Estrogen, Serotonin & Mood Swings Before Your Period

ByRohan Smith
How Estrogen and Serotonin Affect Mood Swings Before a Woman's Period

Author: Rohan Smith | Functional Medicine Practitioner | Adelaide, SA

Quick Answer

Premenstrual mood swings are primarily associated with fluctuations in estrogen and their downstream effects on serotonin (5-hydroxytryptamine), a key neurotransmitter involved in emotional regulation. As estrogen declines during the late luteal phase, serotonin synthesis, receptor sensitivity, and synaptic availability may decrease, contributing to symptoms such as irritability, low mood, anxiety, and emotional sensitivity commonly observed in premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) (1–3).

At a Glance

  • Estrogen upregulates tryptophan hydroxylase (TPH2), the rate-limiting enzyme in serotonin biosynthesis, linking hormonal fluctuations directly to neurotransmitter availability (6,7).
  • Estrogen withdrawal during the late luteal phase may reduce serotonin transporter (SERT) inhibition, decreasing synaptic serotonin and increasing vulnerability to mood changes (10,11).
  • Premenstrual dysphoric disorder (PMDD) affects an estimated 3–8% of women of reproductive age, with symptoms driven by heightened sensitivity to normal hormonal fluctuations (3,14).
  • Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine have demonstrated efficacy in reducing premenstrual mood symptoms, supporting the serotonin-mediated mechanism (19).
  • Estrogen modulates both 5-HT1A and 5-HT2A serotonin receptor subtypes, influencing mood stability, anxiety regulation, and emotional processing (8,9).

Understanding Estrogen and Serotonin

Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter that plays a central role in regulating mood, emotional stability, anxiety, sleep, and appetite. Approximately 90% of the body’s serotonin is produced in the gastrointestinal tract, while the remainder is synthesised in the central nervous system, primarily within the dorsal raphe nucleus of the brainstem. Serotonin is closely linked to hormonal mood changes (4).

Estrogen (primarily estradiol, or E2) is a steroid hormone best known for its role in reproductive health, but it also has wide-ranging effects on brain function, neurotransmitter activity, and emotional processing. Research by Roberta Brinton and colleagues has demonstrated estrogen’s significant influence on synaptic plasticity and neuroprotection within the central nervous system (5).

How Estrogen Influences Serotonin Function

Estrogen modulates serotonin through multiple interconnected mechanisms, each of which may contribute to the mood changes observed across the menstrual cycle.

Mechanism Effect of Estrogen Impact on Mood
Tryptophan hydroxylase (TPH2) activity Upregulates serotonin synthesis Higher serotonin production may support mood stability (6,7)
5-HT1A and 5-HT2A receptor expression Enhances receptor sensitivity More effective serotonergic signalling and emotional regulation (8,9)
Serotonin transporter (SERT) expression Reduces reuptake activity Serotonin remains active longer in the synaptic cleft (10,11)
Monoamine oxidase (MAO) activity May reduce serotonin degradation Preserves serotonin availability between neurons (11)

Serotonin Synthesis

Estrogen has been shown to upregulate the activity of tryptophan hydroxylase (TPH2), the rate-limiting enzyme involved in serotonin synthesis, as demonstrated in primate studies by Cynthia Bethea and colleagues at Oregon Health & Science University. Higher estrogen availability is associated with increased serotonin production within the brain, a process that may also be influenced by serotonin synthesis and methylation pathways (6,7).

Serotonin Receptor Sensitivity

Estrogen can enhance the expression and sensitivity of specific serotonin receptors, particularly 5-HT1A and 5-HT2A receptor subtypes, as reported by Hiroi and Neumaier in their research on the dorsal raphe nucleus. Increased receptor sensitivity allows serotonergic signalling to function more effectively and is associated with greater mood stability (8,9).

Serotonin Reuptake and Availability

The serotonin transporter (SERT), encoded by the SLC6A4 gene, is responsible for clearing serotonin from the synaptic space. Research by McQueen and colleagues demonstrated that estrogen reduces SERT expression and activity, allowing serotonin to remain active for longer periods and potentially enhancing its mood-regulating effects (10,11).

The Menstrual Cycle and Premenstrual Mood Changes

Hormonal fluctuations across the approximately 28-day menstrual cycle directly influence serotonergic neurotransmission, with distinct patterns observed in each phase.

Follicular Phase: Rising Estrogen

During the follicular phase of the menstrual cycle, estradiol levels gradually rise under the influence of follicle-stimulating hormone (FSH) from the anterior pituitary gland. This increase is associated with enhanced serotonin production and signalling, which often corresponds with improved mood, motivation, and emotional resilience (12).

Luteal Phase: Estrogen Withdrawal

In the luteal phase, particularly in the days leading up to menstruation, estrogen levels decline following the breakdown of the corpus luteum. This withdrawal can result in reduced serotonin activity, increasing vulnerability to mood symptoms such as irritability, sadness, anxiety, and emotional reactivity. Research by C. Neill Epperson at the University of Pennsylvania confirmed that luteal phase vulnerability to depression is closely linked to these neurochemical shifts. These changes are commonly observed in premenstrual syndrome (PMS) and tend to be more pronounced in premenstrual dysphoric disorder (PMDD) (13,14).

