Arch Womens Ment Health (2010) 13:99–105

DOI 10.1007/s00737-009-0107-0

ORIGINAL CONTRIBUTION

Association between depressive symptoms

and reproductive variables in a group of perimenopausal
women attending a menopause clinic in México City
Mónica Flores-Ramos & Gerhard Heinze &
Roberto Silvestri-Tomassoni

Received: 16 January 2009 / Accepted: 19 August 2009 / Published online: 4 September 2009
# Springer-Verlag 2009

Abstract The aim of this study was to explore the
association between depressive symptoms and some vari-
ables related to the reproductive life, such as history of
premenstrual dysphoric disorder, antecedent of postpartum
depression, previous use of hormonal contraceptives, and
current hot flushes, in a group of perimenopausal women
attending a menopause clinic. Perimenopausal women, 45
to 55 years old, who had not received hormonal replace-
ment therapy and/or psychotropic medication, were invited
to participate in this study. 141 perimenopausal women
were included; we obtained their psychiatric and gyneco-
logical data, and we evaluated their depressive symptom-
atology using the CES-D scale. There were a significantly
higher number of cases of previous depressive episodes,
PMDD and PPD history in depressed patients compared
with non-depressed women; current hot flushes prevalence
was similar between depressed and non-depressed women.
Patients with a PMDD history were more likely to have
experienced previous depressive episodes, a PPD history,
M. Flores-Ramos (*)
Psychiatry and Mental Health Department,
Universidad Nacional Autónoma de México (UNAM),
Soledad 25-2, Col. Florida,
CP 01030 México, D.F, México
e-mail: flores_ramos@hotmail.com
G. Heinze
Psychiatry and Mental Health Department,
Universidad Nacional Autónoma de México (UNAM),
Av. Universidad 3000, circuito exterior, Facultad de Medicina,
edificio F,
Mexico, Mexico
R. Silvestri-Tomassoni
Instituto Nacional de Perinatología (INPER),
Montes Urales 800, Col. Lomas Virreyes,
Mexico, Mexico
and high levels of depression. Variables associated with the
level of depression were a previous history of PMDD,
current hot flushes, and previous depressive episodes. The
occurrence of perimenopausal depression is related to a
previous history of PMDD, PPD, and depressive episodes;
hot flushes only increase the severity of the depressive
episode.
Keywords Perimenopausal depression .
Premenstrual dysphoric disorder . Postpartum depression .
Hot flushes . Women
Introduction
Perimenopause is a period of time between regular
menstrual cycles and the final menstrual period (FMP),
characterized by biological, endocrine and clinical changes
(WHO 1981). According to the Stages of Reproductive
Aging Workshop (STRAW), perimenopause begins at stage
2 (when menstrual cycles are associated with erratic cycle
lengths, with changes of more than 7 days from normal
cycles) and ends 12 months after the FMP (Soules et al.
2001). Fugate and Sullivan (2005) reported that mood
symptoms are present in 23 to 28% of women during the
menopausal transition, whereas the Harvard Study of
Moods and Cycles, using the Center for Epidemiologic
Studies Depression Scale (CES-D), registered a score of 16
or more in 22.4% of surveyed women, and 8.6% scored 25
points or more (Harlow et al. 1999). Furthermore, in a
prospective cohort study (Cohen et al. 2006), it was
observed that premenopausal women with no lifetime
history of major depression who entered the perimenopause
were twice as likely to develop significant depressive
symptoms as women who remained premenopausal, after
100
adjustment for age at study enrollment and history of
negative life events. These findings indicate that perime-
nopause is a period of increased risk for depressive
symptoms, as it was suggested by Soares and Zytek
(2008). It is well known that a previous depressive episode
is the most important risk factor for a new depressive
episode during the menopausal transition (MT) (Avis et al.
