27±4.38 years) participated in the study (9 oral contraceptive users, 9 intrauterine device users, 27 women in follicular and 11 women in luteal phase of their menstrual cycle). In emotion regulation task participants were instructed to simply view the pictures or use reappraisal strategy to down-regulate or up-regulate emotions towards low and high intensity negative images. The electroencephalogram (EEG) was recorded. The late positive potential (LPP) and global field power (GFP) were calculated for each group and condition. Participants rated perceived negativity after each stimulus. Resting state EEG was used to assess frontal alpha asymmetry (FAA). Saliva samples were collected to determine sex steroid concentrations.
Perceived negativity was lower in down-regulation and higher in up-regulation compared to viewing condition. High and low intensity negative pictures induced higher LPP amplitude than neutral images. LPP amplitude was higher for all emotion regulation conditions in comparison to viewing condition. LPP amplitude did not differ between hormonal contraceptive users and naturally cycling women. Oral contraceptive users tended to have higher GFP versus naturally cycling women. FAA analysis revealed that higher left frontal activity was related to better emotion down-regulation.
Effects of oral contraceptive intake duration on verbal fluency and navigation
Universität Salzburg, Österreich
In this study, we investigated whether the current intake duration and prior use of combined oral contraceptives (COC) have an impact on grey matter volume, neuronal activity and performance during a navigation and verbal fluency task depending on the androgenicity of the progestin contained in the COC. We report preliminary results from thirty-one women taking androgenic COC (Levonorgestrel & Ethinylestradiol), thirteen women taking anti-androgenic COC (Drospirenone/Chlormadinone acetate & Ethinylestradiol) and 60 women with natural cycle (NC), who performed a verbal fluency and navigation task in the fMRI during the active intake phase (COC) or during menstruation (NC).
Both current and previous intake duration of COC was found to be related to GM volumes, brain activity and performance in the verbal fluency and navigation task. Importantly, opposite effects were observed depending on the androgenicity of the progestin. Unexpectedly, particularly anti-androgenic COC seem to have a positive impact on navigation, but a negative impact on verbal fluency. These findings suggest that the effect of COC use on brain and cognition accumulates over time, with some effects still visible after discontinuation of contraceptive treatment.