Journal of Affective Disorders 217 (2017) 34–41

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Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research paper

Preconception gynecological risk factors of postpartum depression among MARK

Japanese women: The Japan Environment and Children's Study (JECS)
Sifa Marie Joelle Muchangaa,b, Kahoko Yasumitsu-Lovella,c, Masamitsu Eitokua,
Etongola Papy Mbelambelaa, Hitoshi Ninomiyad, Kaori Komoria, Rahma Tozinb,
⁎
Nagamasa Maedae, Mikiya Fujiedaf, Narufumi Suganumaa, , for the Japan Environment and
Children's Study Group1
a
Department of Environmental Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan
b
Department of Obstetrics and Gynecology, Medical Faculty, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
c
Gilbert Neuropsychiatry centre, University of Gothenburg, Gothenburg, Sweden
d
Integrated Center for Advanced Medical Technologies, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan
e
Department of Obstetrics and Gynecology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan
f
Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Postpartum depression is one of the major causes of disability among women who are on their
Postpartum depression childbearing years. Identifying people at risk of postpartum depression may improve its management. The
Gynecological morbidities objective of this study was to determine the probable association between postpartum depression and some
The JECS preconception gynecological morbidities.
Methods: Data from a nationwide birth cohort study, the Japan Environment and Children's study (JECS), up to
one month of postpartum were analyzed. To assess postpartum depression, the Edinburgh Postnatal Depression
Scale (EPDS) was used; 11 preconception gynecological morbidities were considered as risk factors. Covariates
included psychiatric illness history, psychosocial factors, some pregnancy adverse outcomes, birth outcomes,
socio-demographic and health behavioral factors.
Results: Except for the prevalence of previous miscarriage, leiomyoma and polycystic ovarian syndrome,
depressive women had more gynecological morbidities compared to non-depressive ones.
In logistic regression model, endometriosis (OR, 1.27; 95%CI: 1.15–1.41), dysmenorrhea (OR, 1.13; 95%CI:
1.06–1.21) and abnormal uterine bleeding (OR, 1.21; 95%CI: 1.15–1.29) were associated with postpartum
depression.
Limitations:

• We could not specify in detail which type of gynecological morbidity was associated with postpartum
depression, because the current design was not exclusively oriented by the JECS research question.
• A part of gynecological morbidities were self-reported.
Conclusion: Women with endometriosis and menstrual problems were at risk of developing postpartum
depression.
This study suggests a perinatal mental health screening for predisposed women.

1. Introduction Mental Disorders (DSM V)(American Psychiatric Association, 2013), PPD

Postpartum depression (PPD), a most common disorder of the child-
bearing (O'Hara, 2009), is one of the major causes of disease burden for
women in their reproductive age (World Health Organisation, 2016).
According to the fifth edition of Diagnostic and Statistical Manual of
can occur anytime from the childbirth to one month after, even later, up
to one year (Gaynes et al., 2005; Stuart-Parrigon and Stuart, 2014). Its
prevalence varies from one country to another ranging from 13% to 19%
(O'Hara and McCabe, 2013) in Western countries and almost 4 – 63% in
Asian countries (Klainin and Arthur, 2009).

⁎
Correspondence to: Department of Environmental Medicine, Kochi Medical School, Kochi University, Oko-cho Kohasu, Nankoku, Kochi 783-8505, Japan.
E-mail address: nsuganuma@kochi-u.ac.jp (N. Suganuma).
1
The complete membership of the author group can be found in the Acknowledgments.