1994; Callegari et al. 2007); however, some other factors
have been implicated with depression at the perimenopausal
period, including socio-demographic characteristics, vaso-
motor symptoms, premenstrual affective symptoms, history
of postpartum depression, hormonal changes and stressful
life-events. Several events during the menopausal transition
could be the cause of depression, such as job changes or
retirement, death of parents, empty nest syndrome, eco-
nomic problems, as well as the loss of youth and fertility
(Dooley and Bell 2007). Some studies have suggested that
stressful life events influence mood more than menopausal
status (Kaufert et al. 1992; Bromberger and Matthews
1996). Other possible sources of this kind of stress could
be: demanding jobs, family responsibilities, dual demands
by career and family, little time for oneself, poverty or
employment status stressors, insufficient sleep, and changes
in social relationships (Brandon et al. 2008). On the other
side, studies that analyzed the correlation between vaso-
motor symptoms (VMS) and depression reported that
perimenopausal women suffering VMS were more likely
to be depressed than those without these symptoms (Joffe et
al. 2002; Cohen et al. 2006), while other authors contend
that VMS are less important than a history of anxiety
disorders and life-stress in contributing to a first depressive
episode (Bromberger et al. 2009). Furthermore, Oztûrk et
al. (2006) did not find any correlation between severity of
vasomotor symptoms and severity of depression.
The inconsistencies among risk factors reported by these
authors could be accounted for the different methodologies
used in the aforementioned studies in addition to the
different risk factors that were evaluated; however, it
should be noted that prospective, community-based studies
are quite consistent and agree that the transition to
menopause itself is an important factor that increases the
depressive symptomatology (Maartens et al. 2002; Freeman
2004a; Bromberger et al. 2007). In Freeman study (2004a),
for example, a population-based sample was followed
during 4 years, and an increased risk for developing
depressive symptoms during transition to menopause was
observed followed by a decreased risk after menopause.
Likewise, Cohen et al. (2006) observed an increased risk of
a first depressive episode during perimenopause in a
population-based sample, after adjustment for age at study
enrollment and history of negative life events. This is an
important finding because suggest that perimenopause is a
period of risk for depression independently of other factors
M. Flores-Ramos et al.
like previous depressive episodes or negative life events. As
noted by Frey et al. (2008) “longitudinal studies provide
compelling evidence that the transition to menopause
confers a higher risk for the development of depression
and that multiple risk factors appear to independently
modulate such risk”.
An important theory proposes that perimenopausal
depression is caused by changes in hormonal levels, and
the evidence that supports this hypothesis includes mood
disturbances occurring during significant hormonal transi-
tions (Douma et al. 2005). Not only depression can be
caused by hormonal changes, a report suggests that periods
of hormonal changes represent a major trigger for bipolar
episodes in some women (Robertson Blackmore et al.
2008). Several clinic-based studies have observed that
women reporting severe premenstrual mood symptoms also
report perimenopausal affective symptoms (Stewart and
Boydel 1993; Novaes et al. 1998). For example, Richards et
al. (2006) observed that 26% of depressed women reported
premenstrual symptoms in comparison with 9% of non-
depressed patients who attended a menopause clinic.
However, depression was not invariably accompanied by
premenstrual dysphoria at perimenopause. In a population-
based cohort, Freeman et al. (2004b) observed that
premenstrual syndrome significantly predicted menopausal
hot flushes, depressed mood, decreased libido and poor
sleep in models adjusting for diagnosis of major depression,
age, race and estradiol levels. Evidence is more scarce
regarding postpartum depression, but a preliminary study of
72 women with depression found significant correlations
between premenstrual and perimenopausal mood ratings
(r=0.41), and between postpartum and perimenopausal
mood ratings (r=0.87) (Gregory et al. 2000). Another field
of investigation on the subject is the relationship between
the use of hormone-based contraceptives and mood
changes, with controversial results in several studies (Joffe
et al. 2003; Oinonen and Masmanian 2002; Young et al.
2007).
Finally, the hypothesis that hormonal changes are
associated with depression is supported by several studies
evaluating hormone levels in women coursing menopausal
transition; for example, increased levels of follicle-
stimulating hormone (FSH) and luteinizing hormone (LH),
and an increased variability of estradiol, FSH and LH
regarding a woman´s own mean levels were each signifi-
cantly associated with high CES-D scores in a longitudinal
study (Freeman et al. 2006). Additionally, Daly et al.
(2003) observed a significant association between the
changes in FSH plasma levels and the CES-D scale scores
when measured during a 6-week period. Deecher et al.
