Premenstrual Dysphoric Disorder (PMDD)

Overview

Premenstrual Dysphoric Disorder (PMDD) affects roughly 3–9% of women of reproductive age and manifests as severe mood, behavioral, and physical symptoms tightly linked to the luteal phase of the menstrual cycle, distinguishing it from milder premenstrual syndrome (PMS).^[1][2] Central to PMDD’s pathophysiology is an altered sensitivity of the central nervous system to normal fluctuations of ovarian hormones, particularly progesterone and its metabolite allopregnanolone, which modulate GABAergic and serotonergic neurotransmission and contribute to mood dysregulation.^[3][4] Neuroimaging studies show abnormal activation of prefrontal brain regions and cerebellum, correlating with symptom severity.^[5] Disruptions in biological rhythms, such as reduced nocturnal melatonin and elevated core body temperature, further exacerbate symptoms.^[6] Although direct investigation of the microbiome in PMDD is sparse across these sources, emerging evidence highlights the gut-brain axis’s role in mood and hormonal regulation, suggesting that microbial metabolites may influence neurotransmitter systems and inflammation implicated in PMDD.^[7] This microbiome-brain interaction remains a promising but underexplored area for understanding PMDD’s etiology and developing novel therapies. Clinically, effective treatment strategies include selective serotonin reuptake inhibitors administered during the luteal phase or symptom onset, hormonal interventions, and cognitive behavioral therapy, with a growing emphasis on individualized, multidisciplinary approaches.^[8][9]

Diagnosis

The diagnosis of PMDD predominantly relies on prospective symptom tracking aligned with DSM-5 criteria, emphasizing the cyclical nature of emotional, behavioral, and physical symptoms occurring in the luteal phase and remitting shortly after menstruation begins.^[10][11] Tools such as the Premenstrual Symptoms Screening Tool for Adolescents (PSST-A) and daily symptom diaries are commonly used for clinical assessment and research validation.^[12] Emerging non-invasive diagnostic approaches including microbiome, metabolomic, and metallomic signatures remain underexplored but show promising potential. Although the microbiome’s role in modulating neuroendocrine and inflammatory pathways implicated in PMDD has been suggested, specific microbial or metabolite markers for diagnostic use have yet to be validated. Current research highlights the need for integrative biomarkers combining symptomatology with biological signatures to enhance early, objective diagnosis and personalize treatment strategies.^[13] Future investigations focusing on gut-brain axis modulation, hormonal metabolomics, and trace metal profiling could provide novel, non-invasive tools that complement traditional clinical assessments, improving diagnostic precision and patient outcomes.

Causal Theories

PMDD arises from a multifaceted interplay of neurobiological, hormonal, genetic, and environmental factors. Central to its pathogenesis is an abnormal sensitivity to neurosteroids, particularly progesterone and its metabolite allopregnanolone, which modulate GABA_A receptor activity and affect mood regulation, although receptor expression varies and evidence remains indirect with limited sample sizes.^[14][15] Serotonergic dysregulation also contributes to PMDD symptoms, but biomarker replication is inconsistent, and overlap with depressive disorders complicates interpretations.^[16] Disruptions in circadian rhythms, including altered melatonin secretion and core body temperature, have been observed, though causal links remain unclear due to mixed findings.^[17] Genetic predispositions involving polymorphisms in hormone receptor and neurotransmitter genes suggest a heritable component, yet the polygenic and complex nature of PMDD challenges isolation of specific causal variants.^[18] Emerging research highlights the gut-brain axis and microbiome as potential modulators of neuroinflammation and hormonal metabolism, proposing new pathways influencing PMDD pathophysiology, but clinical validation remains preliminary.^[19]