http://dx.doi.org/10.1016/j.jad.2017.03.049
Received 12 January 2017; Received in revised form 17 March 2017; Accepted 24 March 2017
Available online 30 March 2017
0165-0327/ © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
S.M.J. Muchanga et al.
Studying PPD is important because beside the disability experienced
by the depressed women, the born children are also exposed to various
negative effects (Theme Filha et al., 2016). Parenting roles of women
are affected and this can negatively impact on the child's health from
birth to the childhood period (Field, 2010; Santos et al., 2014;
Sundaram et al., 2014). PPD is widely studied and a large variety of
risk factors have been described (O'Hara and McCabe, 2013). Many
studies are oriented on psychosocial factors, history of mental illnesses
and few others on obstetrical conditions. The most important risk
factors are history of depression before and/or during pregnancy,
anxiety during pregnancy, low socioeconomic status, stressful life
events, poor marital relationship and lack of social support by family,
friends and/or the partner (Robertson et al., 2004; Shrivastava et al.,
2015).
Regarding obstetrical conditions, unplanned pregnancy, low hemo-
globin level during pregnancy, preterm birth, stillbirth, and having an
infant with medical illness were described to be associated with PPD
(Norhayati et al., 2015).
In Japan, a recent nationwide survey (n=33,998) had reported in
2013 a prevalence of 8.4% for high PPD risk in women during their first
month postpartum (Yamagata, 2015) and 15.2% for three cumulated
months after birth (Asano et al., 2014). Recent reports on a regional
(Tachibana et al., 2015) and on a multihospital cohort study (Iwata
et al., 2016), assessing antenatal risk factors of PPD focusing on
psychosocial factors, found almost as similar risk factors as others
countries; with primiparity, perceiving lack of family cohesion, current
physical illness and current psychiatric illness treatment being the main
risk factors. Apart from the previously cited factors, another multi-
center prospective study on five University hospitals, enlisting only
primiparous and examining psychosocial factors, reported that the
unhappiness about the sex of the newborn is also a risk factor of PPD
(Kitamura et al., 2006). Others studies involving single cities or
facilities found that anxiety during pregnancy, bonding failure
(Kokubu et al., 2012) and lack of social support (Morikawa et al.,
2015) were associated with PPD in Japan; conversely having a full-time
job was associated with reduction risk of PPD (Miyake et al., 2011). On
the other hand, a recent prospective study conducted by Iwata et al.,
had reported that the first month postpartum was the time for the peak
prevalence of depressive symptoms in a Japanese sample (Iwata et al.,
2016).
All those previous studies were either local or regional; the national
study calculated only the prevalence of PPD without consideration of
associated risk factors (Yamagata, 2015). Most studies mainly focused
on psychosocial and socioeconomic factors. There is a need for
conducting studies related to physical, biological and cultural factors
of PPD (Norhayati et al., 2015). Gynecological morbidities, one of the
physical conditions, could also have an impact on PPD. In non pregnant
women, depression was found to be associated with a variety of
gynecological morbidities (Balik et al., 2014; Barry et al., 2011;
Denny, 2009; Dokras, 2012; Facchin et al., 2015; Gagua et al., 2013;
Heller-Boersma et al., 2009; Kayhan et al., 2016; Laggari et al., 2009;
Landen and Eriksson, 2003; Podfigurna-Stopa et al., 2015; Sepulcri Rde
and do Amaral, 2009). During the postpartum period, apart from
studies on association between PPD with premenstrual syndrome
(Buttner et al., 2013; Lee et al., 2015) or previous miscarriage
(Bicking Kinsey et al., 2015; Blackmore et al., 2011; Giannandrea
et al., 2013), there is no study assessing the relationship between the
PPD and other gynecological conditions prior to the conception.
1.1. Aim of this study
This study aimed to determine the relationship between PPD at one
month postpartum and some gynecological morbidities in Japan, using
a prospective, large and nationwide birth cohort study, the “Japan
Environment and Children's study (JECS).
35
Journal of Affective Disorders 217 (2017) 34–41
2. Methods
2.1. Study design and participants
The JECS is an ongoing, population-based prospective birth cohort
study initiated by the Japanese Ministry of the Environment. Its
primary objective was to investigate the influence of exposure to
environment factors such as chemicals and pollutants from fetal period
up to 13 year-old, in order to give evidence to policy-makers for
preparation of a next generation safe environment (Kawamoto et al.,
2014; Michikawa et al., 2015).
Pregnant women were recruited between January 2011 and March
2014.
Based on their geographical distributions, fifteen Regional Centers
(Hokkaido, Miyagi, Fukushima, Chiba, Kanagawa, Koshin, Toyama,
Aichi, Kyoto, Osaka, Hyogo, Tottori, Kochi, Fukuoka, and south
Kyushu/Okinawa) were selected. Women were recruited in early
pregnancy at obstetric facilities and/or at local pregnancy registration
government office.
Eligibility criteria were as follow: pregnant woman who is residing
in the study area, who expected to live continually in Japan, to deliver
between August 1st, 2011 and March 31st, 2014 and who is able to
understand Japanese language for filling the self-administered ques-
tionnaire.
2.2. Data collection
During pregnancy, self-administered questionnaires were distribu-
ted at prenatal examinations or by mail to the women in their first
trimester (T1) and again during their second/third trimester (T2).
Information on demographic factors, medical and obstetric history,
physical and mental health, lifestyle, occupation, environmental ex-
posure, dwelling conditions, and socioeconomic status were obtained
from T1 and T2. Information on maternal and infant medical records
were also extracted from medical transcripts at T1, at delivery and at
one month after birth. At one and six months after delivery, ques-
tionnaire on mother's lifestyle and health condition, social environment
and baby's care, social support, breastfeeding and relation mother-child
was given to mothers. From six months up to 13 years, questionnaires
will be sent each six months.
The present study is a secondary analyze of data, i.e., jecs-ag-
20160424, from pregnancy up to one month postpartum. We mainly
focused on the first month postpartum based on recent reports in
Japanese population which showed peak prevalence for depressive
symptoms at this time (Ishikawa et al., 2011; Iwata et al., 2016). The
study included all women with single live birth who replied to the
Edinburgh Postnatal Depression Scale (EPDS) (Cox et al., 1987) and
who filled information about their income. All women who had
stillbirth, multiple pregnancies, who didn’t give information on their
income and those who didn’t reply to the EPDS questionnaire were
excluded. Patients who were diagnosed as depressed during pregnancy
were also excluded. For women who attend the study more than once
during the recruitment period, the last attendance was considered in
the study.
2.2.1. Postpartum depression
Postpartum depression was measured at one month using the
Japanese validated version of the EPDS. This is a self-report of postnatal
depression with 10 items rated on a 4-point scale (from 0 to 3). The
total score ranges from 0 to 30 with higher scores indicating more
severe depressive symptoms (Cox et al., 1987). The validity and the
reliability of the Japanese version of the EPDS were reported by Okano
et al. (Okano et al., 1996). A score of 9 or greater indicated having
postpartum depression (PPD).
S.M.J. Muchanga et al. Journal of Affective Disorders 217 (2017) 34–41

