Journal of Mood & Anxiety Disorders 8 (2024) 100082

Contents lists available at ScienceDirect

Journal of Mood & Anxiety Disorders

journal homepage: www.journals.elsevier.com/journal-of-mood-and-anxiety-disorders

A systematic review on the bidirectional relationship between

trauma-related psychopathology and reproductive aging
Amanda R. Arnold a,*,1, Trinidi Prochaska a , Maximilian Fickenwirth a, Abigail Powers a ,
Alicia K. Smith b, E. Britton Chahine b, Jennifer S. Stevens a , Vasiliki Michopoulos a,b
a
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
b
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, United States

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

Keywords: Objective: Natural variation in ovarian steroid hormones across the female lifespan contributes to an increased
Trauma risk for depressive and posttraumatic stress disorder (PTSD) symptoms in women. However, minimal work has
PTSD focused on understanding the impacts of reproductive aging on the brain and behavioral health of trauma-
Depression
exposed women. This systematic review examines the bidirectional relationship between trauma-related psy­
Menopause
chopathology and reproductive aging.
Method: Following PRISMA guidelines, a systematic review of PubMed, PsychInfo, and Medline databases was
undertaken to identify controlled studies on how trauma history impacts psychopathology and menopause
symptoms during reproductive aging.
Results: Twenty-one studies met the eligibility criteria, with only four utilizing the gold standard STRAW+ 10
criteria for defining reproductive aging stages. The peri and postmenopausal periods appear to be particularly
vulnerable phases for individuals with trauma exposure. Menopause symptoms and trauma-related psychopa­
thology symptom severity increase during reproductive aging with increases in the degree of trauma exposure.
However, mechanistic insights that may explain this interaction are currently neglected in this area of research.
Conclusion: There is a significant lack of understanding regarding how reproductive aging and its related
neuroendocrine changes impact the brain to influence PTSD and depression symptoms related to trauma
exposure. This lack of basic understanding impedes the ability to identify, assess, and treat PTSD and depressive
symptoms in trauma-exposed women most effectively, and mitigate the long-term consequences of these
behavioral health symptoms on morbidity and mortality in aging women.

1. Introduction account for the overall sex difference in the prevalence of depression and
PTSD in individuals who have experienced trauma [16].
Seventy to ninety percent of people will experience at least one Accumulating translational evidence from reproductive aged women
traumatic event in their lifetime [1]. Trauma exposure can result in indicates that natural variation in ovarian steroid hormones (e.g.,
chronic mental health conditions that increase the risk for the devel­ estradiol and progesterone) over the course of the menstrual cycle and in
opment of chronic morbidity and mortality [2–6]. Depression and the postpartum period contribute to an increased risk for depressive and
posttraumatic stress disorder (PTSD) are among the most common re­ PTSD symptoms in women [17–23] Estradiol withdrawal that occurs in
actions to trauma [7,8]. Importantly, depression and PTSD are more the luteal phase of the menstrual cycle and in the postpartum period can
than twice as prevalent in women than men [9–13]. Women have impact the brain and exacerbate PTSD symptoms [24,25]. Decreasing
increased exposure to specific types of traumatic events, including sex­ levels of allopregnanolone, a progesterone-derived neurosteroid that
ual assault, and have greater prevalence of comorbid psychiatric disor­ declines in the late luteal phase of the menstrual cycle and in the post­
ders compared to men [9,14,15]. However, these differences do not fully partum period, have also been implicated in the etiology of depression

* Correspondence to: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Emory University, Atlanta, GA 30322, United
States.
E-mail address: amanda.renee.arnold@emory.edu (A.R. Arnold).
1
ORCiD: https://orcid.org/0009–0001-0233–2944

https://doi.org/10.1016/j.xjmad.2024.100082
Received 17 July 2024; Received in revised form 26 August 2024; Accepted 26 August 2024
Available online 29 August 2024
2950-0044/© 2024 The Authors. Published by Elsevier Inc. on behalf of Anxiety and Depression Association of America. This is an open access article under the
CC BY license (http://creativecommons.org/licenses/by/4.0/).
A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

and PTSD [26–28]. Although changes in estradiol and progesterone are transition, with a clearly defined measure of trauma exposure. Only
linked to increased mood symptoms in premenopausal women [29–31], studies assessing the impact of reproductive aging on trauma-related
research to date has primarily focused on reproductive-aged women, mental health outcomes and menopause symptom severity in in­
with minimal attention to the menopause transition that is also char­ dividuals with a trauma history were included. Reviews, opinion pieces,
acterized by robust changes in estradiol and progesterone levels [32]. case reports, and letters to the editor were excluded from consideration.
Reproductive aging refers to the gradual decline in ovarian function One reviewer (TP) searched using the terms cited above in the eligibility
and fertility throughout a woman’s life, culminating in menopause. In criteria to identify relevant studies. This same reviewer (TP) screened
the current review, we use the term ‘reproductive aging’ to encompass titles and abstracts to remove duplicates. Then titles and abstracts were
all stages related to the menopause transition (perimenopause), meno­ assessed independently by two reviewers (TP and AA) and articles were
pause itself, and the postmenopausal period. The Stages of Reproductive excluded if both reviewers decided that the articles did not meet the
Aging Workshop + 10 (STRAW+10) criteria are recognized as the gold criteria. In case of disagreement, the two reviewers had to reach a
standard for characterizing reproductive aging and provide a compre­ consensus. Then, the same two reviewers assessed the full-text versions
hensive framework for assessing stages through the menopause transi­ of the remaining articles independently against inclusion and exclusion
tion and into postmenopause [33]. According to STRAW+ 10, the criteria. In case of disagreement, the two reviewers had to reach a
menopause transition begins with the onset of menstrual cycle irregu­ consensus.
larity and concludes with the final menstrual period (FMP). This tran­
sition includes early and late stages of perimenopause, characterized by 3. Results
increased variability in the intervals between menstrual cycles (>7 day
different from normal) and periods of amenorrhea. The occurrence of The initial search on PubMed, PsycInfo, and Medline was conducted
menopause is defined as 12 months of amenorrhea and marks the end of from January 2024 to April 2024, and provided 249 potentially eligible
the menopause transition. The postmenopausal period that follows is studies. Once duplicates had been removed, a total of 111 titles and
defined as the time after this 12-month mark [33]. Throughout the abstracts were screened. We excluded 52 articles because they were not
menopause transition, women experience erratic fluctuations in estra­ primary data manuscripts. After full text reviews of the 59 remaining
diol and progesterone as ovarian function declines. These changes in reports, 38 were excluded as they did not assess women of menopausal
estradiol and progesterone occur alongside increases in age, trauma history, and the impact of trauma on psychopathology or
follicle-stimulating hormone (FSH) and decreases in Anti-Mullerian menopause symptoms (Fig. 1). Of the 21 studies that met inclusion
Hormone (AMH) [32,33] and have been linked to various symptoms criteria, 8 focused on depression in trauma-exposed women of meno­
of reproductive aging, including vasomotor symptoms, sleep distur­ pausal age, 3 on PTSD in trauma-exposed women of menopausal age,
bances, sexual dysfunction, and cognitive changes [34,35], however the and 15 on the effects of trauma and PTSD on menopause onset and
specific mechanisms and factors that confer risk for trauma-related symptoms, including cognitive function, in trauma-exposed women of
mood disruptions during reproductive aging remain unclear. menopausal age (Tables 1 and 2). It’s important to note that some
Despite evidence showing that changes in mood symptoms during studies contributed findings to more than one of these categories,
perimenopause are linked to increased risk for all-cause mortality in reflecting the interconnected nature of these outcomes in trauma
women [36,37], minimal research has directly investigated the bidi­ exposed women during reproductive aging. In addition, only four out of
rectional associations between trauma-related psychopathology and these 21 studies explicitly used the STRAW+ 10 criteria to define
reproductive aging. Here, we conducted a systematic review to address menopausal stages of reproductive aging (Tables 1 and 2). The
this gap. We examined the intersection of trauma-related psychopa­ remaining studies used various methods, including self-reported men­
thology and reproductive aging in trauma-exposed individuals. Our strual patterns, age-based estimates, or did not clearly specify their
objectives were to systematically identify existing evidence linking 1) assessment methods.
reproductive aging to risk for trauma-related psychopathology, focusing
on PTSD and depression; 2) trauma and PTSD to menopause onset and 3.1. Increased depression in trauma-exposed women during reproductive
symptoms, including effects on cognitive and brain function; and 3) to aging
identify gaps in our understanding of how reproductive aging impacts
trauma-related psychopathology and vice versa, and the underlying Results from our systematic review suggest that women of meno­
biological mechanisms by which this occurs. Increasing our basic pausal age, who experienced trauma at various points in their lives, are
knowledge about how biological changes during reproductive aging more susceptible to depression than those who do not experience trauma
impact the brain to influence mental health is critical for the identifi­ (Table 1).
cation, assessment, and treatment of PTSD and depressive symptoms in Childhood trauma. There has been a particular focus on the effects of
women who have experienced trauma. By synthesizing insights from the exposure to childhood trauma, including maltreatment and adverse
available literature, we aim to guide future research and clinical practice childhood experiences (ACES) on depression and depressive symptoms
to ultimately mitigate the long-term consequences of trauma exposure during reproductive aging. Shea et al. conducted a cross-sectional study
on women’s health during reproductive aging. that revealed that greater exposure to childhood maltreatment were
associated with more severe depressive symptoms in postmenopausal
2. Methods women [39]. Metcalf et al. found that both early child adversity and
current life stressful events predicted an increased likelihood of clini­
The current systematic review of the literature was performed ac­ cally significant depression in women of menopausal age within their
cording to PRISMA systematic review guidelines [38]. Utilizing longitudinal study [40]. Epperson et al., whom also conducted a longi­
PubMed, PsychInfo, and Medline databases, we searched in the tudinal study, found that a history of childhood adversity (≥2 ACEs) and
title/abstract field employing the terms “Menopause” OR “Menopausal.” adolescent/adult adversity (≥2 ACEs after menarche) increased risk of a
Each search incorporated one of the following additional terms: “Post­ first major depressive episode during the menopause transition [41].
traumatic Stress Disorder,” “Trauma Exposure,” “Interpersonal Adulthood trauma. In addition to risk due to early adverse childhood
Violence,” “Domestic Violence,” “Sexual Assault,” “Sexual Trauma,” experiences, three papers from our systematic review presented findings
“Adverse Childhood Experiences,” “Childhood Trauma,” and “Child­ that support the notion that trauma exposure in adulthood also increases
hood Abuse.” Articles were chosen based on predefined inclusion and depressive symptoms throughout reproductive aging. Moraes et al.
exclusion criteria. Eligibility criteria deemed a study suitable if it pre­ found within their cross-sectional study that peri and postmenopausal
sented original data about women undergoing the menopausal women with histories of domestic or sexual violence had significantly