(2008), in an important review, discussed relevant data
supporting the hypothesis that hormonal changes increase
the vulnerability to perimenopausal depression. In summa-
Association between depressive symptoms and reproductive variables
ry, causes of depression in menopausal transition are still
not well established, but some factors contributing to it are
known, especially reproductive life events. Therefore, we
conducted a study in order to evaluate the association
between depressive symptoms and some reproductive life
variables such as a history of premenstrual dysphoric
disorder (PMDD), antecedent of postpartum depression
(PPD), previous use of hormonal contraceptives, and
current hot flushes, in a group of perimenopausal women
attending a menopause clinic.
Material and methods
The study was carried out at the Menopause and Climacteric
Clinic at the National Institute of Perinatology in Mexico
City. This hospital is a referral center, specialized in female
health. All women attending the clinic between February
2007 and March 2008, who were 45 to 55 years old, were
invited to participate in this study. Patients were evaluated at
enrollment in a brief first interview, in order to assess the
perimenopausal criteria (variability in menstrual cycle length
≥7 days from normal cycle lengths for at least three
consecutive months, and/or amenorrhea for no longer than
1 year). Patients also were asked to complete the Center for
Epidemiologic Studies on Depression Scale. The standard
cutoff score of ≥16 was used to define their participation.
The patients were contacted by psychiatry trainees, who
carried out the first interview. All subsequent evaluations
were made by the same experienced psychiatrist.
Patients with CES-D scores higher than 16 were
evaluated one more time in order to confirm a clinical
diagnosis of depression according to the Diagnostic and
Statistical Manual, 4th edition (DSM-IV). A period no
longer than 1 week was allowed from the first evaluation to
the second interview. The diagnosis of depression was
based exclusively on the clinical interview, which was
carried out by an experienced psychiatrist specialized in
affective disorders. Patients suffering psychotic disorders,
severe personality disorders, bipolar disorder, substance
abuse and obsessive compulsive disorder according to the
DSM-IV were excluded from the study, based on clinical
evaluation.
In a first brief interview, we assessed if the women met
the criteria for perimenopause. At the second interview, we
obtained the socio-demographic, gynecological and psychi-
atric backgrounds. We also confirmed that the perimeno-
pausal criteria were adequately assessed at the recruitment.
Women taking hormonal replacement therapy or another
hormone-based drug and/or psychiatric medication were
excluded from the study. Pregnancy, breast-feeding, surgical
menopause and serious health conditions known to compro-
mise the ovarian function, were exclusion criteria as well.
101
The variables evaluated were: socio-demographic data,
medical conditions, history of premenstrual dysphoric
disorder (PMDD), history of postpartum depression
(PPD), previous use of hormonal contraceptives, response
to previous use of hormone-based contraceptives, and
current hot flushes. We created a questionnaire consisting
in 20 questions to be administered by the investigator in
order to assess socio-demographic variables; gynecological
variables were assessed using a customized questionnaire
commonly used at the Perinatology Institute.
Previous history of PMDD, according to the DSM-IV
criteria, was inquired about during the clinical interview,
with an emphasis on dysfunction and symptoms present in
the patient’s life in at least 10 cycles over the last year.
Postpartum depression was evaluated in the same manner,
according to the DSM-IV criteria.
The presence of hot flushes was considered to be
positive when women reported 3 or more hot flushes per
day, or 3 or more days per week, independently of severity.
We decided to include just women with these characteristics
at positive cases of hot flushes in order to avoid inclusion
of women with occasional hot flushes, which could not be
influencing mood. Previous episodes of depression were
graded as follows: 0 = no depressive episodes, 1 = one or
two previous episodes, 2=3 to 5 previous episodes, and 3=
5 or more previous depressive episodes.
Statistics
The differences between depressed and non-depressed
women in terms of age, menarche, parity, miscarriages,
PPD and PMDD history, and current hot flushes were
compared with the chi-square test or the Student´s t-test, as
appropriate. Mean differences in the CES-D scores were
evaluated by the t-test in order to compare patients with or
without a history of PMDD and PPD; an analysis of
variance (ANOVA) was used to compare CES-D scores by
number of previous depressive episodes. A χ² test was
performed to compare previous PPD in patients with and
without a PMDD history, and a t-test was performed in
order to compare previous depressive episodes according to
previous history of PMDD. Finally, a linear regression
analysis was carried out to evaluate associations between
the severity of depression as assessed by CES-D and
reproductive life variables.