2.2.2. Preconception gynecological morbidities 104,102 births

Preconception gynecological morbidity was defined as any gyneco-
logical adverse condition before the onset of the current pregnancy.
381 stillbirths.
Conditions considered in this case included: endometriosis, adenomyo-
1,958 multiple births.
sis, abnormal uterine bleedings (any trouble of menstrual cycle includ-
1 Apgar score>10.
ing changes in the duration, volume and/or frequency of bleeding)
(Bradley and Gueye, 2016; Munro et al., 2012), dysmenorrhea,
leiomyoma, previous miscarriage, polycystic ovarian syndrome, ovar- 101,762 single live births
ian benign tumor, gynecological cancers (breast, cervical, endometrial),
uterine deformation, urogenital anomalies.
For the adjustment in the analyses, covariates included psychiatric 5,513 previous births of multiples
illness history (depression, anxiety, schizophrenia and any mental attendant mothers.
illness during pregnancy), psychosocial factors related to the pregnancy
(feeling towards the pregnancy, partner support, verbal violence,
96,249 infant-mother pairs in the last 6,608 mothers didn’t reply to the
physical violence, lack of social support, stressful life events), some
attendance. EPDS.
obstetrical factors (parity, mode of conception, mode of delivery,
threatened abortion, delivery complications, preterm labor, premature 281 had depression during
rupture of membrane, pregnancy induced hypertension, gestational pregnancy.
diabetes), birth outcome variables (infant sex, fetal distress at birth, 6,871 didn’t provide information
small for gestational age, Intensive Care Unit admission, birth defect, on their income
Apgar score < 7 at 5 min), socio-demographic factors (age, education,
marital status, income) and health behavioral factors (feeding, smoking 82,489 eligible infant-mother pairs
status, alcohol intake). Most of these covariates were selected from a
recent review (Norhayati et al., 2015).
Fig. 1. Study flow chart.

