Menopause: The Hidden Neurochemical Shifts That Make Women Feel “Rubbish”

Menopause: The Hidden Neurochemical Shifts That Make Women Feel “Rubbish”

Dr. Mindy Pelz — New York Times bestselling author of Fast Like a Girl and Eat Like a Girl — is one of the world’s leading functional medicine experts on women’s hormones. Through her top-rated The Resetter Podcast, she’s transforming the menopause conversation and helping women reclaim their energy, clarity, and sense of purpose.

SISTERLY is excited to share a sneak peek into Dr. Mindy’s latest research, soon to be featured in her forthcoming book Age Like a Girl. Her work reveals what many women have long sensed: menopause isn’t just about hot flushes or changing cycles — it’s about the brain.

When oestrogen and progesterone decline, they don’t just affect the ovaries; they trigger a cascade of neurochemical changes that alter how you think, feel, and function. These hormonal shifts can reduce vital brain messengers — dopamine, serotonin, acetylcholine, glutamate, GABA, oxytocin, and BDNF — all of which play major roles in mood, motivation, memory, sleep, and emotional balance.

Let’s explore what’s really happening — and what you can do to feel like yourself again.

Oestrogen and Progesterone: The Brain’s Hidden Modulators

Oestrogen and progesterone aren’t just reproductive hormones — they’re also neuromodulators that influence how your brain cells communicate.

  • Oestrogen enhances the activity of serotonin, dopamine, acetylcholine, and glutamate — all linked to energy, clarity, and mood.

  • Progesterone supports GABA, the brain’s main calming chemical.1

This is why menopause symptoms often stretch to brain fog, depression, anxiety and memory lapses.2

Serotonin: Mood and Sleep

Serotonin is often described as the brain’s “feel-good” chemical because of its role in mood stability, emotional regulation, sleep and even appetite. 

Oestrogen stimulates serotonin production so when oestrogen falls during menopause, serotonin also takes a nose dive.3 The result? Irritability, anxiety, low mood and restless nights, classic symptoms that many menopausal women recognise all too well. 

Fortunately, nutrients found in SISTERLY such as vitamin B6, folate, vitamin B12, magnesium and zinc help support serotonin production.

Dopamine: Motivation and Reward

Dopamine drives motivation, focus, reward and pleasure. Oestrogen normally enhances dopamine release, so its loss leaves many women struggling with apathy, fatigue, lack of focus and “brain fog”.4 

Key nutrients in SISTERLY like vitamin B6, folate, copper and magnesium support dopamine balance, improving motivation and mental vitality.

Acetylcholine: Memory and Focus

Acetylcholine provides brain cells with energy so it’s closely linked to memory, learning and attention. Oestrogen boosts the enzyme that makes it, so when levels fall, you may experience word-finding issues, forgetfulness, or “tip-of-the-tongue” moments.5 

Vitamin B5 (found in SISTERLY) supports cognitive function and mental performance. Lifestyle hacks such as learning new skills, practising meditation and even simple brain-training games (hello sudoku and crosswords!) help keep your neurons firing.

 


Glutamate: Learning and Focus

Glutamate is the main excitatory neurotransmitter, essential for the creation of new neural connections. Oestrogen and progesterone work together to balance glutamate activity, but when they fall, it may lead to mental sluggishness and difficulty learning new things.6,7 

Magnesium and vitamin D help regulate glutamate and protect neurons - both key nutrients found in SISTERLY.

GABA: Calm and Restful Sleep

GABA is the brain’s major calming neurotransmitter, melting stress and overstimulation. Progesterone helps boost GABA, aiding relaxation.8 As progesterone falls, GABA activity falls too, leaving you anxious, tense, or struggling to switch off.

To support GABA naturally, think of magnesium rich foods (nuts, seeds and leafy greens), green tea (l-theanine) and calming practices like yoga, mindfulness and slow breathing. 

