Menopause: The Journal of The North American Menopause SocietyVol. 19, No. 9, pp. 949/951DOI: 10.1097/gme.0b013e3182651d8d
* 2012 by The North American Menopause Society
Depression and heavy bleeding during the menopausal transition:adjusting our gaze
Researchpublishedduringthepastthreedecadeshas every1to2hours.Abnormalbleedingwasdefinedasmenstrual
explored the relationship between mood and menstrual
flow lasting more than 10 days; bleeding or spotting between
bleeding. Investigators have established the relation-
periods in more than 50% of the cycle; or menstrual flow usu-
ship between cyclical mood symptoms and the menstrual cycle,
ally lasting less than 2 days or more than 8 days and PMS
characterizing perimenstrual symptoms, premenstrual syndrome
(including two mood symptoms [such as changes in mood or
(PMS), and premenstrual dysphoric disorder.1<3 Although each
being anxious, jittery, or nervous] and one of five physical
of these has been defined with respect to clusters of multiple
symptoms [abdominal pain or cramps, breast pain, tenderness
symptoms (such as mood and fluid retention), severity, and
or swelling, weight gain or feeling bloated, back, joint, or
interference with daily living, evidence supporting their rela-
muscle pain, or severe headaches]) on the week before the onset
tionship with endocrine fluctuation has been mixed. Data sup-
of menses that interfered with work and/or home activities and
port associations between levels of estradiol and progesterone
ceased within a few days of menses onset. Findings from the
and perimenstrual symptoms4,5 and fluctuations in these same
SWAN MHS supporting a link between depression and heavy
bleeding invite attempts to explain this relationship.
Additional evidence supports the persistence of these cycli-
It is well established that rising levels of estradiol, in re-
cal symptoms in women after the age of 40 years6 and as women
sponse to FSH stimulation, induce the development of the
approach menopause.7 Hypotheses relating entrainment of
endometrial lining of the uterus. Progesterone levels increase
mood symptoms to circamensual (menstrual cycle) rhythm have
after ovulation and transform the endometrium in preparation
been augmented by evidence supporting the relationships of
for the implantation of a fertilized embryo. In the absence
the same symptoms and symptom clusters to the context of
of ovulation, progesterone levels remain low, and the endo-
women’s lives, including their socialization about menstruation,
metrium does not continue to develop and is shed with men-
relationship and material stressors, and perceived stress.5,8<10
ses. Indeed, progesterone withdrawal is used therapeutically
As the oldest of the baby boomers began to enter the
menopausal transition, the gaze of many researchers refocused
One of the perturbations that can suppress menses or ovula-
on this birth cohort of women. Efforts to understand an in-
tion is exposure to extreme stress. An early study of depression
creasingly irregular menstrual rhythm and its relationship to
and menorrhagia among adult women not yet experiencing the
depressed mood once again examined levels of and variability
menopausal transition (aged up to 42 y) linked depression to
in hypothalamic-pituitary-ovarian (HPO) axis hormones.11<13
menorrhagia.15 Sixty percent of women experiencing menor-
To date, there have been studies on the relationship of men-
rhagia experienced a severely stressful event within a year
opausal transition stages, estrogen, testosterone, and follicle-
versus 40% of those without menorrhagia. Moreover, 50% of
stimulating hormone (FSH) to depressed mood symptoms or
those with menorrhagia had experienced a severe loss versus
major depressive disorder. Evidence indicates that depression
only 17% of those without menorrhagia. In addition, 78% of the
during the menopausal transition was related to the level and
women with menorrhagia experienced menorrhagia after the
variability of estradiol12 and that the severity of depressed
loss experience. The more recent Harvard Study of Women’s
mood symptoms is greatest during the late menopausal tran-
Moods and Cycles revealed that a lifetime history of phy-
sition stage, when cycles vary by more than 60 days from one
sical and sexual abuse was associated with elevated FSH
cycle to the next.13 Moreover, depressed mood symptoms
levels and low estradiol levels, suggesting that exposure to
and major depressive disorder during the menopausal tran-
violence, especially before adulthood, may lead to neuro-
sition were related to a history of depression earlier in life and
a history of PMS and postpartum depression.7,13
The impact of stress or shock on the endocrine system was
Up until Bromberger et al14 published results from the
described long ago by traditional Chinese medicine (TCM)
Study of Women’s Health Across the Nation Mental Health
scholars. Classic theory relates a feedback loop between the
Study (SWAN MHS), there has been little, if any, attention to
Heart* Qi (including emotions, much as western culture also
the association between depression and menstrual characteris-tics, including heavy bleeding in women during perimenopause. Bromberger et al defined heavy bleeding as passing clots larger
*A capitalized organ name indicates the TCM physiological and/or anatomical
than a dime; flooding or gushing; or heavy or very heavy flow
concept of an organ. This differs from the biomedical physiological function of
on the heaviest days of menstrual flow, changing protection
Copyright 2012 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
associates emotions and feelings with the heart) and the
importance of the HPO-HPA axes in modulating both bleeding
Kidney Qi (often related to biomedical functions of generat-
ing estrogen and progesterone) via the Bao Mai (uterus ves-
Yet another explanation for the relationship between de-
sel) and the Bao Luo (uterus channel).17 Heart Qi is supposed
pression and heavy bleeding involves the role of depression
to descend, thus promoting timely ovulation and menses.
