An exploratory dimensional approach to premenstrual manifestation of
obsessive–compulsive disorder symptoms: A multicentre study☆
Luciana Moreiraa,b, Helena Binsb, Ricardo Toressana,c, Cláudia Ferroa,d, Thiago Harttmannb,
Kátia Petribúa,d, Mário Francisco Juruenae,g, Maria Conceição do Rosárioa,f, Ygor Arzeno Ferrãoa,b,h,⁎
aThe Brazilian Research Consortium on Obsessive–Compulsive Spectrum Disorders, São Paulo, Brazil
bDepartment of Psychiatry, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
cDepartment of Psychiatry, São Paulo State University, Botucatu, Brazil
dDepartment of Psychiatry, Federal University of Pernambuco, Recife, Brazil
eDepartment of Psychiatry, University of São Paulo at Ribeirão Preto, Ribeirão Preto, Brazil
fDepartment of Psychiatry, Federal University of São Paulo, São Paulo, Brazil
gInstitute of Psychiatry, King's College London, London, UK
hPsychiatric Clinic, President Vargas Hospital for Mothers and Children, Porto Alegre, Brazil
a b s t r a c ta r t i c l ei n f o
Received 9 September 2012
Received in revised form 1 December 2012
Accepted 3 December 2012
courseof the menstrual cycle.The objective ofthispaper was to compare female OCD patients with and without
premenstrual worsening of obsessive–compulsive symptoms (OCS), in terms of the clinical characteristics of
Methods: This was a cross-sectional study involving 455 women with OCD, of whom 226 (49.7%) had expe-
rienced premenstrual OCS worsening and 229 (50.3%) had not (PMOCS-worse and PMOCS-same groups, re-
spectively). Data were collected with the original and dimensional versions of the Yale–Brown Obsessive–
Compulsive Scale, as well as with the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).
Results: We found significant differences between the PMOCS-same and PMOCS-worse groups, the latter
showing a higher frequency of suicidal ideation (Pb.001), suicide attempts (P=.027), current use of selec-
tive serotonin reuptake inhibitors (P=.022), lifetime use of mood stabilisers (P=.015), and sexual/reli-
gious obsessions (Pb.001; OR=1.90), as well as higher scores on the BDI (Pb.001) and BAI (Pb.001).
Conclusion: Underscoring the fact that OCD is a heterogeneous disorder, there appears to be a subgroup of
female OCD patients in whom the premenstrual period is associated with a higher frequency of sexual/
religious obsessions, depression, anxiety, and suicidality. This might be attributable to hormonal fluctua-
tions. Further studies are warranted in order to investigate this hypothesis by evaluating such patients
at different phases of the menstrual cycle, as well as measuring hormonal levels.
© 2012 Elsevier Inc. All rights reserved.
der that has been described as burdensome [1,2], affecting 1–3% of the
world population [3,4], across all age groups and cultures [5–7]. It is
characterised by waxing and waning obsessive–compulsive symptoms
(OCS). The obsessive symptoms include intrusive thoughts, fears, and
images, whereas the compulsive symptoms are ritualised physical
behaviours or mental processes, which are typically performed to re-
lieve the anxiety or distress caused by the obsessions.
Patients with OCD generally respond adequately to conventional
treatments such as cognitive behavioural therapy and selective seroto-
nin reuptake inhibitors (SSRIs), response rates ranging from 60% to 80%
. However, logically, 20–40% of OCD patients are partial responders
or non-responders [9–11]. This difference in treatment response
might reflect the fact that OCD is a heterogeneous disorder, comprising
many possible subgroups in relation to symptom severity, age at onset,
course of the disease, family functioning, metabolic capacity, neuro-
biology, brain development, and genetic background [12,13].
A number of studies have identified clinical factors that are predic-
tive of OCD refractoriness: sexual/religious obsessions [9,14,15]; hoard-
ing symptoms [16–18]; psychiatric comorbidity [19–22]; poor insight
[23,24]; early onset and chronic course of OCS [24–27]; absence of
Journal of Psychosomatic Research 74 (2013) 313–319
of Porto Alegre, Porto Alegre, Brazil.
⁎ Corresponding author at: Rua Padre Chagas, 185/903, CEP: 90570-080, Porto Alegre,
RS, Brazil. Tel./fax: +55 51 3346 1077.
E-mail address: email@example.com (Y.A. Ferrão).