Cognitive Function and Neuroprotection

Estrogen–serotonin interactions extend beyond mood regulation to play an important role in cognitive processes including memory consolidation, learning, and emotional regulation. Research by Yuko Hara and colleagues, published in The Journal of Neuroscience, demonstrated that estrogen supports synaptic plasticity and hippocampal neuroprotection, in part through its influence on serotonergic pathways. Karyn Frick’s work further established that estrogen-mediated memory effects are particularly relevant during reproductive transitions (15,16).

Menopause and Mood Vulnerability

During the menopausal transition (perimenopause), sustained declines in circulating estradiol can disrupt serotonergic signalling in the prefrontal cortex and limbic system. Research by Claudio Soares and Ellen Freeman has demonstrated that this neurochemical shift may contribute to the increased risk of depressive symptoms, anxiety, and mood instability reported by some women during perimenopause and postmenopause, even in those with no prior psychiatric history (17,18).

Why This Matters Clinically

Understanding how estrogen modulates serotonin through tryptophan hydroxylase activation, receptor sensitisation, and SERT inhibition helps explain why mood symptoms often follow predictable hormonal patterns across the menstrual cycle. It also provides insight into why broader hormonal imbalances may further influence mood regulation and emotional wellbeing. This understanding also helps explain why certain interventions—such as selective serotonin reuptake inhibitors (SSRIs) or hormone-based therapies—may reduce premenstrual mood symptoms in some individuals, as demonstrated in the landmark fluoxetine trial by Meir Steiner and colleagues (19,20).

When to Consider Further Support

Premenstrual mood changes that are severe, persistent, or disruptive to daily functioning may warrant further assessment by a qualified healthcare practitioner.

Symptom Pattern Possible Consideration
Mood changes occurring predictably in the luteal phase PMS or PMDD assessment
Severe irritability, anxiety, or depressive episodes premenstrually Hormonal and neurotransmitter evaluation
Emotional symptoms alongside fatigue and sleep disruption Comprehensive hormonal and nutritional testing
Worsening mood symptoms during perimenopause Estrogen metabolism and adrenal function review

Next Steps

  1. Track your cycle and symptoms: Record mood changes, energy levels, and emotional patterns across your menstrual cycle to identify whether symptoms align with hormonal phases.
  2. Assess hormonal and nutritional status: Consider comprehensive hormone testing to evaluate estrogen metabolism, cortisol patterns, and serotonin-supporting nutrient levels including vitamin B6, folate, zinc, and tryptophan.
  3. Seek personalised support: If premenstrual mood changes are severe or disruptive, a functional medicine assessment can help identify the hormonal and neurochemical patterns driving your symptoms.

Frequently Asked Questions

Why do mood swings happen before a woman’s period?
Mood swings before a period are commonly linked to fluctuations in estrogen and their effects on serotonin, a neurotransmitter involved in mood regulation. As estrogen levels fall in the late luteal phase, serotonin production, receptor sensitivity, and availability may decrease, increasing vulnerability to irritability, low mood, anxiety, and emotional sensitivity.

Is premenstrual low mood a psychological issue or a hormonal one?
Premenstrual mood changes are driven primarily by physiological processes rather than personal weakness or poor coping. Hormonal fluctuations influence brain chemistry, particularly serotonergic signalling, which can affect emotional regulation even in individuals with otherwise stable mental health.

When should premenstrual mood changes be investigated further?
Further assessment may be appropriate when mood symptoms are severe, persistent, or interfere with daily functioning, particularly if they occur predictably across the menstrual cycle. This includes symptoms suggestive of PMS or PMDD, or mood changes accompanied by fatigue, sleep disruption, or other hormonal irregularities.

Key Insights

  • Estrogen plays a regulatory role in serotonin production, receptor sensitivity, and reuptake via tryptophan hydroxylase, 5-HT receptors, and the serotonin transporter (SERT)
  • Declining estrogen levels in the luteal phase may reduce serotonin activity in the dorsal raphe nucleus and prefrontal cortex
  • These neurochemical changes help explain common premenstrual mood symptoms including irritability, anxiety, and low mood
  • Hormonal mood shifts reflect physiological processes, not personal weakness

Citable Takeaways

  1. Estrogen upregulates tryptophan hydroxylase (TPH2) activity, increasing serotonin biosynthesis in the brain, as demonstrated by Pecins-Thompson et al. in primate models (6).
  2. Premenstrual dysphoric disorder (PMDD) is estimated to affect 3–8% of women of reproductive age, with symptoms linked to heightened neurochemical sensitivity to normal hormonal fluctuations, according to Yonkers et al. in the New England Journal of Medicine (3).
  3. Estrogen reduces serotonin transporter (SERT) expression, allowing serotonin to remain active for longer in the synaptic cleft, as reported by McQueen et al. in Molecular Psychiatry (10).
  4. Fluoxetine (an SSRI) demonstrated significant efficacy in reducing premenstrual dysphoric symptoms in a controlled trial by Steiner et al. published in Archives of General Psychiatry (19).
  5. Research by Schmidt et al. in the New England Journal of Medicine showed that women with PMS may have differential behavioural sensitivity to gonadal steroid fluctuations compared to women without PMS (20).
  6. Luteal phase vulnerability to depression is associated with estrogen withdrawal effects on serotonergic neurotransmission, as reviewed by Epperson et al. in the American Journal of Psychiatry (13).

