Journal of Traumatic Stress

February 2015, 28, 1–7

Menstrual Cycle Effects on Psychological Symptoms in Women

With PTSD
Yael I. Nillni,1,2 Suzanne L. Pineles,1,2 Samantha C. Patton,1 Matthew H. Rouse,2,3 Alice T. Sawyer,2,3
and Ann M. Rasmusson1,2
1
National Center for PTSD, Women’s Health Sciences Division, VA Boston Healthcare System, Boston, Massachusetts, USA
2
Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA
3
VA Boston Healthcare System, Boston, Massachusetts, USA

The menstrual cycle has been implicated as a sex-specific biological process influencing psychological symptoms across a variety of
disorders. Limited research exists regarding the role of the menstrual cycle in psychological symptoms among women with posttraumatic
stress disorder (PTSD). The current study examined the severity of a broad range of psychological symptoms in both the early follicular
(Days 2–6) and midluteal (6–10 days postlutenizing hormone surge) phases of the menstrual cycle in a sample of trauma-exposed women
with and without PTSD (N = 49). In the sample overall, total psychological symptoms (d = 0.63), as well as depression (d = 0.81)
and phobic anxiety (d = 0.81) symptoms, specifically, were increased in the early follicular compared to midluteal phase. The impact of
menstrual cycle phase on phobic anxiety was modified by a significant PTSD × Menstrual Phase interaction (d = 0.63). Women with
PTSD reported more severe phobic anxiety during the early follicular versus midluteal phase, whereas phobic anxiety did not differ across
the menstrual cycle in women without PTSD. Thus, the menstrual cycle appears to impact fear-related symptoms in women with PTSD.
The clinical implications of the findings and future research directions are discussed.

Compared to men, women are twice as likely to be diagnosed
with posttraumatic stress disorder (PTSD) and experience a
more chronic course of the disorder (Breslau et al., 1998), sug-
gesting a sex-specific vulnerability for risk and/or maintenance
of PTSD. One potential sex-specific vulnerability factor is the
cyclical variability of estradiol and progesterone levels across
the menstrual cycle. Hormone patterns associated with certain
phases of the menstrual cycle have been associated with an
increase in the occurrence or symptoms of a variety of psycho-
logical disorders and conditions (Hendrick, Altshuler, & Burt,
1996), including panic disorder (e.g., Kaspi, Otto, Pollack, Ep-
pinger, & Rosenbaum, 1994), bipolar disorder (e.g., Rasgon,
Bauer, Glenn, Elman, & Whybrow, 2003), major depressive
disorder (e.g., Kornstein et al., 2005), eating disorders (e.g.,
Lester, Keel, & Lipson, 2003), and alcohol (e.g., Allen, 1996)
or substance use (e.g., Evans, Haney, & Foltin, 2002) disorders.
Support for this work was provided by a VA Career Development Award
(Principal Investigator: S. L. Pineles) from the Clinical Sciences R&D Service,
Department of Veterans Affairs
Correspondence concerning this article should be addressed to Yael Nillni,
National Center for PTSD, Women’s Health Sciences Division, Veteran’s Af-
fairs Boston Healthcare System, 150 South Huntington Ave. (116B-3), Boston,
MA 02130. E-mail: yael.nillni@va.gov
Published 2015. This article is a US Government work and is in the public
domain in the USA. View this article online at wileyonlinelibrary.com
DOI: 10.1002/jts.21984
Typically, although not universally, there is an exacerbation of
symptoms of these disorders during the late luteal phase (Days
5 to 1 relative to the start of menses), when progesterone and
estradiol are declining, and during the early follicular phase
(Days 1 to 5 after the start of menses), when levels of proges-
terone and estradiol are both at their lowest levels (Hendrick
et al., 1996). For example, women with panic disorder exhibit
an increase in the frequency or intensity of panic attacks dur-
ing the late luteal phase as compared to other menstrual cycle
phases (Kaspi et al., 1994). The possible contribution of estra-
diol and progesterone to menstrual cycle phase-related differ-
ences in affect may be related to these hormones’ influence on a
variety of systems, including hypothalamus–pituitary–adrenal
(HPA) axis response to stressors (Kirschbaum, Kudielka, Gaab,
Schommer, & Hellhammer, 1999), and function of the sero-
tonergic (Rubinow, Schmidt, & Roca, 1998), gamma-amino-
butyric acid (GABA) ergic, and noradrenergic (Rasmusson &
Friedman, 2002) systems. There may also be cultural beliefs or
stereotypes about symptoms during specific phases of the men-
strual cycle that contribute to symptom fluctuations (Klebanov
& Jemmott, 1992).
