Menopause: The Journal of The North American Menopause Society
Vol. 23, No. 12, pp. 1272-1274
DOI: 10.1097/GME.0000000000000791
ß 2016 by The North American Menopause Society
EDITORIAL
Menopause and depression: keep your eye on the long run
M
ost researchers and experienced clinicians would
agree, in this day and age, that the ‘‘jury is no
longer out’’ on the potential effects of reproduc-
tive hormones on mood and the extent to which hormone
fluctuations/changes may impact overall functioning through-
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out the female reproductive life cycle. Premenstrual Dys-
phoric Disorder, for example, has now been officially
recognized and incorporated as a new diagnostic category
for the DSM-5, representing an acknowledgment by experts
and peers of the severe functional impairment that some—but
not all—women experience during the luteal phase of their
cycles. There is also little dispute about the wide spectrum of
mood and behavioral changes that may occur during the
postpartum period—ranging from the commonly observed
dysphoria or ‘‘baby blues’’ to the occurrence of postpartum
depression or even the rare but severe postnatal psychosis.
On the contrary, after many decades of accumulated
research, some of the controversy surrounding the existence
of a ‘‘menopause-associated depression’’ still persists. As
previously discussed,1 part of the confusion could be attrib-
uted to misinformation and insufficient knowledge dissem-
ination on what is already known about the ‘‘window of
vulnerability’’ for depression in midlife years. Methodologic
limitations have also contributed contradictory findings,
including the heterogeneity of subpopulations studied, the
lack of standardized criteria to define menopause staging, or
appropriate diagnostic tools to characterize the nature and
severity of psychiatric symptoms. Moreover, the presence of
comorbid conditions such as anxiety and/or sleep problem has
not always been taken into consideration or even documented,
despite their impact on the well-being of midlife women.2-4
Fortunately, the last few decades have also produced well-
designed, well-executed population studies, shedding some
light on the risk for new and recurrent depression among
women approaching menopause and beyond.5-9 Prospective
cohort studies have unequivocally demonstrated an increased
risk for the development of depression during the menopausal
transition and helped us to disentangle some of its various
components (sociodemographic, clinical, hormonal). We
have learned, for example, that past history of depression
is one of the strongest predictors for the occurrence of a major
depressive episode during midlife years, and that greater
within-subject variations in gonadal steroids over time
(rather than absolute levels at one point in time) could be
associated with heightened risk for developing depression.
The nature and magnitude of the role played by vasomotor
1272 Menopause, Vol. 23, No. 12, 2016
Copyright @ 2016 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
symptoms and sleep problems in midlife depression continue
to intrigue clinicians and researchers, both from the etiologic
and therapeutic viewpoints. The multifaceted nature of
depression has encouraged collaborative, multidisciplinary
work and led to the development and testing of novel thera-
peutic interventions—ranging from hormonal interventions
to antidepressants, telephone-based cognitive-behavioral
therapies, yoga, exercise, acupuncture, just to name a few.
More recently, some investigators have refocused their
attention to patterns of depressive symptoms (or patterns of
symptom change) as well as to the course depression or
depressive symptoms taking place over time; such an
approach is likely to provide clinicians with relevant infor-
mation and ultimately influence treatment and prevention
strategies. SWAN (Study of Women’s Health Across the
Nation) investigators have recently published a study in which
the course of clinical depression was examined over a 13-year
follow-up period.10 They indicated that a substantial pro-
portion of women who presented with depression at some
point during the study actually progressed toward a persistent
or recurrent condition; this detrimental course was observed
even among those who had never experienced depression
before midlife, that is, new-onset cases of depression. More-
over, sleep problems and recent upsetting life events were
found to increase the risk for a more persistent/recurrent
outcome. If further confirmed or replicated, indicators like
those would certainly shape clinical assessment and manage-
ment of risk factors for depression in midlife women.
In this issue of Menopause, Hickey et al11 give their
contribution to this important discussion by taking a
‘‘long-run approach’’ and examining 15 years of prospective
data from a population-based cohort study—the Australian
Longitudinal Study on Women’s Health. The authors
explored different trajectories for depressive symptoms and
attempted to determine risk factors over time in four distinct
cohorts of Australian women born in the 1920s, 1940s to
1950s, 1970s, and 1980s to 1990s. Women were on average
between 45 and 50 years old at study entry and approximately
6,000 could be included in the analysis based on the com-
pletion of prospective surveys. Data collected over the course
of the follow-up were used to document surgical events such
as hysterectomy (with or without oophorectomy), use of oral
contraceptives and hormone therapies (HT), as well as
changes in menstrual patterns—all of that being used to define
the reproductive staging of each study participant at each
point in time (2001 STRAW criteria).
