Psychology, Health & Medicine

Vol. 15, No. 1, January 2010, 105–115

Impact of oral contraception and neuroticism on cardiovascular stress

reactivity across the menstrual cycle
Sabine Schallmayera and Brian M. Hughesb*
a
Clinic for Psychosomatic Medicine and Psychotherapy, Justus Liebig University, Giessen,
Germany; bCentre for Research on Occupational and Life Stress, National University of Ireland,
Galway, Ireland
(Received 28 July 2009; final version received 19 November 2009)

In order to avoid interpretation problems relating to the impact of reproductive

hormones on cardiovascular variables, research on the psychosomatic etiology of
cardiovascular disease frequently excludes women who use oral contraceptives
(OCs), and sometimes women as a whole, from study samples. However, such
conventions are based on a body of research that suffers from methodological
limitations and, in any event, has produced inconclusive findings. Further, the
relevant research fails to control for personality differences between users and
non-users of OC that may, in turn, lead to differences in stress reactivity. In the
present study, using a counterbalanced mixed-factorial design, 24 women (12 OC
users and 12 non-users), drawn from a screening sample of 110, were tested across
a 4-month timeframe. Cardiovascular reactivity (CVR) was measured during
both the follicular and luteal phases of each woman’s menstrual cycle. Menstrual
phase and OC use were found to exert synergistic effects on CVR. A significant
relationship between neuroticism and systolic blood pressure reactivity was
observed, which was found to be contingent on menstrual phase. It is concluded
that while menstrual phase and OC use are relevant, their contaminating influence
on CVR research can be circumvented.
Keywords: cardiovascular reactivity; menstrual phase; neuroticism; oral
contraception

Introduction
The correlation between resting blood pressure and cardiovascular disease risk is
well established (Prospective Studies Collaboration, 2002), as is the fact that surges
in blood pressure from resting levels pose an immediate threat among vulnerable
groups (Kario, 2006). However, it is less well appreciated that even modest
cardiovascular reactivity (CVR) to psychological stress among healthy persons is
positively associated with lifetime risk of heart disease (Treiber et al., 2003). Stress-
related elevations in cardiovascular parameters far exceed what is required to deal
physically with metabolic demands of stress (Carroll, Phillips, & Balanos, 2009).
Accordingly, if of sufficient frequency and/or intensity, CVR can promote
hypertension development by precipitating cardiac hypertrophy and gradual
homeostatic upward-shifts in blood pressure (Lovallo, 2005; Schwartz et al.,
2003). In this context, CVR research has flourished in the belief that understanding

*Corresponding author. Email: brian.hughes@nuigalway.ie

ISSN 1354-8506 print/ISSN 1465-3966 online

Ó 2010 Taylor & Francis
DOI: 10.1080/13548500903499391
http://www.informaworld.com
106 S. Schallmayer and B.M. Hughes