2.3. Statistical analysis

remaining single live births, women with multiple attendances had
The outcome variable was PPD. The population was separated into 5513 previous attendances; 6608 women did not reply to the EPDS
two groups (with PPD and without PPD), using a cut-off score of 9. questionnaire, 281 had depression during pregnancy and 6871 women
Missing data on the outcome variable (6608) and on the variable did not provide their income information. The study flow chart is
“income” (6871) were dropped from analyzes. Data without information represented in the Fig. 1.
on the income shared a large amount of missing data with important Out of the 82,489 remaining participants who answered to the EPDS
known risk factors such as psychiatric illness history, lack of social questionnaire 11,341 (14%) had PPD.
support and partner support. All analysis were performed using the Comparing women according to the presence of gynecological
maximum samples with inclusion of missing values for independent morbidities, except for the prevalence of previous miscarriage
variables and covariates using the multiple imputation. To test the (p < 0.001) and leiomyoma (p < 0.05), which was more in non-
intergroup differences the chi square test and the unpaired student's t- depressive women, those with depression had more gynecological
test were respectively used for categorical and numerical variables. morbidities (p < 0.05) than their non-depressive counterparts.
In order to estimate the association between PPD and gynecological Polycystic ovary syndrome was the only one that had no difference
morbidities, simple and multiple logistic regression analysis were between the two groups (Table 1a).
performed. Psychiatric illness history (depression, anxiety, schizophre- General characteristics of the study population are reported in the
nia and any mental illness during pregnancy) was adjusted in the Table 1b.
model 1. Medical history of mental illness, schizophrenia, anxiety, and
In the model 2, psychosocial factors related to the pregnancy depression were more prevalent in depressive women group
(feeling towards the pregnancy, partner support, verbal violence, (p < 0.001).
physical violence, lack of social support, stressful life events) were
added to the model 1. Table 1a
For model 3: obstetrical factors (parity, mode of conception, mode Prevalence of selected gynecological risk factors according to the presence or absence of
of delivery, threatened abortion, delivery complications, preterm labor, PPD.
premature rupture of membrane, pregnancy induced hypertension,
Risk factors PPD (N=11,341) No PPD (N=71,148) P (p value)
gestational diabetes) and birth outcome variables (infant sex, fetal % %
distress at birth, small for gestational age, Intensive Care Unit admis-
sion, birth defect, Apgar score < 7 at 5 min) were added to model 2. Endometriosisa 4.8 3.5 < 0.001
Dysmenorrheab 12.5 10.2 < 0.001
Model 4 (final model): socio-demographic factors (age, education,
AUBc 16.1 12.0 < 0.001
marital status, income) and health behavioral factors (feeding, smoking Uterine deformationa 0.4 0.3 < 0.01
habits and alcohol intake) were adjusted in addition to model 3. Miscarriage 17.3 19.5 < 0.001
Multicollinearities in the logistic model were tested using the Adenomyosisa 0.5 0.3 < 0.01
variance inflation factor (VIF) at 2.5 or less (Allison, 1999). No Gynecological 1.0 0.9 < 0.01
cancera
collinearity was found after performing the test. The significance level PCOSb 0.7 0.8
was set at 0.05. All data analysis were performed with the Stata Leiomyomaa 6.2 6.3 < 0.05
(STATACORP, USA) Software version 14.0 for Windows. Urogenital 0.0 0.0 < 0.05
anomaliesa
Ovarian tumora 3.7 3.5 < 0.05
3. Results
a
340 missing values {with 64 (0.6%) for PPD and 276 (0.4%) for no PPD}.
Among 104,102 births, 381 were stillbirths, 1958 were multiple b
47 missing values {with 9 (0.08%) for PPD and 38(0.05%) for no PPD}.
c
births, and 1 Apgar score was more than the normal range. Among the 360 missing values {with 68(0.6%) for PPD and 292(0.4%) for no PPD}.

36
S.M.J. Muchanga et al. Journal of Affective Disorders 217 (2017) 34–41

Table 1b Table 1b (continued)