0022-3999/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
Contents lists available at SciVerse ScienceDirect
Journal of Psychosomatic Research
sensory phenomena and greater symptom severity [21,28]; lack of
family history ; and family accommodation [9,29–31].
Recently, Torresan et al.  found that, among OCD patients, men
were significantly more likely than women to present with sexual, reli-
gious, and symmetry obsessions, as well as with mental rituals. The
authors also found that comorbid tic disorders were significantly
more common among the men than among the women. In addition,
OCS onset and functional impairment both occurred at an earlier age
in the men. The women with OCD not only scored significantly higher
on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory
(BAI) but were also more likely to present concomitant simple phobias,
eating disorders, and impulse control disorders . Despite possible
cultural influences on gender differentiation, it is possible that specific
neurobiological aspects, especially those related to hormones, underlie
After more than a decade of research, there is considerable evidence
supporting the neuroprotective and cognition-preserving effects of
oestrogens [33,34] and progesterones [35,36]. Oestrogens have direct
and indirecteffects onneurons. Theydirectlyincreasemembraneexcit-
ability, sensitivity to neurotransmitters or their release to the synapses,
especially by direct binding or by modulating enzymes, channels, and
receptors for specific neurotransmitters. Oestrogens can enter the neu-
ron cytoplasm and nucleus, binding to specific receptors and thereby
inhibiting or stimulating the transcription of specific genes [35,36].
Thus, oestrogens can indirectly affect, for example, the number of den-
dritic spines in the hippocampus . In contrast, progesterone acts by
binding to the inhibitory GABAAreceptors, thereby increasing the chlo-
ride influx into cells, which makes the effects of progesterone similar to
those of benzodiazepines [35,36].
Females are susceptible to hormonal fluctuations, and some women
manifest worsening of depressive and anxious symptoms during the
premenstrual (luteal) phase [38–40]. Female patients with OCD are
more vulnerable to the resurgence or worsening of OCS in the premen-
strual phase, as well as during the postpartum period. Such patients
may also report premenstrual increases in the occurrence of symptoms
of mood disorders [40,41]. The exacerbation of OCD symptoms during
the premenstrual phase could be attributable to psychological as well
as neurobiological mechanisms. Menstruation can be a stressful event
, especially for women with contamination obsessions .
The main objective of the present study was to determine whether
there are differences between women with and without premenstrual
worsening of OCS, in terms of the clinical characteristics of OCD. The a
priori hypothesis was that, among those with premenstrual worsening
of OCS, overall OCD severity would be greater, scores for the aggressive
and contamination/washing dimensions of OCD would be higher, OCS
would more often be intermittent, and late onset of OCS would be
Study design and sample
This was a cross-sectional study conducted as part of the Brazilian
Research Consortium on Obsessive–Compulsive Spectrum Disorders
(BRCOCSD) project, which involves seven centres for education and re-
search located in various regions of Brazil . As of March 2009, 901
patients had been systematically evaluated and information regarding
those patients had been included in the dataset. All of those patients
had a primary diagnosis of OCD, as defined in the Diagnostic and Statis-
tical Manual of Mental Disorders, Fourth Edition (DSM-IV) and con-
firmed by administration of the Structured Clinical Interview for
DSM-IV Axis I Disorders (SCID-I) [45,46]. We excluded 46 patients, for
the following reasons: meeting the DSM-IV diagnostic criteria for
schizophrenia (n=7); being unable to understand the study protocol
and therefore unable to give informed consent (n=1); and declining
to participate in the study (n=38). Sources of referral included
(mostly) outpatient clinics, as well as tertiary care hospitals, primary
or secondary health care facilities, private psychiatric clinics (150 with-
in the state of São Paulo and 20 in the state of Rio Grande do Sul),
self-help groups, and the Brazilian Association for Tourette Syndrome,
Tics, and Obsessive–Compulsive Disorder (www.astoc.org.br). Other
methodological aspects of the study are described elsewhere .
All BRCOCSD research projects were submitted to and approved
by the research ethics committees of the centres involved. Written in-
formed consent was obtained from all participants or from a parent or
legal guardian, in accordance with the principles set forth in the
Declaration of Helsinki.
For the purpose of our analysis, we used the term “premenstrual
phase” to refer to the luteal phase (the approximately 14-day period
from the day after ovulation until the end of the menstrual cycle).
