Mood Changes in Peri/Menopause

May 01, 2024
Blurred image of a woman going from happy to sad and depressed
We often focus on how perimenopause affects the physical body, but it can also trigger mood-related symptoms, including depression. Depression is the most prevalent mental illness worldwide, but disproportionality affects more women than men.

The changing hormonal landscape through perimenopause and the early post-menopause years is associated with an increased risk for depression, anxiety, and other mental health concerns. But why?

Today’s article will dive into the connections between menopause and mood changes. You’ll learn about:

  • Definitions and statistics around midlife mood changes
  • How female hormones affect the brain and mood
  • Why menopause hormone therapy might help mood symptoms
  • How to support a healthy brain through midlife and beyond


Let’s jump into this exciting and very relevant topic!

Menopause Transition Definitions

Before we look at the brain, let’s cover some terms used in this article referring to midlife:

  • Perimenopause, also known as the menopausal transition, is the time leading up to menopause. It starts with the first symptoms of perimenopause while a woman still has a regular menstrual cycle and continues beyond the final menstrual period until menopause. Perimenopause can last for a few years up to a decade or more, and most of the “menopause” symptoms occur during this phase.


  • Menopause is the one-year anniversary of the last menstrual period. It’s simply a point in time that marks the end of reproductive capability.



Midlife Depression and Mental Health

One billion people worldwide are affected by a mental illness at some point in their lives, and depression is the most common affliction. A woman’s risk of depression through her lifetime is twice as high as that of a man’s. Further, depression (and anxiety) is more likely to correlate with a hormonal transition or swing, such as:

  • Puberty
  • The luteal phase (second half) of the menstrual cycle
  • Postpartum
  • Perimenopause

Perimenopause and early post-menopause are considered “windows of vulnerability” for depression and mental health challenges, which include both new onset and recurring cases. Further, depression is often associated with other perimenopausal symptoms, such as hot flashes, insomnia, and vaginal dryness.

One in three women will experience psychological changes, including anxiety and depression, through perimenopause and the beginning of post-menopause. The risk for depression is at its highest before and after menopause, declining two to four years after the last menstrual period, especially in women with no previous history.

Female Hormones and Brain Health

The next question is why? Why do women experience more depression, and why are they more vulnerable during perimenopause and early menopause?

There are likely several compounding reasons, but changing estrogen is a significant factor.

First, perimenopause is a time of significant brain reorganization. Estrogen is important for brain structure, cognition, and mood, and the female brain contains abundant estrogen receptors. During the reproductive years, the female brain has adapted to a higher supply of estrogen.

Then, during perimenopause, estrogen levels fluctuate and eventually decline to a much lower level. It takes the brain some time to adapt, and that adaptation process can cause brain-related symptoms, like:

  • Brain fog
  • Hot flashes
  • Night sweats
  • Sleep disturbances
  • Depression
  • Anxiety

Estrogen has neuroprotective properties; it protects against dementia and other neurodegenerative diseases. Across the menopausal transition, the brain structure changes, putting women more at risk for amyloid plaque (a hallmark of Alzheimer’s disease), neurological diseases, and a loss of brain volume.

Some of these brain-related changes women experience during menopause can overlap with depression and symptoms of mental illness, like poor concentration, fatigue, and insomnia.

Estrogen is also involved with the production of serotonin and dopamine. Fluctuation (and decline) in estrogen can also mean fluctuations in neurotransmitter levels and central nervous system function, which contribute to a destabilized mood.

New research also suggests that women with depression are more likely to have bacterial enzymes in the gut that degrade estrogen, contributing to lower estrogen levels. So, it’s likely that gut health through perimenopause also plays a role.

Other hormones besides estrogen are also involved. For example, DHEA-S (an estrogen precursor made by the adrenal glands) levels decline with age and impact serotonin and nervous system regulation. Lower progesterone levels can mean lower GABA, the primary inhibitory neurotransmitter that helps calm down the nervous system.

Besides hormones, perimenopausal symptoms and depression may be influenced by the same genetic factors. Perimenopause can also be a stressful time as women grapple with aging and physical changes and symptoms that affect quality of life. Stress can make depression and other symptoms worse. One study revealed more depression in perimenopausal women during the Covid pandemic compared to the years before the pandemic.

Antidepressants Vs. Hormone Replacement Therapy

In a Western medical model, the first-line therapy for perimenopausal depression is antidepressant medications. However, hormone replacement therapy might be a helpful alternative for many women.

In 2002 came the historic Women’s Health Initiative publication that led to millions of women stopping their hormonal prescriptions. Subsequent research and reevaluations of the data suggest that hormone therapy is much safer than that study led us to believe. You can read the whole story here.

Many women likely suffered because of a lack of access to hormone therapy over the last two decades. What’s interesting is that after 2002, prescriptions for antidepressants and sleep aids rapidly increased for midlife women.

Now, the medical community, and primarily integrative and functional gynecologists, are circling back to the use of hormone replacement therapy (HRT) as a primary approach to depression treatment. 

Hormone replacement therapy – at TārāMD, we recommend bioidentical estrogen and progesterone options – is shown to be better than placebo for treating depression in perimenopausal and postmenopausal women. Further, HRT helps protect the brain against cognitive decline, supports a healthy mood, reduces menopausal symptoms, and has long-term benefits throughout the body.

A Healthy Midlife Mood

It’s possible to support mood and mental health in perimenopause with holistic and integrative tools and lifestyle changes. There isn’t one set of interventions that will work for every woman, but a personalized combination of natural solutions and hormonal support can be beneficial in preventing and treating depression and other concerns.

Work with your TārāMD provider and team for personalized strategies. Some approaches we recommend include:

  • Integrative gynecology – Dr. Fenske offers the best Western medicine strategies, bioidentical hormone replacement therapy, and nutrition, lifestyle, and supplement suggestions to support women through the perimenopausal years and beyond. If you’ve noticed mood swings or depressive symptoms, it’s time for an appointment.


  • Anti-inflammatory nutrition – Depression and brain changes have an inflammatory component, and inflammation can increase during perimenopause. Reducing inflammation with nutrition is effective (and delicious!) Choose colorful plant foods, such as vegetables, fruits, legumes, and seeds, as the foundations of your diet. Increase omega-3 fats from cold-water fish and meet your daily protein needs. Your TārāMD nutritionist can help you take these broad suggestions and turn them into a personalized plan.



  • Self-care – By the time you’re in your late 30s or 40s and beginning to experience perimenopause, you’ve likely already spent a portion of your life caring for others. Perimenopause is an opportunity to practice and prioritize self-care. Many holistic and relaxation practices can benefit women in perimenopause by reducing stress and supporting the nervous system. For example, acupuncture is a safe modality that can help with depression during perimenopause.


Perimenopause involves significant hormonal changes that influence brain health and depression risk. However, understanding the connection can help put integrative solutions in place to protect mental health or treat mood issues while the brain adjusts to its new hormonal norms. Save yourself time and suffering by working with TārāMD for all your perimenopause and post-menopause needs.


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