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A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

Fig. 1. Summary of literature search

Adapted from PRISMA [38].

more comorbid health conditions, both physical and psychological, Michopoulos et al. found that perimenopausal aged women reported
compared to non-abused controls, with depression being the most higher levels of PTSD symptoms compared to those in premenopausal
common comorbidity (69.4%) [42]. In addition, two cross-sectional and postmenopausal aged women [45]. Further, two studies of female
studies of female veterans of menopausal age with a history of mili­ veterans of menopausal age with an MST history showed an increased
tary sexual trauma (MST) showed an increased likelihood of meeting likelihood of meeting the criteria for a PTSD diagnosis compared to fe­
diagnostic criteria for depression compared to female veterans without male veterans without a history of MST [43,44]. This aligns with the
MST history [43,44]. data mentioned in Section 3.1 indicating more severe depression during
An open question is whether the association of trauma and depres­ reproductive aging, suggesting an increased susceptibility to
sive symptoms is specific to peri or postmenopause, or whether a history trauma-related psychopathology during reproductive aging.
of trauma increases symptom burden in a uniform way across the life­
span. Michopoulos et al. conducted a cross-sectional study that found 3.3. Trauma and PTSD effects on menopause onset and symptoms
that trauma-exposed women of perimenopausal age reported higher
levels of depressive symptoms than pre and postmenopausal aged Most of the studies identified by our systematic review examined the
women, regardless of the timing of trauma exposure (e.g., trauma effects of trauma and/or PTSD on menopause onset and symptom
exposure as a child versus as an adult) [45]. This may vary depending on severity, including impacts on cognitive function (Table 2). In our sys­
whether women were already experiencing significant depressive tematic review, we found 15 studies that investigated the impact of
symptoms prior to entering the menopausal transition. For example, trauma exposure and/or PTSD on menopause timing and onset, meno­
[46] found in their longitudinal study that odds of a major depressive pause symptom severity, and cognition and brain function.
episode (MDE) were greater during perimenopause and postmenopause Timing of menopause. Three studies investigated the timing of
only in women without prior MDD. However, in women with a history menopause in trauma-exposed women, with mixed results. Mendoza-
MDD, childhood maltreatment interacted with menopause status to in­ Huertas et al. (2024) found in their cross-sectional study that violence-
crease MDE risk only in postmenopausal women [46]. exposed women reached menopause approximately 20 months earlier
and 20.7% of these women developed premature ovarian insufficiency
3.2. Increased PTSD in trauma-exposed women during reproductive aging [48]. Alternatively, Nishimi et al. and Kling et al., both concluded that
time to natural cessation of menses was not significantly different be­
Although trauma exposure and PTSD are often co-morbid with tween trauma-exposed and no-trauma groups [49,50]. However, Nish­
depression [47], the effects of reproductive aging on trauma-related imi et al. found in their longitudinal study, which included a sample size
symptoms of PTSD have received minimal research focus to date. We of 46,639 people, that trauma-exposed individuals were more likely to
identified only three studies that directly examined this topic (Table 1). have earlier cessation of menses due to gynecological surgeries, a factor

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A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

Table 1
Summary of current literature evaluating the impact of trauma exposure and menopause status on PTSD, anxiety, and depression in menopausal women. Lifetime
trauma exposure was associated with greater instances of anxiety and depression in women of menopausal age. Perimenopausal women reported greater PTSD and
depression symptoms. ACE: Adverse Childhood Experiences. CM: Childhood Maltreatment. CTQ: Childhood Trauma Questionnaire. FSH: Follicle-Stimulating Hor­
mone. hsCRP: High-Sensitivity C-Reactive Protein. MD: Major Depression. MDD: Major Depressive Disorder. MDE: Major Depressive Episode. MST: Military Sexual
Trauma. PTSD: Posttraumatic Stress Disorder. VMS: Vasomotor Symptoms.
Reference Sample/Age Racial-Ethnic Trauma Type/ Outcome Measure Results Assessment of Menopause
Demographics Independent Stage
Variable

[46] Women (N = 333) 67 % White Current stress, Prevalence of MDEs CM, but not current stress, Used data from the Study of
interviewed annually 33 % Black/ CTQ status, interacted with menopausal Women’s Health Across the
over 15 years African American menopause status, status to increase risk for MD Nation (SWAN), which
42 to 52 years old lifetime MDD during postmenopause in defined menopausal
diagnosis women with MDD. transition stages based on
Women without prior MDD menstrual bleeding patterns
were at increased risk for MD
during peri and
postmenopause.
[42] Women with one year 62.1 % White Violence exposure Menopause symptom Women who experienced Focused on postmenopausal
of amenorrhea (N = 37.1 % Black/ status severity and rate of violence had a higher number women, defined as those who
120) African American comorbid disorders such as of self-reported comorbidities had their last menstrual
40 to 65 years old 0.8 % Asian osteoporosis, depression/ during menopause (average period at least 12 months ago
psychological disorders, of 4 − 5) compared to 2.2 with FSH levels > 45 mU/mL
hypertension, rheumatic comorbidities in the control and estradiol levels < 20 pg/
disease, allergies, group. Total trauma exposure mL
fibromyalgia, varicose was associated with greater
veins in the legs, menopausal symptom
labyrinthitis, diabetes, severity. Sexual violence
herniated disk, cancer specifically was associated
with poorer sexual health
outcomes, but not with other
menopausal symptoms.
[41] Premenopausal 52.7 % White ACE status and Incidence of MDD Women reporting ≥ 2 ACEs Used STRAW+ 10 criteria to
women (N = 243) 47.3 % Black/ menopause stage were at significantly greater define menopause transition
followed over 16 African American risk for lifetime and stages
years1 menopause MDD compared
35 to 47 years old at to those with 0 ACEs. Women
enrollment reporting ≥ 2 ACEs during
the postpubertal period, but
not prepubertal, were 2.3x
more likely to have
menopause MDD.
Women Veterans (N = 63.5 % White MST screening Menopause symptoms and MST was associated with 7.25 Included women aged 55 and
[43]
70,864) 9.8 % Black/ status odds of depression, times the odds of PTSD and older, likely postmenopausal,
Aged 55 + with ≥ 1 African American anxiety, and PTSD over twofold odds of but specific assessment not
documented MST 0.4 % Hispanic depression and suicidal mentioned
0.4 % Asian ideation, as well as increased
25.8 % Other/ odds of anxiety, alcohol use
Unknown disorder, substance use
disorder, and opioid use
disorder. A positive MST
screen was associated with
greater odds of obesity,
chronic pain, back pain,
insomnia, and sleep apnea.
Premenopausal, 53.9 % White ACE/stressful life Depression symptom Among those with high ACEs Used STRAW+ 10 criteria to
[40] perimenopausal (early 46.1 % Black/ event status and severity and a high number of current define menopause transition
and late) and African American inflammatory life stressors, higher levels of stages
postmenopausal marker levels hsCRP were associated with
women (N = 142) higher odds of experiencing
followed over 16 clinically significant
years1 depression symptoms.
Mean baseline age of
45 years
[45] Women (N = 6093) 2.5 % White Menopause stage PTSD and depression Perimenopausal women Used age cutoffs to categorize
18 to 65 years old 93.8 % Black/ (pre, peri, post) symptom severity showed higher depression women as pre, peri, or
< 40 years: African American and PTSD symptom severity postmenopausal
premenopausal 3.8 % Other than premenopausal and
40 - 55 years: (Hispanic/Latino, postmenopausal women.
perimenopausal Asian,
> 55 years: Multiracial)
postmenopausal
[39] Women (N = 97) Not Available CTQ status Depression and menopause ACEs were highly prevalent Included women attending a
40 to 65 years old symptom severity among women seeking care menopause clinic, but specific
for bothersome menopausal assessment not detailed
symptoms (66 %). Higher
CTQ scores were significantly
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A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