The literature examining the role of menstrual cycle phase
in expression of psychological symptoms among individuals
with PTSD is limited. There are a few studies with relevance
to PTSD, but not performed in PTSD patients specifically,
that implicate the menstrual cycle and related hormones in

1
2 Nillni et al.
fear-conditioning models (Milad et al., 2010) and reactivity
to stressors (Nillni, Rohan, & Zvolensky, 2012). To our knowl-
edge, Bryant and colleagues (2011) are the only investigators to
date who have examined PTSD symptom expression in different
phases of the menstrual cycle among trauma-exposed women.
In this study, women assessed 1 to 2 weeks after trauma expo-
sure reported more trauma-related flashbacks on the Clinician
Administered PTSD Scale (CAPS; Blake et al., 1995) if they
were in the midluteal phase either at the time of trauma or the
time of assessment. This study, thus, may contribute to our un-
derstanding of how the menstrual cycle influences expression
of at least one salient PTSD reexperiencing symptom in the
acute aftermath of trauma before PTSD is formally diagnosed.
Most other studies of menstrual phase effects on other psycho-
logical disorders document menstrual cycle related increases in
a range of psychological symptoms during the late luteal and
early follicular phases (Hendrick et al., 1996).
PTSD is a heterogeneous disorder, consisting of both trauma-
specific symptoms (e.g., avoidance of trauma reminders or
physiological or emotional arousal when confronted with a spe-
cific trauma reminder) as well as symptoms of general distress
and dysphoria (e.g., irritability, sleep disturbance, loss of in-
terest, negative mood). Given the extant literature demonstrat-
ing exacerbation of general anxiety and depressive symptoms
across the menstrual cycle, we might expect symptoms in these
more general domains to fluctuate across the menstrual cycle
among women with PTSD as well.
Therefore, the aim of the present study was to examine the
interactive effects of menstrual cycle phase (early follicular vs.
midluteal) and current PTSD diagnosis on self-reported general
psychological symptoms measured by the Symptom Checklist-
90-Revised (SCL-90-R; Derogatis, Lipman, & Covi, 1976).
Based on the larger literature (Hendrick et al., 1996) exam-
ining expression of symptoms across the menstrual cycle, we
were particularly interested in examining a time when estra-
diol and progesterone levels were declining or low to a time
when estradiol and progesterone levels were rising or high.
We therefore examined women in the early follicular phase
(Days 2–6 after onset of menses) and midluteal phase (6–
10 days after the lutenizing hormone [LH] surge). Additionally,
we aimed to improve upon the methodology of many previous
menstrual cycle-focused studies by more precisely assessing
and confirming menstrual phase, assessing the same women
across menstrual cycle phases, and excluding women on hor-
mone contraception. In addition, all participants in the study
were free from psychotropic medications and use of alcohol or
drugs of abuse for at least a month (or longer for medications
with long half-lives) prior to testing as these substances affect
hormone levels.
In this study, we hypothesized that individuals with PTSD
would report more symptoms of fear, depression, anxiety, in-
terpersonal sensitivity, and hostility during the early follicular
phase than the midluteal phase, whereas individuals without
PTSD would not exhibit menstrual cycle phase differences. We
did not expect the trauma control group to exhibit menstrual
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
cycle phase fluctuations in mood because they were screened
to be medically healthy and to have no Axis I psychopathol-
ogy. In addition, due to the rigorous study eligibility criteria for
the PTSD participants, who had to be medically healthy and
free of psychotic disorders, we did not expect to see menstrual
phase effects on symptoms of somatization, obsessive compul-
sive disorder, paranoia, or psychosis in either study group.
Method
Participants
The sample included 49 women (Mage = 32.62 years, SD =
9.58) who met criteria for lifetime trauma exposure accord-
ing to Criterion A of the Diagnostic and Statistical Manual
of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American
Psychiatric Association, 2000) on the CAPS. These women
were recruited from the local Veterans Affairs hospitals and the
surrounding community using flyers and online advertisements.
Measures included in the current study were administered as
part of a larger investigation examining the effects of men-
strual cycle phase on the psychophysiology and neurobiology
of PTSD (Pineles et al., 2014). Plasma was available for assay
of progesterone and estradiol for 75% of the 100 study visits of
the 50 women who initially completed this study. One partici-
pant’s cycle phase was not confirmed by hormone assay; data
from this participant were removed from analysis, resulting in
a total sample size of 49.
