Oral contraceptive use and sexually dimorphic tasks:
Does ‘the pill’ affect verbal memory and emotion recognition?
Maaike van Boven
Bachelor’s Thesis University of Amsterdam
N.R. de Vent & L. van Bedaf (Supervisors) June 2015
2 Abstract Background
Despite widespread use of oral contraceptive (OC) pills, little is known about their effects on cognition. The aim of the current study was to investigate the effects of oral contraceptive use on two domains: verbal memory and emotion recognition.
Method
The study used a between subjects design. Subjects were all OC-using women, aged 18-30 year. Measures of verbal memory and emotion recognition were compared between OC users in the active phase pill (n=17) and OC users in the inactive pill phase (n=12), using independent t-tests. The independent variable was contraceptive pill cycle phase (active pill phase, inactive pill phase). The dependent variables were verbal memory, as measured by the Selective Reminding Test and emotion recognition, measured by the Emotion Recognition Task.
Results and Discussion
No significant effects of pill phase on verbal memory and emotion recognition were found. Based on the limitations of the current research, several recommendations for further research are suggested. Many women volunteer in cognitive research experiments and more insight in potential effects of OCs could enable researchers to control for potential effects.
Conclusion
Neither verbal memory, nor emotion recognition ability differed between active-pill phase OC users and inactive pill phase OC users.
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Combined oral contraceptives are one of the most widely used methods of reversible contraception. Today, almost 200 million women worldwide use oral contraception (United Nations, 2014). However, despite their well-characterized effects on the female reproductive system, surprisingly little is known about their effect on cognitive abilities. Knowledge about the impact of oral contraceptives on cognitive abilities is of great importance equally to the private user and physicians as well as to clinical and fundamental research. Many young women
participate in behavioural studies and a potential effect of oral contraceptive use might influence results. This study therefore set out to assess the effect of oral contraceptive use on verbal memory and emotion recognition.
Oral contraceptives supress the natural production of the female sex hormones progesterone and estradiol. Furthermore, combined OCs reduce testosterone levels (Zimmerman, Eijkemans, Coelingh, Bennink, Blankenstein & Fauser, 2013). The synthetic sex hormones found in OCs are, however, biologically active, meaning that they bind the natural receptor and have largely the same (estrogenic) downstream effects (Marečková et al., 2014). In other words, the synthetic hormones mimic the actions of the natural hormones estradiol and progesterone. As such, during the active pill phase, OC users are daily exposed to high levels of synthetic sex hormones, exerting effects that are, at least at the physiological level, similar to natural sex hormones.
For women who do not use hormonal contraception, hormone fluctuations in estradiol and progesterone occur naturally during the menstrual cycle. There are two peaks in oestrogen levels, one just before ovulation (late follicular phase) and a somewhat lower peak in the mid-luteal phase. Oestrogen levels are relatively low in the early follicular phase and during the menses. Progesterone levels remain low during the follicular phase and peak during the mid-luteal phase. (Silverthorn, Ober, Garrison & Silverthorn, 2009). In addition to these hormones’ effects on reproductive function, they also exhibit modulatory effects on neurochemical systems involved in emotional and cognitive function, i.e. noradrenergic, dopaminergic, serotoninergic, glutamatergic and GABA-ergic systems (Toffoletto, Lanzenberger, Gingnell, Sundström-Poromaa, & Comasco, 2014). These modulatory effects suggest that any potential effect might be found within the faculties of emotional and cognitive function.
Cognitive function is, however, a broad concept and includes a lot of different capacities. Previous research on the effects of cycle-related changes in hormone levels have indicated that it is mainly performance on sexually dimorphic cognitive abilities that might –at least in part-
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depend on levels of ovarian hormones (Hampson, 1990; Kimura & Hampson, 1994; Moody, 1997; Silverman & Phillips, 1993; Mordecai, Rubin & Maki, 2008; Marečková et al., 2014). According to this view, performance on tasks that favour women (e.g. verbal tasks) might be enhanced during periods of elevated oestrogen compared with periods of lowered oestrogen whereas performance on tasks that favour men (e.g. visuospatial tasks) might be diminished during periods of elevated oestrogen. Sex sensitive tasks with a female advantage have mainly been identified in the domains of verbal memory and emotion recognition (Strauss, Sherman, & Spreen, 2006). If the pattern of effects exhibited by endogenous hormones is indeed similar to that of exogenous hormones -as is argued in a previous section- an effect of oral contraceptives may expected to be found in the domains of emotion recognition and verbal memory. The following two sections provide a brief overview of existing literature relating fluctuations in endogenous and exogenous hormones to verbal memory and emotion recognition performance.
