Perimenopausal Depression: Understanding and Treating Hormonal Mood Changes in Midlife

Menopause is a natural and unavoidable part of a woman's life, but the emotional and psychological changes it brings, particularly during the perimenopause, can be significant and challenging. If you are experiencing concerning mood changes around this time, it's important to understand that you are not alone, and effective strategies exist to help manage these symptoms.

More Than Just Mood Swings: Understanding Perimenopausal Depression

The perimenopause, typically occurring between the ages of 42 and 52, is the period immediately preceding menopause, marked by biological, endocrine, and clinical changes. This transition can significantly increase the risk of depression in women over 40. 

Australian data, for example, show the highest age-specific suicide rates for females in the 45–49 and 50-54 age groups, which may be linked to the biological changes during this time. Perimenopausal depression is now recognised as a distinct subtype of depression, sometimes presenting differently from typical depression experienced by younger women or men.

What are the symptoms of Perimenopausal Depression? 

While some symptoms overlap with general depression (like low energy and sleep disturbance), perimenopausal depression (hormonal depression) often has specific characteristics:

• Rapid and Sudden Onset: Symptoms may appear quickly, not necessarily tied to new life stressors.

• Increased Irritability and Anger: Unlike typical depression, which may present as obvious sadness, perimenopausal depression can manifest as quick temper loss or hostility.

• Pronounced Loss of Energy/Fatigue: This fatigue can be constant and independent of sleep quality.

• Decreased Self-Esteem and Self-Worth: A significant nosedive in self-esteem can occur.

• Impaired Memory and Concentration: Many women describe a sudden change in memory, sometimes leading to fears of dementia.

• Weight Gain: Often, a weight gain of 2-3 kg can occur even with a sensible diet and exercise, further contributing to poor self-esteem.

• Fluctuating Sexual Interest: Changes in libido can be notable and sudden.

• Paranoid Thinking: This is usually not delusional, but rather thoughts like "everyone at work thinks I'm pathetic".

• Sleep Disturbance: Insomnia is extremely common, affecting 40-50% of perimenopausal women.

• Anxiety: Women may experience constant worrying, muscle tension, sweating, or nausea. Anxiety symptoms are strongly linked to vasomotor symptoms (hot flushes).

• The physical symptoms of menopause, like hot flashes, often present much later (up to five years) than the psychological symptoms, making early diagnosis challenging. The risk of depression appears higher during perimenopause, when hormone levels are fluctuating, rather than in postmenopause, when levels are low but stable.

Understanding the "Why": Neuroendocrine Mechanisms

Recent research aims to provide new knowledge about the neuroendocrine mechanisms of perimenopausal depression. This includes exploring:

• Epigenetic Changes: Changes in gene expression can influence how a woman's body and brain respond, potentially linking maternal depression to offspring brain development.

• Monoamine Neurotransmitters and Receptor Hypothesis: While traditional antidepressants targeting monoamines (like dopamine, serotonin (5-HT), and norepinephrine (NE)) are not effective in about one-third of Major Depressive Disorder (MDD) patients, these neurotransmitters play a role in hormonal depression. For instance, decreases in dopamine D3 receptor, especially when combined with stress, can induce depressive behaviour during perimenopause. Some studies show that treatments can increase levels of DA, 5-HT, and NE in the hippocampus and serum, and 5-HT3 receptor antagonists have been effective in treating depression and anxiety comorbidity.

• Glial Cell-Induced Neuroinflammation: Chronic stress can lead to the release of inflammatory factors from microglia and damage the function of the glymphatic system induced by neurons and astrocytes, potentially causing depression. Abnormal or decreased astrocytes and dysfunctional glymphatic systems are observed in emotional disorders.

• Estrogen Receptors: Estrogen receptors (ERα, ERβ, and GPER) are distributed in various brain regions and can affect different types of glial cells. Estrogen influences brain function directly and indirectly through genomic and non-genomic signalling pathways, affecting neuroplasticity. This relationship between estrogen and brain function is complex, and hormonal changes are involved in the pathogenesis and course of behavioural abnormalities.

• Interaction between the HPA Axis and HPG Axis: The hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis play crucial roles in stress response and reproductive function, and their interaction is important in perimenopausal depression

A Holistic Approach to Management

Managing perimenopausal depression often requires a comprehensive and integrated approach. It's crucial to keep your health care team in the loop. Treatment intervention should be made known to each woman and initiated at her request, with reassessment every three to five years as needs may change.