Associated Conditions

PMDD is frequently associated with a spectrum of psychiatric, neurological, and physical conditions that often exacerbate its clinical presentation and complicate management. Psychiatric comorbidities are prominent, with high rates of co-occurrence reported for major depressive disorder, generalized anxiety disorder, panic disorder, and particularly bipolar disorder, which shares cyclic mood fluctuations and neurobiological vulnerabilities with PMDD.^[20] Women with bipolar disorder show an increased prevalence of PMDD, which is linked to greater symptom severity, earlier illness onset, and more frequent mood episodes. Additionally, PMDD often coexists with other mood and anxiety spectrum disorders, including post-traumatic stress disorder, which may reflect overlapping dysregulation of neuroendocrine and neurotransmitter systems such as serotonin and GABA.^[21][22]` Neurological conditions like migraine are commonly exacerbated premenstrually, and inflammatory disorders such as fibromyalgia and autoimmune diseases show symptom patterns aligned with the menstrual cycle, suggesting shared neuroimmune and hormonal pathways.^[23] Furthermore, PMDD overlaps with eating disorders like bulimia nervosa and binge eating disorder, likely due to hormonal modulation of appetite and reward systems.^[24] Metabolic and endocrine conditions, including thyroid dysfunction, hyperprolactinemia, and anemia, may mimic or worsen PMDD symptoms, necessitating careful differential diagnosis.^[25] Lifestyle factors such as smoking, obesity, and high stress levels further contribute to symptom severity.

Primer

Unlike typical PMS, PMDD involves heightened sensitivity of the central nervous system to normal fluctuations in ovarian hormones, especially progesterone and its neuroactive metabolite allopregnanolone, which modulate key neurotransmitter systems such as GABA and serotonin.^[26] This neuro-hormonal interplay underlies the cyclical pattern of symptoms and distinguishes PMDD as a distinct neuropsychiatric condition. Emerging evidence highlights the role of major microbial associations (MMAs) within the gut microbiome, which may influence PMDD by modulating neuroinflammation, hormonal metabolism, and neurotransmitter synthesis through the gut-brain axis.^[27] These findings support the potential for microbiome-targeted interventions (MBTIs) aimed at restoring microbial balance to alleviate symptoms. Additionally, metallomic factors, such as trace metal imbalances, could affect neurochemical pathways involved in PMDD, although research in this area is still developing. Understanding these core concepts, hormonal neurosteroid sensitivity, neurotransmitter dysregulation, microbiome interactions including major microbial associations, and potential metallomic influences, is essential to grasp the complex etiology of PMDD and its emerging biomarkers, paving the way for innovative, personalized diagnostic and treatment strategies.

Metallomic Signatures

Current evidence on the metallomic signature in PMDD is limited but suggests that heavy metals and trace elements may influence symptom severity and pathophysiology. Smoking, which introduces heavy metals such as cadmium and lead, is significantly associated with increased risk and severity of PMDD, possibly through neuroendocrine and inflammatory pathways that disrupt hormonal and neurotransmitter balance.^[28][29] Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis seen in PMS/PMDD patients may be exacerbated by toxic metal exposure, compounding stress response impairments. While direct studies on metallomic profiling in PMDD are scarce, parallels from neuropsychiatric and endocrine disorders suggest that alterations in metals like zinc, copper, and magnesium could affect neurotransmission and neuroinflammation, contributing to symptom expression. Understanding these metallomic influences could inform non-invasive biomarker development and novel intervention strategies, including detoxification and nutritional supplementation, to mitigate symptom burden. Further focused metallomic research in PMDD populations is critical to clarify these associations and support targeted clinical applications.

Major Microbial Associations

Recent research indicates significant alterations in the gut microbiota composition in women experiencing PMDD and related premenstrual symptoms. Notably, studies have shown that certain beneficial butyrate-producing bacteria, such as Butyricicoccus and Megasphaera, are decreased in PMDD, potentially reducing short-chain fatty acid production important for neuroprotection and anti-inflammatory effects. Likewise, Parabacteroides, known for producing GABA and modulating brain neurotransmission, is diminished, possibly contributing to impaired GABAergic function implicated in PMDD pathology.^[30] These microbial shifts reflect disruptions in neuroimmune and metabolic pathways via the gut-brain axis, suggesting that targeted microbiome interventions could ameliorate PMDD symptoms.