such mechanisms may elucidate biopsychosocial models of cardiovascular disease

risk (Linden, Gerin, & Davidson, 2003).
However, for many years, there has been concern regarding the possible impact
of menstrual cycle on CVR measurement in women. Firstly, stress-related blood
pressure and heart rate (HR) can be affected by fluctuations in reproductive
hormones (Weidner & Helmig, 1990). And secondly, menstrual cycle-related mood
fluctuations are known to influence the subjective psychological experience of
personal stress (Collins, Eneroth, & Landgren, 1985; Colverson, James, & Gregg,
1996; Davydov, Shapiro, & Goldstein, 2004; Davydov, Shapiro, Goldstein, &
Chicz-DeMet, 2005), further complicating the interpretation of physiological stress
responses. Early findings regarding the relationship between menstrual phase and
CVR were somewhat inconsistent, with some studies reporting enhanced CVR in the
luteal (premenstrual) phase compared with the follicular (postmenstrual) phase (e.g.
Hastrup & Light, 1984), other studies reporting the opposite (Polefrone & Manuck,
1988), and still others reporting no systematic pattern at all (e.g. Carroll, Turner,
Lee, & Stephenson, 1984). It has been suggested that, as a result of such ambiguity,
scientists avoided including women in CVR research to an extent that caused a
discernible lag in the understanding of women’s stress responses compared to men’s
(Turner, 1994).
Most of the early studies were cross-sectional, comparing CVR in separate
groups of women at different menstrual phases (e.g. one group at the luteal phase
and a second group at the follicular phase). Such designs carry the risk that observed
differences result not from menstrual phase, but from unaccounted for non-
menstrual variables that differ across groups. A superior research design involves
repeat-testing a single group of participants over time, in order to establish each
individual woman’s CVR pattern across her own menstrual cycle. When reviewers
began to survey the literature with this in mind, they found that repeated-measures
studies were more likely to show no effects for menstrual phase on CVR (Stoney,
1992). Nonetheless, despite initial enthusiasm that this implied it would be safe to
include women in CVR research without controlling for menstrual phase (Carroll
et al., 1984), the accumulating body of repeated-measures studies has actually
continued to produce conflicting findings (Arangino et al., 1998; Colverson et al.,
1996; Lubianca, Faccin, & Fuchs, 2003).
A second factor suspected of complicating CVR assessment in women is the
possible impact of oral contraceptives (OCs) on cardiovascular measures. Given that
increased blood pressure is a common side-effect of OC use (Nichols, Robinson,
Bounds, Newman, & Guillebaud, 1993; Shen, Lin, Jiang, Li, & Zhang, 1994), many
CVR researchers have adopted a convention of systematically excluding from their
samples any female volunteer who reports using OCs (Garcı́a-León, del Paso,
Robles, & Vila, 2003; Isowa, Ohira, & Mursahima, 2006; Newton, Watters,
Philhower, & Weigel, 2005). However, such a convention threatens the external
validity of research. Given that in developed nations, close to 70% of women in
stable relationships use contraception, with OC the most common method used
(United Nations, 2006), samples that systematically exclude OC users are not likely
to be representative of the population at large.
The hypertensive impact of OC use, which contributes to cardiovascular disease
risk (Thorogood, Mann, Murphy, & Vessey, 1992), is believed to be related to both
estrogenic and progestogenic components of OCs. Orally administered estrogen
must pass through the liver and so can increase fluid retention (which is associated
 Psychology, Health & Medicine 107

with hypertension) through renin–angiotensin system activation (Oelkers, 1996). In

addition, OC estrogens have been associated with altered erythrocyte cation
transport (Stokes et al., 1992; Stokes, Monaghan, & Marwood, 1985), which also
moderates blood pressure (Schwartz, Turner, Moore, & Sing, 2000). Further, some
evidence for estrogen effects on cardiac remodeling has been obtained in animal
studies (Narkiewicz et al., 1995). However, the majority of studies linking OC use
to hypertension have been based on first-generation OCs, which typically contained
50 mg or more of estrogen (Lubianca et al., 2003). Latterly, estrogen doses have
been greatly reduced (to 20–30 mg), with new progestins such as gestodene and
desogestrel introduced to third-generation pills (Arangino et al., 1998). Such
modifications appear to have minimized the negative effects of OC use on resting
blood pressure (Arangino et al., 1998; De Leo et al., 2001). However, the impact
of third-generation OCs on stress-related blood pressure remains largely
unexplored.
Finally, psychometric research has demonstrated that OC use is associated with
personal beliefs, situational factors, and communication between sexual partners
(Ogden, 2005). It has been found that personality predisposes some women to use
or not to use contraception. For example, sexually active women who score high
on social conservatism (McCormick, Izzo, & Folcik, 1985) and/or sex anxiety (Geis
& Gerrard, 1984; Herold & McNamee, 1982) appear less likely to use
contraception, whereas high scores for internal locus of control (Morrison, 1985)
and self-esteem (Lowe & Radius, 1987) have been associated with increased
contraception use. In general, negative emotionality has been found to predict
risky sexual behavior (Trobst, Herbst, Masters, & Costa, 2002). As several of these
traits have common characteristics that cluster around the construct of neuroticism
(Judge, Erez, Bono, & Thoresen, 2002), it might be expected that a given sample of
OC users may differ from the general population in this personality dimension.
This is of relevance as neuroticism has been implicated as a significant moderator
of physiological stress reactivity (Houtman & Bakker, 1991; Kennedy & Hughes,
2004; McCleery & Goodwin, 2001; Phillips, Carroll, Burns, & Drayson, 2005;
Zobel et al., 2004). Hence, when investigating the possible influence of OC use
on CVR, researchers should ensure that observed patterns are not accounted for
by personality differences between OC users and non-users that impinge on
reactivity.
The primary objective of this study was to establish in what way menstrual phase,
third-generation OCs, and/or neuroticism impact independently or synergistically on
CVR. Such data should expand our understanding of the cardiovascular stress
response in OC users in particular and in women in general, thereby clarifying
factors that need to be taken into account when investigating this important
etiological mechanism in female populations.