General characteristics of the study population according to the presence or absence of
PPD. Risk factor PPD (N=11,341) No PPD (N=71,148) P (p value)
% %
Risk factor PPD (N=11,341) No PPD (N=71,148) P (p value)
% % Health behavioral
factors
Psychiatric illness Feeding < 0.001
history Breast 32.6 44.4
MH of depression 7.2 2.1 < 0.001 Mixed 64.5 54.3
Missing 0.6 0.4 Formula 2.5 1.1
MH of anxiety 6.9 2.0 < 0.001 Missing 0.4 0.3
Missing 0.6 0.4 Smoking habit < 0.001
MH of schizophrenia 0.4 0.1 < 0.001 never 51.9 59.4
Missing 0.6 0.4 stopped before 23.3 23.8
Any mental illness 2.0 0.4 < 0.001 pregnancy
during pregnancy stopped after pregnancy 16.7 11.8
Missing 0.2 0.2 Current smoking 6.7 4.0
Missing 1.4 1.0
Psychosocial factors
Alcohol intake < 0.001
Felling towards pregnancy < 0.001
Not 32.4 34.6
Happy 55.4 66.3
Stopped 57.6 54.3
Happy though 29.0 24.9
Still drinking 9.1 10.3
unplanned
Missing 0.9 0.8
Confused though 10.6 6.3
unplanned a
4 missing data. MH: medical history; PPD: Postpartum depression; SD: standard
Confused 1.4 0.4
deviation.
Nothing particular 0.7 0.4
Other 1.8 0.9
Missing 1.1 0.7 For psychosocial factors, depressive women experienced domestics
Partner support < 0.001 violence, had more negative feeling towards pregnancy and had a poor
Always 34.3 38.4
infant care support from their partner (p < 0.001) as opposed to non-
Sometimes 44.9 46.3
Almost never 14.3 11.2 depressive women.
Never 4.7 3.1 When socio-demographics and health behavioral variables were
Missing 1.8 1.0 considered, compared to women without depressive symptoms, those
Stressful event 57.6 40.6 < 0.001 with depressive symptoms were younger, had lower income, had low
Missing 0.7 0.6
Verbal violence < 0.001
education and were single (p < 0.001). They were mostly smokers than
Not at all 74.1 88.1 their non-depressive counterparts (p < 0.001). Inversely, non-depres-
Rare 16.0 8.2 sive women drank more alcohol than depressive ones (p < 0.001).
Sometimes 7.5 2.9 Obstetrical and birth outcome factors are depicted in the Table 1c.
Often 1.9 0.5
For obstetrical factors, compared to non-depressive ones, depressive
Missing 0.5 0.3
Physical violence < 0.001 women were primiparous (p < 0.001) and had more hypertension
Not at all 96.5 98.9 (p < 0.01), threatened abortion, preterm labor, premature rupture of
Rare 2.3 0.7 membranes, delivery complications, cesarean section and assisted
Sometimes 0.7 0.2 delivery (p < 0.001).
Often 0.2 0.0
Missing 0.3 0.2
In term of birth outcome, depressive women had more small for
gestational age newborns (p < 0.01) and birth defect (p < 0.001) than
Socio-demographic
non-depressive women.
factors
Age, mean(SD)a 30.71(5.2) 31.57(5.0) < 0.001 The univariate and multivariate analysis of main predictive factors
Education < 0.001 with exclusion of missing values data are depicted in Table 2. After
Junior high school 6.6 4.0 adjustment for others gynecological morbidities, endometriosis (OR,
High school 35.9 29.6 1.31; 95%CI: 1.19–1.45), dysmenorrhea (OR, 1.20; 95%CI: 1.12–1.27),
Vocational high school 1.6 1.7
Technical 21.6 23.2
abnormal uterine bleeding (OR, 1.38; 95%CI: 1.31–1.46), previous
Junior college 15.6 18.1 miscarriage (OR, 0.87; 95%CI: 0.82–0.91)) and PCOS (OR, 0.73;
University 17.4 21.7 95%CI: 0.58–0.94) remained significant.
Graduate 1.2 1.6 In the final model of the logistic regression, as shown in the Table 3,
Missing 0.2 0.2
after adjustment for all covariates, endometriosis (OR, 1.27; 95%CI:
Marital status < 0.001
Married 92.6 96.1 1.15–1.41), dysmenorrhea (OR, 1.13; 95%CI: 1.06–1.21), and abnormal
Not married 4.8 2.6 uterine bleeding (OR, 1.21; 95%CI: 1.15–1.29), remained significant.
Divorced 1.4 0.6 When endometriosis cases were divided into two groups by having
Widowed 0.0 0.0 severe dysmenorrhea or not, endometriosis with severe dysmenorrhea
Missing 1.2 0.7
Income(million yen) < 0.001
(OR, 1.69; 95%CI: 1.18–2.42) was associated with PPD (Result not
<2 9.2 5.0 shown).
2- < 4 39.3 33.5
4- < 6 30.2 33.8
6- < 8 13.4 16.6 4. Discussion
8- < 10 4.8 6.9
10- < 12 1.8 2.5
12- < 15 0.7 1.0
The association between endometriosis and PPD, firstly reported in
15- < 20 0.4 0.6 this study, supports a probable causal relationship between endome-
≥20 0.2 0.4 triosis-related dysmenorrhea and PPD in our population. In fact,
endometriosis is an estrogen-dependent disease (Chen et al., 2016)
and literature reports a neuromodulation role played by estrogen on the