Microbe	Status in PMDD	Role/Impact
Butyricicoccus	Decreased	Butyrate producer; supports neuroprotection and anti-inflammation.
Megasphaera	Decreased	Produces butyrate; influences brain-derived neurotrophic factor (BDNF).
Parabacteroides	Decreased	GABA producer; modulates neurotransmission, anti-inflammatory effects.
Anaerotaenia	Increased	Positively correlated with symptom severity; role unclear.

Microbiome Signature: Premenstrual Dysphoric Disorder (PMDD)

Interventions

PMDD treatments include pharmacological, nutraceutical, complementary, and microbiome-targeted interventions (MBTIs). SSRIs mainly affect serotonin without directly targeting the microbiome. Probiotics, exercise, and SCFA supplements show promise by restoring gut balance and influencing brain function. Fecal microbiota transplantation (FMT) remains under investigation as a potential therapy to restore a healthy gut microbiome and help alleviate mood and physical symptoms associated with PMDD. Herbal and nutraceutical options like saffron and S-equol provide antioxidant and hormone-modulating benefits, with S-equol’s efficacy partly reliant on gut microbiota metabolism. Emerging neuroactive steroid modulators and acupuncture work through neuroendocrine pathways but don’t directly target the microbiome. These varied approaches reflect PMDD’s complex nature and the growing role of microbiome-focused treatments.

Interventions	Mechanisms of Action	MBTI Status
Probiotics	Modulate gut microbial diversity and metabolite production; reduce pro-inflammatory cytokines; enhance immunological tolerance; influence HPA axis and neurotransmitter synthesis (GABA, serotonin); improve mood regulation via gut-brain axis.^[31][32]	Validated
SCFA Supplementation	Restore gut microbial metabolite balance; enhance gut barrier; reduce systemic inflammation; modulate microglial activation; influence neurotransmitter pathways and neuroimmune signaling, improving mood and cognition.^[33][34]	Under Investigation
Dietary Interventions (Traditional South China Diet (TSCD), Mediterranean diet, micronutrient supplementation)	Promote balanced nutrient intake that supports neurotransmitter synthesis and hormonal regulation; influence gut microbiota composition via increased fiber, vegetables, and antioxidants; reduce systemic inflammation and oxidative stress; modulate serotonin pathways through carbohydrate quality; inverse association with PMD symptom severity.^[35][36]	Promising Candidate
Fecal Microbiota Transplantation (FMT)	Restore healthy gut microbial composition; reestablish microbial diversity; modulate immune and neuroinflammatory pathways; influence gut-brain communication via neurotransmitter and metabolite production, potentially reducing mood symptoms and improving neuroendocrine regulation.[37]^[x]	Experimental
Exercise	Modulates gut microbiota diversity and increases SCFA-producing bacteria; reduces systemic inflammation; improves HPA axis regulation; enhances neuroplasticity and mood via BDNF upregulation; indirectly supports microbiome-brain axis.^[38]	Promising Candidate

FAQs

What is the current understanding of fecal microbiota transplantation (FMT) as a treatment for PMDD, and what challenges remain?

FMT involves the transfer of stool from healthy donors to recipients with gut dysbiosis, aiming to restore microbial diversity and function. This approach has demonstrated remarkable success in treating recurrent Clostridioides difficile infections and is being explored in other neuropsychiatric and metabolic disorders characterized by gut-brain axis dysregulation. In PMDD, FMT could theoretically reset a disrupted microbiome contributing to neuroinflammation, hormonal imbalance, and neurotransmitter abnormalities underlying cyclical mood and physical symptoms. Preliminary studies in related conditions, such as depression and anxiety, suggest FMT can improve mood symptoms and gut microbiota composition. However, the application of FMT in PMDD is experimental, with limited direct evidence. Challenges include donor selection, standardizing transplantation protocols, understanding long-term effects, and managing risks such as infection or adverse immune reactions. Rigorous randomized controlled trials are essential before FMT can be recommended clinically for PMDD.