To date, only two published studies have investigated the effect of OC use on verbal memory. Mordecai et al. (2008) found a difference in performance between OC-users and non-users on a verbal memory task. OC-non-users performed better than naturally cycling women. This finding is consistent with the assumption that oestrogen enhances performance on female-favouring tasks, since a female advantage has generally been reported for verbal memory (Kramer, Delis & Daniel, 1988). In contrast to these findings, an earlier study, investigating the effect of OC use on auditory working memory, found no differences between OC-users and non-users (Rosenberg & Park, 2002). A likely reason for this inconsistency is that the test material used by Rosenberg & Park might be a more adequate measure of divided attention than verbal memory, as it included the execution of mental operations on the items to be memorized.
The findings of Mordecai et al. (2008) are in line with published reports of cycle-related differences in verbal memory (Hampson, 1990; Wharton et al., 2008; Dadin, Salgado & Fernandez, 2009). Overall, the results suggest that verbal memory performance is improved during periods of elevated oestrogen, and that this is true for endogenous as well as exogenous oestrogen.
Results in the domain of emotion recognition are not as straightforward. The only publication regarding the effects of OCs on direct measures of emotion recognition was a coincidental finding by Hamstra, De Rover, De Rijk & Van der Does (2014). They found that OC-users detected fewer facial expressions of sadness, anger and disgust, but found no
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differences in the detection of happy or fearful facial expressions. This was a coincidental finding though and therefore requires replication. Studies regarding cycle-related changes in emotion perception have produced equivocal results. Comparing groups in early follicular, ovulatory and luteal phase, Guapo et al. (2009) found a group difference in the recognition accuracy of angry and sad faces. Both emotions were better recognized during the early follicular phase. So far, the findings on emotion recognition seem to contradict the theory stated in an earlier section, at least for emotions of negative valence (anger, sadness and disgust). A possible interpretation is that the ovarian hormones may have opposite effects on emotions of different valence (negative vs. positive). The next section will review two more studies on the subject.
Derntl, Hack, Kryspin-Exner & Habel (2013) compared groups in early follicular phase and mid-luteal phase and found no differences in emotion recognition accuracy. In addition to emotion recognition measures, they also measured hormone levels, but found no differences between the groups in either estradiol or progesterone levels. This provides a possible
explanation; the groups used by Derntl et al. (2013) may have been heterogeneous with respect to cycle phase and, consequently, hormone levels. Groups may have been less heterogeneous in another study, by Pearson & Lewis (2005). Instead of dividing participants in two cycle-based groups, they compared emotion recognition in four groups, also differing in cycle phase: follicular, ovulatory, luteal and menses. They found a positive correlation between recognition accuracy and estradiol levels, though group differences in recognition accuracy were only significant for fearful faces. To conclude, it appears that the sexual dimorphic tasks theory might be an oversimplification. Moreover, the effects of ovarian hormones might differ between single emotions. This is not completely in contradiction with the sexual dimorphic tasks theory, as a recent review on sex-differences in emotion perception (Kret & De Gelder, 2012) concluded that there appears to be an overall female advantage in emotion recognition, but that it was unclear whether this was true for all emotions. In other words, sex differences in recognition accuracy may depend on the type of emotion.
In sum, it appears from the above literature review that a general understanding of the effect of hormonal contraceptives on verbal memory and emotion recognition ability is still lacking. This study seeks to address the research gaps. The predominant theory is that oestrogen enhances performance on sexually dimorphic tasks that favour women. Evidence on verbal memory generally supports this theory. Evidence on emotion recognition is inconclusive, as
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contradictory results were found when analysing separate emotions and most studies did not publicise results of comparisons on total scores across all emotions. Hormonal contraceptives provide constant high levels of biologically active exogenous oestrogen. Therefore, OC use is expected to enhance performance on sexually dimorphic tasks that favour women.