Method
Participants
One hundred ten female students were recruited from the participant pool in the
psychology department of a European university. All completed an initial 8-week
diary-based menstruation-tracking procedure to determine regularity of menstrual
cycle. From this pool, a total of 24 participants (12 OC users, 12 non-users) were
108 S. Schallmayer and B.M. Hughes

selected on the basis of the following criteria: regular menstrual cycle, normal-range
body mass index, non-smoking, free from chronic illness and family history of heart
disease, and normotensive (resting blood pressure 5140/90 mmHg; see Table 1 for
full descriptive statistics). The OC users had all used third-generation monophasic
OCs for at least 6 months; the non-users were all lifelong non-users.

Design
All participants attended two appointments at a cardiovascular psychophysiology
laboratory. Within each group (OC users and non-users), half attended first during
the follicular phase (Days 1–4) of the menstrual cycle, with their second appointment
scheduled during the luteal phase (Days 21–24). The other participants attended
appointments in the opposite order. Order of appointments for each participant was
determined at random. During each appointment, participants underwent standar-
dized CVR assessment. This procedure underpinned a 2 6 2 6 2 mixed factorial
design, comprising OC use (users, non-users), menstrual phase (follicular, luteal),
and stress (before, during) as independent variables. Dependent variables comprised
cardiovascular measures assessed in the laboratory. To control for neuroticism, each
participant completed the Eysenck Personality Questionnaire (EPQ; Eysenck &
Eysenck, 1991).

Laboratory procedure
Each appointment was managed by a female researcher who was blind to the
participant’s menstrual phase and OC use status. To limit the influence of circadian
cardiovascular rhythms (Giles, 2006), all testing took place in the morning (09:00–
12:00). The participant sat with a computer on a table approximately 30 cm away,
with a blood pressure cuff attached to her non-dominant arm. The researcher sat
operating a Dinamap Pro100 blood pressure monitor (Critikon Corporation,
Tampa, Florida), behind an opaque screen approximately 6 m away. Following an
initial 20-min acclimatization period intended to facilitate genuine relaxation, the
participant was instructed to sit quietly for an initial 6-min resting period, during
which three measures each of systolic blood pressure (SBP), diastolic blood pressure
(DBP), and HR were taken at 2-min intervals. This was followed by a time-pressured
cognitive stressor task presented to participants on the computer. The task required
participants to respond to a series of subtraction problems containing two- to five-
digit numbers. In order to offset variations in mental arithmetic ability across
participants, the task was programmed to adjust the difficulty of problems

Table 1. Descriptive statistics (means with standard deviations in parentheses) for

participants across both groups.

Group
OC users Non-users
Age (years) 21.08 (3.23) 22.42 (7.57)
BMI (kg/m2) 20.79 (1.91) 21.92 (3.15)
Menstrual cycle (days) 29.00 (2.52) 28.75 (2.86)
 Psychology, Health & Medicine 109

(by increasing or decreasing the lengths of the numbers in digits) on the basis of an
ongoing assessment of response accuracy. This task was designed to be similar to
tasks previously used in CVR research (Hughes, 2001; Turner et al., 1986). The task
lasted for 6 min, during which three more measures of SBP, DBP, and HR were
taken at 2-min intervals.

Results
Mean levels of SBP, DBP, and HR for each group and for each menstrual phase are
presented in Table 2. All increases baseline-to-stressor increases were statistically
significant (p 5 0.001), implying that the cognitive task successfully elicited CVR.
OC users had higher scores for neuroticism (M + SD ¼ 13.67 + 3.8) than non-
users (10.14 + 4.2; p ¼ 0.043). Both groups scored near the published population
norm for women aged 21–30 years (12.53 + 4.8; Eysenck & Eysenck, 1991). For
each cardiovascular variable, a separate mixed-factor three-way analysis of
covariance (ANCOVA) was conducted to investigate the impact of OC use,
menstrual phase, and stress. Given its between-group difference, neuroticism was
entered as a covariate in each ANCOVA. Effect sizes are presented as partial Z2 for
ANCOVA effects and Pearson’s r for correlations. Z-squared values of 0.04, 0.25,
and 0.64, and r-values of 0.1, 0.25, and 0.37, are taken as representing small,
medium, and large effect sizes, respectively (Cohen, 1988, 1992).
The ANCOVA for SBP revealed a number of significant interactions (see
Table 3). The significant stress 6 OC use interaction, F(1,21) ¼ 196.90, p ¼ 0.025,
partial Z2 ¼ 0.22, arose from higher CVR among non-users compared with users.
However, this was subordinate to a significant menstrual phase 6 stress 6 OC use
interaction, F(1,21) ¼ 45.60, p ¼ 0.019, partial Z2 ¼ 0.24. Phase-level data showed
that the difference in reactivity between users and non-users was significant during
the luteal phase but not the follicular phase (see Figure 1). The significant menstrual
phase 6 stress interaction, F(1,21) ¼ 49.59, p ¼ 0.015, partial Z2 ¼ 0.25, was in
turn subordinate to the significant menstrual phase 6 stress 6 neuroticism inter-
action, F(1,21) ¼ 62.36, p ¼ 0.007, partial Z2 ¼ 0.30. In summary, this reflected the

Table 2. Mean cardiovascular levels (with standard deviations) at baseline and during stress
for both follicular and luteal Phases, across both groups.