in shaping one’s outlook. Heavy vaginal bleeding is generally
Shock or stress can disrupt this physiological function, causing
regarded as a worrisome sign and is included as one of the
Qi and Blood stagnation. Stagnation can lead to generation of
warning signs for cancer. To a woman who is depressed or
Heat, which may result in depression, anxiety, and/or heavy
troubled by depression symptoms, heavy bleeding is both a
bleeding (depending on the individual). Furthermore, this
sign and a symptom that requires an appraisal of seriousness
feedback loop between the Heart and the Kidneys involves
and frequent attention to menstrual hygiene. Together, these
several additional meridians (where Qi primarily flows), spe-
contribute to a negative view of menses as a bodily function
cifically the Conception, Governing, and Penetrating meridians.
and may be perceived as interfering with activities of daily
The physiological function of these meridians and organs
life. Heavy bleeding also is likely to rise quickly to con-
closely parallels HPO axis physiology and anatomy. The path-
scious awareness and to stimulate stress arousal and symptom
ology of HPO can therefore be understood in both biomedical
In the SWAN MHS cohort, other risk factors for heavy
The plausibility of the relationship between depression
bleeding included being in the early menopausal transition
and menstrual bleeding is supported by the capacity of the
stage, having had more pregnancies, a higher body mass index
hypothalamic-pituitary-adrenal (HPA) axis to modulate HPO
(BMI), and a history of fibroids. BMI has been implicated in
axis functioning in ways that regulate reproductive func-
the extraovarian production of estrogen and in perturbations
tion, including suppressing ovulation and menstruation under
of the HPO axis function.24 Still another pathway may involve
stressful conditions.18 Thus, explanations for the association
the effects of major depression on behavior, such as eating
of depression with heavy bleeding could include stress-
behavior, in turn increasing BMI, which is related to heavy
induced effects on the HPA axis with perturbation of HPO
axis functioning, resulting in both depressed mood and heavy
Yet another explanation for the association of depressed
mood with heavy bleeding can be found in the emergent view
A second contributing factor could be the influence of the
of depression as an illness with a myriad of correlates and
menopausal transition on estradiol levels. In response to in-
consequences, including inflammatory, hemostatic, and lipid
creasing FSH levels, some women experience episodes of
changes.25 Indeed, depression may also be regarded as a sig-
hyperestrogenism, as described by Santoro et al,19 and these
nal of physiological dysregulation, much as one regards heavy
hyperestrogenemic episodes are associated with heavy bleed-
vaginal bleeding. It is possible that both are indicators of
ing. Variable levels of estradiol during these episodes, many
underlying perturbations that are unrelated to one another,
of which may be anovulatory, may also trigger depressed
except through their contribution to allostatic load.26
mood through effects on neurotransmitters such as serotonin
The complexities of the relationship between depression
and norepinephrine.20 Women who are vulnerable to endocrine
and heavy bleeding will be best addressed by conducting re-
changes earlier in life, such as those experiencing PMS or
search tracking women’s experiences during the reproduc-
postpartum depression, may also be troubled by heavy bleed-
tive life span and by incorporating a view spanning molecules
ing during perimenopause. Of interest is that when women
to the organism. Women who experience both depression
undergo hysterectomy, with or without oophorectomy, they are
and heaving bleeding during the menopausal transition will
less likely to experience depressed mood than women who
be served best by researchers redirecting our gaze from only
perimenopause to mood and bleeding patterns that women
Indeed, there may be multiple periods in the life span dur-
experience throughout their reproductive life. Moreover, re-
ing which hormonal dynamics increases vulnerability to both
focusing our view of depression as a discrete mental illness
depression and heavy bleeding. In addition to the postpartum
into an expression of loss of complexity in a highly ordered
period and the menstrual cycle, depressed mood becomes more
dynamic state, as informed by systems biology, will expand
prevalent among girls making the pubertal transition. Angold
our understanding of depression and its myriad correlates.
et al’s22 study of girls in Tanner stages II and III revealed
Such an integrative view prompts scientists to recognize that
that depression was explained by changing estrogen levels. Of
seemingly single phenotypic entities can have multiple etio-
added interest was that morning salivary cortisol levels were
logic and/or pathological processes.27 This integrative view is
20% higher in Tanner stage II+ girls versus boys. Tanner stages
emblematic in TCM. Any given symptom is seen only in
II and III are the periods in pubertal development when the
relationship to other symptoms. For this reason, women with
prevalence of depression increases markedly in young girls,
heavy menses may be diagnosed and treated differently ac-
but not in boys. In addition to changing estradiol levels during
cording to the cluster of symptoms and signs presented.28
the menopausal transition,23 cortisol levels rise during the late
Moreover, taking a broader view of the phenomena reminds
menopausal transition stage, tracking with the rise of estrogen
us that the defining feature of healthy functioning is the ca-
levels during the same stage.24 These relationships suggest the
pacity to respond to unpredictable stimuli29 and that disease
* 2012 The North American Menopause Society
Copyright 2012 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
is an expression of loss of complexity in a highly ordered
12. Freeman E, Sammel M, Lin H, Nelson D. Associations of hormones and
menopausal status with depressed mood in women with no history of
dynamic state.30 The symptom patterns discussed here are
depression. Arch Gen Psychiatry 2006;63:375-382.
thus likely to be local expressions of far-reaching global
13. Woods NF, Smith-DiJulio K, Percival DB, Tao EY, Mariella A, Mitchell
ES. Depressed mood during the menopausal transition and early post-menopause: observations from the Seattle Midlife Women’s Health Study. Menopause 2008;15:223-232.
Financial disclosure/conflicts of interest: None reported.
14. Bromberger JT, Schott LL, Matthews KA, et al. Association of past and
recent major depression and menstrual characteristics in midlife: Study ofWomen’s Health Across the Nation. Menopause 2012;19:959-966.
15. Harris T. Disorders of menstruation. In: Brown GW, Harris TO, eds. Life
Events and Illness. New York, NY: Guilford, 1989:261-294.
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Copyright 2012 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
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