The aim of this study is to examine the effect of hormonal contraceptives on verbal memory and emotion recognition accuracy comparing two groups of female subjects: Women using oral contraceptive pills who are tested during the active pill phase and women using oral contraceptives who are tested during the inactive pill phase. The oral conceptive pill is
hypothesized to affect functions with a female advantage. Both verbal memory and emotion recognition are reported to have a female advantage (Strauss et al., 2006). Therefore, the
expectation is that oral contraceptive users will perform better on the Emotion Recognition Task and on tests of Verbal Memory than non-users. Because of contradictory evidence regarding differences in separate emotions, any comparisons on separate emotions will be of an exploratory nature. This study provides the opportunity to advance our knowledge of the effects of oral contraceptives on cognition. Lots of women volunteer in scientific research, a possible effect of oral contraceptive use might affect the results of those studies. A better understanding of the possible effects of oral contraceptive use could enable researchers to control for the effects.
Method Sample and Participant Selection
A total of 29 healthy women aged 18-30 years (M = 22.3, SD = 2.25) participated in this study. Participants were selected based on the following criteria: a) aged 18-30 years, b) use of combined oral contraceptive pill containing 20-30µg estradiol, c) normal or corrected to normal vision and hearing, d) no history of neurological of psychiatric disease e) no use of psychoactive medication, f) no significant history of drug or alcohol abuse, g) Dutch as primary language.
Assignment to groups was based on pill phase at the moment of testing: participants who were tested during the active pill phase were included in the active pill group (n=17), participants who were tested on the third to seventh day of the inactive pill phase were included in the control group (n=12). By inactive pill phase is meant the seven-day period in which OC users take no pills or placebo pills. The half-life1 of ethinyl estradiol (EE2) is approximately 12 hours (Kanarkowski, Tornatore, D'Ambrosio, Gardner, & Jusko, 1988). Therefore, the EE2
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concentration on the third day will be around !"! of the initial concentration, so it is reasonable to assume this as negligible.
Volunteers were recruited among friends and family members of undergraduate students and from the general community. All subjects gave (written) informed consent to participate in this study, which was approved by the Ethics Committee of the University of Amsterdam (UvA).
Assessments and Measures
SRT. Verbal learning and memory was assessed using the Dutch version of the Selective Reminding Test (SRT). The psychometric properties of the SRT are evaluated as sufficient to good by the COTAN (committee test affairs of the Dutch institute of psychologists).
The SRT (Buschke, 1973; Buschke & Fuld, 1974) consists of 12 unrelated, common Dutch nouns. Participants are instructed to remember as many words as possible. The list of 12 words is read once to the participant, followed by free recall. On consecutive trials, the participant was reminded of only the words he/she failed to recall. This procedure was continued until all 12 words were recalled or until 12 trials had been exhausted. This was followed by a multiple-choice recognition task. To assess long-term retention of the word list, 20-minute delayed free recall was administered.
ERT. Emotion recognition ability was assessed using the Emotion Recognition Task (ERT) (Montagne, Kessels, de Haan & Perrett, 2007; Kessels, Montagne, Hendriks, Perrett, & de Haan, 2014). The ERT is a computerized paradigm in which morphed video clips of facial emotional expressions at different intensities have to be labelled using a six-alternative forced choice response with no time restriction. The task was developed by Montagne et al. (2007) and has been validated in various patient groups (for a complete list, see Kessels et al., 2014). Normative data from healthy subjects has recently been compiled by Kessels et al. as well.
The stimulus material was based on coloured pictures (11.2 x 11.7cm) of four (two males, two females) actors mimicking emotional expressions. The set consisted of dynamic images of six emotional expressions (happiness, anger, disgust, sadness, surprise and fear) at 4 different intensities (40%, 60%, 80%, 100%). An example is shown in figure 1. For each emotion, scores may range from 0 to 16. Total scores on the ERT are the sum of the individual totals per emotion (max = 96). Higher scores represent better emotion recognition.
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Figure 1. Example of facial expressions of the Emotion Recognition Task
Procedure
Tests were administered in a quiet room by an undergraduate student. The tests were conducted as part of a larger test battery, which, in addition to the SRT and ERT, included three other tests. The total test time was between one and two hours including regular breaks in
between tests. The tests were administered in a fixed order. During the retention interval of SRT, no verbal tasks were administered. The ERT was administered using the computerized
DiagnoseIS neuropsychological assessment system (www.diagnoseis.com). Based on preference of the participant, responses could be made either by mouse click or touch pad.
Design
The study used a between subjects design. The independent variable was contraceptive pill cycle phase (active pill phase, inactive pill phase). The dependent variables were verbal memory,
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as measured by the SRT and emotion recognition, measured by the ERT.
