It is a commonly accepted and popular myth that as woman
enters the menopausal years, it is “normal” to feel depressed. Serious depression, however, should never be
viewed as a “normal” event, and women who suffer from it at any time in life should
receive the same attention as for any other medical illness.
Depression affects up to 25% of women at some point in their
lives, a far higher proportion than is seen among men. Depression can be a
debilitating disease, limiting daily activity as much as severe arthritis or
heart disease. Large-scale research studies have shown that most problems with
depression begin when women are in their 20s or younger. It is actually unusual
for depression to appear for the first time after menopause, when all
menstruation has ceased. However, there is a transitional time in mid-life
known as perimenopause when women become somewhat more vulnerable to
depression. This is the time when menstrual periods gradually lighten and become
less frequent. The transition to complete menopause may last anywhere from a
few months to a few years.
Minor mood
problems, insomnia,
and hot
flashes are common during perimenopause. In some women, these symptoms progress
to a more severe mood disorder known as major depression. The risk for major depression is greatest in
women who have a history of depression in the past or who had depression after
childbirth (postpartum depression).
Women who have had problems with depressed mood around the time of their
menstrual periods (premenstrual dysphoric disorder) may also be at higher risk
for major depression in perimenopause.
And some women do become depressed for the first time in their lives
during perimenopause.
Why there is elevated
depression risk associated with Menopause?
Several theories have been proposed to explain the increase in
depression during perimenopause. A traditional psychological view is that the
“empty nest syndrome” or other aspects of middle age lead to feelings of loss
and sadness. More recently, scientists
have focused on
the biological effects
of hormonal fluctuations on
mood, since this
is a time
when the ovaries begin to make less estrogen. Estrogen
interacts with chemicals in the brain that can affect mood. In some women, the decrease in estrogen
during perimenopause may lead to depression. Hot flashes and insomnia during
this transition may also cause emotional distress.
The hypothesis that fluctuations in female reproductive
hormones could influence different neuro-chemical pathways linked to depression
is extensively supported by animal studies and existing clinical data.
Estradiol receptors have been found in different brain regions (such as the
medial amygdala, hippocampus, and limbic system) known to influence mood and
behavior. It is now well established that estrogens interact with membrane and
nuclear receptors; through nuclear receptors, estrogens bind to specific
response elements in DNA and regulate the expression of targeted genes. The
effects of estrogens on membrane receptors, on the other hand, may modulate the
synthesis, release and metabolism of monoamines. Estrogens may also up- or
down-regulate the excitability of neurons quite rapidly, probably acting
through G-protein dependent mechanisms. Estrogens exert an agonist effect on
serotonergic activity by increasing the number of serotonergic receptors and
the transport and uptake of the neurotransmitter; estrogens also increase
synthesis of serotonin, up-regulate 5-HT1 receptors, down- regulate 5-HT2
receptors, and decrease monoamine oxidase activity.
Estrogen availability may also influence the binding
affinity for 5-HT receptors, as shown in animal models and in neuro-imaging
clinical studies. In addition to its effects on 5-HT circuitry, estrogen also
appears to augment noradrenergic (NA) activity by increasing NA turnover and
decreasing NA reuptake, and decreasing the number and sensitivity of dopamine
D2 receptors. This complex modulatory effect of estrogen on brain functioning
reinforces the theory that wide sex hormone fluctuations could result in an
adverse impact on various systems.
The menopausal transition is frequently characterized by the
occurrence of vasomotor symptoms (e.g., hot flushes, night sweats), sleep
disturbances and changes in sexual function. It is still controversial whether
this transition is particularly associated with the occurrence of clinically
significant depressive symptoms or with a particular form of depression; a so-called
“menopause-specific” depression. This controversy is, in part, derived from
inconsistent findings in the literature; heterogeneous studies trying to
investigate this association have included women from different settings
(specialized menopause clinics, other clinical facilities, community-based
samples), which may make generalization of their findings difficult. In most of
these studies, depression was defined based on self-report measures that
indicate distress or depressive symptoms, but do not conclusively indicate a
clinical diagnosis of Major Depression. Contradictory findings also derived
from the fact that menopausal status was, in some of these studies, based on
somewhat simplistic criteria (e.g., only on age or menstrual regularity).
What is major
depression?
Major
depression is a kind of illness called a mood disorder that affects a
person’s ability to experience normal mood states. Mood disorders are
biological illnesses believed to be caused by changes in brain chemistry, and
the tendency to depression is sometimes inherited genetically. Physical or emotional stress can trigger the
biological changes that occur in depression, and the hormonal changes leading
up to menopause may also trigger such changes, especially in women who may be prone
to depression because of underlying brain chemistry or family history.