We defined “premenstrual worsening of OCS” as worsening of the
OCS, as evaluated with the Yale OCD Natural History Questionnaire
(described below), in the week preceding menstruation. Of the 901
patients initially evaluated, 516 (57.3%) were women. Of those 516
female patients, 61 (11.8%) were excluded: 57 because they were
menopausal; and 4 because they provided no information about
their premenstrual period. Therefore, the final study sample com-
prised 455 women with OCD. Possible responses to the question re-
garding premenstrual worsening of OCS were “no”, “I don't know”,
and “yes”. Only “yes” responses were investigated further. Of the
455 women evaluated, 261 (57.4%) answered “yes” to that question.
However, premenstrual worsening of OCS was confirmed in only 226
(49.7%), and those women were collectively designated the premen-
strual OCS worsening (PMOCS-worse) group. The remaining group of
229 women (50.3% of the sample)—although it included 3 women
who actually reported premenstrual improvement of their OCS—was
designated the premenstrual OCS unchanged (PMOCS-same) group.
The current version of the BRCOCSD “Initial Evaluation Protocol” is
an assessment package (available upon request) designed to collect
sociodemographic, socioeconomic, and medical history data, as well
as including a semi-structured interview regarding the family history
of psychiatric disorders, together with other standardised scales,
questionnaires, and inventories (also available upon request). The
protocol also includes questions regarding the personal and family
history of suicidal ideation or behaviour. The other main instruments
used in this study were as follows:
➢ SCID-I [45,46]—We administered the SCID-I, with additional mod-
ules for tic and impulse control disorders . With exception of
schizophrenia, a diagnosis of which was an exclusion criterion,
all DSM-IV axis I disorders (mood disorders, substance use disor-
ders, anxiety disorders, somatoform disorders, eating disorders,
and adjustment disorders) were included in the analysis. Atten-
tion deficit hyperactivity disorder and separation anxiety disorder
were investigated with a module of the Kiddie Schedule for Affec-
tive Disorders and Schizophrenia .
➢ Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) [48,49]—The
Y-BOCS has been used worldwide in order to identify and evaluate
the severity of OCS.
➢ Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS)
—The DY-BOCS evaluates OCS by specific dimension, including
dimensions for obsessions and related compulsions, allowing the
severity of each dimension to be independently quantified. Anoth-
er advantage of this scale is that avoidant behaviours, as well as
mental and physical repetitive rituals, are investigated within
each dimension, providing a more precise evaluation of symptom
severity. It also investigates the time spent on OCS, the level of
anxiety and impact of the symptoms, scores ranging from 0 to 5
with a maximum of 15 for each dimension. The negative impact
L. Moreira et al. / Journal of Psychosomatic Research 74 (2013) 313–319
of OCS on the lives of subjects is also quantified on a scale of 0 to 5
with a maximum score of 15. Therefore, the maximum total
DY-BOCS score is 30. Treatment response can also be evaluated
➢ Yale OCD Natural History Questionnaire (Leckman, J.F., 2002. Yale
OCD Natural History Questionnaire. Unpublished manuscript)—The
Yale OCD Natural History Questionnaire involves a comprehensive
semi-structured interview focusing on the onset and course of
OCS, including life events and situations that could trigger, worsen,
or improve OCS. Part I addresses OCS onset: age at onset; whether
OCS began abruptly or gradually; and whether OCS started after
drug use, family problems, personal problems, emotional problems,
financial problems, or any clinical disease. Part II addresses the
course of OCS, including questions such as those regarding environ-
mental factors that could affect OCS (e.g., alcohol, coffee, tobacco,
certain kinds of food, weather, sleep, fatigue, and mood). Part II
also includes a specific question regarding how the premenstrual
period (the week before menstruation) affects OCS. In the present
study, we used that question in order to define the PMOCS-worse
and PMOCS-same groups. There are four possible responses to the
question: “no effect”; “worsens OCS”; “improves OCS”; and “not ap-
plicable”. When theresponse was“worsensOCS”, thecondition was
confirmed with a semi-structured questionnaire based on the
Y-BOCS, which included the following: 1 — “Which OCS worsened
during this period?”; 2 — (for each OCS mentioned) “Did it occupy
more of your time?”; 3 — (for each OCS mentioned) “Did it interfere
more with your daily tasks? (Please explain further.)”; 4 — (for each
OCS mentioned) “Did it cause more distress than usual? (Please ex-
plain further.)”; 5 — (for each OCS mentioned) “Did it become more
difficult than usual to resist? (Please explain further.)”. Question 2
refers to OCS frequency, whereas questions 3, 4 and 5 refer to OCS
severity. If the interviewer was satisfied with the response to any
to be confirmed. Part III investigates the worst ever period of OCS
manifestation (regardless of the phase of the menstrual cycle) and
includes questions similar to those mentioned above but specially
related to that period.