Ethics
Informed consent was obtained from all patients. The study
was approved by National Institute of Psychiatry and
National Institute of Perinatology ethics committees.
102
Results
A total of 168 patients were evaluated: in 17 cases, the CES-
D was inadequately answered and 10 patients didn´t show up
for the second interview; the remaining 141 patients were
included in the analysis. The mean age of the entire study
group was 49.57 (SD=3.28), CES-D mean score of all
patients was 19.17 points (SD=13.38); 52.2% of the patients
scored≥16 points, and 36% scored more than 24 points.
Mean menarche age was 12.5 years (SD=1.47), mean parity
was 3.09, with a wide range (0 to 11), and mean miscarriages
was 0.73 (range 0 to 6). We didn´t find any significant
difference in socio-demographic variables between depres-
sive and non-depressive patients (Table 1).
Sixty-seven patients (47.5%) were not depressed at
enrollment, 21 (14.9%) suffered a first depressive episode,
and 53 (37.6%), a recurrent depressive episode. Medical
conditions were present in 31.2% of evaluated women, 19
patients suffered high blood pressure (13.5%), 12 patients
had diabetes mellitus (8.5%), and 13 patients reported
another medical condition. The incidence of medical
conditions was not different in depressed and non-
depressed patients. 27 per cent of the whole patient
population had a history of premenstrual dysphoric disorder,
whereas a postpartum depression history was present in
11.3% of the patients. Hot flushes were reported by 87
(61.7%) patients; and nearly half of the patients (54.6%)
reported having used hormone-based contraceptives on one
or more occasions in their life; half of them had experienced
some adverse reaction related with the hormonal agent, such
as nausea, edema or mood alteration. However, there were
no differences in the proportions of depressed or non-
depressed women reporting contraceptive side-effects (χ²=
1.06, p=.211), as well as in women with a history of PMDD
or not (χ²=.231, p=.406). In the case of previous depressive
episodes, we found that 40.4% of the patients had never
experienced a depressive episode, but 29.8% reported having
suffered five or more depressive episodes in their life.
When we compared depressed and non-depressed women
(Table 2), significant differences were observed in the
proportion of previous PPD (χ²=6.64, DF=1, p=0.013),
Table 1 Demographic charac-
teristics of patients: compari-
sons between depressed and
non-depressed women Age, mean (SD)
Marital status (%)
Married
Never married
Divorced
Widowed
Education
Mean years in school (SD)
M. Flores-Ramos et al.
and PMDD (χ²=14.6, DF=1, p=.000), both more common-
ly observed in depressed patients. The proportion of hot
flushes was similar in depressed and non-depressed women,
64.4% and 59.7%, respectively (χ²=.326, DF=1, p=.6).
Significantly earlier ages of menarche were observed in
depressed women (12.19 vs. 12.86, t=2.61, DF=125, p=
0.01), as well as lower parity (2.67 vs. 3.46, t=-2.6, DF=
127, p=0.01), and less number of miscarriages (0.4 vs 1.0,
t=-3.32, DF=124, p=0.001), compared with non-depressed
women.
Patients with a previous history of PMDD were more
likely to have higher CES-D mean scores compared with
those without a PMDD history (25.65 and 16.75, respec-
tively), and the difference was statistically significant (t=
3.60, DF = 134, p = .000). In the case of postpartum
depression, CES-D mean scores were 22.7 and 18.5 in
women with and without this previous condition; however,
the difference didn`t reach a statistical significance
(t=−1.14, DF=134, p=.25). When we compared the CES-
D mean scores in patients suffering hot flushes and patients
without this symptom, we found a significant difference:
20.9 mean CES-D score in patients with hot flushes vs. a
16.5 mean CES-D score in patients without the symptom
(t=-1.95, DF=123, p=0.05). The ANOVA test showed that
patients with more previous depressive episodes were more
likely to have high CES-D scores; a significant difference
was observed between groups (F=7.13, gl=3, p=.000). A
post-hoc analysis using the Bonferrioni method showed a
significant difference between patients without depressive
episodes and patients with 5 or more previous depressive
episodes (p=.000), and between groups with one or two
and 5 or more depressive episodes (p=0.025).