37
S.M.J. Muchanga et al. Journal of Affective Disorders 217 (2017) 34–41

Table 1c Table 2
Obstetrical and birth outcomes characteristics of the study population according to the Unadjusted and adjusted association between gynecological morbidities and PPD.
presence or absence of PPD.
Risk factors OR (CI) aOR (CI)
Risk factor PPD (N=11,341) No PPD (N=71,148) P (p value)
% % Endometriosis 1.39(1.26–1.52)*** 1.31(1.19–1.45)***
Dysmenorrhea 1.26(1.18–1.34)*** 1.20(1.12–1.27)***
Obstetrical factors AUB 1.42(1.34–1.51)*** 1.38(1.31–1.46)***
Parity < 0.001 Uterine deformation 1.38(0.99–1.93) 1.32(0.94–1.84)
Primiparous 37.7 28.2 Miscarriage 0.87(0.82–0.91)*** 0.87(0.82–0.91)***
Multiparous 60.9 70.9 Adenomyosis 1.52(1.12–2.05)** 1.29(0.95–1.75)
Missing 1.3 0.9 Gynecological cancer 1.22(1.00–1.49)* 1.20 (0.99–1.47)
Mode of conception PCOS 0.85(0.67–1.08) 0.73(0.58–0.94)*
Natural 93.1 92.9 Leiomyoma 0.98(0.90–1.06) 0.97(0.89–1.05)
Oviduct flashing 2.5 2.6 Urogenital anomalies 1.26(0.48–3.28) 1.25(0.48–3.26)
AIH 1.0 1.0 Ovarian tumor 1.05(0.95–1.17) 0.99(0.89–1.11)
IVF 1.7 1.6
ICSI 0.7 0.8 CI: confidence interval; aOR: adjusted odds ratio; OR: odds ratio; PCOS: polycystic ovary
Fresh ET 0.0 0.1 syndrome.
Frozen ET 0.5 0.6 * p < 0.05.
Blastocyst T 0.1 0.1 ** p < 0.01.
Missing 0.5 0.5 *** p < 0.001.
Mode of delivery < 0.001
Normal 54.4 58.0
Induction 18.8 17.4 tion of steroid hormones. In addition to the steroid fall, the new mother
Suction 6.4 5.4 is also exposed to the hypogonadal state until the return of ovulation
Forceps 0.3 0.2 (Bloch et al., 2003). The result of the hormonal deficiency states could
Cesarean section 19.7 18.6 be contributing factors to the occurrence of PPD on the endometriosis
Missing 0.5 0.4
pre-existing background.
Threatened abortion 13.2 11.7 < 0.001
Missing 0.2 0.2 Furthermore, the association between dysmenorrhea and PPD could
Delivery 48.8 44.6 < 0.001 be attributable to the hormonal variation seen during menstrual cycles.
complications In fact, the drop of progesterone during the late luteal phase is
Missing 2.0 1.9
associated with an imbalanced production of prostaglandins implicated
Preterm labor 21.3 18.9 < 0.001
Missing 0.2 0.2
in the genesis of menstrual pain (Dawood, 2006). On the other hand,
PROM 9.3 8.0 < 0.001 dysmenorrhea coexists with premenstrual symptoms in many women
Missing 0.2 0.2 (Kitamura et al., 2012). Although the etiology of premenstrual symp-
Hypertension 2.8 2.1 < 0.001 toms remains unclear, it is considered to be resulted from multiples
Missing 0.2 0.2
interactions between ovarian hormones changes of the menstrual cycle
Gestational diabetes 1.2 1.1
Missing 0.2 0.2 and various neurotransmitters including GABA and serotonin (Ismaili
et al., 2016). It is widely reported that fluctuations of ovarian hormones
Birth outcome factors
Infant sex during premenstrual, postnatal and perimenopausal periods are asso-
Male 51.7 51.0 ciated with depression (Lokuge et al., 2011; Studd, 2015). Both
Female 48.3 49.1 estrogen and progesterone have their receptors localized in brain
Missing 0.0 0.0 region implicated in emotional and cognitive regulation (Brinton
Fetal distress 2.7 2.4
Missing 0.2 0.2
et al., 2008; Wharton et al., 2012). Indeed, the estrogen fluctuation of
SGA 2.3 1.9 < 0.01 these vulnerable periods may cause an alteration in serotonin neuro-
Missing 0.2 0.2 transmission, which then can lead to mood disorders (Lokuge et al.,
ICU admission 0.1 0.1 2011). It has also been reported that progesterone plays a mediating
Missing 0.2 0.2
role on mood disturbances (Wharton et al., 2012). Thus, women with
Birth defect 6.9 5.9 < 0.001
Missing 2.2 2.2 history of dysmenorrhea are more sensitive to the post-delivery
Apgar < 7 at 5 min 0.7 0.5 < 0.05 hormone withdrawal. Our result is in accordance with previous studies
Missing 5.0 5.0 which found an association between premenstrual symptoms and
postpartum depression (Buttner et al., 2013; Lee et al., 2015). Unlike
AIH: artificial insemination by husband; Blastocyst T: blastocyst transfer; Fresh ET: fresh
other authors who have examined dysmenorrhea in the context of
embryo transfer, Frozen ET: frozen embryo transfer, ICSI: intracytoplasmic sperm
injection; ICU: intensive care unit; IVF: in vitro fertilization; PPD: Postpartum depression;
premenstrual syndrome, in our case, dysmenorrhea was an independent
PROM: premature rupture of membranes; SD: standard deviation; SGA: small for predictor of PPD.
gestational age. The imbalanced hormonal state found in abnormal uterine bleeding
(AUB) could explain its association with PPD. Evidence shows that the
imbalance innervations of endometriosis (Liang and Yao, 2016). onset of depressive symptoms temporally coincides with the abrupt fall
Depression is a consequence of endometriosis and/or its association of steroids hormones at delivery, leading to assign the change in
with dysmenorrhea; whether the infertility, or the inflammation play a hormones as a promoting factor in susceptible women (Schiller et al.,
certain role remains to be clearly described (Pope et al., 2015). The 2015). In fact, AUB has different etiologies, structural or not (Munro
pelvic pain (Facchin et al., 2015; Lorencatto et al., 2006) and/or only et al., 2012), and most of them are hormone-related disorders. Thus,
the fact of being diagnosed with endometriosis (Denny, 2009)could be women suffering from AUB prior to the conception are more sensitive to
the causal factor. Studies conducted in non-pregnant women had the sudden post-delivery hormonal changes. However, a study con-
demonstrated an association between endometriosis and depression ducted in non parturient women, found a strong correlation between
(Lorencatto et al., 2006; Sepulcri Rde and do Amaral, 2009) and the AUB, mood and anxiety disorders (Kayhan et al., 2016).
abrupt fall of steroids hormones during the parturition contributes to We found a negative association between previous miscarriage and
the PPD (Brummelte and Galea, 2016). This hypothesis suggests that PPD in the model 1 and 2; this relationship did not maintain
women with endometriosis may be more affected by the large fluctua- significance after adjustment for obstetrics and birth outcome con-

