Navigating the transition through menopause can feel like a physical and emotional maze. Vasomotor symptoms like hot flashes are widely recognized. However, the impact of menopause on mental health — ranging from brain fog to severe clinical depression and bipolar disorder — can be especially disruptive.
At the Parsemus Foundation, we believe that understanding the biological roots of these changes is the first step toward better care. Here’s a breakdown of the latest science on sex hormones and mental health.
The biological foundation: why hormones matter for the mind
Hormones are not just about reproduction; they’re powerful chemical messengers that dictate how our brains function. In all people, sex hormones such as estrogen, progesterone, and testosterone are active in the brain.
- Estrogen: Often called the “master regulator,” estrogen influences the production of neurotransmitters, including serotonin, dopamine, and norepinephrine. It helps maintain the health of brain regions such as the hippocampus and the prefrontal cortex, which are responsible for memory and emotional regulation.
- Progesterone: This hormone has a natural calming effect. It produces a neurosteroid that acts on the same brain receptors as anti-anxiety medications. Progesterone also supports the repair of brain tissue and the blood-brain barrier.
- Testosterone: In both sexes, testosterone supports cognitive clarity, libido, and mood stability. It helps maintain the health of brain neurons and reduces amyloid, which has been related to Alzheimer’s disease.
Despite the importance of these hormones for brain health, they’re rarely considered by physicians treating patients with psychological issues like anxiety or depression. Antidepressants, psychological therapy, and lifestyle changes are used as the primary treatments for depression in perimenopausal and menopausal women. Hormone levels are rarely checked, even when the onset of symptoms aligns perfectly with life transitions like perimenopause or andropause (a decline in testosterone levels in middle-aged men). This “hormone-blind” approach can lead to years of trial-and-error with antidepressants that may not address the underlying hormonal trigger.
Perimenopause is an understudied window of psychiatric vulnerability
Perimenopause is the time leading up to the last menstrual cycle (when menopause occurs). It’s characterized by changes in menstrual cycle length and variable circulating hormone levels in the hypothalamus, pituitary, and ovaries. It’s also a time of increased variability in neurological symptoms, along with a decline in glucose metabolism in the brain. According to research by Dr. Roberta Brinton of the University of Southern California, a substantial proportion of women are vulnerable to the neurological shifts that can occur during this transition and are at increased risk of neurological decline.
Recent research has confirmed what many women have long suspected: the fluctuating hormones of perimenopause create a high-risk window for mental health crises.
A landmark 2024 study published in Nature Mental Health utilized data from over 128,000 women in the UK Biobank to track first-time psychiatric diagnoses. The research team led by Prof. Arianna Di Florio found that during the four years surrounding the final menstrual period, the risk of developing a psychiatric disorder for the first time increased significantly:
- Bipolar disorder: The risk of a first-onset manic episode increased by a staggering 112%.
- Major depression: The risk of a first episode of major depressive disorder rose by 30%.
112%
Increase in the risk of a first-onset manic episode in bipolar disorder
Corroborating these findings, a 2025 UK Biobank study specifically focused on depressive symptoms in 143,685 women. Using a depression screening tool, researchers found that women within one year of their final menstrual period had the highest rates of significant depressive symptoms (7.6%). The study concluded that the proportion of women experiencing these symptoms increases in the years immediately surrounding the menopause compared to years further away from the transition.
“In my clinic, I found that some women, previously living lives without any experience of severe mental health issues, developed severe mental illness around the time of the menopause… We have been able to expand our knowledge of the mental health changes associated with perimenopause, which can help provide explanations, diagnoses, and support for women who have previously been left in the dark about what is happening to them.”
— Arianna Di Florio, MD, PhD
Professor of Psychiatry
Cardiff University School of Medicine
The promise of modern hormone therapy
The good news is that we’re entering a new era of hormone replacement therapy to address mental well-being. Modern hormone therapy focuses on individualized care and body-identical formulations. Rather than a “one size fits all” pill, doctors are increasingly using:
- Transdermal estradiol: Patches or gels that provide a steady level of estrogen.
- Micronized progesterone: A body-identical form of progesterone may avoid some of the side effects sometimes seen with older, synthetic progestins.
- Testosterone therapy: For women with low testosterone levels, supplementation has shown remarkable promise.
Two 2025 publications led by Dr. Sarah Glynne of Newson Health shed light on how modern hormone therapy affects mental health. A retrospective study in the Archives of Women’s Mental Health evaluated 510 menopausal women using transdermal testosterone therapy for 4 months and found significant improvements in mood (47%), cognition (39%), and libido (52%). A second study, published in the British Journal of Psychiatry, compared different hormone combinations in 920 women during the menopause transition. The authors reported a significant improvement in mood for all hormone therapy regimens studied, including estradiol with or without progesterone (micronized or levonorgestrel-releasing IUD) or transdermal testosterone.
Moving forward
Mental health issues during the menopausal transition are not “all in your head” — they’re in your biology. If you’re experiencing new or worsening mood symptoms, it’s essential to work with a provider who understands the complex interplay between your endocrine system and your brain. Each person responds differently to menopause and to hormone replacement. An individualized plan is key.
Learn more about our work in providing accurate, evidence-based information on Hormones for Menopause and on Hormonally.org.