Patients with a previous PMDD history were more likely
to also have a PPD history (χ²=24.68, DF=1, p=.000) and
they had a significantly higher number of previous
depressive episodes as well (t=2.21, DF=139, p=0.028).
Finally, a linear regression model showed that CES-D
scores were significantly associated with a previous history
of PMDD (β=6.97, t=2.72, p=.007), hot flushes (β=5.23,
t=2.40, p=.018) and with the number of previous depres-
sive episodes (β=3.11, t=3.61, p=.000).
Depressed (N=67) Non depressed (N=74)
49.7 (3.29) 49.46 (3.29)
65.6 67.5
5.9 4.05
17.9 16.2
10.4 12.6
6.6 (2.01) 7.0 (2.05)
Association between depressive symptoms and reproductive variables
Table 2 Psychiatric and gyne-
cological profile of patients
according to diagnosis group
Menarche, mean age (SD)
Parity, mean (SD)
Miscarriages, mean (SD)
PMDD history (%)
Significant differences= a p= PPD history (%)
0.01, b p=0.001, c p=.000, d p Current hot flashes (%)
=0.013.
Discussion
The prevalence of depression in this perimenopausal
women sample was elevated in comparison with prevalence
reported in epidemiological studies. As observed by Harlow
et al. (1999) 22.4% of perimenopausal women exhibited
CES-D scores≥16, whereas 52.5% of the patients evaluated
in our study were currently depressed. This is an unusual
prevalence, and we think that it could be explained by the
type of patients accepted in the National Institute of
Perinatology, who are usually seriously ill women.
Significantly more women with perimenopausal depres-
sion met the criteria for premenstrual dysphoric disorder
and postpartum depression compared with non-depressed
women. The prevalence of PMDD in our patients must be
considered high compared with other reports. Richards et
al. (2006), who examined premenstrual symptoms in 70
depressed perimenopausal women and 35 non-depressed
perimenopausal women, observed that 21% of the de-
pressed women met the criteria for premenstrual dysphoria
(Richards et al. 2006). Our results showed higher values
than this reported rate (40.5% of depressed patients
reported a history of premenstrual dysphoria), it could be
explained by a retrospective evaluation of PMDD. Never-
theless, the relationship observed between a previous
history of PMDD, PPD and perimenopausal depression
supports the theory that some periods over the reproductive
age increase the susceptibility to depression. In the case of
PPD, we didn´t find a significant association with the CES-
D scores at perimenopause, indicating that PPD is more
common in depressed patients at perimenopause, but it’s
not a factor that influences the severity of depression. It is
possible that premenstrual dysphoria, postpartum depres-
sion and perimenopausal depression are part of a continuum
of disorders sharing a similar pathophysiology, as several
authors have suggested (Arpels 1996; Stewart and Boydel
1993; Novaes et al. 1998).
As already mentioned, it is believed that the response to
hormone-based contraceptives could be related with mood
changes. In our sample, we observed a high percentage of
women reporting adverse reactions to contraceptives, but
no difference between depressed and non-depressed women
in the proportion of intolerance to hormonal contraceptives.
103
Depressed (N=67) Non depressed (N=74)
12.19 (1.46) 12.86 (1.42)a
2.67 (1.37) 3.46 (1.95) a
0.41 (0.67) 1.0 (1.25)b
40.5 11.9c
29.7 11.9d
64.4 59.7
The same phenomenon occurred when we compared
patients with or without a PMDD history. Studies analyzing
this issue had reported inconsistent results (Joffe et al.
2003; Oinonen and Masmanian 2002). It is important to
note that the specific data about the type of contraceptives
used for by patients were not available, which was an
important source of bias, since findings in this field
demonstrate that progestin, estrogen or the combination of
both, produce different effects on mood (Kurshan and Neill
Epperson 2006). Moreover, we analyzed mood changes and
other adverse events together, which makes our results
weaker regarding the use of contraceptives.