Oxytocin: Connection and Bonding

Oxytocin is often called the “bonding hormone”. It promotes trust, intimacy, stress resilience and even supports bone health.9 Oestrogen is known to enhance oxytocin10, but when hormones decline, oxytocin diminishes, and women may experience loneliness, social withdrawal and stress.11

Supporting oxytocin can be surprisingly simple — hugging, spending time with loved ones and pets, all stimulate oxytocin. Magnesium and vitamin D also help.

BDNF: Brain Fertiliser

Brain-Derived Neurotrophic Factor (BDNF) helps your brain grow new connections and stay adaptable — vital for learning, resilience, and mood. Falling oestrogen and progesterone mean lower BDNF, which can lead to “brain fog,” slower recall, and being less resilient to stress.12, 13, 14 

Aerobic exercise is the single most effective stimulator of BDNF. Combine that with good sleep, mental challenges, and nutrients like zinc, magnesium, and vitamin D to keep your brain thriving.

Why Menopause Feels So Overwhelming

When all these brain chemicals dip at once, it’s no wonder menopause can feel like an emotional rollercoaster. The good news? You’re not “losing it” — your brain chemistry is shifting, and there are many ways to support it.

Practical Ways Forward

  • Feed your brain: Try foods rich in tryptophan (turkey, oats, seeds, bananas) for serotonin; tyrosine (chicken, fish, almonds, legumes) for dopamine; and choline (eggs, salmon, peanuts) for acetylcholine.

  • Move daily: Aerobic and resistance exercise boost dopamine, serotonin, and BDNF.

  • Stay connected: Social time and cuddles support oxytocin and serotonin.

  • Balance your mind: Mindfulness, meditation, and deep breathing help raise GABA and serotonin.

  • Support with supplements: Nutrients including B-vitamins, magnesium, zinc, copper and many more, all found in SISTERLY, support hormone regulation.

  • Consider HRT: For some women, hormone replacement can make a dramatic difference to mood, memory, and sleep.

SISTERLY Summary

The decline of oestrogen and progesterone during menopause triggers powerful neurochemical shifts that affect mood, memory, and motivation — but knowledge is power.

By combining smart nutrition, lifestyle strategies, and your daily SISTERLY sachet, you can nourish your brain chemistry, restore balance, and rediscover your sense of vitality and joy — through menopause and beyond.

References

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  2. Turek J, Gąsior Ł. Estrogen fluctuations during the menopausal transition are a risk factor for depressive disorders. Pharmacol Rep. 2023 Feb;75(1):32-43. doi: 10.1007/s43440-022-00444-2. Epub 2023 Jan 14. PMID: 36639604; PMCID: PMC9889489. https://pubmed.ncbi.nlm.nih.gov/36639604/

  1. Carretti N, Florio P, Reis FM, Comai S, Petraglia F, Costa CV. Menopause alters the metabolism of serum serotonin precursors and their correlation with gonadotropins and estradiol. Climacteric. 2007 Oct;10(5):393-9. doi: 10.1080/13697130701378198. PMID: 17852142. https://pubmed.ncbi.nlm.nih.gov/17852142/

  2. Russell JK, Jones CK, Newhouse PA. The Role of Estrogen in Brain and Cognitive Aging. Neurotherapeutics. 2019 Jul;16(3):649-665. doi: 10.1007/s13311-019-00766-9. PMID: 31364065; PMCID: PMC6694379. https://pubmed.ncbi.nlm.nih.gov/31364065/

  3. Newhouse P, Dumas J. Estrogen-cholinergic interactions: Implications for cognitive aging. Horm Behav. 2015 Aug;74:173-85. doi: 10.1016/j.yhbeh.2015.06.022. Epub 2015 Jul 14. PMID: 26187712; PMCID: PMC4573353. https://pubmed.ncbi.nlm.nih.gov/26187712/