Participants were diagnosed with current PTSD based on the
CAPS. For the current study, we formed two groups: a PTSD
group and a trauma control group. Members of the PTSD group
reported at least one reexperiencing symptom, three avoidance
symptoms, and two hyperarousal symptoms, and had a total
severity score (frequency plus intensity) of 40 or greater on
the CAPS (MCAPS = 67.05, SD = 19.10). Because we were
interested in symptom fluctuations over time, we added the ad-
ditional severity criteria to ensure a sufficient level of symptoms
in the PTSD group. Members of the trauma control group expe-
rienced a Criterion A traumatic event, but did not meet criteria
for lifetime or current PTSD based on the criteria stated above
(MCAPS_CURRENT = 11.00, SD = 10.36). Furthermore, partic-
ipants in the trauma control group were excluded if they met
DSM-IV-TR criteria for a current Axis I psychological disorder
(with the exception of a specific or public speaking phobia)
or had a lifetime history of recurrent major depression based
on the Structured Clinical Interview for DSM-IV-TR Axis I
Disorders (SCID-I; First, Spitzer, Gibbon, & Williams, 2007).
Other exclusion criteria for all participants included these con-
ditions: (a) infectious illness; (b) current or past organic brain
disorder; (c) major neurological problems; (d) endocrine dis-
orders; (e) schizophrenia; (f) psychotic disorder; (g) Bipolar I
disorder; (h) active substance or alcohol abuse or dependence
within 6 months of the study; (i) irregular menstrual cycle;
(j) current participation in active trauma-focused psychother-
apy; (k) use of psychotropic medications, alcohol, or illicit
 Menstrual Cycle and PTSD 3

Table 1
Demographic Characteristics for Total Sample and by Group
Total (n = 49) PTSD (n = 22) Trauma control (n = 27)
Variable n % n % n % χ2
Ethnicity 2.56
Hispanica 2 4 2 9 0 0
Non-Hispanic 47 96 20 91 27 100
Race 8.46
Caucasian 17 35 5 23 12 44
African American 20 41 9 41 12 41
Asian American 5 10 4 18 1 4
American Indian 1 2 1 5 0 0
Other 4 8 1 5 3 11
Years of education 11.33
<High school 1 2 1 5 0 0
High school/GED 6 12 6 27 0 0
Some college 21 43 8 36 13 48
2- or 4-year degree 14 29 4 18 10 37
Graduate school 7 14 3 14 4 15
Employment 9.65
Full- or parttime 16 33 5 23 11 41
Full- or parttime school 9 18 3 14 6 22
Unemployed 18 37 10 45 8 30
Working and in school 6 12 4 18 2 7
Marital status 2.74
Married/cohabitating 5 10 3 14 2 7
Widowed 1 2 1 5 0 0
Divorced 3 6 2 9 1 4
Separated 2 4 1 5 1 4
Never married 38 78 15 68 23 85
Current smoker 1.20
Yes 8 16 5 23 3 11
No 41 84 22 77 24 89
Current Axis I disorders
Anxiety 16 33 13 59 3 11 12.69**
Mood 10 20 10 45 0 0 15.42**
Binge eating 2 4 2 9 0 0 2.56
Body dysmorphic 2 4 2 9 0 0 2.56
Note. PTSD = posttraumatic stress disorder; Anxiety = panic disorder, specific phobia, obsessive compulsive disorder, social phobia, anxiety disorder, not otherwise
specified, and generalized anxiety disorder; Mood = major depressive disorder and dysthymia; GED = General Educational Development.
a The two participants who identified as Hispanic did not indicate a race.

**p < .01.

drugs in the month before the study (or longer if previously us-
ing an antidepressant such as fluoxetine with a long half-life);
and (l) use of hormonal contraceptives. Participants were also
required to have a normal physical exam and normal results on
a standard medical laboratory test to be eligible for the study.
See Table 1 for complete diagnostic and demographic informa-
tion for the participants. As expected given the study design,
the participant groups differed for comorbid diagnoses, but did
not differ significantly on the other demographic variables.
Procedure and Measures
This study was approved by the VA Boston Healthcare Sys-
tem institutional review board; all participants gave informed
consent prior to participation. During the initial screening ses-
sion, participants were administered the CAPS, a highly reliable
(Weathers, Keane, & Davidson, 2001) semistructured interview
considered the gold standard for PTSD diagnosis. Both the
frequency (0 = the symptom does not occur to 4 = the symptom
occurs nearly every day) and intensity (0 = not distressing to
4 = extremely distressing) of the 17 core DSM-IV symptoms of
PTSD were rated. The SCID-I, a widely used semistructured
clinical interview used to assess Axis I disorders according to
the DSM-IV-TR, was also administered to establish the presence
of comorbid current and past psychiatric disorders. The study
principal investigator (Pineles) completed all CAPS and SCID
interviews; the results were reviewed in a weekly diagnostic
consensus meeting with the study team.