As expected, a greater number of previous depressive
episodes were related to more severe depression symptoms,
with this difference being more evident when we evaluated
women reporting 5 or more depressive episodes throughout
their lives. A previous depressive episode is the most
important predictor for suffering depression at menopausal
transition (Avis et al. 1994; Callegari et al. 2007). However,
we did not find any data regarding the influence of previous
episodes in the severity of current episodes in studies about
female depression.
Interestingly, our patients with a history of PMDD were
more likely to have higher CES-D scores, a history of PPD
and a larger number of previous depressive episodes. This
finding is consistent with the affirmation that women who
suffer PMDD are more prone to suffer other affective
disorders, as several authors have observed (Hsiao et al.
2002; Critchlow et al. 2001; Yonkers 1997).
Hot flushes are also implicated in an increase of the risk
of depression at MT (Joffe et al. 2002). Our data, as well as
those reported by Schmidt et al. (2004) and Steinberg et al.
(2008), showed no differences between diagnosis groups in
the presence of hot flushes or not. However, we observed
higher CES-D scores in patients suffering hot flushes
compared with patients without this symptom; moreover
the linear regression model demonstrated a significant
association between the presence of hot flushes and the
CES-D scores, suggesting that hot flushes do not trigger a
depressive episode, but the severity of the depression is
increased by this symptom.
Finally, when we assessed all the reproductive variables
in a linear regression model, we observed that the CES-D
104
scores were significantly associated with a history of
PMDD, current hot flushes and with the number of
previous depressive episodes, and they were not associated
with a history of PPD and a negative reaction to hormone-
based contraceptives. The first three variables had been
found to relate with perimenopausal depression consistently
in isolated studies. It has been suggested that all of these
disorders share a serotonin-related pathophysiology, which
could be modulated by estrogens (Rybaczyk et al. 2005).
Sex differences in serotonergic neurotransmission have
been documented by means of tryptophan depletion,
suggesting that women are at higher risk of depressive
symptoms in response to low levels of serotonin (Moreno et
al. 2006). In the case of PMDD, serotonergic transmission
alteration has also been documented in several studies
(Menkes et al. 1994; Eriksson et al. 2006; Halbreich and
Tworek 1993). Moreover, a relationship between serotonin
and endocrine changes has been observed, thus strengthen-
ing the hypothesis that some women are vulnerable of
suffering depression with intense hormonal fluctuations
(Soares and Zytek 2008). Diverse actions exerts estrogen
on the serotonin metabolism: increase serotonin by de-
creasing expression of monoamine oxidases, increase
serotonin availability by increasing activity of tryptophan
hydroxylase, modulate expression of serotonin reuptake
transporter, and affect the distribution and state of serotonin
receptors (Deecher et al. 2008). The same author proposes
that the ability to compensate for the unpredictable estrogen
fluctuations and overall decline of ovarian hormones is
compromised in some women, resulting in an increased
susceptibility to depression during the menopausal transi-
tion. In addition, the physiopathologic mechanism proposed
to explain the presence of hot flushes through the
menopause transition includes the serotonergic and norad-
renergic regulation of temperature, alike modulated by
estrogens (Rybaczyk et al. 2005). Together, all this
evidences suggest that there is a group of women more
vulnerable to suffer mood alterations when hormonal
fluctuations are presents.
Our study has important limitations: it is well known that
cross-sectional studies are unable to asses the nature of the
associations between variables; additionally, the assessment
of the previous history of PMDD and PPD was obtained by
self-report; therefore it is impossible to affirm that the
diagnoses were accurate. Moreover, a prospective evalua-
tion in two consecutive menstrual cycles is necessary for
the diagnosis of PMDD, according to the DSM-IV criteria.
With respect to contraceptives use, we think that observed
data are weak due to the significant biases of the study on
this regard and incomplete information about kind of
contraceptives, dosage and delivery method. Another
source of bias is the type of patients attended at our
hospital, usually severely ill. On the other side, clinical
M. Flores-Ramos et al.
confirmation of the diagnosis and the absence of psycho-
tropic and hormonal drugs in our patients further support
our results.