Phase
Follicular Luteal
Group Baseline Stressor Baseline Stressor
OC users
SBP 112.36 (5.00) 117.03 (7.92) 110.64 (6.75) 114.39 (8.46)
DBP 67.53 (5.51) 71.92 (6.30) 64.75 (5.58) 66.06 (4.15)
HR 71.89 (10.99) 77.89 (10.81) 70.64 (7.85) 77.83 (10.22)
Non-users
SBP 112.33 (6.01) 121.22 (11.90) 112.28 (7.90) 123.36 (10.29)
DBP 66.75 (6.61) 71.97 (7.51) 66.50 (7.53) 72.53 (8.21)
HR 73.56 (10.79) 86.33 (17.39) 74.97 (5.96) 87.19 (8.83)

SBP, systolic blood pressure (in mmHg); DBP, diastolic blood pressure (in mmHg); HR, heart rate (in
bpm).
110 S. Schallmayer and B.M. Hughes

Table 3. Summary of two- and three-way interactions from menstrual phase 6 stress 6
OC-use analysis of covariance (with neuroticism as covariate), for each cardiovascular
measure.

Significance (p)
Source of variance SBP DBP HR
Two-way interactions
Menstrual phase 6 stress 0.015 – –
Menstrual phase 6 OC use – 0.023 –
Menstrual phase 6 neuroticism – – –
Stress 6 OC use 0.025 – –
Stress 6 neuroticism – – –
OC use 6 neuroticism – – –
Three-way interactions
Menstrual phase 6 stress 6 OC use 0.019 – –
Menstrual phase 6 stress 6 neuroticism 0.007 – –

SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; –, not significant (i.e.
p 4 0.05).

Figure 1. Mean levels of SBP during baseline and stress for OC users and non-users, during
luteal and follicular phases.

fact that neuroticism was moderately and inversely correlated with the reactivity
during the follicular phase (r ¼ 70.25), but effectively uncorrelated during the luteal
phase (r ¼ þ0.07).
The occurrence of an interaction involving neuroticism raised the possibility that
neuroticism mediated the relationship between OC use and reactivity. This was
explored statistically using the four-step rationale outlined by Baron and Kenny
(1986). The first step required the establishment of an effect for OC use (i.e. the
predictor) on reactivity (i.e. the outcome), which was evident from the significant
stress 6 OC use interaction. The second step required the establishment of an
association between OC use and neuroticism (i.e. the mediator), which was evident
from the significant between-group difference in neuroticism (p ¼ 0.043). The third
step required the establishment of an association between neuroticism (i.e. the
mediator) and reactivity (i.e. the outcome) having controlled for OC use (i.e. the
predictor). For this purpose, reactivity was defined as the arithmetic difference
 Psychology, Health & Medicine 111

between resting and stressor SBP across both follicular and luteal phases for each
participant. The partial correlation between neuroticism and reactivity controlling
for OC use was non-significant (p ¼ 0.64). As such, neuroticism was found not to
mediate the association between OC use and reactivity.
The ANCOVA for DBP revealed a significant menstrual phase 6 OC use
interaction, F(1,21) ¼ 113.45, p ¼ 0.030, partial Z2 ¼ 0.21, which was reflected by
lower luteal DBP than follicular DBP among non-users, but no phase differences
among users (see Figure 2). Finally, the ANCOVA for HR revealed no significant
interaction effects. In all ANCOVAs, main effects for menstrual phase or OC use
were non-significant.