Eligible participants then completed the Symptom Checklist-
90-Revised (SCL-90-R; Derogatis et al., 1976) during both their
early follicular and midluteal cycle phases in pseudo-random
order. The SCL-90 is a reliable and valid self-report measure
that has been shown to be sensitive in a variety of contexts
(Derogatis, 1992). Although it assesses psychological symp-
toms across nine symptom constructs, only the global severity
index and five symptom constructs most relevant to the study

Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
4 Nillni et al.
population were analyzed for the current study: interpersonal
sensitivity (e.g., “your feelings being easily hurt”), depression
(e.g., “feeling no interest in things”), anxiety (e.g., “feeling
tense or keyed up”), hostility (e.g., “temper outbursts that you
could not control”), and phobic anxiety (e.g., “feeling afraid to
go out of your house alone”). Participants rated distress asso-
ciated with each symptom during the past week from 0 = not
at all to 4 = extremely. Mean intensity ratings were then de-
rived for each of the subscales as was the global severity index.
Coefficient α for all scales at each phase ranged from .85 to .98.
To schedule early follicular phase sessions, participants noti-
fied study staff when they began menstruating and were sched-
uled to come to the laboratory in the next 2–6 days (Mday =
4.31, SD = 1.40) . To schedule midluteal-phase sessions, partic-
ipants used a home urine LH surge test kit daily and were sched-
uled 6–10 days after detection of the LH surge (Mday = 7.80,
SD = 1.54). Therefore, during the early follicular assessment,
participants were reporting on symptoms during the recent pre-
menstrual/late luteal phase as well as the early follicular phases
when estradiol and progesterone were either declining or low.
During the midluteal assessment, participants were reporting
on symptoms during the early and midluteal cycle phases when
estradiol and progesterone were either increasing or relatively
high and stable. Blood samples were taken at each visit for assay
of estradiol and progesterone levels used to confirm menstrual
cycle phase.
Concentrations of progesterone were measured by a solid-
phase radioimmunoassay (RIA; Coat-A-Count) with kits pro-
vided by Siemens Healthcare Diagnostics (Deerfield, IL). The
assay has an intraassay coefficient of variation (CV) of ࣈ4%
and an interassay CV of ࣈ6 %. The standard range is from 0.1
to 40 ng/ml, with an assay sensitivity of ࣈ0.03 ng/ml. Estra-
diol levels were measured using a solid-phase RIA (Siemens
Healthcare Diagnostics), with a sensitivity of 8 pg/ml and a
working range of 12 to 3900 pg/ml. The cross reactivities of the
estradiol antibody are as follows: estrone 10.0%; estriol 0.32%;
DHEA 0.001%; 5α-dihydrotestosterone 0.004%; testosterone
0.0001%; and progesterone, 11-deoxycortisol, cortisol, andros-
terone, androstenedione, and aldosterone < 0.001%. At the 50%
intercept, the intra- and interassay CVs for this assay are 4%
and 7%, respectively.
Data Analysis
Given that we did not expect to see menstrual phase effects
on symptoms of somatization, obsessive compulsive disorder,
paranoia, or psychosis in either study group because of eligibil-
ity criteria, we did not include these subscales in the analyses in
an effort to reduce the familywise error rate. We were interested
in within-person menstrual cycle-phase differences; therefore,
participants were only included if they completed assessments
at both cycle phases. Eight participants only completed one
menstrual cycle-phase visit and were not included in the analy-
ses. First, demographic characteristics were compared between
the PTSD and trauma control groups using independent samples
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
t tests and χ2 analyses. Then, a series of 2 × 2 repeated mea-
sures analyses of variance were conducted to examine the main
effect of PTSD diagnosis (between-subjects factor), the main
effect of cycle phase (within-subject factor), and the interactive
effects of PTSD group and cycle phase on psychological symp-
toms measured by the SCL-90-R. Two participants had slightly
lower levels of progesterone than would be expected during the
midluteal phase and one participant had a slightly higher level
of progesterone than would be expected during the early fol-
licular phase. Estradiol levels for all three of these participants
were in the expected range. Analyses were run with and without
these participants and results were unchanged; therefore, data
from these participants were retained in the final analyses.
Results
As shown in Table 2, analyses revealed significant main ef-
fects for PTSD across all of the SCL-90-R symptom constructs
(ps < .001), such that the PTSD group consistently reported
higher symptoms than the trauma control group. There was also
a significant main effect for menstrual cycle phase, such that
women reported significantly greater overall symptom severity
in the early follicular phase (M = 0.73, SE = 0.07) than in
the midluteal phase (M = 0.65, SE = 0.07), F(1, 47) = 4.55,
p = .038, d = 0.63. Specifically, women reported increased
symptoms of depression in the early follicular phase (M = 1.06,
SE = 0.11) versus the midluteal phase (M = 0.47, SE = 0.08),
F(1, 45) = 7.42, p = .009, d = 0.81, and increased phobic
anxiety in the early follicular phase (M = 0.90, SE = 0.09)
compared to the midluteal phase (M = 0.39, SE = 0.08), F(1,
47) = 7.45, p = .009, d = 0.81. There was also a significant
interaction between PTSD group and menstrual cycle phase for
phobic anxiety symptoms, F(1, 47) = 4.79, p = .034, d = 0.63.