38
S.M.J. Muchanga et al. Journal of Affective Disorders 217 (2017) 34–41

Table 3
Adjusted final model for the association between gynecological morbidities, others covariates and PPD.

Risk factors Model 1 OR (CI) Model 2 OR (CI) Model3 OR (CI)) Model 4 OR (CI)

Endometriosis 1.26(1.14–1.39)*** 1.25(1.13–1.39)*** 1.24(1.11–1.38)*** 1.27(1.15–1.41)***

Dysmenorrhea 1.17(1.10–1.25)*** 1.19(1.11–1.27)*** 1.13(1.05–1.20)*** 1.13(1.06–1.21)***
AUB 1.28(1.21–1.36)*** 1.20(1.14–1.28)*** 1.19(1.12–1.27)*** 1.21(1.15–1.29)***
Uterine deformation 1.27(0.90–1.78) 1.34(0.94–1.91) 1.36(0.95–1.95) 1.30(0.91–1.84)
Miscarriage 0.86(0.81–0.9)*** 0.84(0.80–0.89)*** 1.04(0.98–1.11) 1.06(1.00–1.12)
Adenomyosis 1.29(0.94–1.77) 1.33(0.97–1.84) 1.15(0.81–1.64) 1.31(0.95–1.80)
Gynecological cancer 1.13(0.93–1.39) 1.08(0.88–1.33) 1.10(0.88–1.36) 1.06(0.86–1.30)
PCOS 0.74(0.58–0.95)* 0.78(0.60–1.00) 0.69(0.52–0.90)** 0.79(0.62–1.02)
Leiomyoma 0.96(0.88–1.05) 1.00(0.92–1.09) 0.94(0.86–1.03) 1.01(0.92–1.10)
Urogenital anomalies 1.12(0.42–2.97) 1.08(0.39–2.99) 1.21(0.43–3.37) 1.16(0.42–3.27)
Ovarian tumor 0.97(0.87–1.08) 0.95(0.85–1.07) 0.95(0.84–1.07) 1.02(0.92–1.14)

CI: confidence interval; OR: odds ratio.