To reduce the number of (interdependent) comparisons for verbal memory scores, a
composite z-score was created for verbal memory. The composite z-score included the following SRT measures: total recall across all trials, consistent long-term retrieval (CLTR), and long-term retrieval (LTR). Delayed recall (SRT DR) was not included in the composite z-score, because the assumption of normality was violated for this variable. For each of the other measures, individual z-scores were computed, which were then averaged to one single verbal memory z-score.
Data analysis
Statistical analyses were performed using SPSS Statistics software version 21.0. A
multivariate analysis of variance (MANOVA) was planned for group comparisons of normally distributed data. Because the ultimate sample size ultimately differed between the SRT and ERT data, independent sample t-tests with bonferroni correction were used instead. Mann-Whitney U tests were used for group comparisons of non-normally distributed data. For the Mann-Whitney U-test comparisons, the exact significance value (2*[1- tailed Sig.]) was used. All t-tests were two-sided with α = .05 before bonferroni correction.
Results
Of the total sample (n=29) of oral contraceptive users that were included, 17 participants were in the active-pill phase and 12 participants were in the inactive pill phase. All of the participants in the inactive pill phase were between day three and day seven of the inactive pill phase. Because of incomplete data for the SRT, three of the 29 subjects were excluded from the analysis of verbal memory data. From these excluded subjects, two belonged to the active-pill phase group and one to the inactive pill phase group. Therefore, verbal memory analyses were conducted on a total sample of 26 participants, comparing participants in the active pill phase (n=15) against a control group (n=11) in the inactive pill phase. Emotion recognition analyses were conducted on a total sample of 29 participants, comparing participants in the active pill phase (n=17) against a control group (n=12) in the inactive pill phase.
The resulting sample sizes and demographic variables are presented in table 1. Independent t-tests were used to assess whether the groups in either the verbal memory analysis or the groups in the emotion recognition analysis differed in age and education level (UNESCO ISCED).
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Neither the groups in the verbal memory analysis differed in age, t(24) = 0.336, p = .740, or education level t(23.85) = 1.576, p = .128, nor did the groups in the ERT analysis differ in age t(27) = -0.045, p = .964, or education level t(26.75) = 1.471, p = .153. Outliers were not excluded because scores fell within normal variation so there was no reason to exclude extreme values.
Table 1.
Demographic Variables of participants in SRT (top) and ERT (bottom)
Total Total Active OC users Control
SRT n 26 15 11 Age 22.4 (±2.23) 22.67 (±2.66) 22.36 (±1.567) Education levela 3.69 (±0.97) 3.98 (±1.03) 3.36 (±0.809) ERT n 29 17 12 Age 22.3 (±2.25) 22.29 (±2.71) 22.33 (±1.497) Education levela 3.62 (±0.942) 3.82 (±1.02) 3.33 (±0.778)
Note. OC = Oral contraception; SRT = Selective Reminding test; ERT = Emotion Recognition Task.
aEducation level UNESCO ISCED
Verbal Memory
Table 2 shows the test-scores (M and SD) for the SRT as well as the SRT composite z-score for the active OC group and the control group. An independent samples t-test indicated that that there was no difference between the groups on the composite z-score, t(24) = -1.418, p = 0.169. To verify that this result was not a consequence of adding the three different SRT variables together in a single composite z-score, a bar graph of the three SRT variables is presented in Figure 2.
11 Table 2.
Mean scores on SRT variables of Active Pill Phase Group and Inactive Pill Phase Group
Variables Group
Active Pill Phasea Inactive Pill Phaseb
M SD M SD SRT Total Recall 94.07 20.2431 105.27 19.422 LTR 86.67 22.980 99.82 18.438 CLTR 78.81 23.404 82.18 14.162 DR 10.67 1.676 11.09 0.831 Composite z-score -0.19 1.037 0.26 0.756
Note. LTR = Long-term Retrieval; CLTR = Consistent Long-Term Retrieval; DR = Delayed Recall; SRT= Selective Reminding Test.
an = 15. bn = 11.
Potential group differences on the delayed recall (SRT-DR) scores were assessed using a Mann-Whitney U test. Delayed Recall scores of the active pill phase group (Mdn = 11) did not differ from scores of the control group (Mdn = 11), U = 106.0, z = 0.046, p = 1.00, r = .009.