Follow-up paired t tests revealed that women with PTSD re-
ported significantly more symptoms of phobic anxiety in the
early follicular phase (M = 0.85, SD = 0.75) than the midluteal
phase (M = 0.70, SD = 0.77), t(21) = 2.47, p = .022, whereas
women without PTSD reported no menstrual cycle phase differ-
ences in phobic anxiety severity, t(26) = 0.68, p = .502. There
were no other significant main or interactive effects (Fs < 2.39,
ps > .05).
Discussion
The goal of the current study was to examine the influence of
menstrual cycle phase on the expression of a range of psycho-
logical symptoms in a sample of trauma-exposed women with
and without PTSD. Studies of other psychological disorders
implicating the menstrual cycle in exacerbation of symptoms
of the target disorder studied, typically demonstrate symptom
worsening in the late luteal and early follicular cycle phases
(Hendrick et al., 1996). Initial research among trauma-exposed
women also supports a role for the menstrual cycle in the
expression of flashbacks during the early weeks following
 Menstrual Cycle and PTSD 5

Table 2
Main Effects and Interactions for PTSD Group × Menstrual Cycle Phase for Selected SCL 90-R Subscales
Early follicular Midluteal Effect sizea
PTSD No PTSD PTSD No PTSD
N = 22 n = 27 n = 22 n = 27
Group ×
Variable M SD M SD M SD M SD Group Phase Phase
Interpersonal sensitivity 1.20 0.90 0.41 0.51 1.05 0.79 0.38 0.50 1.15*** 0.41 0.23
Depression 1.62 0.89 0.50 0.54 1.37 0.73 0.42 0.52 1.67*** 0.81* 0.41
Anxiety 0.98 0.66 0.19 0.23 0.91 0.75 0.15 0.21 1.63*** 0.46 0.00
Hostility 1.02 0.99 0.27 0.43 0.79 0.78 0.28 0.36 1.06*** 0.41 0.41
Phobic anxiety 0.85 0.74 0.10 0.20 0.70 0.77 0.08 0.20 1.34*** 0.81** 0.63*
Global Severity Index 1.16 0.67 0.31 0.30 1.03 0.64 0.28 0.30 1.74*** 0.63* 0.41
Note. SCL-90-R = Self-Report Checklist 90-Revised; PTSD = posttraumatic stress disorder.
a Cohen’s d.

*p < .05. **p < .01. ***p < .001.

trauma exposure, but the influence of particular menstrual cycle
phases on a broad range of self-reported psychological symp-
toms among women with PTSD had yet to be examined.
As would be expected, the current study found that women
with PTSD were more likely to report psychological symptoms
across all SCL-90 symptom clusters regardless of cycle phase
as compared to a nonclinical trauma-exposed control group.
Additionally, among all participants, women assessed in the
early follicular phase when ratings encompassed the late luteal
to early follicular cycle phases reported more symptoms of
depression over the past week than when they were assessed
in the midluteal phase when ratings encompassed the early
to midluteal phases. These findings are in line with literature
documenting increases in anxiety and depressive symptoms
during the late luteal and early follicular cycle phases among
clinical (Hendrick et al., 1996) and nonclinical samples (e.g.,
Gonda et al., 2008). This suggests that menstrual cycle impacts
affect, particularly depression and anxiety, across a wide range
of women.
Although there was a main effect of menstrual cycle phase
on phobic anxiety, this effect was qualified by a significant
PTSD × Menstrual Phase interaction. Specifically, women with
PTSD reported more symptoms of phobic anxiety during the
early follicular phase compared to the midluteal phase, whereas
phobic anxiety did not change across the menstrual phase in
women without PTSD. The items on the phobic anxiety sub-
scale include fear-related symptoms (e.g., “feeling afraid in
open spaces or on the streets”) and behavioral avoidance symp-
toms (e.g., “having to avoid certain places or activities because
they frighten you,” “feeling afraid to travel on buses, subways,
or trains”). Thus, it is possible that periods of declining or low
estradiol and progesterone are periods in which women with
PTSD are particularly susceptible to fear-related symptoms and
associated avoidance, symptoms that may or may not be PTSD
specific. For example, women with PTSD may be more likely
to avoid trauma-related triggers during the late luteal and early
follicular cycle phases.
