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DEPRESSION DURING THE TRANSITION TO MENOPAUSE:
A Guide for Patients and Families
David A. Kahn, MD, Margaret L. Moline, PhD, Ruth W. Ross, MA, Lori L. Altshuler, MD,
and Lee S. Cohen, MD
It is a common myth that as women enter 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. This guide is intended to answer commonly asked
questions about depression that occurs around menopause.
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.
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.
Many treatments for depression during perimenopause have been suggested, but most
have not yet been evaluated in scientific studies. We therefore recently surveyed 36
leading experts in this field about the treatment of major depression in relation to
menopause. The recommendations described in this article are based on the results of
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.
• Fatigue or lack of energy • Restlessness or feeling slowed down
• 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
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
•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.
Treatment recommendations for major depression that occurs in association with
menopause depend on how severe the woman’s symptoms are and whether she has
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
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, one 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
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.
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 one 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.
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 patients 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 its 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 treat or prevent
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.
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
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
FOR MORE INFORMATION
American Menopause Foundation, Inc. (AMF)
147-154 Haouala 076.qxp:Layout 1 29.4.2010 8:53 Uhr Seite 147 Cardiovascular drug interactions with tyrosine kinase inhibitors Amina Haoualaa, Nicolas Widmera, Michael Montemurrob, Thierry Buclina, Laurent Decosterda a Division of Clinical Pharmacology, Département de Médecine, CHUV, University hospital, Lausanne, Switzerland b Multidisciplinary Oncology Centre, Centre Hospitalier Uni
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