In conclusion, we observed that the occurrence of
depression at perimenopause is influenced by a history of
PMDD, PPD, and previous depressive episodes, whereas
current hot flushes could be related to the severity of the
depressive episode.
References
Arpels JC (1996) The female brain hypoestrogenic continuum from
the premenstrual syndrome to menopause: a hypothesis and
review of supporting data. J Reprod Med 41:633–639
Avis NE, Brambilla D, McKinlay SM et al (1994) A longitudinal
analysis of the association between menopause and depression.
Results from the Massachusetts Women´s Health Study. Ann
Epidemiol 4:214–220
Brandon AR, Shivakumar G, Freeman M (2008) Perimenopausal
depression: covering mood and vasomotor symptoms. Curr
Psychiatry online 7(10). Accessed Dec 25, 2008
Bromberger JT, Matthews KA (1996) A longitudinal study of the effects
of pessimism, trait anxiety, and life stress on depressive symptoms
in middle-aged women. J Pers Soc Psychol 70:591–598
Bromberger JT, Matthews KA, Schott LL et al (2007) Depressive
symptoms during the menopausal transition: the Study of
Women´s Health Across the Nation (SWAN). J Affect Disord
103(1–3):267–72
Bromberger J, Kravitz H, Matthews K et al (2009) Predictors of first
lifetime episodes of major depression in midlife women. Psychol
Med 39(1):55–64
Callegari C, Buttarelli M, Cromi A et al (2007) Female psychopath-
ologic profile during menopausal transition: a preliminary study.
Maturitas 56(4):447–451
Cohen LS, Soares CN, Vitonis AF et al (2006) Risk for new onset of
depression during the menopausal transition: the Harvard study
of moods and cycles. Arch Gen Psychiatry 63(4):385–390
Critchlow DG, Bond AJ, Wingrove J (2001) Mood disorder history
and personality assessment in premenstrual dysphoric disorder. J
Clin Psychiatry 62(9):688–693
Daly R, Danaceau M, Rubinow D et al (2003) Concordant restoration
of ovarian function and mood in perimenopausal depression. Am
J Psychiatry 160:1842–1846
Deecher D, Andree TH, Sloan D, Schechter LE (2008) From
menarche to menopause: exploring the underlying biology of
depression in women experiencing hormonal changes. Psycho-
neuroendocrinology 33:3–17
Dooley M, Bell B (2007) Psychosocial aspects of the menopause. In:
Springer (ed) Psychological challenges in Obstetrics and Gyne-
cology: The clinical management, p. 332
Douma SL, Husband C, O’Donell ME et al (2005) Estrogen-related
mood disorders. Reproductive life cycle factors. Adv Nursing Sci
28(4):364–375
Eriksson O, Wall A, Marteinsdottir I et al (2006) Mood changes
correlate to changes in brain serotonin precursor trapping in
women with premenstrual dysphoria. Psychiatry Res 146:107–116
Freeman EW, Sammel MD, Liu L et al (2004a) Hormones and
menopausal status as predictors of depression in women in
transition to menopause. Arch Gen Psychiatry 61(1):62–70
Freeman EW, Sammel MD, Rinaudo PJ et al (2004b) Premenstrual
syndrome as a predictor of menopausal symptoms. Obstet
Gynecol 103(5 Pt 1):960–966
Association between depressive symptoms and reproductive variables
Freeman EW, Sammel MD, Lin H et al (2006) Associations of
hormones and menopausal status with depressed mood in women
with no history of depression. Arch Gen Psychiatry 63(4):375–382
Frey BN, Lord C, Soares CN (2008) Depression during menopausal
transition: a review of treatment strategies and pathophysiolog-
ical correlates. Menopause Int 14:123–128
Fugate WN, Sullivan ME (2005) Symptoms during the perimeno-
pause: prevalence, severity, trajectory, and significance in
women´s lives. Am J Med 118(12B):14S–24S
Gregory R, Masand P, Yohai N (2000) Depression across the
reproductive life cycle: correlations between events. Primary
Care Companion J Clin Psychiatry 2:127–129
Halbreich U, Tworek H (1993) Altered serotonergic activity in women
with dysphoric premenstrual syndromes. Int J Psychiatry Med
23:1–27
Harlow BL, Cohen LS, Otto MW (1999) Prevalence and predictors of
depressed symptoms in older premenopausal women: the
Harvard study of moods and cycles. Arch Gen Psychiatry 56
(5):418–424
Hsiao MC, Liu CY, Chen KC et al (2002) Characteristics of women
seeking treatment for premenstrual syndrome in Taiwan. Acta
Psychiatr Scand 106:150–155
Joffe H, Hall JE, Soares CN et al (2002) Vasomotor symptoms are
associated with depression in perimenopausal women seeking
primary care. Menopause 9(6):392–398
Joffe H, Cohen LS, Harlow BL (2003) Impact of oral contraceptive
pill use on premenstrual mood: predictors of improvement and
deterioration. Am J Obstet Gynecol 189:1523–1528
Kaufert PA, Gilbert P, Tate R (1992) The Manitoba project: a re-
examination of the link between menopause and depression.