➢ BDI and BAI [51,52]. The BDI and BAI are widely used in order to
identify and determine the severity of symptoms of depression
Initially, we calculated the frequency and distribution of the se-
lected variables for the sample as a whole, using mean (±standard
deviation), percentages, and medians (with minimum and maxi-
mum values). For the differences between groups, we used Pearson's
or Yates' chi-square tests for categorical (polytomous or dichoto-
mous) variables. For all pairwise comparisons, tests were adjusted
using Bonferroni correction. When an association showed statistical
significance, we also calculated the OR. Scores (on the Y-BOCS,
DY-BOCS, BDI, and BAI) were analysed as continuous variables and
compared with the Student's t-test or Mann–Whitney U test,
according to the result of the Kolmogorov–Smirnov test for normal
distribution. To calculate the probability of an event as a function of
ies with several variables, we employed two stepwise logistic regres-
sions (probabilities for entry and removal of .05 and .10, respectively)
ing of OCS (dependent variable), controlling for confounding factors
(sociodemographic and clinical aspects). The first model included
aspects directly related to the phenotypic expression of OCD (intrinsic
variables), whereas the second included aspects not directly related to
such expression but deemed relevant for clinical practice (extrinsic
porated into the models. Regression models of the intrinsic or extrinsic
psychopathological features of OCD have previously been employed in
the investigation of factors associated with treatment response .
The level of statistical significance was set at 5%. Analyses were
performed with SPSS version 15.0 (SPSS Inc., Chicago, IL).
The sociodemographic and clinical characteristics of the two groups are described
in Table 1. There were no significant differences between the PMOCS-worse and
PMOCS-same groups regarding these variables.
Sociodemographic characteristics of patients with and without premenstrual worsen-
ing of obsessive–compulsive symptoms
Premenstrual worsening of OCS
Mean SDMean SD
Body mass index, kg/m2
aAccording to the scale devised by the Brazilian Association of Market Research
Institutes (class A has the highest per capita income).
Clinical and psychiatric aspects of patients with and without premenstrual worsening
of obsessive–compulsive symptoms
worsening of OCS
Has undergone psychotherapy
Hospitalization for a psychiatric
Lifetime history of suicidal ideation
Lifetime history of suicide attempts
Family history of suicide
Lifetime use of medications
Current use of medications
OCS=obsessive–compulsive symptoms, SSRIs=selective serotonin reuptake inhibitors.
aOR was calculated when Pb.05.
L. Moreira et al. / Journal of Psychosomatic Research 74 (2013) 313–319
Clinical features, as well as the lifetime history of psychiatric medication use,
suicidality, and psychiatric treatment, are described in Table 2. Hypothyroidism was
more common in the PMOCS-same group (P=.042), whereas aspects of suicidality
(suicidal ideation and suicide attempts) were more common in the PMOCS-worse
group (Pb.001 and P=.027, respectively), as were the current use of SSRIs (P=.022)
and lifetime use of mood stabilisers (P=.015). For the purpose of sample description,
the most common current psychiatric comorbidities in PMOCS-worse and PMOCS-
same group patients were determined to be as follows: major depressive disorder (in
42% and 25.3%, respectively—χ2Yates=13.09, Pb.001); generalised anxiety disorder
(in 39.8% and 28.8%, respectively—χ2Yates=5.63, P=.018); specific phobias (in 38.9%
and 36.7%, respectively—χ2Yates=0.16, P=.69); and social anxiety disorder (in 38.1%
and 24.5%, respectively—χ2Yates=9.18, P=.002).
The mean BDI score was higher for the patients with a history of suicidal ideation
than for those without (20.79±11.80 vs. 13.88±11.02, tStudent=−8.67, Pb.001), as it
was for those with a history of suicide attempts in comparison with those without
(22.29±12.76 vs. 15.74±11.47, tStudent=−5.23, Pb.001). In terms of the mean
Y-BOCS score, there was no statistical difference between the patients with and with-
out a history of suicidal ideation (25.98±8.05 vs. 24.96±8.14, tStudent=−1.713, P=
.076) or suicide attempts (26.73±7.66 vs. 25.17±8.16, tStudent=−1.76, P=.078).
