Depression is a significant mental health concern, affecting around 280 million people in the world–most of them women. [1] In most women, the risk of experiencing depression spikes in midlife (ages 45 to 54), with about 20-30% facing first or recurrent episodes of major clinical depression during this time. [2] While concerns about aging, dealing with workplace issues, and challenges in intimate relationships are a few reasons to blame, menopause is another crucial factor.

The transition to menopause is accompanied by notable psychological changes, such as mood swings and anxiety, in nearly one in three women. Even women with no prior history of depression are two to four times more likely to experience depressive symptoms during perimenopause than their younger or older counterparts. [3]

The Menopausal Transition

According to the American College of Obstetricians and Gynecologists (ACOG), menopause is the time when a woman’s menstrual periods stop permanently following 12 consecutive months of no periods.[4]

​The period leading up to menopause is called perimenopause, which can span a period of 3-7 years on average. During this time, the hormone levels, particularly estrogen, begin to decline, causing irregular menstrual cycles and symptoms like hot flashes, insomnia, anxiety, mood swings, and depressive feelings.

​Depressive symptoms during the menopause transition can manifest in several ways:

• Fatigue or low-energy

• Irritability, restlessness, or agitation

• Difficulty concentrating or making decisions

• Persistent sadness or feeling of emptiness

• Sleep disorders, such as insomnia or oversleeping

• Loss of interest in activities once enjoyed

• Feelings of worthlessness or guilt

• Changes in appetite or weight

• Suicidal thoughts

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Most women get relief from depressive symptoms in the post-menopause years, but some may continue to experience mood disturbances. This could be due to poor social support, unaddressed mental health concerns, substance abuse, and others.

Are Hormones The Only Thing To Blame?

In the past, researchers have studied the association between mood changes and hormones like follicle-stimulating hormone (FSH) and estradiol. The results were inconsistent, with some studies linking higher levels of these hormones to increased depressive symptoms while others not confirming this connection.

During perimenopause, the estrogen and progesterone levels start to fall. Since estrogen acts as a protective agent in the brain, a decline in estrogen levels plays a crucial role in increasing the risk of developing depression, particularly in those who have suffered major depression in the past. Estrogen also impacts serotonin transmission (a neurotransmitter that promotes feelings of happiness) by influencing serotonin receptor expression. When the estrogen levels fall, it disrupts serotonin balance, potentially destabilizing moods and leading to irritability, anxiety, and sadness. [5]

​Changes in the transmission of other neuropeptides, such as dehydroepiandrosterone sulfate (DHEAS) and gamma-aminobutyric acid (GABA), may also happen during perimenopause and can cause depressive symptoms. Lower levels of DHEAS and GABA in older women have been associated with increased symptoms of depression, similar to those seen in major depressive disorders. [6] [7]

​Beyond hormonal changes, studies have also shown two major risk factors–biological and psychological–that shape a woman’s experience during menopause. Biological risk factors include hot flashes, night sweats, sleep disturbances, and unrelated chronic medical conditions. For instance, hot flashes occur as a result of the dysregulation in the brain’s thermoregulatory center due to ovarian failure and estrogen loss. It can lead to poor sleep quality, making women feel low and anxious and, ultimately, depressed. [8] Sleep disturbances and chronic health conditions can also add stress, which increases the likelihood of experiencing mood changes.

A history of depression/ postpartum depression, an adverse perception of menopause, and higher levels of neuroticism—a personality trait associated with negative emotions–are psychological factors that are strongly related to depressive symptoms during the menopause transition. [9]

​Lastly, additional life challenges such as relationship conflicts, caregiver responsibilities, career transitions or job demands, financial stress, retirement planning, or even kids moving out can contribute to feeling depressed and anxious during menopause.

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How Is Menopausal Depression Managed/ Treated?​

​Current guidelines recommend treating menopausal depression with a combination of antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), psychological therapy, and lifestyle changes. [10] However, antidepressants may not work for everyone and can cause side effects like serotonin syndrome, emotional numbness, diarrhea, agitation, nausea, anorexia, excessive sweating, insomnia, headache, decreased libido, etc. [11] For example, some menopausal women with

significant insomnia, irritability, or anxiety may not respond well to common SSRIs like escitalopram, or they might experience an exacerbation of symptoms with fluoxetine. For this reason, the choice of antidepressants should be tailored for each woman.

Newer medications, like desvenlafaxine (an SNRI) and agomelatine, have shown promise for perimenopausal women, with agomelatine proving to help treat insomnia. [12] [13] [14]

When it comes to psychosocial treatment, it is effective in women with perimenopausal depression that stems from work or relationship stresses common in midlife. In addition, exercise, mindfulness techniques, yoga, and dietary adjustments are also helpful in managing symptoms of depression to some extent.

​According to the data so far, menopausal hormone therapy (MHT) has shown promise in treating mild perimenopausal depression linked to hormonal fluctuations, but its effectiveness for postmenopausal depression remains unclear. [15] Recently, newer MHT regimens like low-dose hormones and transdermal estradiol, which can cross the blood-brain barrier, are also being explored. [16]

​However, MHT is not suitable for women with a history of hormone-dependent cancers or venous thromboembolism. The Australasian Menopause Society (AMS) has evidence-based guidelines that healthcare providers should follow when prescribing MHT. [17] [18]​

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How effective are lifestyle changes such as meditation, exercise and choice of diet?

​Hormonal treatments are not generally prescribed for women who smoke, have high blood pressure, have a history of blood clotting, have heart or liver diseases, have conditions like diabetes or epilepsy or are already postmenopausal.

​For these patients, lifestyle adjustments are recommended, such as adopting a balanced diet [19], practicing meditation, exercising regularly, and limiting caffeine and alcohol intake. These strategies can promote mental well-being and significantly ease perimenopausal symptoms. While these adjustments may alleviate symptoms, they cannot fully resolve the major depressive disorder and should be combined with medication and/or psychological therapy for the best outcomes.