Table 1 (continued )
Reference Sample/Age Racial-Ethnic Trauma Type/ Outcome Measure Results Assessment of Menopause
Demographics Independent Stage
Variable

associated with higher

depression scores, as well as
with a greater burden of
menopausal symptoms.
[44] Women Veterans 72.8 % White MST screening VMS, vaginal symptoms, MST was associated with the Included women aged
(N = 232) 10.3 % Black/ status sleep difficulty, depressive presence of VMS, vaginal 45 − 64, but specific
45 to 64 years old African American symptoms, anxiety symptoms, insomnia, menopause assessment not
3.9 % Asian symptoms, and PTSD clinically significant mentioned
0.4 % American symptoms depressive symptoms,
Indian/Alaskan anxiety, and PTSD.
Native
1.7 % Native
Hawaiian/Pacific
Islander
12.1 % Other

1Perimenopausal and postmenopausal status categorized using Stages of Reproductive Aging Workshop + 10 criteria (STRAW+10).

that was not considered in the Mendoza-Huertas study. aging. Despite the failure of the majority of existing studies to utilize a
Menopause symptom severity. Across the eight studies examining reliable definition of menopausal status in the reviewed articles, the
trauma exposure among women of menopausal age, there is consistent existing studies provide evidence for a bidirectional relationship be­
evidence linking trauma history, including ACEs, intimate partner tween trauma-related psychopathology and reproductive aging. Our
violence, and sexual trauma to greater overall menopausal symptom review not only synthesizes the current knowledge but also highlights
burden (Table 2). Most investigated the impact on trauma history on the critical need for the field to assess and use the STRAW+ 10 criteria in
menopause symptom severity broadly [39,42,48,51,52], one examined future research to enhance our understanding of how different stages of
sexual function specifically [53], two investigated vasomotor symptoms reproductive aging may differentially impact trauma-related
specifically [54,55], and one investigated sleep symptoms specifically psychopathology.
[56]. Associations were found between trauma exposure and higher The minimal data to date from eight studies indicate reproductive
total scores on menopausal symptom measures like the Kupperman aging can impact depression and PTSD symptoms in trauma-exposed
Menopausal Index [42], Greene Climacteric Scale [39], Cerventes Scale women [39–46]. In addition, women with a history childhood
[48] and Menopause Rating Scale [52]. Notably, women who experi­ maltreatment and sexual trauma appear to be at heightened risk for the
enced abuse in both childhood/adolescence and adulthood had the emergence or exacerbation of PTSD and depression during reproductive
highest scores on the menopause symptom questionnaire [42]. aging [39–41,43,44,46]. Although this vulnerability is reflected in the
Cognitive and brain function. Four studies examined the impact of increased prevalence and severity of depression and PTSD symptoms
ACEs on cognitive and brain function in menopausal aged women compared to non-trauma-exposed women, the effects of reproductive
(Table 2). Metcalf et al. (2022) and Shanmugan et al. (2017a) found that aging on these symptoms of trauma-related psychopathology were
women with high ACE scores showed poorer performance on objective sometimes apparent in perimenopausal [45] or postmenopausal women
cognitive tests during the menopausal transition [57–59]. Metcalf et al. [39,42,44,48,50,51,56], or both [46]. These findings suggest that vari­
(2022) conducted a longitudinal study and found that childhood ation in estradiol and progesterone over the course of reproductive aging
adversity interacted with inflammatory markers to predict worse verbal may contribute to an increased risk for depressive and PTSD symptoms
memory performance during perimenopause [57]. Similarly, Shanmu­ in trauma-exposed women, similar to what is seen during the menstrual
gan et al. (2017a) found in their cross-sectional study that high child­ cycle and in the postpartum period [17–23,26–31].
hood adversity was associated with worse performance on tests of Published findings from three studies identified by our systematic
sustained attention and working memory in menopausal women [59]. review described the impact of trauma exposure and/or PTSD on
These deficits in attention and working memory linked to childhood menopause timing. Although one report indicated that trauma exposure
adversity were also associated with decreased activation in brain regions was associated with earlier age at menopause [48], two other studies
supporting executive function [58], lower functional connectivity concluded that time to natural cessation of menses was not significantly
within and between executive control networks [59], and reduced different due to trauma exposure [49,50]. However, one of those studies
network flexibility [60] in women of menopausal age. reported that trauma-exposed individuals were more likely to have
earlier cessation of menses due to gynecological surgeries [49]. These
4. Discussion minimal findings linking trauma to reproductive senescence aligns with
existing research that connects PTSD to an increased risk of gyneco­
The current systematic review identified 21 studies that have focused logical complications, such as fibroids, endometriosis, and polycystic
on the impacts of reproductive aging on risk for trauma-related psy­ ovarian syndrome, which often necessitate gynecological surgeries [51,
chopathology, focusing on PTSD and depression and the impacts of 61]. Further, each of these three studies examined the effects of trauma
trauma exposure and PTSD on menopause onset and symptoms, at different timepoints in life on menopause timing with
including effects on cognitive and brain function. We found considerable Mendoza-Huertas et al. (2024) examining partner violence in adult­
variation in how reproductive aging stages were defined and assessed. hood, [49] examining lifetime trauma and PTSD symptomology, and
Only four studies utilized the standardized STRAW+ 10, while the Kling et al. examining ACEs. Further studies are needed to delineate if
remaining studies used a range of other methods. These methods timing of trauma exposure has differential effects on menopause onset or
included self-reported menstrual patterns, age-based estimates, and in risk for the development of gynecological conditions.
some cases, the assessment methods were not clearly specified. Eight studies identified by our systematic review linked various types
Furthermore, only three studies compared symptoms of menopause or of trauma exposure, including ACEs, intimate partner violence, and
trauma-related psychopathology across different stages of reproductive sexual trauma, to greater overall menopause symptom burden [39,42,

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A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

Table 2
Summary of current literature analyzing the impact of trauma exposure on menopause onset and symptomatology. Greater trauma history was associated with greater
menopausal symptom burden but mixed effects on menopause onset. Childhood trauma was associated with poor cognitive outcomes during menopause. ACE: Adverse
Childhood Experiences. CET: Conditional Exclusion Test. CPT: Penn Continuous Performance Task. CTQ: Childhood Trauma Questionnaire. DLPFC: Dorsolateral
Prefrontal Cortex. FSD: Female Sexual Dysfunction. FSH: Follicle-Stimulating Hormone. IPV: Intimate Partner Violence. PTSD: Posttraumatic Stress Disorder. TD:
Tryptophan Deletion. VAW: Violence Against Women. VMS: Vasomotor Symptoms.
Reference Sample/Age Racial-Ethnic Trauma Type/ Outcome Measure Results Assessment of Menopause
Demographics Independent Stage
Variable

[55] Perimenopausal and 73.22 % White CTQ status VMS during wake and Childhood sexual or physical Used STRAW+ 10 criteria to
postmenopausal 26.78 % Non- sleep abuse was associated with define menopause transition
womena (N = 295) white 1.5-two-fold the number of stages
40 to 60 years old physiologically recorded
VMS during sleep.
[42] Women with one year 62.1 % White Violence exposure Menopause symptom Women who experienced Focused on postmenopausal
of amenorrhea 37.1 % Black/ status severity and rate of violence had a higher women, defined as those
(N = 120) African American comorbid disorders such as number of self-reported who had their last menstrual
40 to 65 years old 0.8 % Asian osteoporosis, depression/ comorbidities during period at least 12 months
psychological disorders, menopause (average of ago with FSH levels > 45
hypertension, rheumatic 4 − 5) compared to 2.2 mU/mL and estradiol levels
disease, allergies, comorbidities in the control < 20 pg/mL
fibromyalgia, varicose group. Total trauma
veins in the legs, exposure was associated
labyrinthitis, diabetes, with greater menopausal
herniated disk, cancer symptom severity. Sexual
violence specifically was
associated with poorer
sexual health outcomes, but
not with other menopausal
symptoms.
[51] Women (N = 2016) 39.4% White Lifetime physical or Menopause symptom Symptoms of PTSD and Included women aged
40 to 80 years old 21.3% Black/ emotional severity emotional interpersonal 40 − 80, but specific
African American interpersonal violence were associated menopause assessment not
20% Hispanic violence, sexual with difficulty sleeping, mentioned
19.2% Asian assault, and current VMS, and vaginal symptoms.
symptoms of PTSD Physical interpersonal
violence was associated with
VMS and sexual assault was
associated with vaginal
symptoms.
[56] Women Veterans 74.1% White Lifetime IPV Current clinical insomnia Lifetime history of IPV was Included midlife women
(N = 232) 10.3% Black/ via the Insomnia Severity associated with twofold to veterans, but specific
45 to 64 years old African American Index fourfold odds of current menopause assessment not
3.9% Asian clinical insomnia, including mentioned
1.7% Native overall, physical,
Hawaiian psychological, and sexual
3.9% American IPV.
Indian
3.4% Other
[52] Women (N = 1670) 93% White ACE status Menopause symptom The authors observed a Included midlife women, but
40 to 65 years old severity significant association specific menopause
between severe menopausal assessment not mentioned
symptoms and higher
childhood adversity (ACE
score 1 − 3 or ≥ 4 vs. ACE =
0).
[50] Postmenopausal 92.9% White ACE status Timing of natural No association between Menopause stage was
women (N = 350) menopause ACEs and age of natural determined by a medical
Mean age of 59.2 years menopause observed. provider using menstrual
bleeding patterns
[48] Postmenopausal Not Reported Lifetime incidence Timing of natural Violence exposure was Specific menopause
women (N = 118) and type of VAW- menopause and severity of associated with increased assessment not clear from
40 to 68 years old economic, menopause symptoms menopausal symptoms and the available information
psychological, poorer quality of life.
sexual, or physical Violence-exposed women
violence reached menopause
approximately 20 months
earlier and 20.7% of these
women developed
premature ovarian
insufficiency.
[57] Premenopausal (early 51.5% White ACE status and Inflammation (cytokines), Advancing menopause stage Used STRAW+ 10 criteria to
and late) and 48.5% Black/ menopause stage verbal memory was associated with worse define menopause transition
postmenopausal African American performance on immediate stages
women (N = 167) verbal recall and delayed
followed over 14 verbal recall. During
years1 perimenopause, higher ACE
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A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