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Figure 2. Bar graph showing mean scores on SRT variables CLTR, LTR and Total Recall. Error bars represent confidence intervals. SRT = Selective reminding test; CLTR = Consistent Long term Retrieval; LTR = Long Term Retrieval.
Emotion Recognition
Total ERT scores of the Active Pill group (M = 64.76, SD = 6.07) and Inactive Pill group (M = 60.58, SD = 5.88) were compared using an independent-samples t-test. Opposed to prediction, no differences in emotion recognition were found t(27) = 1.850, p = .075. Further examination of potential differences for single emotions was done with a boxplot, which is presented in figure 3. Additional group comparisons for single emotions were assessed with Mann-Whitney U tests. Results are summarized in Table B3, which can be found in the appendix. No group differences on ERT scores for single emotions were found.
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Figure 3. Boxplot showing Emotion Recognition Task scores on single emotions of participants in active pill phase and inactive pill phase
Discussion
The aim of this study was to determine the effects of OC use on verbal memory and emotion recognition. It was expected that OC use would improve verbal memory and emotion recognition ability. Based on the results of this study however, no support for the hypothesis can be found. Neither verbal memory, nor emotion recognition ability differed between active-pill phase OC users and inactive pill phase OC users.
The finding that verbal memory did not differ between women in the active pill phase and inactive pill phase is in contrast with the findings of Mordecai, Rubin and Maki (2008) who did find an increase in verbal memory during the active pill phase, compared to the inactive pill phase. In part, this discrepancy might be explained by the research design that was used. The current study used a between-group design to assess differences in verbal memory during the active pill phase and the inactive pill phase while Mordecai et al. (2008) used a repeated measures design. As a repeated measures design has more power, the failure to replicate the
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findings of Mordecai et al. (2008) may therefore reflect limitations in the power to detect differences in the current study.
Regarding the effect of OCs on emotion recognition, this study was unable to replicate the coincidental finding of Hamstra, De Rover, De Rijk & Van der Does (2014), who found a decrease in recognition of negative emotions in OC-users, compared to non-users. As this is the first study to assess the direct effect of OC use on total emotion recognition performance, the results cannot be readily compared to earlier findings. The expectation that OCs would enhance emotion recognition was based on the sexual dimorphic tasks theory, combined with the
consistently reported female advantage on emotion recognition. It is not completely clear whether the effect of exogenous oestrogen is similar to the effect of endogenous oestrogen. If a comparison is made under the tentative assumption that the effects of endogenous and exogenous are in fact similar, the exploratory findings on single emotions of the current study contradict the findings of two earlier studies, which either reported a negative effect of oestrogen on negative emotions and no effect on other emotions (Guapo et al., 2009), or a positive relation between estradiol levels and emotion recognition, but only for the recognition of fearful faces (Pearson & Lewis, 2005).
There are several possible explanations for this difference. The first and most obvious explanation is that the assumption underlying the comparison is false and the effect of exogenous oestrogen differs from the effect of endogenous oestrogen. This explanation is implausible however, as other studies into the effects of oestrogen on other cognitive functions show a generally similar pattern of effects for endogenous and exogenous oestrogen. The comparison is, however, not likely to hold for the other ovarian hormone found in OCs. While oestrogens are quite a homogenous class, different progestins can have quite divergent actions, as was
underscored by a recent article of Pletzer, Kronbichler & Kerschbaum (2015). The groups in the current study were based on type of pill (combined) and amount of ethinyl estradiol, but did not distinguish between different progestins. If different progestins have opposing actions, as Pletzer et al. postulate, any potential effect will be neutralized when group means are compared.
A further limitation of the current study is that it may have lacked the adequate power to detect differences. In addition to the earlier noted limitations in the design, a further decrease in power to detect differences in emotion recognition ability may partly be due to the psychometric properties of the ERT. Especially the scores on happiness and anger exhibited considerable
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ceiling effects. Consequently, the ERT had low discriminative power. It is recommended to use a test with more discriminative power when comparing emotion recognition ability in similar populations. This could easily be achieved by making use of video clips with lower intensities, for example from 20% to 60%.
Taking in consideration the factors noted above, further studies regarding the effect of OCs on verbal memory and emotion recognition are recommended. When doing so, a number of important changes to the design of the current study would need to be made. Based on the findings of the current study, it is strongly recommended that future researchers into this topic should take great care to ensure that the instruments that are used to assess verbal memory and emotion recognition have enough discriminatory power in the population of interest. A second recommendation is to take the type of progestin in the participants’ OC pills into account.