The findings of the current study align with previous studies
describing menstrual cycle-related patterns in the expression of
symptoms of other psychological disorders. Previous literature
has documented late luteal and/or early follicular exacerba-
tion of symptoms in a variety of mood and anxiety disorders
(Hendrick et al., 1996; Hsiao, Liu, & Hsiao, 2004). These find-
ings are partially consistent with those of Bryant and colleagues
(2011) who found that women who experienced a trauma in the
midluteal phase reported more flashbacks (i.e., a fear-related
PTSD symptom) when assessed an average of 7.19 ± 10.4
(SD) days later, meaning that most were likely assessed dur-
ing the late luteal phase or early follicular phase—a finding
consistent with the current study. They also found, however,
increases in flashbacks for women assessed in the midluteal
phase, who had experienced a trauma 7.2 ± 10.4 (SD) days
prior. These divergent results may be due, at least in part, to
several methodological differences between the study by Bryant
et al. (2011) and the current study. In contrast to Bryant et al.
(2011), the current study (a) included participants with chronic
PTSD and more remote trauma, (b) compared symptoms across
menstrual phases within individual participants, and (c) focused
on a range of psychological symptoms not unique to PTSD. It is
possible that specific menstrual cycle phases may differentially
influence the effects of acute trauma versus chronic PTSD. For
example, better encoding of trauma memories may occur in the
midluteal phase (Bryant et al., 2011; Soni, Curran, & Kamboj,
2013), which may influence the development of psychopathol-
ogy after acute trauma. Extinction deficits and increased fear
symptoms occurring during the late luteal and early follicu-
lar phases, however, may contribute to maintenance of PTSD
once developed. Future work that disentangles menstrual cycle
influences on PTSD risk and PTSD specific symptoms versus
a range of general mood and anxiety symptoms in both the

Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
6 Nillni et al.
acute and long term phases following trauma exposure is thus
warranted.
Although this study provides important information regard-
ing the influence of particular menstrual cycle phases on
psychological symptom reports, it does not elucidate the un-
derlying mechanisms responsible for this effect. In fact, the
literature examining correlations between estradiol or pro-
gesterone and anxiety or depressive symptoms has been
mixed (Hsiao et al., 2004). This suggests that future ex-
aminations of the relationship between hormone levels and
such symptoms may require inclusion of moderating vari-
ables (e.g., diagnostic group), examination of dynamic hor-
monal changes, and/or examination of neuroactive metabolites
of these hormones. Specifically, changes in levels of estradiol
and progesterone have been shown to modulate many of the
neurobiological systems (e.g., noradrenergic, serotonergic,
GABAergic, hypothalamus–pituitary–adrenal axis) implicated
in PTSD (Rasmusson & Friedman, 2002). For example, de-
clining levels of progesterone during the late luteal phase are
thought to influence anxiety via a decline in levels of the neu-
rosteroid, allopregnanolone, a potent GABAergic metabolite
of progesterone (Nillni, Toufexis, & Rohan, 2011). Allopreg-
nanolone has also been related to PTSD reexperiencing and
depressive symptoms in women with PTSD (Rasmusson et al.,
2006). Low estrogen levels have also been associated with
deficits in extinction (i.e., the ability to learn that a previ-
ously dangerous stimulus is no longer dangerous) in women
with PTSD (Glover et al., 2012). High estradiol has been as-
sociated with enhanced extinction retention (i.e., the ability to
retain extinction learning at a later assessment) in women with-
out psychopathology (Milad et al., 2010; Zeidan et al., 2011).
In contrast, recent work from our group suggests that women
with PTSD may exhibit a different pattern of menstrual phase
effects on extinction retention (Pineles et al., 2013). Thus, ex-
amination of dynamic changes in hormones and their associated
neurosteroid metabolites will be an important next step toward
understanding the impact of menstrual cycle phase on symptom
expression in women with PTSD.
It is important to note several study limitations. First and
foremost, this study did not include a PTSD symptom mea-
sure anchored to the specific menstrual phases of interest. In
addition, the “past 7 day” time frame queried in the SCL-90
caused women to report their experiences during the late luteal
to early follicular phases, as well as during the early to mid-
luteal phases. Combining distinct menstrual cycle phases into
one phase for assessment may have obscured more precise
menstrual cycle-phase effects. Thus, future research should ex-
amine PTSD specific symptoms across multiple, more precisely
circumscribed menstrual cycle phases to further elucidate the
unique impact of the menstrual cycle and related hormones or
hormone metabolites on expression of symptoms. The PTSD
group reported more symptoms than the trauma control group
across all subscales of the SCL-90-R. Therefore, it is possible
that the individuals in the PTSD group had a negative reporting
bias. Finally, it is important to note that the six scales of the
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
SCL-90-R included in this study are highly correlated (rs range
from .71 to .93).