Understand Your Hormonal Mood Patterns

Premenstrual mood changes can be distressing, especially when they recur predictably each month or begin to affect relationships, work, or overall wellbeing. At Elemental Health and Nutrition, we take an evidence-informed functional medicine approach that considers hormonal rhythms, nervous system regulation, nutritional status, and lifestyle factors together to help clarify contributing drivers and guide appropriate next steps.

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References

  1. Albert PR et al. Why is depression more prevalent in women? Role of progesterone and estrogen in the regulation of serotonin. Front Neurosci. 2015 Jul 31;9:267. https://doi.org/10.3389/fnins.2015.00267
  2. Bethea CL et al. Ovarian steroids and serotonin neural function. Mol Psychiatry. 2002;7(1):3-10. https://doi.org/10.1038/sj.mp.4000997
  3. Yonkers KA et al. Premenstrual dysphoric disorder. N Engl J Med. 2008 Apr 17;358(16):1695-703. https://doi.org/10.1056/NEJMcp0707465
  4. Young SN. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007 Nov;32(6):394-9. https://pubmed.ncbi.nlm.nih.gov/18043762/
  5. Brinton RD. Estrogen-induced plasticity from cells to circuits: predictions for cognitive function. Trends Endocrinol Metab. 2009 Jun;20(5):212-20. https://doi.org/10.1016/j.tem.2008.12.006
  6. Pecins-Thompson M et al. Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus monkeys. J Neurosci. 1999 Jul 1;19(13):5570-9. https://doi.org/10.1523/JNEUROSCI.19-13-05570.1999
  7. Sanchez MG et al. Estradiol enhances the effects of serotonin on rat dorsal raphe neurons. Brain Res. 2005 Sep 28;1059(2):164-71. https://doi.org/10.1016/j.brainres.2005.08.015
  8. Moses-Kolko EL et al. Estrogen receptor binding in the human brain: effects of menstrual cycle phase and estrogen status. Psychiatry Res. 2003 Nov 30;123(3):193-203. https://doi.org/10.1016/j.pscychresns.2003.07.004
  9. Hiroi R, Neumaier JF. Differential effects of estradiol on serotonin receptor subtypes in rat dorsal raphe nucleus. Brain Res. 2009 Mar 3;1260:1-9. https://doi.org/10.1016/j.brainres.2008.12.053
  10. McQueen JK et al. Estrogen regulation of serotonin transporter mRNA expression in rat brain. Mol Psychiatry. 1997 Mar;2(2):109-13. https://doi.org/10.1038/sj.mp.4000238
  11. Fink G et al. Estrogen and the central nervous system: the role of estrogen in the regulation of mood and cognition. J Neuroendocrinol. 1998 May;10(5):325-32. https://doi.org/10.1046/j.1365-2826.1998.00208.x
  12. Farage MA et al. Cognitive, sensory, and emotional changes across the female lifespan. CNS Drugs. 2008;22(10):821-39. https://doi.org/10.2165/00023210-200822100-00003
  13. Epperson CN et al. Luteal phase vulnerability to depression: a review of the evidence. Am J Psychiatry. 2012 Mar;169(3):245-53. https://doi.org/10.1176/appi.ajp.2011.11010187
  14. Halbreich U. The etiology of premenstrual dysphoric disorder: 5 interwoven threads. Psychoneuroendocrinology. 2003 Dec;28 Suppl 3:1-10. https://doi.org/10.1016/j.psyneuen.2003.08.001
  15. Hara Y et al. Estrogen and synaptic plasticity in the hippocampus. J Neurosci. 2015 Feb 11;35(6):2546-55. https://doi.org/10.1523/JNEUROSCI.4106-14.2015
  16. Frick KM. Estrogens and memory in women: the role of reproductive status and menopausal hormone therapy. Horm Behav. 2012 Feb;61(2):231-9. https://doi.org/10.1016/j.yhbeh.2011.11.003
  17. Soares CN. Depression in peri- and postmenopausal women: prevalence, pathophysiology and pharmacological management. Drugs Aging. 2014 Jul;31(7):547-57. https://doi.org/10.1007/s40266-014-0192-9
  18. Freeman EW. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Menopause. 2010 May;17(3):541-8. https://doi.org/10.1097/gme.0b013e3181c8b2c3
  19. Steiner M et al. Fluoxetine in the treatment of premenstrual dysphoria. Arch Gen Psychiatry. 1995 Nov;52(11):939-46. https://doi.org/10.1001/archpsyc.1995.03950230035005
  20. Schmidt PJ et al. Differential behavioral effects of gonadal steroids in women with and without premenstrual syndrome. N Engl J Med. 1998 Jan 22;338(4):209-16. https://doi.org/10.1056/NEJM199801223380401

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