The symptoms of major depression include:
- Depressed mood most of the day, nearly every day for 2 weeks or longer and/or
- Loss of interest or pleasure in activities that the person usually enjoys.
Other symptoms can include:
- Fatigue or lack of energy
- Restlessness or feeling slowed down
- Feelings of guilt or worthlessness
- Difficulty concentrating
- Trouble sleeping or sleeping too much
- Recurrent thoughts of death or suicide.
Mood disorders like major depression are not the fault of the
person suffering from them or the result of a “weak” or unstable personality. Rather,
they are treatable medical illnesses
for which there are specific medications and psychotherapy approaches that help most
people.
How is depression
assessed in a woman nearing menopause?
A woman who
feels depressed and
thinks she also
may be entering menopause should
be evaluated by a gynecologist to determine whether her symptoms could be
related to the hormonal transition. She should also see a psychiatrist or other mental
health professional, especially if her depression is severe or if she has been
depressed in the past. As part of the evaluation, the doctor will:
- Take a careful history of current and past symptoms, both emotional and physical
- Perform a physical exam and do blood tests to evaluate the function of the woman’s ovaries (if she is still having some menstrual periods) and thyroid gland (which may cause depression when underactive)
- Ask about life stressors that may be affecting the woman.
Treatments
Treatment recommendations for major depression that occurs in
association with menopause depend on how severe the woman’s symptoms are and
whether she has had previous episodes of depression.
Whenever
symptoms are severe,
the experts recommend treatment with
antidepressant medication, generally
in combination with hormone
replacement therapy (usually estrogen plus progesterone, or occasionally
estrogen alone). The combination of an antidepressant and hormones is advised
whether or not the woman has had depression in the past.
If the woman’s
symptoms are relatively
mild and she has never
been depressed before,
experts do not
agree on a
single best strategy but suggest trying hormones or antidepressants, 1 at a
time. Hormone replacement therapy
by itself will usually relieve physical symptoms such as hot flashes and will
sometimes improve mood significantly. On the other hand, some women prefer to
avoid hormones, especially if they have few physical symptoms, and may do
better with an antidepressant.
In women who are clearly in menopause rather than transition,
the experts believe that antidepressant medication is more likely to relieve
depression than hormone replacement.
However, many women should consider hormone replacement for its other
health benefits.
In all of these situations, experts also recommend the use
of psychotherapy along with whatever medication is chosen. Just working with a psychotherapist, however,
is unlikely to help severe depression unless medication is used as well.
Antidepressant
medication
Many types of antidepressants are
available, with different chemical mechanisms
of action and
potential side effects.
For women with depression associated with menopause, the experts prefer
a type of antidepressant that affects a brain chemical called serotonin. These medications are called selective
serotonin reuptake inhibitors (SSRIs). Among these, the expert panel
prefers fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) as first
choices, with citalopram (Celexa) an alternative.
SSRIs can have
the following side
effects: nervousness, insomnia,
restlessness, nausea, diarrhea,
and sexual problems. Side effects differ from 1 person
to another. Also, what may be a side effect for 1 person (e.g., drowsiness) may
benefit someone else (e.g., a woman with insomnia). Fortunately, most women with depression do
not have many problems with side effects from the SSRIs. To try to reduce the
risk of side effects, many doctors start with a low dose and increase it slowly. If you are having problems with side effects,
tell your doctor right away. If side effects
persist, your doctor may lower the dose or suggest trying a different SSRI.
Hormonal treatments
While antidepressants are the most appropriate treatment for
severe major depression in perimenopausal women, estrogen
may also
be appropriate for
mild to moderate
symptoms, particularly if the
woman has never been depressed before. Studies are underway to compare estrogen
and antidepressants and to determine for which patient’s estrogen may be preferred.
Estrogen can be given either as a pill (e.g., Premarin, Estrace, and Estratab)
or through the skin by a patch. The woman should discuss the benefits and risks
of each formulation with her doctor. There is no doubt that estrogen controls
the physical symptoms of menopause, especially hot flashes. There is
controversy over how long it should be taken and whether it’s other general
health benefits, such as keeping bones strong and possibly preventing memory
problems and heart disease, may be outweighed by risks of breast cancer and
stroke.
Progesterone, the other major female hormone, does not by itself
treats or prevents perimenopausal depression or physical symptoms. However,
it is
often combined with
estrogen (except in women who
have had a hysterectomy) to ensure that excessive buildup of the uterus does
not occur, which may lead to a risk
of cancer. The major disadvantage of progesterone can be
uncomfortable side effects such as bloating, headaches, and even mood changes. Should side effects occur, different forms
and dose schedules of progesterone may help.
