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Event-Related Potentials in Women on the Pill: Neural Correlates of Positive and Erotic Stimulus Processing in Oral Contraceptive Users.

ABSTRACT: Background/Aims: Exposure toward positive emotional cues with - and without - reproductive significance plays a crucial role in daily life and regarding well-being as well as mental health. While possible adverse effects of oral contraceptive (OC) use on female mental and sexual health are widely discussed, neural processing of positive emotional stimuli has not been systematically investigated in association with OC use. Considering reported effects on mood, well-being and sexual function, and proposed associations with depression, it was hypothesized that OC users showed reduced neural reactivity toward positive and erotic emotional stimuli during early as well as later stages of emotional processing and also rated these stimuli as less pleasant and less arousing compared to naturally cycling (NC) women. Method: Sixty-two female subjects (29 NC and 33 OC) were assessed at three time points across the natural menstrual cycle and corresponding time points of the OC regimen. Early (early posterior negativity, EPN) and late (late positive potential, LPP) event-related potentials in reaction to positive, erotic and neutral stimuli were collected during an Emotional Picture Stroop Paradigm (EPSP). At each appointment, subjects provided saliva samples for analysis of gonadal steroid concentration. Valence and arousal ratings were collected at the last appointment. Results: Oral contraceptive users had significantly lower endogenous estradiol and progesterone concentrations compared to NC women. No significant group differences in either subjective stimulus evaluations or neural reactivity toward positive and erotic emotional stimuli were observed. For the OC group, LPP amplitudes in reaction to erotic vs. neutral pictures differed significantly between measurement times across the OC regimen. Discussion: In this study, no evidence regarding alterations of neural reactivity toward positive and erotic stimuli in OC users compared to NC was found. Possible confounding factors and lines for future research are elaborated and discussed.

SUBMITTER: Schmidt NM

PROVIDER: S-EPMC8764149 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We recently investigated the effects of the noradrenergic antidepressant reboxetine and the antipsychotic amisulpride compared to placebo on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects. Whereas, amisulpride left subjective sexual functions and corresponding neural activations unimpaired, attenuated neural activations were observed under reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral sexual functioning. However, a global dampening of the reward system under reboxetine seemed not intuitive considering the complementary role of the noradrenergic to the dopamine system in reward-related learning mediated by prediction error processing. We therefore investigated the sample of 17 healthy males in a mean age of 23.8 years again by functional magnetic resonance imaging (fMRI), to explore the noradrenergic effects on neural reward prediction error signaling. Participants took reboxetine (4 mg/d), amisulpride (200 mg/d), and placebo each for 7 days within a randomized, double-blind, within-subject cross-over design. During fMRI, we used an established monetary incentive task to assess neural reward expectation and prediction error signals within the bilateral Nacc using an independent anatomical mask for a region of interest (ROI) analysis. Activations within the same ROI were also assessed for the erotic picture paradigm. We confirmed our previous results from the whole brain analysis for the selected ROI by significant (p < 0.05 FWE-corrected) attenuated activations within the Nacc during visual sexual stimulation under reboxetine compared to placebo. However, activations in the Nacc concerning prediction error processing and monetary reward expectation were unimpaired under reboxetine compared to placebo, along with unimpaired reaction times in the reward task. For both tasks, neural activations and behavioral processing were not altered by amisulpride compared to placebo. The observed attenuated neural activations within the Nacc during visual erotic stimulation along with unimpaired neural prediction error and monetary reward expectation processing provide evidence for a differential modulation of the neural reward system by the noradrenergic agent reboxetine depending on the presence of primary reinforcers such as erotic stimuli in contrast to secondary such as monetary rewards.

Project description:BackgroundVenous thromboembolism (VTE) is a complex multifactorial disease influenced by genetic and environmental risk factors. An example for the latter is the regular use of combined oral contraceptives (CC), which increases the risk to develop VTE by 3 to 7 fold, depending on estrogen dosage and the type of progestin present in the pill. One out of 1'000 women using CC develops thrombosis, often with life-long consequences; a risk assessment is therefore necessary prior to such treatment. Currently known clinical risk factors associated with VTE development in general are routinely checked by medical doctors, however they are far from being sufficient for risk prediction, even when combined with genetic tests for Factor V Leiden and Factor II G20210A variants. Thus, clinical and notably genetic risk factors specific to the development of thrombosis associated with the use of CC in particular should be identified.Methods and findingsStep-wise (logistic) model selection was applied to a population of 1622 women using CC, half of whom (794) had developed a thromboembolic event while using contraceptives. 46 polymorphisms and clinical parameters were tested in the model selection and a specific combination of 4 clinical risk factors and 9 polymorphisms were identified. Among the 9 polymorphisms, there are two novel genetic polymorphisms (rs1799853 and rs4379368) that had not been previously associated with the development of thromboembolic event. This new prediction model outperforms (AUC 0.71, 95% CI 0.69-0.74) previously published models for general thromboembolic events in a cross-validation setting. Further validation in independent populations should be envisaged.ConclusionWe identified two new genetic variants associated to VTE development, as well as a robust prediction model to assess the risk of thrombosis for women using combined oral contraceptives. This model outperforms current medical practice as well as previously published models and is the first model specific to CC use.

Project description:ImportanceHormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation.ObjectiveTo evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs.Design, setting, and participantsThis case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria.ExposureCOC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses.Main outcomes and measuresNegative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed.ResultsA total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause.Conclusions and relevanceIn this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.

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Event-Related Potentials in Women on the Pill: Neural Correlates of Positive and Erotic Stimulus Processing in Oral Contraceptive Users.

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