Table 3 shows the presence of specific OCS dimensions according to the DY-BOCS
and the severity of each dimension, as well as the scores on the Y-BOCS subscales (ob-
sessions and compulsions), together with the total scores on the DY-BOCS, Y-BOCS, BDI,
and BAI. The mean BDI and BAI scores were significantly higher for the PMOCS-worse
group patients than for the PMOCS-same group patients. Although statistically signifi-
cant, the difference in severity, as measured by the DY-BOCS, had no clinical relevance.
Table 4 presents the results of the logistic regression. In the initial model, we en-
tered the following intrinsic psychopathological OCS variables: presence of the aggres-
sion, sexual/religious, and miscellaneous dimensions; severity of the sexual/religious
and miscellaneous dimensions; and age at which OCS became severe enough to inter-
fere with daily activities. The DY-BOCS total score did not enter the regression model
because of its co-linearity with the symptom dimensions cited above.
In the second regression model, we entered the following extrinsic psychopathologi-
cal OCS variables: comorbidity with current major depression, social anxiety disorder, or
generalised anxiety disorder; ethnicity; employment status; BDI and BAI total scores;
hypothyroidism; aspects of suicidality (suicidal ideation); lifetime use of mood stabilisers
and neuroleptics; and current use of SSRIs.
As can be seen, the main intrinsic factors associated with premenstrual worsening
of OCS were the presence of sexual/religious DY-BOCS dimension (OR=1.90) and
early onset of OCS (OR=1.03). The main extrinsic factors that were significantly asso-
ciated with premenstrual worsening of OCS were suicidality, represented by suicidal
ideation (OR=2.07), and comorbidity with social anxiety disorder (OR=1.84).
In this study, we analysed a large OCD dataset , focusing on the
female patients. We drew comparisons between those with premen-
strual worsening of OCS and those without. The patients in the
PMOCS-worse group scored significantly higher on the DY-BOCS sex-
ual/religious dimension than did those in the PMOCS-same group. As
hypothesised, suicidality was significantly more common in the
PMOCS-worse group. Of the most common psychiatric comorbidities,
social anxiety disorder seems to be strongly associated with premen-
strual worsening of OCS. Our findings suggest that premenstrual
worsening of OCS is associated with hormonal influences and defines
a distinct OCD subgroup. The following clinical features were also
more common in the PMOCS-worse group but did not retain their sig-
nificance after the regression analysis: presence of aggression and
miscellaneous DY-BOCS dimensions; severe sexual/religious and mis-
cellaneous dimensions; early onset of OCS; comorbidity with current
majordepressionor generalised anxietydisorder; ethnicity;beingun-
employed; BDI and BAI total scores; hypothyroidism; lifetime use of
mood stabilisers and neuroleptics; and current use of SSRIs.
The results of studies investigating hormonal influences in OCD
[53,54], have demonstrated that there are changes in OCS in the pre-
period, and during menopause, suggesting that there is a relationship
between menstrual/reproductive cycle changes and OCD symptom
Prevalence and severity of specific obsessive–compulsive symptom dimensions
Premenstrual worsening of OCS
Sexual/religious 141 62.410345.0
Onset of obsessions
Onset of compulsions
DY-BOCS dimensions (severity)
Mean SD Mean SD
DY-BOCS total score
Age at OCS onset,
Age at onset of
OCS=obsessive–compulsive symptoms, DY-BOCS=dimensional Yale–Brown Obsessive–
Compulsive Scale, Y-BOCS=Yale–Brown Obsessive–Compulsive Scale, UMW=Mann–
Whitney U test.
aOR was calculated when Pb.05.
bInterfering with daily activities.
Variables independently associated with premenstrual worsening of obsessive–com-
pulsive symptoms after logistic regression analyses
Odds ratio 95% confidence interval
Early onset of OCS severitya
Beck Anxiety Inventory score
Social anxiety disorder
aInterfering with daily activities.
bVariable entered in step 1: Beck Anxiety Inventory scores; variable entered in step
2: suicidal ideation; variable entered in step 3: hypothyroidism.