Moreover, further research should preferentially use a repeated measures design, testing the same subjects during the active pill phase and for instance, the last day of the inactive-pill phase. In terms of further research directions, it would be interesting to contrast the activating effects of oestrogen (i.e. the acute consequences of elevated serum levels) with the longer lasting,
structural effects of OC use. To assess the structural effects of OC use, a repeated measures study among women who are starting or stopping with pill use could be undertaken, with an inter-test interval of six months, for example.
Furthermore, in order to gain insight in the complete picture, more interdisciplinary research is needed. Until now, an inadequate understanding about the pharmacological profiles of
different progestins has hampered research on the effect of OCs on cognition. Studies that do distinguish between contraceptive pills with different types of progestins, such as the study by Pletzer et al., only make a distinction according to androgenicity; whether the progestin is structurally related to androgen or to progesterone (Brinton et al., 2008). Androgenicity is, however, only one characteristic on which progestins can be classified. Moreover, to add to the complexity, androgenic progestins also exhibit anti-androgenic effects (Stanczyk, 2003;
Guennoun et al., 2015). Likewise, a recent review on the many different signaling mechanisms and interactions of progestogens (Guennoun et al., 2013) shows a more complex picture. The variety of progestins, differing in receptor affinities, potency and signaling mechanisms,
highlights the importance of the need for an interdisciplinary approach. A better understanding of the pharmacological profile of the oral contraceptive pill under investigation could enable
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cognitive researchers to formulate hypotheses that are stronger embedded in neuroscientific theory, thereby allowing sharper hypotheses to be tested.
To conclude, more research is needed in order to gain a more complete picture of the impact of hormonal contraceptive use on cognitive abilities, brain structure, and function. It is an
important topic, not only to the daily pill user, but also in clinical and basic research.
Traditionally, scientific research, mainly in the field of medical sciences, has focussed on male participants, partly because cycle-related hormonal fluctuations were suspected to affect the results. Nowadays, numerous women partake in scientific research, and while people who use medication are usually excluded, very few researchers control for the use of contraceptives. To improve future research in many fields, it is time to bring together a team of pharmacologists, neurobiologists and cognitive psychologists in order to formulate an evidence-based, unified oestrogen theory.
17 References
Brinton, R. D., Thompson, R. F., Foy, M. R., Baudry, M., Wang, J., Finch, C. E., ... & Nilsen, J. (2008). Progesterone receptors: form and function in brain. Frontiers in neuroendocrinology, 29(2), 313-339.
Buschke, H. (1973). Selective reminding for analysis of memory and learning. Journal of Verbal Learning and Verbal Behavior, 12, 543–550.
Buschke, H., & Fuld, P. A. (1974). Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology, 24, 1019–1025.
Dadin, C. O., Salgado, D. R., and Fernandez, E. A. (2009). Natural sex hormone cycles and gender differences in memory. Actas Esp. Psiquiatr. 37, 68–74.
Derntl, B., Hack, R. L., Kryspin-Exner, I., & Habel, U. (2013). Association of menstrual cycle phase with the core components of empathy. Hormones and behavior, 63(1), 97-104.
DiagnoseIS [Computer Software]. Heerlen, Netherlands: Metrisquare Platform 2.1.0.5
Guapo, V. G., Graeff, F. G., Zani, A. C. T., Labate, C. M., dos Reis, R. M., & Del-Ben, C. M. (2009). Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces. Psychoneuroendocrinology, 34(7), 1087-1094.
Guennoun, R., Labombarda, F., Deniselle, M. G., Liere, P., De Nicola, A. F., & Schumacher, M. (2015). Progesterone and allopregnanolone in the central nervous system: Response to injury and implication for neuroprotection. The Journal of steroid biochemistry and molecular biology, 146, 48-61.
Hamstra, D. A., De Rover, M., De Rijk, R. H., & Van der Does, W. (2014). Oral contraceptives may alter the detection of emotions in facial expressions. European
18
Hampson, E. (1990). Variations in sex-related cognitive-abilities across the menstrual-cycle. Brain and cognition, 14(1), 26-43.
Kanarkowski, R., Tornatore, K. M., D'Ambrosio, R., Gardner, M. J., & Jusko, W. J. (1988). Pharmacokinetics of single and multiple doses of ethinyl estradiol and levonorgestrel in relation to smoking. Clinical Pharmacology & Therapeutics, 43(1), 23-31.