 EDITORIAL
Depressive symptoms were assessed through Center for
Epidemiologic Studies Depression Scale (CES-D) scores as a
continuous measure rather than the adopting predetermined
CES-D cutoff points to define clinical depression. The
approach taken by Hickey et al is certainly welcomed; it
underscores the high prevalence and potential functional
impairment associated with depressive symptoms in this
targeted population, even in the absence of a clinically
confirmed depressive disorder. By uncovering distinct pat-
terns or trajectories of depressive symptoms over time, the
authors contribute to the development of preventative strat-
egies and help influence clinical care.
Four distinct trajectories were recognized in this study:
although most women (almost 80%) exhibited a ‘‘stable low’’
trajectory over time (ie, the presence of minimal, nonsigni-
ficant depressive symptoms—mean CES-D score of 4.0),
others had their depressive symptoms either increase or
decrease over time (9.0% and 8.5%, respectively). Lastly, a
small percentage (2.5%) showed persistent, ‘‘stable high’’
CES-D scores (mean score of 18) for the duration of the
follow-up. What could be learned about the women who fell
into each of these trajectories?
First, a small percentage (approximately 10%-12%)
showed stable high or ‘‘increasing’’ CES-D scores over
time, a confirmation that most women will not experience
depressive symptoms during midlife years; second, the data
reinforced the notion that persistent depressive symptoms in
this population could be driven by longstanding, ‘‘contin-
uum of risk’’12 factors such as previous diagnosis or treat-
ment for depression or the presence of enduring, challenging
socioeconomic issues; third, stable high or increasing CES-
D scores were also linked to timing, context-related risk
factors, that is, risks factors associated with a window of
vulnerability during midlife years. For example, high/per-
sistent scores occurred among those who experienced a
lengthy perimenopause or those with a surgically induced
menopause. One could speculate that hormone variations
played an important role for the emergence and persistence
of depressive symptoms—either through wider fluctuations
in hormone production during perimenopausal years or due
to abrupt changes in hormone levels induced by a surgical
procedure. Fourth, initiation and/or discontinuation of HT
were associated with stable high or increasing depressive
symptoms. The study did not provide us with information on
preexisting symptoms that led to HT use in the first place, or
inform us of potential differences based on use/discontinu-
ation of various HT regimens, doses, and routes of admin-
istration; nonetheless, this finding reinforced the argument
made by some that a closer monitoring on mood and
behavior should take place when HT is being introduced
or stopped. Based on our clinical experience, this monitoring
is essential for women with a history of depression, even
more so when previous depressive episodes were somewhat
‘‘hormonally related’’ and included premenstrual and/or
postpartum exacerbations. Special attention should be paid
to midlife women who are stable while on antidepressants
Copyright @ 2016 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
and concurrent use of HT; in this context, the potential
consequences of changing or discontinuing HT and the
impact of these changes on sustained wellness should not
be underestimated.
Fifth, not surprisingly, some questions remained unan-
swered with regard to the nature and direction of the inter-
action between vasomotor symptoms and depressive
symptoms, although few would dispute the adverse impact
of severe vasomotor symptoms on perceived sleep quality or
daytime functioning.
Lastly, as already recognized by the investigators, approxi-
mately half of the 13,000þ women who were originally
enrolled in this Australian study could not be included in
the analysis as they had incomplete surveys over time. A
closer look into the characteristics of those who were
excluded, however, suggests that the percentages of stable
high or increasing CES-D scores could have been even
greater. Those excluded due to incomplete survey questions
actually exhibited a significant number of continuum of risk
factors, ranging from medical to psychosocial and psychiatric
(ie, previous history of depression).
In sum, there are lessons to be learned and further utilized
from this long-run approach. These results corroborate find-
ings from previous cohort studies that were shorter in duration
or had fewer participants; they dovetail nicely with some of
the theoretical concepts on precipitating and contributing
factors to midlife depression.
Most of all, they help build a more solid narrative, a
rationale to be used by clinicians and start an important
conversation on risk factors, prevention, and monitoring of
depressive symptoms before midlife years.
Financial disclosure/conflicts of interest: None reported.
Claudio N. Soares, MD, PhD, FRCPC, MBA
Department of Psychiatry
Queen’s University School of Medicine
Kingston, Ontario, Canada
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1274 Menopause, Vol. 23, No. 12, 2016 ß 2016 The North American Menopause Society

Copyright @ 2016 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.