What role do short-chain fatty acids (SCFAs) play in PMDD management, and what is the evidence base for their supplementation?

SCFAs, primarily butyrate, acetate, and propionate, are microbial fermentation products of dietary fibers that exert wide-ranging effects on gut and brain health. SCFAs support the integrity of the gut epithelial barrier, preventing translocation of endotoxins that can trigger systemic and central inflammation, a key pathway implicated in mood disorders like PMDD. They also modulate microglial cells in the brain, attenuating neuroinflammatory responses and promoting neuroprotection. SCFAs influence neurotransmitter systems, including serotonin and dopamine pathways, by regulating precursor availability and receptor sensitivity. Experimental animal studies and preliminary human trials indicate that SCFA supplementation can reduce depressive and anxiety-like behaviors, improve cognitive function, and restore metabolic balance. In PMDD, where inflammation and neurotransmitter dysregulation are prominent, SCFAs represent a mechanistically targeted intervention. Nonetheless, clinical research specific to SCFA supplementation in PMDD is limited and ongoing, warranting further trials to assess efficacy, safety, and formulation.

How do probiotics function to alleviate PMDD symptoms, and what evidence supports their clinical use?

Probiotics act by colonizing the gut with beneficial bacterial strains that increase microbial diversity and support the production of neuroactive compounds essential for central nervous system function. These include GABA and serotonin precursors that regulate mood and anxiety—core components of PMDD symptomatology. Probiotics also improve gut barrier integrity, reducing intestinal permeability (“leaky gut”) which otherwise promotes systemic inflammation and neuroinflammation. Clinical studies using strains such as Lactobacillus paragasseri OLL2809 have demonstrated reductions in premenstrual psychological symptoms, including mood swings, irritability, and anxiety, as well as improvements in sleep quality. Probiotics modulate immune responses by decreasing pro-inflammatory cytokines and increasing anti-inflammatory mediators, which may reduce the neuroinflammatory burden implicated in PMDD. While probiotic formulations and dosing vary, current evidence suggests they are safe, well-tolerated, and a promising adjunct to standard pharmacological treatments. However, larger randomized controlled trials are necessary to confirm efficacy, determine optimal strains, and define treatment duration specific to PMDD.

Research Feed

October 12, 2016

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What was studied?

This paper studied the efficacy and tolerability of symptom-onset dosing of sertraline, a selective serotonin reuptake inhibitor (SSRI), for the treatment of premenstrual dysphoric disorder (PMDD). The focus was on assessing whether administering sertraline starting at the onset of PMDD symptoms, rather than continuous or luteal-phase dosing, could effectively reduce symptom severity and improve clinical outcomes over six menstrual cycles. The study also explored the side effect profile and discontinuation symptoms associated with this targeted treatment approach.

Who was studied?

The study population comprised 252 women with prospectively confirmed PMDD, aged approximately 34 years on average, predominantly white (around 70%), and without significant medical or psychiatric comorbidities. These participants were randomized into two groups: 125 women received flexible doses of sertraline (50–100 mg/day) beginning at symptom onset and continuing until menstruation began, while 127 women received placebo treatment following the same schedule.

What were the most important findings?

The study demonstrated that symptom-onset treatment with sertraline significantly reduced the severity of PMDD symptoms compared to placebo. Specifically, women treated with sertraline showed statistically significant improvements in depressive symptoms as measured by clinician-rated scales and a significant reduction in the daily record of problem severity, including the anger/irritability subscale. While the reduction in premenstrual tension ratings narrowly missed statistical significance, sertraline outperformed placebo in global improvement ratings and had higher clinical response rates (67% vs. 52%). Noticeably, emission rates were not significantly different. The average duration of sertraline use was only about seven days per menstrual cycle, minimizing exposure to the drug and related side effects. Adverse effects, primarily nausea and insomnia, were more common in the sertraline group, but abrupt discontinuation did not lead to withdrawal symptoms. These findings indicate that targeted, short-term SSRI treatment timed to symptom onset is effective and well tolerated in managing PMDD.