Discussion
Although neither variable exerted a significant effect on its own, menstrual phase and
OC use combined synergistically to influence blood pressure and, in particular,
reactivity to stress: non-users of OCs demonstrated higher SBP reactivity during the
luteal phase than during the follicular phase. This is consistent with previous
research (Hastrup & Light, 1984; Manhem, Jern, Pilhall, Shanks, & Jern, 1991;
Tersman, Collins, & Eneroth, 1991), and with the view that the estrogenic hormones
reduce sympathetic nervous system arousal, as previously inferred from differences
in CVR across gender (Stoney, Matthews, McDonald, & Johnson, 1988), among
pre- and post-menopausal women (Saab, Matthews, Stoney, & McDonald, 1989),
and among women before and during pregnancy and compared to non-pregnant
controls (Matthews & Rodin, 1992). Unlike much previous research, the present
study used a repeated-measures protocol (thus ensuring that between-phase
differences were unaffected by sampling heterogeneity), with order of testing by
phase counterbalanced across participants (thus obviating order effects, such as
habituation).
Among OC users, CVR was no higher in the luteal than in the follicular phase.
As these women’s estrogen (and progesterone) levels would be elevated throughout
the menstrual cycle, the findings suggest that high hormone levels may protect
against exaggerated CVR. Although small, the observed effects may be of
epidemiological significance at a population level. James (2004) has computed that
reducing average daily SBP across the general population by just 4 mmHg per
person would, in time, reduce premature deaths from coronary heart disease by 14%

Figure 2. Mean overall levels of DBP for OC users and non-users, during follicular and
luteal phases.
112 S. Schallmayer and B.M. Hughes

and from stroke by 20% (cf., Prospective Studies Collaboration, 2002; Wolf-Maier
et al., 2003). Considering also the implications of CVR for lifetime disease risk
(Lovallo, 2005), the present findings corroborate suggestions that female reproduc-
tive hormones are protective to cardiovascular health.
The data also suggested a significant relationship between neuroticism and
SBP reactivity, contingent on menstrual phase: specifically, neuroticism was
associated with reduced follicular-phase CVR. As neuroticism is believed to lead
to pessimism-related task disengagement and poor performance (Dobson, 2000),
high-neuroticism participants might reasonably be expected to show less task-related
physiological arousal. The fact that this emerged only for the follicular phase
suggests a systemic relationship among personality, menstruation, task performance,
and CVR. For example, one interpretation of the present data is that neuroticism
exacerbates follicular-phase (i.e. premenstrual) effects on CVR, such that the
tendency for neurotic persons to disengage from tasks was more pronounced
during this phase. In future, such interpretations could be explored by monitoring
task performance patterns as well as arousal. In the present study, the lack of a
measure of performance or engagement can be acknowledged as a potential
limitation.
The effect for neuroticism on SBP reactivity was statistically independent of the
fact that OC users had higher neuroticism than non-users. This difference in
neuroticism appears inconsistent with previous research suggesting that contra-
ception users have internal loci of control and high self-esteem. This divergence may
relate to the fact that measures of locus of control and self-esteem appear susceptible
to social desirability bias (Kraus, 1985; Riketta, 2005), unlike measures of
neuroticism (McKelvie, 2004). Thus, in studies of sexual behavior, high-neuroticism
participants may return exaggeratedly self-flattering responses leading to the
erroneous association of OC use with socially desirable traits.
Some limitations in the present research warrant consideration. The sample was
relatively small, well educated, and young, and included only women with regular
menstrual cycles. However, this homogeneity enhanced internal validity by reducing
confounding with extraneous participant characteristics, and the use of a repeated-
measures design and counterbalancing further enhanced methodological rigor.
Nonetheless, while the sample size had acceptable power to detect large between-
group differences, within-group effects, and correlations individually (Cohen, 1992),
the incorporation of all effects together within an ANCOVA design weakened
overall statistical power. Future research should employ larger samples and
investigate whether the effects generalize to participants of different ages and
backgrounds.
In conclusion, while menstrual phase and OC use impact synergistically on CVR,
the observed effects were somewhat limited and there appears to be little justification
to systematically exclude female participants, or women using OCs, from CVR
research. The main problems for researchers arise when participants undergo
assessments over a period of weeks. With male participants, high test–retest
reliability in CVR over such periods might be expected; however, for women not
using OCs, this may not be the case. Instead, researchers could arrange for female
participants to be tested during the same menstrual phase. Testing participants
during the follicular phase should reduce the interpretational problems of OC use, in
that differences between users and non-users are unlikely to be significant.
Alternatively, given that OC users’ CVR appears to be depressed (artificially)
 Psychology, Health & Medicine 113

during this phase, researchers could test CVR during the luteal phase while factoring
OC use into statistical analyses. The present findings also highlight the usefulness of
controlling for personality when studying CVR.
Given the number of women who use OCs, coupled with the increasing extent to
which both psychological stress and cardiovascular disease are recognized as
impacting on women as well as on men, the exclusion of OC users from relevant
research appears regrettable. The present findings suggest that the anticipated
complications for researchers are not at all insurmountable, and therefore that such
exclusion cannot be justified on methodological grounds.

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