Model 1: adjusted for psychiatric illness history.
Model 2: Model 1 plus psychosocial factors.
Model 3: Model 2 plus obstetrical and birth outcome factors.
Model 4 (final model): Model 3 plus socio-demographic factors and health behavioral factors.
* p < 0.05.
** p < 0.01.
*** p < 0.001.

founders in the model 3. Indeed, some reports had shown the previous
miscarriage as risk factors of PPD at one month and even in the late
postpartum (Blackmore et al., 2011; Giannandrea et al., 2013), while
others did not show any association (Bicking Kinsey et al., 2015;
Hughes et al., 1999). It is possible that the apparent protection of
previous miscarriage on the onset of PPD may not be of clinical
significance; cultural and psychosocial factors having an important
role on the difference between populations. Thus, obstetrical and birth
outcome factors should be taken into account for the assessment of the
concerned relationship.
4.1. Strengths
PPD, found in this study, could not be affected.
4.3. Clinical implications
Currently, implicated gynecological morbidities are not routinely
considered as risk factor for postpartum depression same as, for
instance, past psychiatric illnesses or psychosocial factors. Our findings
suggest that a succinct assessment of those gynecological morbidities
would be valuable as predictor of PPD and as possible markers for
intervention. As most of risk factors were hormone-related, we en-
courage a possible use of hormone therapy in addition to usual
treatment of PPD for predisposed women.

This study is the only one nationwide in Japan, to evaluate 5. Conclusion

association between PPD and preconception gynecological morbidities
with adjustment of many potential confounders. It is the first to
elucidate the association between preconception endometriosis, AUB
and dysmenorrhea with PPD.
These findings extend our knowledge on predictors of postpartum
depression.
Even the EPDS is just a screening tool and not a diagnostic one, the
measurement of PPD with the EPDS has been widely used and validated
in Japan (Okano et al., 1996).
4.2. Limitations
Despite those strengths, the original research design was not
exclusively oriented by the main research question. This couldn’t allow
us to specify in detail different characteristics of gynecological morbid-
ities.
Among the significant risks factors found in this study, in contrary
to dysmenorrhea and AUB which were extracted from medical report,
endometriosis was self-reported doctor diagnosis. In fact the diagnosis
of endometriosis is clinically difficult unless after direct observation via
laparotomy or laparoscopy and confirmation by histology. In Japan,
gynecologist use transvaginal ultrasound in their routine practice when
they firstly examine patients. Fortunately, the diagnosis accuracy of
transvaginal ultrasound for endometriosis is almost 90% whatever its
type (Guerriero et al., 2015). Although we do not have information on
how the diagnosis was conducted, we can argue that this diagnosis is a
secondary report of the medical diagnosis.
On the other hand, the selection of participants and the adminis-
tration of the questionnaire were uniformly done regardless of the
depressive state or not. Thus the association between endometriosis and
We demonstrated that women affected by endometriosis and
menstrual problems experienced postpartum depression. Indeed, these
findings support the hypothesis that predisposed women are more
susceptible to develop PPD.
Further studies are needed to define whether which kind of
endometriosis (which stage; which extension), menstrual problems (of
which etiology) and uterine deformation are at risk of PPD.
Acknowledgments
We thank the JECS staff members for supporting our study and all
participants.
Members of JECS as of 2016 (principal investigator, Toshihiro
Kawamoto): Hirohisa Saito (Medical Support Center for JECS,
National Center for Child Health and Development, Tokyo, Japan),
Reiko Kishi (Hokkaido Regional Center for JECS, Hokkaido University,
Sapporo, Japan), Nobuo Yaegashi (Miyagi Regional Center for JECS,
Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima
Regional Center for JECS, Fukushima Medical University, Fukushima,
Japan), Chisato Mori (Chiba Regional Center for JECS, Chiba
University, Chiba, Japan), Shuichi Ito (Kanagawa Regional Center for
JECS, Yokohama City University, Yokohama, Japan), Zentaro
Yamagata (Koshin Regional Center for JECS, University of
Yamanashi, Chuo, Japan), Hidekuni Inadera (Toyama Regional Center
for JECS, University of Toyama, Toyama, Japan), Michihiro Kamijima
(Aichi Regional Center for JECS, Nagoya City University, Nagoya,
Japan), Toshio Heike (Kyoto Regional Center for JECS, Kyoto
University, Kyoto, Japan), Hiroyasu Iso (Osaka Regional Center for
JECS, Osaka University, Suita, Japan), Masayuki Shima (Hyogo

39
S.M.J. Muchanga et al.
Regional Center for JECS, Hyogo College of Medicine, Nishinomiya,
Japan), Yasuaki Kawai (Tottori Regional Center for JECS, Tottori
University, Yonago, Japan), Narufumi Suganuma (Kochi Regional
Center for JECS, Kochi University, Nankoku, Japan), Koichi Kusuhara
(Fukuoka Regional Center for JECS, University of Occupational and
Environmental Health, Kitakyushu, Japan), and Takahiko Katoh (South
Kyushu/Okinawa Regional Center for JECS, Kumamoto University,
Kumamoto, Japan).
We also acknowledge all members of Environmental Medicine
Department of Kochi University for their support.
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