Despite these limitations, the current study is the first study
we are aware of that documents late luteal/early follicular
menstrual phase exacerbations of depressive and fear-related
symptoms in women previously exposed to trauma. Given that
women tend to have a more chronic course of PTSD than men
(Breslau et al., 1998), elucidating potential mechanisms in-
volved in the maintenance of PTSD for women may have im-
portant implications—both for prevention and for treatment.
Further work to establish the precise means by which late
luteal/early follicular menstrual status exacerbates fear and anx-
iety in this population is therefore warranted, so that targeted
therapies can be developed.
There are likely multiple factors contributing to fluctua-
tions of symptoms across the menstrual cycle. Consistent
with biopsychosocial models, psychological (e.g., psychologi-
cal vulnerability), biological (e.g., hormone changes), and so-
cial or cultural (e.g., cultural expectations regarding menstrua-
tion) factors likely interact to influence the cyclicity of affective
symptoms during the menstrual cycle. The current study exam-
ined the interaction between psychological (i.e., PTSD diagno-
sis) and biological (i.e., menstrual cycle phase) vulnerabilities.
Future work would benefit from incorporation of other moder-
ating variables that may influence the impact of the menstrual
cycle on affect.
References
Allen, D. (1996). Are alcoholic women more likely to drink pre-
menstrually? Alcohol and Alcoholism, 31, 145–147. doi:10.1093/
oxfordjournals.alcalc.a008125
American Psychiatric Association. (2000). Diagnostic and statistical manual
of mental disorders (4th ed., text rev.). Washington, DC: Author.
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman,
F. D., Charney, D. S., & Keane, T. M. (1995). The development of a
clinician-administered PTSD scale. Journal of Traumatic Stress, 8, 75–90.
doi:10.1002/jts.2490080106
Breslau, N., Kessler, R. C., Chilcoat, H. D., Schultz, L. R., Davis, G. C.,
& Andreski, P. (1998). Trauma and posttraumatic stress disorder in the
community: The 1996 Detroit Area Survey of Trauma. Archives of General
Psychiatry, 55, 626–632. doi:10.1001/archpsyc.55.7.626
Bryant, R. A., Felmingham, K. L., Silove, D., Creamer, M., O’Donnell, M.,
& McFarlane, A. C. (2011). The association between menstrual cycle and
traumatic memories. Journal of Affective Disorders, 131, 398–401. doi:
10.1016/j.jad.2010.10.049
Derogatis, L. R. (1992). SCL-90-R: Administration, scoring or procedures
manual-II for the revised version and other instruments of the Psychopathol-
ogy Rating Scale series. Towson, MD: Clinical Psychometric Research In-
corporated.
Derogatis, L. R., Lipman, R. S., & Covi, L. (1976). SCL-90 (Symptom Check-
List). Self-Report Symptom Inventory. ECDEU assessment manual for psy-
chopharmacology. Rockville, MD: National Institute of Mental Health.
Evans, S. M., Haney, M., & Foltin, R. W. (2002). The effects of smoked cocaine
during the follicular and luteal phases of the menstrual cycle in women.
Psychopharmacology, 159, 397–406. doi:10.1007/s00213-001-0944-7
 Menstrual Cycle and PTSD
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2007). Structured
Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-
I, 1/2007 revision). New York, NY: Biometrics Research, New York State
Psychiatric Institute.
Glover, E. M., Jovanovic, T., Mercer, K. B., Kerley, K., Bradley, B., Ressler, K.
J., & Norrholm, S. D. (2012). Estrogen levels are associated with extinction
deficits in women with posttraumatic stress disorder. Biological Psychiatry,
72, 19–24. doi:10.1016/j.biopsych.2012.02.031
Gonda, X., Telek, T., Juhasz, G., Lazary, J., Vargha, A., & Bagdy, G.
(2008). Patterns of mood changes throughout the reproductive cycle
in healthy women without premenstrual dysphoric disorders. Progress
in Neuro-Psychopharmacology & Biological Psychiatry, 32, 1782–1788.
doi:10.1016/j.pnpbp.2008.07.016
Hendrick, V., Altshuler, L. L., & Burt, V. K. (1996). Course of psychiatric
disorders across the menstrual cycle. Harvard Review of Psychiatry, 4, 200–
207. doi:10.3109/10673229609030544
Hsiao, C., Lui, C., & Hsiao, M. (2004). No correlation of depression and anxiety
to plasma estrogen and progesterone levels in patients with premenstrual
dysphoric disorder. Psychiatry and Clinical Neurosciences, 58, 593–599.
doi:10.1111/j.1440-1819.2004.01308.x
Kaspi, S. P., Otto, M. W., Pollack, M. H., Eppinger, S., & Rosenbaum, J.