L. Moreira et al. / Journal of Psychosomatic Research 74 (2013) 313–319
fluctuation [53–55]. Some authors have found that not only symptom
exacerbation but also OCS onset is associated with menarche , the
premenstrual phase , pregnancy [57–59] and the puerperium
From a neurobiological viewpoint, there is direct and indirect
evidence that gonadal steroids influence the appearance of specific
OCD symptoms. There is direct evidence that oral contraceptives can
worsen or improve OCD symptoms [62,63], and their use has been
shown to be a risk factor for premenstrual mood disturbance in
women with a history of depression . However, other studies have
found that oral contraceptive use has a beneficial effect on mood and
affect [65–67]. Although it is possible that mood disturbance in the pre-
menstrual phase increases OCS severity, we found no evidence of that
in our sample of female OCD patients. Nevertheless, gonadal steroids
might indirectly influence OCD symptoms through their effect on dopa-
mine function. Preclinical research has shown that oestradiol influences
the dopamine system, primarily by increasing dopamine release in the
caudate-putamen and nucleus accumbens , then by reducing dopa-
mine uptake in the nucleus accumbens , and finally by rapidly
shifting striatal D2dopamine receptors from high- to low-affinity states
by variants in the oestrogen receptor alpha gene, especially that of
oestrogen receptor 1 . This is in line with the results of Vulink et al.
, who reported an increase in OCD symptoms in two-thirds of the
overactivityofthemesocorticolimbic system might play a central role in
the emergence of obsessions, manifesting as excessive computation
about the predictability of the event . Such overactivity might also
be quite important in the production of compulsive and repetitive be-
haviours, supporting the use of a behavioural approach aimed at reduc-
ing the distress generated by the irruption of intrusive thoughts.
In the present study, there were no significant differences between
the female OCD patients who experienced OCS worsening during the
premenstrual phase and those who did not in terms of symptom sever-
ity, as evaluated with the Y-BOCS. However, according to the DY-BOCS,
there were significant differences between the two groups in some of
the OCS dimensions. After logistic regression, the DY-BOCS sexual/reli-
gious dimension remained significantly associated with premenstrual
worsening of OCS (OR=1.90). Vulink et al. studied specific OCS with
the Y-BOCS and premenstrual worsening of OCS . The authors
found no differences between the women with and without such
worsening . Other authors studied pregnancy and childbirth to
hormones. Some of those authors reported more contamination/wash-
ing obsessions in relation to OCS worsening or onset at postpartum
[55,74], whereas others reported more aggressive obsessions in sub-
jects with postpartum OCD [53,75].
To our knowledge, this is the first study to relate a subtype of OCD
(sexual/religious dimension) to the premenstrual period. Although the
mechanisms responsible for the modulatory effects of hormones on OCS
remain unknown , it is possible to hypothesise that hormonal imbal-
ance in the premenstrual phase influences this specific neurocircuitry di-
mension. This could be explained by the evidence that the emergence of
symptoms pertaining to the different OCS dimensions causes differential
patterns of cortical activation [76–80]. It has been shown that the ventral
prefrontal, limbic, and dorsal prefrontal regions are preferentially activat-
regions are predominantly activated in response to checking-related im-
by hoarding-related images.
Dysfunction of the hippocampus (an important structure in learn-
ing tasks, converting recent memories to long-term memories and
recording/decoding perceptual patterns) might be related to the het-
erogeneous manifestation of OCD . Recent data indicates that the
hippocampus is affected by gonadalsteroids, becausegonadalsteroids
maintain the sex-specific acetylcholine release in the dorsal hippo-
campus, and neonatal activation of oestrogen receptors is sufficient
to mediate masculinisation of the septo-hippocampal cholinergic sys-
tem in rats . In rodents, endogenous oestradiol and progesterone
produced by the ovaries also seem to modulate dendritic spine
morphology and synaptic protein expression in the hippocampus,
as well as hippocampal-dependent learning and memory ,
suggesting that the presentation of OCS can be varied, in terms of con-
tent. Another structure that might be involved is the amygdala, be-
cause it modulates the startle circuit during threat situations .
Bannbers et al.  showed that, in patients with premenstrual dys-
phoric disorder, startle modulation in response to positive and nega-
tive anticipation stimuli was greater in the luteal phase than in the
follicular phase, as well as being greater in such patients than in con-
trols during the luteal phase. This OCS worsening involving the amyg-
dala might be due to the negative mood induced by the use of
progesterone and progestins, most probably via their GABAAreceptor
active metabolites . Negative mood symptoms occur when the
serum concentration of allopregnanolone is similar to endogenous lu-
on mood. It has also been shown that progesterone/allopregnanolone
treatment in women increases the activity in the amygdala (as mea-
sured with functional magnetic resonance imaging) in a way similar
to that seen during anxiety reactions .