Maturitas 14:143–155
Kurshan N, Neill Epperson C (2006) Oral contraceptives and mood in
women with and without premenstrual dysphoria: a theoretical
model. ArchWomens Ment Health 9(1):1–14
Maartens LW, Knottnerus JA, Pop VJ (2002) Menopausal transition
and increased depressive symptomatology: a community based
prospective study. Maturitas 42(3):195–200
Menkes DB, Coates DC, Fawcett JP (1994) Acute tryptophan depletion
aggravates premenstrual syndrome. J Affect Disord 32:37–44
Moreno FA, McGahuey CA, Freeman MP et al (2006) Sex differences
in depressive response during monoamine depletions in remitted
depressive subjects. J Clin Psychiatry 67:1618–1623
105
Novaes C, Almeida OP, de Melo NR (1998) Mental health among
perimenopausal women attending a menopause clinic: possible
association with premenstrual syndrome? Climacteric 1:264–270
Oinonen KA, Masmanian D (2002) To what extent do oral contra-
ceptives influence mood and affect? J Affect Disord 70:229–240
Oztürk O, Eraslan D, Mete HE et al (2006) The risk factors and
symptomatology of perimenopausal depression. Maturitas 55
(2):180–186
Richards M, Dr R, Daly RC et al (2006) Premenstrual symptoms and
perimenopausal depression. Am J Psychiatry 163:133–137
Robertson Blackmore E, Craddock N, Walters J et al (2008) Is the
perimenopause a time of increased risk of recurrence in women
with a history of bipolar affective postpartum psychosis? A case
series. Arch Women Ment Health 11:75–78
Rybaczyk LA, Bashaw M, Pathak DR et al (2005) An overlooked
connection: serotonergic mediation of estrogen-related physiolo-
gy and pathology. BMC Women´s Health 5:12
Schmidt PJ, Murphy JH, Haq N et al (2004) Stressful life events,
personal loses, and perimenopause-related depression. Arch
Womens Ment Health 7(1):19–26
Soares CN, Zytek B (2008) Reproductive hormone sensitivity and risk
for depression across the female cycle: a continuum of
vulnerability? J Psychiatry Neurosci 33(4):331–343
Soules MR, Sherman Sh, Parrot E et al (2001) Executive summary:
stages of reproductive aging workshop (STRAW). Fertil Steril 76
(5):874–878
Steinberg EM, Rubinow DR, Bartko JJ et al (2008) A cross-sectional
evaluation of perimenopausal depression. J Clin Psychiatry 69
(6):973–80
Stewart DE, Boydel KM (1993) Psychologic distress during meno-
pause: associations across the reproductive cycle. Int J Psychiatry
Med 23:157–162
World Health Oganization (1981) Report of a WHO Scientific group:
Research on the menopause. World Health Organization, Geneva
1981. WHO Technical Report Series, No. 866
Yonkers KA (1997) The association between premenstrual dysphoric
disorder and other mood disorders. J Clin Psychiatry 58(15):19–
25
Young E, Kornstein S, Harvey A et al (2007) Influences of hormone-
based contraception on depressive symptoms in perimenopausal
women with major depression. Psychoneuroendocrinology 32
(7):843–853