Table 2 (continued )
Reference Sample/Age Racial-Ethnic Trauma Type/ Outcome Measure Results Assessment of Menopause
Demographics Independent Stage
Variable

Mean baseline age of exposure was associated

44 years with worse immediate verbal
recall at higher levels of
TNF-α.
[49] Registered nurses 92.9% White Trauma/PTSD Status Timing of natural Women with trauma Used self-reported age at
(N = 46,639) 0.9% Black/ menopause or cessation of exposure, low, and high natural menopause
Aged 25 to 42 at African American menses due to surgery and PTSD symptoms had earlier
enrollment in 1989 4.9% Other incidence of gynecologic cessation of menses due to
Followed for up to 26 (Hispanic/Latino, surgeries surgery but did not have
years Asian, earlier natural menopause
Multiracial) than those without trauma
exposure.
[53] Women (N = 1572) 96% White ACE status Sexual function Women with a greater Included midlife women, but
40 to 65 years old number of ACEs were more specific menopause
likely to be sexually inactive. assessment not mentioned
Among sexually active
women, the proportion of
women with FSD increased
sequentially as the number
of ACEs increased.
[58] Women (N = 40) 75% White ACE status, TD Functional network ACEs were associated with Included hypogonadal
48 to 60 years old 17.5% Black/ flexibility during a letter n- lower within-network women based on menstrual
African American back working memory task connectivity while TD had cycle changes with FSH
5% Asian no effect on connectivity in levels > 30 IU/mL
2.5% Other the low ACE group. TD
increased connectivity in the
high ACE group. Lower
within network connectivity
was associated with poor
performance on the CPT
attention task.
[59] Women (N = 33) 75.8% White ACE status, Brain activation during In the absence of exogenous Included early hypogonadal
48 to 60 years old 18.2% Black/ tryptophan depletion working memory task in estradiol, TD increased right women based on menstrual
African American and, estradiol menopausal women DLPFC activation in high cycle changes with FSH
6% Asian treatment ACE subjects but decreased levels > 30 IU/mL
activation in low ACE
subjects. Treatment with
estradiol attenuated the
effects of ACE and TD.
[60] Healthy hypogonadal Not Reported ACE status, TD Functional network ACEs were associated with Specific menopause
women (N = 40) flexibility during a letter n- higher flexibility across assessment not clear from
48 to 60 years old back working memory task networks. There was no the available information
interaction between ACE and
TD, however TD increased
network flexibility in both
ACE groups in comparison to
sham. depletion. TD was
associated with worse CET
performance, however there
was no significant
association of ACE status on
CET performance.
[39] Women (N = 97) Not Available CTQ status Depression and ACEs were highly prevalent Included women attending a
40 to 65 years old menopause symptom among women seeking care menopause clinic, but
severity for bothersome menopausal specific assessment not
symptoms (66%). Higher detailed
CTQ scores were
significantly associated with
higher depression scores, as
well as with a greater burden
of menopausal symptoms.
[54] Women (N = 332) 67% White CTQ status VMS Childhood abuse or neglect Used data from the Study of
interviewed annually 33% Black/ was associated with Women’s Health Across the
over eight years African American increased reporting of hot Nation (SWAN), which
42 to 52 years old flashes and night sweats. defined menopausal
transition stages based on
menstrual bleeding patterns
a
Perimenopausal and postmenopausal status categorized using Stages of Reproductive Aging Workshop + 10 criteria (STRAW+10).

51,52], including sexual function [53], vasomotor symptoms [54,55] was associated with worse performance on tests of sustained attention
and sleep symptoms [56]. An additional four studies examined the and working memory, as well as with decreased activation in brain re­
impact of ACEs on cognitive and brain function in menopausal aged gions supporting executive function [58], lower functional connectivity
women [57–60]. These studies showed that high childhood adversity within and between executive control networks [59], and reduced

7
A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

network flexibility [60]. hormones during the menopause transition contribute to symptoms of
The studies identified by our systematic review had several trauma-related psychopathology and menopause symptom severity
strengths, including the use of validated measures of trauma exposure, [76]. To address these limitations, future research should use the stan­
depression and PTSD symptoms, the inclusion of diverse trauma types dardized STRAW+ 10 criteria for assessing menopausal status, clearly
and assessment of their unique contribution to trauma-related psycho­ report assessment methods, conduct more longitudinal studies tracking
pathology, and the examination of multiple mental and physical health women through different menopausal stages, and integrate biological
outcomes that are impacted by the reproductive aging. It’s important to markers alongside clinical assessments. In addition, studies should focus
note that while our review focused on trauma-related psychopathology, specifically on the perimenopause phase and encourage interdisci­
there is strong evidence from large longitudinal studies, such as the plinary collaboration between mental health researchers and repro­
Study of Women’s Health Across the Nation (SWAN), the Personality ductive endocrinologists to ensure accurate assessment and
and Total Health (PATH) Through Life Project, and the Harvard Study of interpretation of menopausal status in the context of trauma-related
Moods and Cycles demonstrating increased risk for depression during psychopathology.
reproductive aging outside the context of trauma exposure [62–64]. This An additional limitation of the identified studies is the predominance
vulnerability during reproductive aging is also highlighted by other of studies focused on childhood abuse and military sexual trauma as
studies showing that hormonal changes during the menopausal transi­ specific contributors to affective disturbances during reproductive
tion are associated with increased risk of depressive symptoms even in aging. Future work should include a broader range of trauma types and
women with no history of depression [65]. systematically examine the role of developmental timing of exposure on
The susceptibility during reproductive aging extends beyond psy­ perimenopausal mental health. Future research should also prioritize
chological health, as vasomotor symptoms during reproductive aging multi-modal and objective physiological assessments of vasomotor
are associated with increased cardiovascular risk [66] and higher frac­ symptoms, sleep, cardiovascular function, and brain activity rather than
ture incidence [67]. Overall existing studies suggest that the peri and relying solely on self-report measures of depression, PTSD, and meno­
postmenopausal periods represent a unique phase of vulnerability for pause symptoms. Integrating objective physiological indices will pro­
various negative health outcomes, even in the absence of trauma vide a more comprehensive understanding of the mechanisms
exposure. However, comparable large-scale longitudinal data for PTSD contribute to trauma-related psychopathology during reproductive
as an outcome during reproductive aging is lacking, despite the fact that aging.
biological factors that influence PTSD symptoms, such as inflammation Finally, most of the identified studies primarily feature White par­
[68] and hormonal fluctuations [22] also contribute to health vulnera­ ticipants, highlighting a potential gap in understanding perimenopausal
bilities of reproductive aging [69]. Indeed, inflammation and activity of risk for increased trauma-related psychopathology or menopause
the immune system are modulated by ovarian hormones [70–74] and symptoms among diverse racial and ethnic groups. The underrepresen­
serum cytokine concentrations are associated PTSD [68] and psycho­ tation of diverse women in studies may exacerbate already existing
logical symptoms in midlife women [75]. In addition, hormonal fluc­ health inequities in trauma-related adverse health outcomes, as
tuations, including changes in neurosteroid levels, and HPA axis minoritized Black women face elevated risks of trauma exposure and
dysregulation are linked to PTSD [22] and to perimenopausal depression depression and PTSD over the lifespan [77–81]. In addition, research
[30]. suggests that Black women may have higher estradiol levels during the
Several limitations of the existing literature should be noted. First, menstrual cycle and perimenopausal transition than non-Black women
our review revealed significant inconsistency in how menopause is [82,83], as well as a greater likelihood of experiencing severe vasomotor
defined and assessed across studies. Out of 21 studies included, only four and depressive symptoms during perimenopause [84–86]. Despite the
(Epperson et al., 2017; Metcalf et al., 2022; Metcalf et al., 2023; Carson established evidence for greater risk for trauma-related psychopathol­
and Thurston 2019) explicitly used the standardized STRAW+ 10 ogy and menopause symptoms, these minoritized women remain un­
criteria to define menopausal stages [40,41,55,57]. The remaining derrepresented in research on women’s reproductive and mental health.
studies employed various methods, including self-reported menstrual To address this inequity, future studies should embrace more diverse
patterns, age-based estimates, or did not clearly specify their assessment sample populations to not only bridge critical knowledge gaps but also
methods. This variability presents a significant challenge in interpreting inform the development of tailored treatment and prevention strategies
and comparing results across studies. Moreover, only three studies for mood disturbances during reproductive aging.
compared symptoms of menopause or trauma-related psychopathology While the results of our systematic review highlight the existing
across menopause stages [45,46,57]. Most of the identified studies limited data supporting the premise that depression and PTSD symptoms
treated menopause status as a confounding factor, eliminating the op­ are impacted by reproductive aging and that trauma exposure and the
portunity to examine the role of the hormonal transition in affecting presence of trauma-related psychopathology can impact menopause
symptom severity directly. Comparing outcomes across menopause symptoms, the exact mechanisms underlying these associations remain
stages, ideally within longitudinal cohorts, is necessary to assess to be fully characterized. The bidirectional relationship suggests com­
whether the transition represents a particularly vulnerable period for mon underlying mechanisms for both mood and menopause-related
trauma-exposed women. symptoms, including deficits in cognitive function. The fluctuations
The examination how changes in specific hormone levels (e.g., and relative decline in estradiol and allopregnanolone levels during the
estradiol, progesterone, FSH, AMH) across reproductive aging is also menopause transition may disrupt emotional regulation and cognitive
necessary to better understand the mechanisms contributing to function in ways that exacerbate trauma-related symptoms by influ­
increased risk for depression and PTSD during this reproductive stage. encing the activity of common neurocircuitry. Indeed, estradiol and
While most studies identified by our review verified menopause status progesterone modulate the activity of the amygdala, hippocampus, and
through cycle tracking, and few included hormone assessments of fol­ prefrontal cortex [87–89], all regions important for emotional regula­
licle stimulating hormone and estradiol to verify menopause stage, none tion and cognitive function [19,90–96]. These neuroendocrine hor­
used hormone levels as predictors of trauma-related psychopathology. mones exert their effects by impacting neurotransmitter systems,
The longitudinal assessment of these hormones is currently limited by including serotonin, dopamine, and GABA, which are implicated in both
our ability to quantify them on the dynamic time scale on which they depression and PTSD when dysfunctional [97–99]. Alterations in the
fluctuate during the menopause transition. The development and structure and functional connectivity of the amygdala, hippocampus,
implementation of nanobiosensors and other technologies that can and prefrontal cortex are central to the pathophysiology of depression
constitutively measure estradiol and progesterone levels is critical for [100,101], PTSD [100,102,103], and deficits in executive function [104,
determining how the erratic and unpredictable fluctuations in these 105].