What are the greatest implications of this study?

This research challenges traditional views that antidepressants require continuous administration to be effective in PMDD treatment by demonstrating that symptom-onset dosing with sertraline is both efficacious and has a favorable side effect profile. This approach minimizes medication exposure and associated adverse effects, potentially improving adherence and reducing treatment costs. It provides a practical strategy to manage PMDD symptoms precisely when needed, aligning with the disorder's cyclical nature. Future research is needed to compare symptom-onset dosing directly with luteal-phase and continuous dosing regimens and to explore treatment strategies for non-responders to symptom-onset sertraline. Clinically, this study supports personalized, flexible pharmacotherapy for PMDD, enhancing therapeutic outcomes while mitigating risks.

December 28, 2023

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What was reviewed?

This paper provides a comprehensive review of premenstrual disorders (PMDs), with a specific focus on premenstrual dysphoric disorder (PMDD). It synthesizes current knowledge regarding the definitions, classification, prevalence, diagnosis, etiology, and treatment of PMDs and PMDD. The review covers consensus guidelines from professional bodies such as the International Society for Premenstrual Disorders (ISPMD), diagnostic criteria from DSM-V and ICD-11, and evaluates various therapeutic approaches, including non-pharmacological interventions, pharmacotherapy (particularly SSRIs), hormonal treatments, novel agents targeting neuroactive steroids, and surgical options. It also highlights challenges in diagnosis, the significant impact on quality of life and suicidality risk, and research gaps.

Who was reviewed?

The review critically assesses a wide body of clinical, epidemiological, and mechanistic studies involving women experiencing PMDs and PMDD worldwide. It references population prevalence data, genetic and neurobiological studies, clinical trials evaluating treatments such as SSRIs and combined oral contraceptive pills (COCPs), and guidelines developed by multidisciplinary expert panels. The authors draw upon systematic reviews, randomized controlled trials, observational studies, and consensus statements to present a balanced perspective. The review specifically incorporates data related to symptom measurement tools like the Daily Record of Severity of Problems (DRSP) and discusses patient management strategies applicable in primary and specialist care settings.

What were the most important findings?

The review clarifies that PMDD represents a severe subset of PMDs, affecting approximately 5% of women, and carries significant physical, psychological, and social burdens, including a markedly increased risk of suicide attempts. It emphasizes that PMDD symptoms arise from abnormal sensitivity to normal menstrual hormonal fluctuations, especially allopregnanolone's paradoxical effect on GABA-A receptors, rather than altered hormone levels per se. Genetic factors, serotonergic dysregulation, inflammation, and stress history also contribute to pathophysiology. Accurate diagnosis depends on prospective symptom tracking over at least two menstrual cycles to confirm symptom cyclicity, severity, and functional impact.

Treatment must be multidisciplinary and individualized. SSRIs are the first-line pharmacological treatment, acting rapidly and effectively even when dosed intermittently in the luteal phase or symptom-onset, mitigating side effects associated with continuous dosing. Hormonal treatments, particularly COCPs containing drospirenone, show efficacy, though hormonal sensitivity varies and progestogen intolerance complicates therapy. Emerging therapies targeting allopregnanolone modulation and 5-alpha reductase inhibitors are under investigation but require further evidence. GnRH analogues and surgical oophorectomy remain options for severe refractory cases but carry significant risks, including bone density loss. Non-pharmacological approaches, including cognitive behavioral therapy (CBT), dietary modifications, and supplements (calcium, magnesium, vitamin B6), provide complementary benefits.

What are the greatest implications of this review?

