Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness

Petersen, Nicole; Kearley, Nicholas W; Ghahremani, Dara G.; Pochon, Jean‐Baptiste; Fry, Megan E.; Rapkin, Andrea J.; London, Edythe D.

doi:10.1038/s41380-020-00990-2

Cited by 27 publications

(12 citation statements)

References 57 publications

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“…Evidence increasingly points to considerable effects on brain circuitry and structure following administration of metabolic hormones in form of OC-use [e.g., (26,27,57)], however, we do not fully understand the action of OCs on brain and behavior. The present null finding extends the scarce literature on OCeffects on value-based decision-making, especially on the behavioral level.…”

Section: Discussionmentioning

confidence: 99%

No Differences in Value-Based Decision-Making Due to Use of Oral Contraceptives

et al. 2022

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Fluctuating ovarian hormones have been shown to affect decision-making processes in women. While emerging evidence suggests effects of endogenous ovarian hormones such as estradiol and progesterone on value-based decision-making in women, the impact of exogenous synthetic hormones, as in most oral contraceptives, is not clear. In a between-subjects design, we assessed measures of value-based decision-making in three groups of women aged 18 to 29 years, during (1) active oral contraceptive intake (N = 22), (2) the early follicular phase of the natural menstrual cycle (N = 20), and (3) the periovulatory phase of the natural menstrual cycle (N = 20). Estradiol, progesterone, testosterone, and sex-hormone binding globulin levels were assessed in all groups via blood samples. We used a test battery which measured different facets of value-based decision-making: delay discounting, risk-aversion, risk-seeking, and loss aversion. While hormonal levels did show the expected patterns for the three groups, there were no differences in value-based decision-making parameters. Consequently, Bayes factors showed conclusive evidence in support of the null hypothesis. We conclude that women on oral contraceptives show no differences in value-based decision-making compared to the early follicular and periovulatory natural menstrual cycle phases.

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Section: Discussionmentioning

confidence: 99%

No Differences in Value-Based Decision-Making Due to Use of Oral Contraceptives

et al. 2022

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“…Accordingly, the different study designs may capture different populations of women. Placebo-controlled trials usually report a mood worsening within the first 6 months of COC treatment . Population-based studies, on the other hand, usually report improved mental health in long-term users of COCs (>6 months of COC use) .…”

Section: Introductionmentioning

confidence: 99%

“…To predict causality between COC use and mood, placebo-controlled, randomized clinical trials (RCTs) using different COC formulations were conducted. Most of these trials observed significantly lower mental well-being during the first few months of COC intake [11][12][13][14][15] (except for a study by Scheuringer et al 16 ), although only a few studies reported an increase in clinical depression scores. 15,17,18 Two factors may contribute to those seemingly contradictory results between non-RCTs and RCTs.…”

Section: Introductionmentioning

confidence: 99%

Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal

Noachtar,

Frokjaer,

Pletzer

2023

JAMA Netw Open

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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 &lt; .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 &gt;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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“…Nevertheless, our knowledge about the effects of OCs on the female brain and behavior is still limited. The majority of studies have compared OC users to non-users ( 20 ) and a very small number of prospective studies have reported short-term effects of contraceptive use on the brain ( 21 – 24 ). Likewise, potential long-term effects are not well understood and it is still unknown if possible neurocognitive effects are reversible.…”

Section: Introductionmentioning

confidence: 99%

Duration of oral contraceptive use relates to cognitive performance and brain activation in current and past users

2022

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Previous studies indicate effects of oral contraceptive (OC) use on spatial and verbal cognition. However, a better understanding of the OC effects is still needed, including the differential effects of androgenic or anti-androgenic OC use and whether the possible impact persists beyond the OC use. We aim to investigate the associations of OC use duration with spatial and verbal cognition, differentiating between androgenic and anti-androgenic OC. Using functional magnetic resonance imaging (MRI), we scanned a group of 94 past and current OC-users in a single session. We grouped current OC users (N=53) and past OC users with a natural cycle (N=41) into androgenic and anti-androgenic user. Effects of OC use duration were observed for current use and after discontinuation. Duration of OC use was reflected only in verbal fluency performance but not navigation: The longer the current OC use, the less words were produced in the verbal fluency task. During navigation, deactivation in the caudate and postcentral gyrus was duration-dependent in current androgenic OC users. Only during the verbal fluency task, duration of previous OC use affects several brain parameters, including activation of the left putamen and connectivity between right-hemispheric language areas (i.e., right inferior frontal gyrus and right angular gyrus). The results regarding performance and brain activation point towards stronger organizational effects of OCs on verbal rather than spatial processing. Irrespective of the task, a duration-dependent connectivity between the hippocampus and various occipital areas was observed. This could suggest a shift in strategy or processing style with long-term contraceptive use during navigation/verbal fluency. The current findings suggest a key role of the progestogenic component of OCs in both tasks. The influence of OC use on verbal fluency remains even after discontinuation which further points out the importance of future studies on OC effects and their reversibility.

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Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness

Cited by 27 publications

References 57 publications

No Differences in Value-Based Decision-Making Due to Use of Oral Contraceptives

No Differences in Value-Based Decision-Making Due to Use of Oral Contraceptives

Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal

Duration of oral contraceptive use relates to cognitive performance and brain activation in current and past users

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