Depression, Low Mood and Menopause
A deeper dive into hormone therapy and antidepressants
The menopause transition (the years leading up to the final period) and menopause are both associated with an increased risk of low mood and depression. That the chaotic hormone fluctuations of the menopause transition might play a role in depression isn’t surprising, given the existence of premenstrual dysphoric disorder (PMDD) and postpartum depression. However, it’s also important to consider that women are more likely to experience social stressors associated with depression, such as poverty and intimate partner violence, as well as ageism, so it’s important to try to sort out what may be hormones, social factors, or both.
Here, we’ll cover the basics of depression in menopause, the risk factors, and two of the treatments: hormone therapy and antidepressants. I know some social media accounts demonize antidepressants for women in the menopause translation and menopause, but that isn’t helpful and can actually end up harming some women. As you will see, estrogen can be a therapy, antidepressants can be a therapy, and they may even work better when given together. It’s always good to have more options so that care can be individualized.
It is important to study depression in the menopause transition and menopause because we want to identify who needs treatment as well as the right therapy. We also need rigorous studies because it can be complicated as symptoms of depression can be similar to symptoms of menopause, for example, brain fog, sleep disturbance, and feeling unwell.
Depression and Low Mood
Depression, meaning major depressive disorder, is a medical condition associated with nine symptoms:
Sleep disturbance
Decreased interest or pleasure
Guilt feelings or thoughts of worthlessness
Energy changes/fatigue
Concentration/attention impairment
Appetite/weight changes
Psychomotor disturbances
Suicidal thoughts
Depressed mood
Major depression is diagnosed by talking with someone and ruling out medical conditions that can masquerade as depression. Questionnaires are often used to help with the diagnosis, such as the Patient Health Questionnaire (PHQ) or the Center for Epidemiologic Studies Depression Scale (CES-D). It’s not important to remember these names, but it’s good to know there are validated questionnaires. When you are being evaluated for symptoms in the menopause transition/menopause, you should be asked to complete one of them. We also use the same questionnaire in follow-up to determine response to therapy.
People can also have symptoms of depression that don’t reach the threshold for a formal diagnosis. Maybe the symptoms aren't as intense or don’t occur as often, but they still have an impact on how you feel and on your quality of life. These symptoms might be referred to as symptoms of depression, mild depression, or low mood.
For our purposes here, when we say depression, we mean major depression, and we'll use low mood for symptoms of depression/low mood/mild depression.
The difference between depression and low mood highlights one of the problems with the medical literature because sometimes the two are lumped together; other times, there are formal questionnaires that separate people into distinct groups (depression vs. low mood); and some studies only consider depression, and anyone who doesn’t score high enough for depression is considered in the not depressed group, even though some may have bothersome symptoms.
Studies can be tricky to compare for other reasons. Some look at the general population, and others at people attending menopause clinics, which increases their risk of having depression because most people are only attending a menopause clinic if they have symptoms. Some studies look at women at a single point in time, and then some follow them for years to see if and how things change over time. Some researchers collect blood samples to help determine where women are in their menopause transition/menopause, and others just ask about the last period. In addition, some studies divide women into the menopause transition (before the last period) and menopause (the last period onwards), but some use perimenopause (menopause transition plus the first year of menopause) and menopause (after the first year).
At times, comparing these studies is like comparing apples with oranges. This is a long-winded way of saying there is a reason the rate of depression over the menopause transition and menopause varies from 8-62%. Depending on which studies you keep or throw out, you could easily say no one is depressed in the menopause transition versus the baseline in the population, or almost everyone is. This is why thoughtful analysis of the studies with no preconceived bias is important.
What is the Risk of Low Mood and Depression in Menopause?
The best data that evaluates the risk of depression and low mood comes from studies that follow women from before their menopause transition through to their last period and beyond and have used validated questionnaires. That way, it is possible to tell if low mood and depression are linked with hormonal changes, aging, or other factors, such as social stressors.
Most studies show an increased risk of depression and/or low mood in the menopause transition and also menopause. In the Study of Women’s Health Across the Nation (SWAN), women were two to four times more likely to experience depression during the menopause transition and early post-menopause compared with premenopause. In most studies, the risk of depression increases further into the menopause transition and then starts to decrease again a year after the last period. It is also important to remember that many women go through menopause with no depression or low mood. In SWAN, 50% of women did not develop low mood, never mind depression.
One of the strongest risk factors for depression in the menopause transition is a previous history of depression (in fact, this is probably the most important one). This suggests that some women have a biological vulnerability to the interplay between hormonal changes and depression, as the existence of PMDD and postpartum depression suggests. It seems for some women, the menopause transition unmasks a predisposition to depression. This information is useful because it informs women without a history of depression that their risk is lower, and it informs women with a history of depression that this is something to watch carefully. In the Study of Women’s Health Across the Nation, the risk of depression for women with a previous history of depression was 59% compared with 28% for those without a history.
An interesting, albeit small, study started a group of women who did not currently have depression on a 100-microgram transdermal estradiol patch for three weeks and then randomized them in a blinded way to either continue the estradiol patch or a placebo patch. None of the women had depression at the start of the study or during the initial estradiol portion of the trial, but after the switch, 36% of those with a history of depression who received the placebo patch developed depression, while the result was 0% for those without a previous history of depression who had received the placebo. This supports the data that points to previous depression as a major risk factor.
Other risk factors for depression in the menopause transition and menopause include:
Frequent hot flashes and night sweats
Lower physical activity
Poor sleep
Low social support
Stressful life events
Anxiety
Previous history of PMDD or postpartum depression
Some people have wondered about a domino effect, specifically that hot flashes at night lead to poor sleep, which then leads to depression, but the data here is not exactly clear. It seems that these risk factors may be more important for those without a history of depression, and overall, poor sleep is probably one of the most important risk factors.
Is it Depression or PMS/PMDD?
Tracking symptoms over time can help sort this out; basically, if it’s PMS/PMDD, there should be periods of time when you feel really good. Meaning, the symptoms should definitely be cyclic. It’s important to distinguish between depression and PMS/PMDD because the therapies might be different. PMS/PMDD is typically treated with estrogen-containing oral contraceptives or antidepressants, not menopause hormone therapy.
Treatment of Depression in the Menopause Transition and Menopause
Estrogen Therapy
Two small clinical trials have looked at estrogen for the treatment of depression