This review bridges the knowledge gap between evolving scientific insights into PMDD's neuroendocrine mechanisms and practical clinical management strategies. It advocates for a precision medicine approach tailored to individual hormonal sensitivities and symptom profiles. By synthesizing current evidence, it empowers clinicians to improve diagnostic accuracy through prospective symptom monitoring, recognize the disorder’s profound impact on mental health, and adopt evidence-based treatments, minimizing side effects. The emphasis on rapid SSRI efficacy and flexible dosing regimens offers clinicians practical tools to enhance adherence and patient quality of life. Moreover, highlighting the multidisciplinary nature of optimal care and emerging pharmacotherapies signals future directions for research and therapeutic innovation.

September 16, 2015

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What was reviewed?

This paper presents a thorough review of the epidemiology, pathophysiology, and treatment options for premenstrual dysphoric disorder (PMDD). It examines PMDD’s diagnostic criteria as established by DSM-5, highlighting the importance of mood symptoms and prospective symptom tracking for accurate diagnosis. The review synthesizes current understanding of PMDD’s biological underpinnings, including the role of neurosteroids like allopregnanolone, estrogen’s influence on serotonergic systems, brain-derived neurotrophic factor (BDNF) polymorphisms, and the impact of stress and inflammation. It further explores neuroimaging and psychophysiological findings that differentiate PMDD from other affective disorders. The review then evaluates therapeutic approaches, emphasizing SSRIs as the first-line treatment and discussing intermittent dosing strategies, hormonal therapies, cognitive-behavioral therapy, and alternative treatments.

Who was reviewed?

The authors critically analyzed studies involving women diagnosed with PMDD across community and clinical samples worldwide. The review includes epidemiological data, genetic and neurobiological research, and clinical trials assessing treatment efficacy. It references consensus guidelines from psychiatric and gynecological professional bodies, neuroimaging studies comparing PMDD patients to healthy controls, and meta-analyses evaluating pharmacologic and psychotherapeutic interventions. The paper also integrates findings from animal models of hormone sensitivity and neurosteroid modulation relevant to PMDD pathophysiology.

What were the most important findings?

Women with PMDD do not differ in peripheral hormone levels but show altered GABA_A receptor function and neurosteroid sensitivity, contributing to affective symptoms. Estrogen’s modulation of serotonin receptors and transporters further implicates serotonergic dysregulation in PMDD. Genetic factors such as polymorphisms in estrogen receptor and serotonin transporter genes, as well as BDNF variants, may increase susceptibility. Stress history correlates with PMDD diagnosis and may influence neurosteroid responses and HPA axis regulation. Neuroimaging reveals structural and functional brain differences in areas regulating emotion and cognition, including the amygdala and prefrontal cortex, with altered GABA and glutamate levels detected in PMDD patients.

Regarding treatment, SSRIs demonstrate moderate to large effect sizes in symptom reduction, with rapid onset of action allowing for intermittent or symptom-onset dosing regimens that minimize side effects and improve adherence. Hormonal treatments, particularly combined oral contraceptives containing drospirenone, show some efficacy but with high placebo responses and variable individual tolerance. Cognitive-behavioral therapy provides sustained symptom improvement and complements pharmacotherapy, though combined approaches do not necessarily enhance outcomes beyond monotherapy. Alternative therapies such as calcium supplementation and omega-3 fatty acids offer limited benefits and require further validation.

What are the greatest implications of this review?

This review consolidates the complex neurobiological, genetic, and psychosocial factors contributing to PMDD, underscoring its distinction from other mood disorders and the importance of precision in diagnosis and treatment. It reinforces SSRIs as the cornerstone of pharmacotherapy and advocates for flexible dosing strategies tailored to symptom patterns, enhancing patient quality of life and medication adherence. The emerging understanding of neurosteroid modulation opens promising avenues for novel therapeutics targeting GABAergic pathways. The findings call for multidisciplinary, individualized treatment plans incorporating pharmacological, psychological, and lifestyle interventions. The review highlights gaps in long-term safety data for hormonal therapies and the need for improved diagnostic tools and biomarkers. Overall, it equips clinicians with an evidence-based framework to optimize PMDD management and encourages ongoing research to address unmet clinical needs.