Kessels, R. P., Montagne, B., Hendriks, A. W., Perrett, D. I., & Haan, E. H. (2014). Assessment of perception of morphed facial expressions using the Emotion Recognition Task: Normative data from healthy participants aged 8–75. Journal of neuropsychology, 8(1), 75-93.
Kimura, D., & Hampson, E. (1994). Cognitive pattern in men and women is influenced by fluctuations in sex hormones. Current Directions in Psychological Science, 3, 57–61.
Kramer, J. H., Delis, D. C., & Daniel, M. (1988). Sex differences in verbal learning. Journal of Clinical Psychology, 44(6), 907-915.
Kret, M. E., & De Gelder, B. (2012). A review on sex differences in processing emotional signals. Neuropsychologia, 50(7), 1211-1221.
Montagne, B., Kessels, R. P., De Haan, E. H., & Perrett, D. I. (2007). The emotion recognition task: A paradigm to measure the perception of facial emotional expressions at different intensities. Perceptual & Motor Skills, 104(2), 589−598.
Moody, M. S. (1997). Changes in scores on the mental rotations test during the menstrual cycle. Perceptual and Motor Skills, 84, 955–961.
Mordecai, K. L., Rubin, L. H., and Maki, P. M. (2008). Effects of menstrual cycle phase and oral contraceptive use on verbal memory. Hormones and behavior, 54(2), 286-293.
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Pearson, R., & Lewis, M. B. (2005). Fear recognition across the menstrual cycle. Hormones and Behavior, 47(3), 267-271.
Pletzer, B., Kronbichler, M., & Kerschbaum, H. (2015). Differential effects of androgenic and anti-androgenic progestins on fusiform and frontal gray matter volume and face recognition performance. Brain research, 1596, 108-115.
Rosenberg, L., & Park, S. (2002). Verbal and spatial functions across the menstrual cycle in healthy young women. Psychoneuroendocrinology, 27, 835–841.
Silverman, I., & Phillips, K. (1993). Effects of estrogen changes during the menstrual cycle on spatial performance. Ethology and Sociobiology, 14, 257–270.
Silverthorn, D. U., Ober, W. C., Garrison, C. W., & Silverthorn, A. C. (2009). Human physiology: an integrated approach. London: Pearson/Benjamin Cummings. Stanczyk, F. Z. (2003). All progestins are not created equal. Steroids, 68(10), 879-890.
Strauss, E., Sherman, E. M., & Spreen, O. (2006). A compendium of neuropsychological tests: Administration, norms, and commentary. Oxford: Oxford University Press.
Toffoletto, S., Lanzenberger, R., Gingnell, M., Sundström-Poromaa, I., & Comasco, E. (2014). Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: A systematic review. Psychoneuroendocrinology, 50, 28-52.
United Nations (2014). Population Growth and universal access to reproductive health. Report of the United Nations Population division on population growth and access to contraception. Retrieved from
http://www.un.org/en/development/desa/population/publications/pdf/popfacts/PopFacts_2014 -6.pdf
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Wharton, W., Hirshman, E., Merritt, P., Doyle, L., Paris, S., & Gleason, C. (2008). Oral contraceptives and androgenicity: influences on visuospatial task performance in younger individuals. Experimental and clinical psychopharmacology, 16(2), 156.
Zimmerman, Y., Eijkemans, M. J. C., Bennink, H. C., Blankenstein, M. A., & Fauser, B. C. J. M. (2014). The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis. Human reproduction update, 20(1), 76-105.
21 Footnotes
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Table B3. Mann-Whitney U tests summary for ERT single Emotion Scores of Active Pill phase group and Inactive Pill phase group
Variables Group
Active Pill Phasea Inactive Pill Phaseb
Mdn Mean Rank Mdn Mean Rank U z p r
ERT Anger 15.0 14.50 15.5 15.71 93.5 -0.395 .711 0.132 Disgust 12.0 16.88 9.0 12.33 134.0 1.429 .166 0.031 Fear 7.0 15.97 6.0 13.62 118.5 0.736 .471 0.087 Happy 15.0 17.03 15.0 12.12 136.5 1.664 .128 0.024 Sad 8.0 16.38 8.0 13.04 125.5 1.056 .303 0.056 Surprise 9.0 16.47 8.0 12.92 127.0 1.119 .283 0.053
Note. ERT = Emotion Recognition Test. an = 17. bn = 12