Depression is sometimes
a side effect
of hormone replacement
therapy, for reasons
that are not
understood. (It may also occur in
some younger women who take birth control pills.) When this happens in a woman,
who has never been depressed before, it may help to try a different hormone preparation.
However, in women who have significant histories of depression and become
depressed again when starting hormone replacement therapy, the experts usually
advise treating with antidepressant medication and/or stopping hormones
altogether.
Psychotherapy
Two types of psychotherapy
are highly recommended for depression related to menopause. Interpersonal
therapy focuses on understanding how changing human relationships may contribute
to, or relieve, depression. Cognitive-behavioral
therapy (CBT) focuses on identifying and changing the pessimistic thoughts
and beliefs that accompany depression. When
used alone, psychotherapy usually works more gradually than medication, taking
2 months or more to show its full effects. However, the benefits may be
long-lasting. Psychotherapy is usually combined with medication in major
depression. It is unlikely to help severe depression if used by itself.
What if the first
treatment isn’t helping?
It is important to give each treatment strategy enough time to
work before considering another. If hormones are tried first, a response should
be seen within 2-4 weeks. If the response is not satisfactory, the experts
strongly suggest adding an antidepressant. If an antidepressant is used first,
it must be adjusted to a high enough dose, and then given for at least 1–2
months to tell if it will help. If an SSRI antidepressant does not work in this
time frame or produces intolerable side effects and has to be stopped
sooner, the experts strongly recommend switching to a second SSRI. The
doctor may also suggest combining the SSRI with a second medication, which
could be either another kind of antidepressant or hormone replacement therapy
if not already in use.
Latest research
One of the latest
studies investigating connection between menopause and depression were
performed by Seattle Midlife Women’s Health Study in 2008. Most of the 302
participating women were in their late 30s or early 40s in the early 1990s,
when the 15-year study began. The women recorded depressive symptoms, kept
daily menstrual calendars (to determine stage of menopausal transition), and
answered questions about hot flashes. Nearly half of them provided regular
urine samples for hormone assays. The study also assessed a range of health and
psychosocial factors, including those related to the menopausal transition,
age, and depression at other times in life.
The researchers analyzed these factors individually and in
various combinations. The results confirmed findings from other studies
correlating depressive symptoms with later-stage perimenopause, sleep
disruption, current stress, and the presence of hot flashes. Other factors
associated with depression during perimenopause were negative life-event
stress, a history of postpartum depression or sexual abuse, and a family history
of depression. Women who had not borne children and women who had taken
antidepressants were also at greater risk. Striking by its absence was any
significant connection between depression and levels of hormones associated
with perimenopause — primarily estrogen or follicle-stimulating hormone.
The results of this study argue that the picture of
depressive symptoms during perimenopause is far more complex than fluctuating
hormone levels or hot flashes. A variety of factors — including past emotional distress
— may increase a woman’s vulnerability to depression during these years. And
the menopausal transition presents its own set of challenges, both
physiological and psychosocial.
The Seattle researchers say their findings should serve as a
reminder that depressed mood during the menopausal transition “is attributable
not only to this time of a woman’s life but also to the cumulative history of
events over the life course.” One important implication is that for some women,
treating depression during perimenopause requires not only antidepressants but
also psychotherapy, which can help address current difficulties rooted in the
past.
While the weight of the different factors increasing risk of
depression in this critical life stage is still subject of discussion, there is
no doubt that the risk itself multiplies during this period.
Researchers at the University of Pennsylvania followed 231
premenompausal women (aged 35-47) who had never been depressed for eight years.
Depression was four times more likely
to occur in a woman during her perimenopausal period. It was independently
associated with deranged hormonal blood levels, hot flashes and weight gain.
A Harvard Study followed 460 premenopausal women (35-46
years old) who had never been depressed for up to nine years. Perimenopausal
women were 2-4 times more likely to
become depressed than premenopausal women. Risks were increased by hot flashes
independent of negative stressful life events.
Depression symptoms include: sadness, emptiness, decreased
pleasure or interest, appetite and weight changes, difficulty sleeping or
excessive sleepiness, restlessness or retardation, loss of energy, feelings of
worthlessness, inappropriate guilt, difficulty thinking concentrating or
deciding, morbid thoughts even without a plan for suicide.
If you notice first signs of depression, and you need to get
more information on this health condition, feel free to explore different
aspects of it on my blog devoted to Depression.
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