F. (1994). Premenstrual exacerbation of symptoms in women with panic
disorder. Journal of Anxiety Disorders, 8, 131–138. doi:10.1016/0887-
6185(94)90011-6
Kirschbaum, C., Kudielka, B. M., Gaab, J., Schommer, N. C., & Hellhammer,
D. H. (1999). Impact of gender, menstrual cycle phase, and oral contracep-
tives on the activity of the hypothalamus–pituitary–adrenal axis. Psychoso-
matic Medicine, 61, 154–162. doi:10.1097/00006842-199903000-00006
Klebanov, P. K., & Jemmott, J. B. (1992). Effects of expectations and bodily
sensations on self-reports of premenstrual symptoms. Psychology of Women
Quarterly, 16, 289–310. doi:10.1111/j.1471-6402.1992.tb00256.x
Kornstein, S. G., Harvey, A. T., Rush, A. J., Wisniewski, S. R., Trivedi, M. H.,
Svikis, D. S., . . . Harley, R. (2005). Self-reported premenstrual exacerbation
of depressive symptoms in patients seeking treatment for major depression.
Psychological Medicine, 35, 683–692. doi:10.1017/S0033291704004106
Lester, N. A., Keel, P. K., & Lipson, S. F. (2003). Symptom fluctuation in
bulimia nervosa: Relation to menstrual-cycle phase and cortisol levels. Psy-
chological Medicine, 33, 51–60. doi:10.1017/s0033291702006815
Milad, M. R., Zeidan, M. A., Contero, A., Pitman, R. K., Klibanski, A., Rauch,
S. L., & Goldstein, J. M. (2010). The influence of gonadal hormones on
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
7
conditioned fear extinction in healthy humans. Neuroscience, 168, 652–658.
doi:10.1016/j.neuroscience.2010.04.030
Nillni, Y. I., Rohan, K. J., & Zvolensky, M. J. (2012). The role of menstrual
cycle phase and anxiety sensitivity in catastrophic misinterpretation of phys-
ical symptoms during a CO2 challenge. Archives of Women’s Mental Health,
15, 413–422. doi:10.1007/s00737-012-0302-2
Nillni, Y. I., Toufexis, D. J., & Rohan, K. J. (2011). Anxiety sensitivity,
the menstrual cycle, and panic disorder: A putative neuroendocrine and
psychological interaction. Clinical Psychology Review, 31, 1183–1191.
doi:10.1016/j.cpr.2011.07.006
Pineles, S. L., Nillni, Y. I., King, M. W., Patton, S. C., Bauer, M. R., Mostoufi,
S., . . . Orr, S. P. (2014). Menstrual cycle variations in fear conditioning and
extinction: A different pattern of associations for women with and without
PTSD. Manuscript submitted for publication.
Rasgon, N., Bauer, M., Glenn, T., Elman, S., & Whybrow, P. C. (2003).
Menstrual cycle related mood changes in women with bipolar disorder.
Bipolar Disorders, 5, 48–52. doi:10.1034/j.1399-5618.2003.00010.x
Rasmusson, A. M., & Friedman, M. J. (2002). Gender issues in the neurobi-
ology of PTSD. In R. Kimerling & P. Ouimette (Eds.), Gender and PTSD
(pp. 43–75). New York, NY: Guilford Press.
Rasmusson, A. M., Pinna, G., Paliwal, P., Weisman, D., Gottschalk, C., Char-
ney, D., . . . Guidotti, A. (2006). Decreased cerebrospinal fluid allopreg-
nanolone levels in women with posttraumatic stress disorder. Biological
Psychiatry, 60, 704–713. doi:10.1016/j.biopsych.2006.03.026
Rubinow, D. R., Schmidt, P. J., & Roca, C. A. (1998). Estrogen-serotonin
interactions: Implications for affect regulation. Biological Psychiatry, 44,
839–850. doi:10.1016/S0006-3223(98)00162-0
Soni, M., Curran, V. H., & Kamboj, S. K. (2013). Identification of a narrow
post-ovulatory window of vulnerability to distressing involuntary memories
in healthy women. Neurobiology of Learning and Memory, 104, 32–38.
doi:10.1016/j.nlm.2013.04.003
Weathers, F. W., Keane, T. M., & Davidson, J. R. (2001). Clinician-
Administered PTSD Scale: A review of the first ten years of research.
Depression and Anxiety, 13, 132–156.
Zeidan, M. A., Igoe, S. A., Linnman, C., Vitalo, A., Levine, J. B., Kliban-
ski, A., Goldstein, J. M., & Milad, M. R. (2011). Estradiol modu-
lates medial prefrontal cortex and amygdala activity during fear extinc-
tion in women and female rats. Biological Psychiatry, 70, 920–927.
doi:10.1016/j.biopsych.2011.05.016
Copyright of Journal of Traumatic Stress is the property of John Wiley & Sons, Inc. and its
content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.