  4. Bendis PC, Zimmerman S, Onisiforou A, Zanos P, Georgiou P. The impact of estradiol on serotonin, glutamate, and dopamine systems. Front Neurosci. 2024 Mar 22;18:1348551. doi: 10.3389/fnins.2024.1348551. PMID: 38586193; PMCID: PMC10998471. https://pubmed.ncbi.nlm.nih.gov/38586193/

  5. Kaur P, Jodhka PK, Underwood WA, Bowles CA, de Fiebre NC, de Fiebre CM, Singh M. Progesterone increases brain-derived neuroptrophic factor expression and protects against glutamate toxicity in a mitogen-activated protein kinase- and phosphoinositide-3 kinase-dependent manner in cerebral cortical explants. J Neurosci Res. 2007 Aug 15;85(11):2441-9. doi: 10.1002/jnr.21370. PMID: 17549730; PMCID: PMC2693123. https://pubmed.ncbi.nlm.nih.gov/17549730/

  6. Gilfarb RA, Leuner B. GABA System Modifications During Periods of Hormonal Flux Across the Female Lifespan. Front Behav Neurosci. 2022 Jun 16;16:802530. doi: 10.3389/fnbeh.2022.802530. PMID: 35783228; PMCID: PMC9245048. https://pubmed.ncbi.nlm.nih.gov/35783228/

  7. Breuil V, Panaia-Ferrari P, Fontas E, Roux C, Kolta S, Eastell R, Ben Yahia H, Faure S, Gossiel F, Benhamou CL, Euller-Ziegler L, Amri EZ. Oxytocin, a new determinant of bone mineral density in post-menopausal women: analysis of the OPUS cohort. J Clin Endocrinol Metab. 2014 Apr;99(4):E634-41. doi: 10.1210/jc.2013-4126. Epub 2014 Jan 21. PMID: 24446658. https://pubmed.ncbi.nlm.nih.gov/24446658/

  8. Choleris E, Gustafsson JA, Korach KS, Muglia LJ, Pfaff DW, Ogawa S. An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6192-7. doi: 10.1073/pnas.0631699100. Epub 2003 May 2. PMID: 12730370; PMCID: PMC156348. https://pubmed.ncbi.nlm.nih.gov/12730370/ 

  9. Korkmaz H, Deveci CD, Üstün Y, Pehlivanoğlu B. Comparison of plasma oxytocin level in women with natural and surgical menopause. Endocrine. 2023 Oct;82(1):209-214. doi: 10.1007/s12020-023-03453-0. Epub 2023 Jul 21. PMID: 37477780. https://pubmed.ncbi.nlm.nih.gov/37477780/

  10. Pluchino N, Cubeddu A, Begliuomini S, Merlini S, Giannini A, Bucci F, Casarosa E, Luisi M, Cela V, Genazzani AR. Daily variation of brain-derived neurotrophic factor and cortisol in women with normal menstrual cycles, undergoing oral contraception and in postmenopause. Hum Reprod. 2009 Sep;24(9):2303-9. doi: 10.1093/humrep/dep119. Epub 2009 Jun 2. PMID: 19491202. https://pubmed.ncbi.nlm.nih.gov/19491202/

  11. Konishi K, Cherkerzian S, Aroner S, Jacobs EG, Rentz DM, Remington A, Aizley H, Hornig M, Klibanski A, Goldstein JM. Impact of BDNF and sex on maintaining intact memory function in early midlife. Neurobiol Aging. 2020 Apr;88:137-149. doi: 10.1016/j.neurobiolaging.2019.12.014. Epub 2019 Dec 24. PMID: 31948671; PMCID: PMC7961845. https://pubmed.ncbi.nlm.nih.gov/31948671/

  12. Sohrabji F, Lewis DK. Estrogen-BDNF interactions: implications for neurodegenerative diseases. Front Neuroendocrinol. 2006 Dec;27(4):404-14. doi: 10.1016/j.yfrne.2006.09.003. Epub 2006 Oct 27. PMID: 17069877; PMCID: PMC1828910.  https://pubmed.ncbi.nlm.nih.gov/17069877/

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