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A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

In addition to directly impacting the neurocircuitry contributing to techniques could map symptom interactions over time, potentially
affective and cognitive dysfunction, the estradiol and progesterone revealing distinct patterns for menopause-related versus trauma-related
fluctuations during the menopause transition can also impact other depression and PTSD symptoms. Combining hormone measurements
physiological systems that can contribute to depression and PTSD with other biological markers, including psychophysiology and neuro­
symptoms in trauma-exposed women. Estradiol and progesterone imaging, in comprehensive mechanistic studies could provide more
modulate the activity of the hypothalamic pituitary adrenal (HPA) axis nuanced models of symptom etiology. Experimental manipulations
and influence glucocorticoid signaling [106–108], both of which using hormone replacement therapy or trauma-focused interventions
contribute to the etiology of PTSD and depression [109,110]. Estradiol could observe differential effects on various symptoms. Qualitative
and progesterone can also impact inflammatory processes throughout research through in-depth interviews could provide insights into how
the body, which can also contribute to depression and PTSD symptoms women themselves differentiate between menopause-related and
[68,111]. Moreover, these hormonal changes can affect autonomic trauma-related symptoms. Advanced statistical techniques like machine
nervous system (ANS) function, potentially altering heart rate vari­ learning could identify complex patterns in symptom presentation that
ability and ANS responsivity, which are often dysregulated in may distinguish between reproductive aging and trauma-related origins.
trauma-exposed individuals with PTSD and depression [112,113]. Finally, neuroimaging studies comparing brain activity patterns during
Furthermore, because estradiol and progesterone can influence the ac­ symptom provocation in menopausal women with and without trauma
tivity of these systems independently, they also may modulate how these histories could provide valuable insights. By employing these methods,
physiological systems interact with each other to contribute to researchers could begin to disentangle the complex relationships be­
trauma-related psychopathology. Together, these data indicate that tween menopausal symptoms and trauma-related psychopathology,
neuroendocrine changes over reproductive aging can modulate the ac­ leading to more targeted and effective interventions for this population.
tivity of multiple biological systems that can contribute to heightened This approach would not only advance our understanding of the inter­
risk for depression and PTSD in trauma-exposed women. section between trauma and reproductive aging but also potentially
The collective findings from the studies identified have important improve clinical outcomes for affected women.
implications for clinical practice and future research. Screening for
trauma history and monitoring for the emergence of mental health 5. Summary and conclusions
symptoms during the menopause transition may help identify women at
risk and facilitate timely intervention. Trauma-informed approaches to In conclusion, trauma-exposed women appear uniquely susceptible
menopause care, which acknowledge the potential impact of prior to reemergence and exacerbation of PTSD, depression, cognitive
trauma on current symptoms and treatment response, may improve changes, and physical symptoms during reproductive aging. While exact
outcomes for trauma-exposed women. It’s important to note that several mechanisms require further characterization, neuroendocrine alter­
effective treatments for traumatic stress exist and are likely to benefit ations likely sensitize women to adverse mental and physical health
women experiencing increased symptoms during reproductive aging. effects during this time. Screening for trauma history and mood/
These include evidence-based psychotherapies such as cognitive cognitive changes during perimenopause could enable earlier inter­
behavioral therapy, cognitive processing therapy, prolonged exposure, vention to mitigate long-term consequences of affective disturbances
and eye movement desensitization and reprocessing, as well as phar­ during the menopause transition. While there remains a significant lack
macological interventions like selective serotonin reuptake inhibitors of research into this critical window of reproductive aging for trauma-
(SSRIs) [114]. In addition, evidence suggests estrogen may help alle­ impacted women’s health, the importance of understanding the inter­
viate PTSD symptoms [115]. This finding raises the possibility that play between PTSD, depression, and reproductive aging is underscored
hormone replacement therapy, commonly used for perimenopausal by recent federal initiatives. In 2023, the White House launched the
symptoms, might also benefit those with PTSD. Further, evidence sug­ Initiative on Women’s Health Research, which prioritizes research on
gests hormone therapy may interact with SSRIs, as studies show that women’s midlife health and menopause-related conditions [119].
hormone therapy increases the effectivity of SSRIs in the treatment of Concurrently, the National Institutes of Health launched an agency-wide
depression [116–118]. Adapting these existing evidence-based treat­ effort to close gaps in women’s health research across the lifespan, with
ments to address the unique challenges of reproductive aging may a specific focus on the impact of reproductive aging on various health
enhance their efficacy for this population. Future studies should inves­ outcomes [119]. These initiatives highlight the growing recognition of
tigate the mechanisms by which biological changes during reproductive the complex, multisystem effects of reproductive aging and the need for
aging, including the role of specific hormone profiles, inflammatory interdisciplinary research to identify mechanism that confer risk for
markers, and brain changes, contribute to risk for new onset and exac­ adverse mental health outcomes. Furthering our basic understanding of
erbation of depression and PTSD symptoms in trauma-exposed women. how biological changes during this period impact the brain and behavior
These studies are necessary to inform the development of novel in­ is essential for effectively identifying, assessing, and treating PTSD and
terventions that address the unique needs of trauma-exposed women depression in trauma-exposed women.
during this transitional period late in life.
It is noteworthy that many symptoms of menopause overlap with Declaration of Competing Interest
those of PTSD and depression, which presents both challenges and op­
portunities for future research. Key overlapping symptoms include sleep The authors declare that they have no known competing financial
disturbances, mood changes, cognitive difficulties, fatigue, anxiety and interests or personal relationships that could have appeared to influence
autonomic dysfunction. This overlap necessitates careful consideration the work reported in this paper.
in future studies to disentangle the causal relationships between
menopausal status, trauma exposure, and depression and PTSD symp­ Acknowledgements
tom presentation. To address this, future research in this area could
apply several innovative approaches. Longitudinal studies tracking The current work was funded by the following support from the
symptoms from premenopause through postmenopause in both trauma- National Institutes of Health: MH115174 (VM), MH117009 (JSS),
exposed and non-exposed women could help establish temporal re­ AG062334 (VM), AG078248 (VM) and MH128244 (VM, JSS).
lationships between hormonal changes, trauma history, and symptom
onset. Ecological momentary assessment (EMA) could capture real-time
symptom fluctuations in mood and their relationship to hormonal
changes and menopause-related symptoms. Network analysis