Concomitant major depression has been found to reduce functional
activity in the caudate nucleus and thalamus , and, according to our
tients in the PMOCS-worse group. Therefore, we could argue that the
association of the sexual/religious dimension and premenstrual OCS
worsening is mediated by affective symptomatology. However, major
depression was not found to be associated with the premenstrual OCS
worsening group in our regression analysis, which suggests that there
is an independent association between the sexual/religious dimension
and premenstrual worsening of OCS.
It is of note that depression and anxiety scores were higher in our
and antipsychotics. These results indicate that OCD was more severe in
thePMOCS-worsegroup, withthe citedfindings beingsecondary to the
OCD severity. Suicidality (ideation and attempts) was also a relevant
clinical aspect, given that the chance of also having a history of suicidal
ideation was nearly doubled in the PMOCS-worse group (OR=1.9). It
could be expected to be a collinear consequence of the severity of the
ation or a history of suicide attempts seem to have higher depressive
symptoms scores, which might be a consequence of higher OCD scores
. Similarly, in a study conducted by Labad et al., the number of pre-
menstrual mood symptoms, including anxiety, irritability, mood labili-
ty, and depressed mood, was associated with premenstrual worsening
of OCS . Unfortunately, those authors did not investigate whether
phase. Therefore, further studies are warranted.
The association between premenstrual OCS worsening and social
anxiety disorder, as indicated by the regression analysis, could be
explained by the fact that OCD patients frequently exhibit avoidant be-
haviours that could be confused with social anxiety when structured
clinical interviews (such as the SCID-IV) are applied. The overlap be-
anxiety diagnostic could lead investigators to overestimate the preva-
lence of comorbid social anxiety disorder in OCD patients . The typ-
ical symptoms of the premenstrual phase (irritability, pain, depressed
ing to a more frequent confusion in the comorbid diagnosis of social
anxiety disorder. Studies with an appropriate design and an adequate
sample size should be conducted in order to differentiate between sec-
ondary avoidant behaviour and comorbid social anxiety disorder in
L. Moreira et al. / Journal of Psychosomatic Research 74 (2013) 313–319
OCD patients. The present study has certain limitations. First, the SCID-I
does not investigate the diagnostic criteria for premenstrual syndrome
or premenstrual dysphoric disorder, neither of which could therefore
be diagnosed via the interview. Second, because our study was based
on a cross-sectional dataset designed to explore the clinical and thera-
peutic features of OCD, data collection on hormonal changes was not
the main focus. Therefore, in future studies, it would be worthwhile to
investigate follicle-stimulating hormone levels or basal temperature
during the cycle phases. Fluctuation of OCD symptoms during the men-
strual cycle could obviously have consequences for patients participat-
ing in pharmacological studies, making the menstrual cycle in women
animportantconfounderin the assessmentofthe severity and specific-
ityofOCS. Third, becausethis wasa cross-sectional study,therewas the
potentialfor a recall biasregarding thepremenstrual worseningof OCS,
which could have produced false-negative responses. Therefore, clini-
cians should carefully evaluate patients for exogenous and endogenous
changes in gonadal hormones when evaluating the onset or exacerba-
tion of OCD and specific OCS. Consequently, it is recommended that
themenstrualcycle betakeninto account whenconductingclinical, ep-
idemiological, or pharmacological studies in women. Despite these lim-
itations,ourstudyprovides novelinformationregardingaputative OCD
Conflict of interest statement
All authors of the entitled paper “An exploratory dimensional ap-
proach of premenstrual manifestation of obsessive–compulsive disor-
der symptoms: A multicentre study.” do declare that they do not have
any actual or potential conflict of interest including any financial,
personal or other relationships with other people or organizations
within three (3) years of beginning the work submitted that could
inappropriately influence (bias) this work.
The authors thank Euripedes Constantino Miguel, Maria Alice de
Mathis, Ana Gabriela Hounie, Roseli Gedanke Shavitt, Aristides Volpato
Cordioli, Christina Hojaij Gonzalez, Juliana Belo Diniz, Daniela Tusi
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