1. Hormonal Therapies

Menopause Hormone Therapy (MHT) / Hormone Replacement Therapy (HRT): For recent-onset depression without suicidality in otherwise healthy women experiencing other perimenopausal symptoms, hormone therapy alone may be appropriate. MHT has been shown to improve depressive symptoms significantly and can even lead to remission of depressive disorders in perimenopausal women (hormonal depression), particularly those with co-occurring vasomotor symptoms. It is part of an overall health strategy for midlife women and should be personalised in terms of dose and type. Balancing estrogen levels with HRT can lead to better physical and mental health outcomes and may allow for lower doses of other medications.

2. Psychological Therapies

Psychological approaches are crucial in managing perimenopausal depression.  

NICE (UK) guidance suggests that antidepressants should not be used as a first-line treatment for clinical depression, making therapies like CBT crucial. CBT is not an alternative to HRT; rather, it can further enhance the psychological symptom improvements achieved with appropriate HRT

3. Lifestyle and General Well-being Approaches

These approaches are fundamental to supporting mental health during perimenopause.

• Prioritise Self-Care: Engage in activities that bring pleasure and joy, making time for leisure, laughter, and social connection. Self-care is not selfish; it is essential to reduce stress and maintain well-being. An attitude of self-compassion and curiosity towards your emotions is helpful.

• Regular Exercise: Physical activity is a powerful tool to change how you feel; "emotion follows motion". It can reduce the risk of cardiovascular disease and osteoporosis. Regular exercise also positively influences a woman’s sense of well-being and may improve hot flushes, though evidence is conflicting.

• Balanced Diet: Aim for a plate of food that is very colourful, with deep greens, bright reds, yellows, and orange, as these foods are nutrient-dense. Eating small amounts every two to three hours and combining protein with carbohydrates can help maintain steady blood sugar levels. Ensure adequate intake of calcium, magnesium, and potassium. Minimising alcohol use is very important for both mental state and physical health. Smoking cessation is also important for overall health. Flavonoids, found in plant foods, have versatile health benefits, including reducing the risk of cardiovascular disease and cancer.

• Sleep Hygiene: Be mindful of screen time before bed, as it can interfere with melatonin production and delay sleep quality. While sleep hygiene is important, recognise that it may not always be sufficient to address insomnia problems related to hormonal changes.

• Stress Management and Social Support: Maintaining social contact with others and promoting family and social support can significantly help. Carers, for instance, benefit from interventions aimed at reducing emotional distress

• Cultivate Self-Compassion: An attitude of self-compassion, kindness, and curiosity can help you understand and respond to difficult emotions more effectively, rather than just wanting the symptoms to disappear. Recognise that while menopause is unavoidable, suffering is optional. CBT, for instance, helps you change your relationship with these sensations and transform the narrative around your difficulties.

Overall, recent research emphasises the unique nature of perimenopausal depression and highlights the need for comprehensive, individualised treatment plans that combine hormonal, psychological, and lifestyle interventions, supported by accurate assessment tools.

Why Choose Blue Fig Clinic in Sydney?

Blue Fig Clinic is dedicated to providing expert, compassionate, and holistic care.  We specialise in women’s mental health across the lifespan, with a particular focus on perimenopausal depression, hormonal mood changes, and midlife wellbeing.

​​We work collaboratively to ensure you receive integrated support tailored to your unique needs. We are committed to:

• Recognising and validating your experiences, including the often-misunderstood presentation of anger and irritability.

• Offering a comprehensive approach that extends beyond symptom management to address the underlying biopsychosocial factors impacting your health.

• Utilising evidence-based practices and staying current with the latest research in women's mental health during menopause.

• Supporting not just you, but also your family, in understanding this significant life transition and its impact.

You don't have to suffer in silence. Menopause is unavoidable, but suffering is optional. 

Let our Sydney-based women’s mental health clinic, Blue Fig Clinic, guide you through this journey with understanding, expertise, and practical solutions. Treating perimenopause and any mental health challenges in parallel, rather than in isolation, is likely to lead to a speedier recovery and better long-term outcomes. You have the power to make informed choices for your health and well-being.