9
A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

References [30] Gordon JL, Girdler SS, Meltzer-Brody SE, Stika CS, Thurston RC, Clark CT, et al.
Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in
perimenopausal depression: a novel heuristic model. Am J Psychiatry 2015;172
[1] Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ.
(3):227–36.
National estimates of exposure to traumatic events and PTSD prevalence using
[31] Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, et al.
DSM-IV and DSM-5 criteria. J Trauma Stress 2013;26(5):537–47.
Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal
[2] McKay MT, Cannon M, Chambers D, Conroy RM, Coughlan H, Dodd P, et al.
Depression: A Randomized Clinical Trial. JAMA Psychiatry 2015;72(7):714–26.
Childhood trauma and adult mental disorder: A systematic review and meta-
[32] Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary
analysis of longitudinal cohort studies. Acta Psychiatr Scand 2021;143(3):
of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished
189–205.
agenda of staging reproductive aging. J Clin Endocrinol Metab 2012;97(4):
[3] Hendrickson CM, Neylan TC, Na B, Regan M, Zhang Q, Cohen BE. Lifetime
1159–68.
trauma exposure and prospective cardiovascular events and all-cause mortality:
[33] Jaff NG, Snyman T, Norris SA, Crowther NJ. Staging reproductive aging using
findings from the Heart and Soul Study. Psychosom Med 2013;75(9):849–55.
Stages of Reproductive Aging Workshop + 10 in black urban African women in
[4] Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Medical comorbidity of full
the Study of Women Entering and in Endocrine Transition. Menopause 2014;21
and partial posttraumatic stress disorder in US adults: results from Wave 2 of the
(11):1225–33.
National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom
[34] Nelson HD. Menopause. Lancet 2008;371(9614):760–70.
Med 2011;73(8):697–707.
[35] Maki PM, Thurston RC. Menopause and Brain Health: Hormonal Changes Are
[5] Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic
Only Part of the Story. Front Neurol 2020;11:562275.
factor in coronary heart disease: a meta-analysis of 6362 events among 146 538
[36] Smoller JW, Pollack MH, Wassertheil-Smoller S, Jackson RD, Oberman A,
participants in 54 observational studies. Eur Heart J 2006;27(23):2763–74.
Wong ND, et al. Panic attacks and risk of incident cardiovascular events among
[6] Xia W, Jiang H, Di H, Feng J, Meng X, Xu M, et al. Association between self-
postmenopausal women in the Women’s Health Initiative Observational Study.
reported depression and risk of all-cause mortality and cause-specific mortality.
Arch Gen Psychiatry 2007;64(10):1153–60.
J Affect Disord 2022;299:353–8.
[37] Wassertheil-Smoller S, Shumaker S, Ockene J, Talavera GA, Greenland P,
[7] Hovens JG, Giltay EJ, Spinhoven P, van Hemert AM, Penninx BW. Impact of
Cochrane B, et al. Depression and cardiovascular sequelae in postmenopausal
childhood life events and childhood trauma on the onset and recurrence of
women. The Women’s Health Initiative (WHI). Arch Intern Med 2004;164(3):
depressive and anxiety disorders. J Clin Psychiatry 2015;76(7):931–8.
289–98.
[8] Petereit-Haack G, Bolm-Audorff U, Romero Starke K, Seidler A. Occupational risk
[38] Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for
for post-traumatic stress disorder and trauma-related depression: a systematic
systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med
review with meta-analysis. Int J Environ Res Public Health 2020;17(24).
2009;151(4):264–9. W64.
[9] Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress
[39] Shea AK, Frey BN, Gervais N, Lopez A, Minuzzi L. Depression in midlife women
disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52(12):
attending a menopause clinic is associated with a history of childhood
1048–60.
maltreatment. Climacteric 2022;25(2):203–7.
[10] Dell’Osso L, Carmassi C, Massimetti G, Stratta P, Riccardi I, Capanna C, et al. Age,
[40] Metcalf CA, Johnson RL, Duffy KA, Freeman EW, Sammel MD, Epperson CN.
gender and epicenter proximity effects on post-traumatic stress symptoms in
Depressed, stressed, and inflamed: C-reactive protein linked with depression
L′Aquila 2009 earthquake survivors. J Affect Disord 2013;146(2):174–80.
symptoms in midlife women with both childhood and current life stress. Stress
[11] Kline A, Ciccone DS, Weiner M, Interian A, St. Hill L, Falca-Dodson M, et al.
Health 2023.
Gender differences in the risk and protective factors associated with PTSD: a
[41] Epperson CN, Sammel MD, Bale TL, Kim DR, Conlin S, Scalice S, et al. Adverse
prospective study of National Guard troops deployed to Iraq. Psychiatry 2013;76
Childhood Experiences and Risk for First-Episode Major Depression During the
(3):256–72.
Menopause Transition. J Clin Psychiatry 2017;78(3):e298–307.
[12] Steven BK, Williams G, Najman J, Alati R. Exploring the female specific risk to
[42] Moraes SD, da Fonseca AM, Soares JM, Jr, Bagnoli VR, Souza MA, Arie WM, et al.
partial and full PTSD following physical assault. J Trauma Stress 2013;26(1):86.
Construction and validation of an instrument that breaks the silence: the impact
[13] Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime
of domestic and/or sexual violence on women’s health, as shown during
prevalence and age-of-onset distributions of DSM-IV disorders in the national
climacterium. Menopause 2012;19(1):16–22.
comorbidity survey replication. Arch Gen Psychiatry 2005;62(6):593–602.
[43] Gibson CJ, Maguen S, Xia F, Barnes DE, Peltz CB, Yaffe K. Military Sexual Trauma
[14] Olff M, de Vries GJ, Guzelcan Y, Assies J, Gersons BP. Changes in cortisol and
in Older Women Veterans: Prevalence and Comorbidities. J Gen Intern Med 2020;
DHEA plasma levels after psychotherapy for PTSD. Psychoneuroendocrinology
35(1):207–13.
2007;32(6):619–26.
[44] Travis KJ, Huang AJ, Maguen S, Inslicht S, Byers AL, Seal KH, et al. Military
[15] Breslau N, Chilcoat HD, Kessler RC, Peterson EL, Lucia VC. Vulnerability to
Sexual Trauma and Menopause Symptoms Among Midlife Women Veterans.
assaultive violence: further specification of the sex difference in post-traumatic
J Gen Intern Med 2024;39(3):411–7.
stress disorder. Psychol Med 1999;29(4):813–21.
[45] Michopoulos V, Huibregtse ME, Chahine EB, Smith AK, Fonkoue IT, Maples-
[16] Tolin DF, Foa EB. Sex differences in trauma and posttraumatic stress disorder: a
Keller J, et al. Association between perimenopausal age and greater posttraumatic
quantitative review of 25 years of research. Psychol Bull 2006;132(6):959.
stress disorder and depression symptoms in trauma-exposed women. Menopause
[17] Deecher D, Andree TH, Sloan D, Schechter LE. From menarche to menopause:
2023;30(10):1038–44.
exploring the underlying biology of depression in women experiencing hormonal
[46] Bromberger JT, Chang Y, Colvin AB, Kravitz HM, Matthews KA. Does childhood
changes. Psychoneuroendocrinology 2008;33(1):3–17.
maltreatment or current stress contribute to increased risk for major depression
[18] Altemus M. Neuroendocrine Networks and Functionality. Med Clin North Am
during the menopause transition? Psychol Med 2022;52(13):2570–7.
2019;103(4):601–12.
[47] O’Donnell ML, Creamer M, Pattison P. Posttraumatic stress disorder and
[19] Glover EM, Jovanovic T, Mercer KB, Kerley K, Bradley B, Ressler KJ, et al.
depression following trauma: understanding comorbidity. Am J Psychiatry 2004;
Estrogen levels are associated with extinction deficits in women with
161(8):1390–6.
posttraumatic stress disorder. Biol Psychiatry 2012;72(1):19–24.
[48] Mendoza-Huertas L, Mendoza N, Godoy-Izquierdo D. Impact of violence against
[20] Graham BM, Milad MR. Blockade of estrogen by hormonal contraceptives impairs
women on quality of life and menopause-related disorders. Maturitas 2024;180:
fear extinction in female rats and women. Biol Psychiatry 2013;73(4):371–8.
107899.
[21] Wegerer M, Kerschbaum H, Blechert J, Wilhelm FH. Low levels of estradiol are
[49] Nishimi K, Thurston RC, Chibnik LB, Roberts AL, Sumner JA, Lawn RB, et al.
associated with elevated conditioned responding during fear extinction and with
Posttraumatic stress disorder symptoms and timing of menopause and
intrusive memories in daily life. Neurobiol Learn Mem 2014;116:145–54.
gynecological surgery in the Nurses’ Health Study II. J Psychosom Res 2022;159:
[22] Ravi M, Stevens JS, Michopoulos V. Neuroendocrine pathways underlying risk
110947.
and resilience to PTSD in women. Front Neuroendocr 2019;55:100790.
[50] Kling JM, Saadedine M, Faubion SS, Shufelt CL, Mara KC, Enders FT, et al.
[23] Schiller CE, Meltzer-Brody S, Rubinow DR. The role of reproductive hormones in
Associations between childhood adversity and age at natural menopause.
postpartum depression. CNS Spectr 2015;20(1):48–59.
Menopause 2023.
[24] Yang R, Zhang B, Chen T, Zhang S, Chen L. Postpartum estrogen withdrawal
[51] Gibson CJ, Huang AJ, McCaw B, Subak LL, Thom DH, Van Den Eeden SK.
impairs GABAergic inhibition and LTD induction in basolateral amygdala
Associations of Intimate Partner Violence, Sexual Assault, and Posttraumatic
complex via down-regulation of GPR30. Eur Neuropsychopharmacol 2017;27(8):
Stress Disorder With Menopause Symptoms Among Midlife and Older Women.
759–72.
JAMA Intern Med 2019;179(1):80–7.
[25] Gupta RR, Sen S, Diepenhorst LL, Rudick CN, Maren S. Estrogen modulates
[52] Kapoor E, Okuno M, Miller VM, Rocca LG, Rocca WA, Kling JM, et al. Association
sexually dimorphic contextual fear conditioning and hippocampal long-term
of adverse childhood experiences with menopausal symptoms: Results from the
potentiation (LTP) in rats(1). Brain Res 2001;888(2):356–65.
Data Registry on Experiences of Aging, Menopause and Sexuality (DREAMS).
[26] Chen S, Gao L, Li X, Ye Y. Allopregnanolone in mood disorders: Mechanism and
Maturitas 2021;143:209–15.
therapeutic development. Pharm Res 2021;169:105682.
[53] Saadedine M, Faubion S, Kingsberg S, Enders F, Kuhle C, Kling JM, et al. Adverse
[27] Meltzer-Brody S, Howard LM, Bergink V, Vigod S, Jones I, Munk-Olsen T, et al.
childhood experiences and sexual dysfunction in midlife women: Is there a link?
Postpartum psychiatric disorders. Nat Rev Dis Prim 2018;4:18022.
J Sex Med 2023;20(6):792–9.
[28] Rasmusson AM, Pinna G, Paliwal P, Weisman D, Gottschalk C, Charney D, et al.
[54] Thurston RC, Bromberger J, Chang Y, Goldbacher E, Brown C, Cyranowski JM,
Decreased cerebrospinal fluid allopregnanolone levels in women with
et al. Childhood abuse or neglect is associated with increased vasomotor symptom
posttraumatic stress disorder. Biol Psychiatry 2006;60(7):704–13.
reporting among midlife women. Menopause 2008;15(1):16–22.
[29] Joffe H, de Wit A, Coborn J, Crawford S, Freeman M, Wiley A, et al. Impact of
[55] Carson MY, Thurston RC. Childhood abuse and vasomotor symptoms among
Estradiol Variability and Progesterone on Mood in Perimenopausal Women With
midlife women. Menopause 2019;26(10):1093–9.
Depressive Symptoms. J Clin Endocrinol Metab 2020;105(3):e642–50.

10
A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

[56] Goldstein LA, Jakubowski KP, Huang AJ, Seal KH, Maguen S, Inslicht SS, et al. [83] Haiman CA, Stram DO, Wilkens LR, Pike MC, Kolonel LN, Henderson BE, et al.
Lifetime history of interpersonal partner violence is associated with insomnia Ethnic and racial differences in the smoking-related risk of lung cancer. N Engl J
among midlife women veterans. Menopause 2023;30(4):370–5. Med 2006;354(4):333–42.
[57] Metcalf CA, Johnson RL, Novick AM, Freeman EW, Sammel MD, Anthony LG, [84] Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA, Powell L, et al.
et al. Adverse childhood experiences interact with inflammation and menopause Longitudinal analysis of the association between vasomotor symptoms and race/
transition stage to predict verbal memory in women. Brain Behav Immun Health ethnicity across the menopausal transition: study of women’s health across the
2022;20:100411. nation. Am J Public Health 2006;96(7):1226–35.
[58] Shanmugan S, Loughead J, Cao W, Sammel MD, Satterthwaite TD, Ruparel K, [85] Freeman EW, Sammel MD, Grisso JA, Battistini M, Garcia-Espagna B, Hollander L.
et al. Impact of Tryptophan Depletion on Executive System Function during Hot flashes in the late reproductive years: risk factors for Africa American and
Menopause is Moderated by Childhood Adversity. Neuropsychopharmacology Caucasian women. J Women’s Health Gend Based Med 2001;10(1):67–76.
2017;42(12):2398–406. [86] Grisso JA, Freeman EW, Maurin E, Garcia-Espana B, Berlin JA. Racial differences
[59] Shanmugan S, Satterthwaite TD, Sammel MD, Cao W, Ruparel K, Gur RC, et al. in menopause information and the experience of hot flashes. J Gen Intern Med
Impact of early life adversity and tryptophan depletion on functional connectivity 1999;14(2):98–103.
in menopausal women: A double-blind, placebo-controlled crossover study. [87] Zeidan MA, Igoe SA, Linnman C, Vitalo A, Levine JB, Klibanski A, et al. Estradiol
Psychoneuroendocrinology 2017;84:197–205. modulates medial prefrontal cortex and amygdala activity during fear extinction
[60] Shanmugan S, Cao W, Satterthwaite TD, Sammel MD, Ashourvan A, Bassett DS, in women and female rats. Biol Psychiatry 2011;70(10):920–7.
et al. Impact of childhood adversity on network reconfiguration dynamics during [88] Chang YJ, Yang CH, Liang YC, Yeh CM, Huang CC, Hsu KS. Estrogen modulates
working memory in hypogonadal women. Psychoneuroendocrinology 2020;119: sexually dimorphic contextual fear extinction in rats through estrogen receptor
104710. beta. Hippocampus 2009;19(11):1142–50.
[61] Cohen BE, Maguen S, Bertenthal D, Shi Y, Jacoby V, Seal KH. Reproductive and [89] Jacobs EG, Holsen LM, Lancaster K, Makris N, Whitfield-Gabrieli S, Remington A,
other health outcomes in Iraq and Afghanistan women veterans using VA health et al. 17beta-estradiol differentially regulates stress circuitry activity in healthy
care: association with mental health diagnoses. Women’s Health Issues 2012;22 and depressed women. Neuropsychopharmacology 2015;40(3):566–76.
(5):e461–71. [90] Crimins JL, Wang AC, Yuk F, Puri R, Janssen WGM, Hara Y, et al. Diverse
[62] Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, et al. Synaptic Distributions of G Protein-coupled Estrogen Receptor 1 in Monkey
Depressive symptoms during the menopausal transition: the Study of Women’s Prefrontal Cortex with Aging and Menopause. Cereb Cortex 2017;27(3):2022–33.
Health Across the Nation (SWAN). J Affect Disord 2007;103(1-3):267–72. [91] Hara Y, Punsoni M, Yuk F, Park CS, Janssen WG, Rapp PR, et al. Synaptic
[63] Mulhall S, Andel R, Anstey KJ. Variation in symptoms of depression and anxiety distributions of GluA2 and PKMzeta in the monkey dentate gyrus and their
in midlife women by menopausal status. Maturitas 2018;108:7–12. relationships with aging and memory. J Neurosci 2012;32(21):7336–44.
[64] Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of [92] Hara Y, Yuk F, Puri R, Janssen WG, Rapp PR, Morrison JH. Estrogen Restores
depression during the menopausal transition: the Harvard study of moods and Multisynaptic Boutons in the Dorsolateral Prefrontal Cortex while Promoting
cycles. Arch Gen Psychiatry 2006;63(4):385–90. Working Memory in Aged Rhesus Monkeys. J Neurosci 2016;36(3):901–10.
[65] Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and [93] Machado CJ, Bachevalier J. The effects of selective amygdala, orbital frontal
menopausal status with depressed mood in women with no history of depression. cortex or hippocampal formation lesions on reward assessment in nonhuman
Arch Gen Psychiatry 2006;63(4):375–82. primates. Eur J Neurosci 2007;25(9):2885–904.
[66] Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Matthews KA. Hot [94] Haley GE, Eghlidi DH, Kohama SG, Urbanski HF, Raber J. Association of
flashes and subclinical cardiovascular disease: findings from the Study of microtubule associated protein-2, synaptophysin, and apolipoprotein E mRNA
Women’s Health Across the Nation Heart Study. Circulation 2008;118(12): and protein levels with cognition and anxiety levels in aged female rhesus
1234–40. macaques. Behav brain Res 2012;232(1):1–6.
[67] Crandall CJ, Aragaki A, Cauley JA, Manson JE, LeBlanc E, Wallace R, et al. [95] McCarthy M, Raval AP. The peri-menopause in a woman’s life: a systemic
Associations of menopausal vasomotor symptoms with fracture incidence. J Clin inflammatory phase that enables later neurodegenerative disease.
Endocrinol Metab 2015;100(2):524–34. J Neuroinflamm 2020;17(1):317.
[68] Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in [96] Alexandra Kredlow M, Fenster RJ, Laurent ES, Ressler KJ, Phelps EA. Prefrontal
Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. cortex, amygdala, and threat processing: implications for PTSD.
Neuropsychopharmacology 2017;42(1):254–70. Neuropsychopharmacology 2022;47(1):247–59.
[69] Michopoulos V, Norrholm SD, Jovanovic T. Diagnostic Biomarkers for [97] Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological
Posttraumatic Stress Disorder: Promising Horizons from Translational impact of psychological trauma. Dialog- Clin Neurosci 2011;13(3):263–78.
Neuroscience Research. Biol Psychiatry 2015;78(5):344–53. [98] Bendis PC, Zimmerman S, Onisiforou A, Zanos P, Georgiou P. The impact of
[70] Dai R, Phillips RA, Zhang Y, Khan D, Crasta O, Ahmed SA. Suppression of LPS- estradiol on serotonin, glutamate, and dopamine systems. Front Neurosci 2024;
induced Interferon-gamma and nitric oxide in splenic lymphocytes by select 18:1348551.
estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood [99] Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape
2008;112(12):4591–7. the adult female brain during hormonal transition periods. Front Neurosci 2015;
[71] Lai YJ, Yu D, Zhang JH, Chen GJ. Cooperation of genomic and rapid nongenomic 9:37.
actions of estrogens in synaptic plasticity. Mol Neurobiol 2017;54(6):4113–26. [100] Bromis K, Calem M, Reinders A, Williams SCR, Kempton MJ. Meta-Analysis of 89
[72] Boudot A, Kerdivel G, Habauzit D, Eeckhoute J, Le Dily F, Flouriot G, et al. Structural MRI Studies in Posttraumatic Stress Disorder and Comparison With
Differential estrogen-regulation of CXCL12 chemokine receptors, CXCR4 and Major Depressive Disorder. Am J Psychiatry 2018;175(10):989–98.
CXCR7, contributes to the growth effect of estrogens in breast cancer cells. PLoS [101] Price JL, Drevets WC. Neurocircuitry of mood disorders.
One 2011;6(6):e20898. Neuropsychopharmacology 2010;35(1):192–216.
[73] Mak P, Li J, Samanta S, Mercurio AM. ERbeta regulation of NF-kB activation in [102] Harnett NG, Stevens JS, van, Rooij SJH, Ely TD, Michopoulos V, Hudak L, et al.
prostate cancer is mediated by HIF-1. Oncotarget 2015;6(37):40247–54. Multimodal structural neuroimaging markers of risk and recovery from
[74] Shivers KY, Amador N, Abrams L, Hunter D, Jenab S, Quinones-Jenab V. Estrogen posttrauma anhedonia: A prospective investigation. Depress Anxiety 2021;38(1):
alters baseline and inflammatory-induced cytokine levels independent from 79–88.
hypothalamic-pituitary-adrenal axis activity. Cytokine 2015;72(2):121–9. [103] Fani N, King TZ, Shin J, Srivastava A, Brewster RC, Jovanovic T, et al. Structural
[75] Yasui T, Maegawa M, Tomita J, Miyatani Y, Yamada M, Uemura H, et al. and Functional Connectivity in Posttraumatic Stress Disorder: Associations with
Association of serum cytokine concentrations with psychological symptoms in Fkbp5. Depress Anxiety 2016;33(4):300–7.
midlife women. J Reprod Immunol 2007;75(1):56–62. [104] Meisner OC, Nair A, Chang SWC. Amygdala connectivity and implications for
[76] Ye C, Wang M, Min J, Tay RY, Lukas H, Sempionatto JR, et al. A wearable social cognition and disorders. Handb Clin Neurol 2022;187:381–403.
aptamer nanobiosensor for non-invasive female hormone monitoring. Nat [105] Sigurdsson T, Duvarci S. Hippocampal-Prefrontal Interactions in Cognition,
Nanotechnol 2023. Behavior and Psychiatric Disease. Front Syst Neurosci 2015;9:190.
[77] Schwartz AC, Bradley RL, Sexton M, Sherry A, Ressler KJ. Posttraumatic stress [106] Toufexis D, Rivarola MA, Lara H, Viau V. Stress and the reproductive axis.
disorder among African Americans in an inner city mental health clinic. Psychiatr J Neuroendocr 2014;26(9):573–86.
Serv 2005;56(2):212–5. [107] Heck AL, Handa RJ. Sex differences in the hypothalamic-pituitary-adrenal axis’
[78] Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, et al. response to stress: an important role for gonadal hormones.
Association of FKBP5 polymorphisms and childhood abuse with risk of Neuropsychopharmacology 2019;44(1):45–58.
posttraumatic stress disorder symptoms in adults. Jama 2008;299(11):1291–305. [108] Hantsoo L, Jagodnik KM, Novick AM, Baweja R, di Scalea TL, Ozerdem A, et al.
[79] Gillespie CF, Bradley B, Mercer K, Smith AK, Conneely K, Gapen M, et al. Trauma The role of the hypothalamic-pituitary-adrenal axis in depression across the
exposure and stress-related disorders in inner city primary care patients. Gen female reproductive lifecycle: current knowledge and future directions. Front
Hosp Psychiatry 2009;31(6):505–14. Endocrinol (Lausanne) 2023;14:1295261.
[80] Davis RG, Ressler KJ, Schwartz AC, Stephens KJ, Bradley RG. Treatment barriers [109] Schumacher S, Niemeyer H, Engel S, Cwik JC, Laufer S, Klusmann H, et al. HPA
for low-income, urban African Americans with undiagnosed posttraumatic stress axis regulation in posttraumatic stress disorder: A meta-analysis focusing on
disorder. J Trauma Stress 2008;21(2):218–22. potential moderators. Neurosci Biobehav Rev 2019;100:35–57.
[81] Wingo AP, Fani N, Bradley B, Ressler KJ. Psychological resilience and [110] Ron Mizrachi B, Tendler A, Karin O, Milo T, Haran D, Mayo A, et al. Major
neurocognitive performance in a traumatized community sample. Depress depressive disorder and bistability in an HPA-CNS toggle switch. PLoS Comput
Anxiety 2010;27(8):768–74. Biol 2023;19(12):e1011645.
[82] Setiawan VW, Haiman CA, Stanczyk FZ, Le Marchand L, Henderson BE. Racial/ [111] Felger JC, Treadway MT. Inflammation Effects on Motivation and Motor Activity:
ethnic differences in postmenopausal endogenous hormones: the multiethnic Role of Dopamine. Neuropsychopharmacology 2017;42(1):216–41.
cohort study. Cancer Epidemiol Biomark Prev 2006;15(10):1849–55.

11
A.R. Arnold et al. Journal of Mood and Anxiety Disorders 8 (2024) 100082

[112] Seligowski AV, Harnett NG, Merker JB, Ressler KJ. Nervous and Endocrine [117] Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS.
System Dysfunction in Posttraumatic Stress Disorder: An Overview and Estrogen replacement and response to fluoxetine in a multicenter geriatric
Consideration of Sex as a Biological Variable. Biol Psychiatry Cogn Neurosci depression trial. Fluoxetine Collaborative Study Group. Am J Geriatr Psychiatry
Neuroimaging 2020;5(4):381–91. 1997;5(2):97–106.
[113] Holsen LM, Lee JH, Spaeth SB, Ogden LA, Klibanski A, Whitfield-Gabrieli S, et al. [118] Schneider LS, Small GW, Clary CM. Estrogen replacement therapy and
Brain hypoactivation, autonomic nervous system dysregulation, and gonadal antidepressant response to sertraline in older depressed women. Am J Geriatr
hormones in depression: a preliminary study. Neurosci Lett 2012;514(1):57–61. Psychiatry 2001;9(4):393–9.
[114] Schrader C, Ross A. A review of PTSD and current treatment strategies. Mo Med [119] The White House. FACT SHEET: President Biden Issues Executive Order and
2021;118(6):546–51. Announces New Actions to Advance Women’s Health Research and Innovation
[115] Glover EM, Jovanovic T, Norrholm SD. Estrogen and extinction of fear memories: 2024 [updated March 18, 2024. Available from: 〈https://www.whitehouse.go
implications for posttraumatic stress disorder treatment. Biol Psychiatry 2015;78 v/briefing-room/statements-releases/2024/03/18/fact-sheet-president-bide
(3):178–85. n-issues-executive-order-and-announces-new-actions-to-advance-womens-healt
[116] Zanardi R, Rossini D, Magri L, Malaguti A, Colombo C, Smeraldi E. Response to h-research-and-innovation/〉.
SSRIs and role of the hormonal therapy in post-menopausal depression. Eur
Neuropsychopharmacol 2007;17(6-7):400–5.

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