October 7, 2024

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What was reviewed?

This paper systematically reviewed the existing literature on biological rhythm disruptions in women with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). The focus was on circadian and other biological rhythms, including sleep–wake cycles, melatonin secretion, core body temperature, cortisol, prolactin, and thyroid-stimulating hormone levels. The review synthesized findings from 25 studies that compared women diagnosed with PMS/PMDD to healthy controls, assessing both subjective and objective markers of biological rhythms to clarify their association with premenstrual symptoms and the underlying pathophysiology.

Who was reviewed?

The review analyzed studies published between 1989 and 2022 across multiple countries, involving women aged 18 to 45 diagnosed with PMS or PMDD using standardized criteria, mostly DSM-III-R to DSM-5. The total sample sizes varied widely, with some studies including over 600 participants. Healthy control groups consisted of women without PMS/PMDD or psychiatric disorders. Studies included diverse methodologies such as polysomnography, actimetry, hormonal assays, core body temperature measurements, and subjective sleep quality assessments, enabling comprehensive evaluation of biological rhythms in the premenstrual context.

What were the most important findings?

The review found consistent evidence that women with PMS/PMDD exhibit significant disruptions in biological rhythms compared to healthy controls. Notably, they present with lower nocturnal melatonin levels, elevated nighttime core body temperature, and poorer subjective sleep quality, all indicating altered circadian regulation. While objective sleep parameters and activity rhythms showed mixed or nonsignificant differences, hormonal rhythms such as cortisol and prolactin demonstrated inconsistent findings across studies. These rhythm disturbances likely contribute to the psychological and physiological symptoms experienced during the luteal phase. The review highlights melatonin dysregulation as a potential key factor in PMS/PMDD pathophysiology and calls for further research into circadian-based mechanisms and their therapeutic implications.

What are the greatest implications of this review?

This review highlights the importance of biological rhythm disruptions in PMS and PMDD, positioning circadian dysfunction, especially melatonin alterations, as a promising target for understanding symptom development and designing novel interventions. Clinicians should recognize that sleep complaints and temperature regulation abnormalities in these disorders reflect deeper circadian disturbances rather than isolated symptoms. The review advocates for integrating chronobiological assessments into clinical evaluations and exploring circadian-modulating treatments, such as light therapy or melatonin supplementation, to improve patient outcomes. It also calls for future research to clarify inconsistent findings in hormonal rhythms and to investigate the potential of personalized circadian therapies tailored to premenstrual symptom profiles.

July 15, 2014

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What was reviewed?

This paper reviewed the neurological basis of premenstrual dysphoric disorder (PMDD), emphasizing its recognition as a distinct mood disorder linked to menstrual cycle hormonal fluctuations. It summarized advances in brain imaging and neurophysiological studies demonstrating altered brain function in PMDD patients, particularly in prefrontal cortex regions involved in executive function and emotion regulation. The review highlighted the significance of hormone sensitivity, especially to estradiol and progesterone, and how these hormonal changes affect cerebral blood flow and neural activation patterns in women with PMDD compared to controls.

Who was reviewed?

The review focused on women diagnosed with PMDD according to rigorous DSM criteria, including prospective symptom tracking. It integrated findings from neuroimaging studies (fMRI, PET), hormonal manipulation paradigms (gonadotropin-releasing hormone agonist followed by hormone add-back), and psychophysiological assessments conducted on small to moderate cohorts of women with PMDD and matched healthy controls. The studies collectively evaluated brain activation, cerebral blood flow, neurotransmitter activity, and behavioral correlates of hormone-driven mood symptoms.

What were the most important findings?

The review underscored that women with PMDD show abnormal activation in the dorsolateral prefrontal cortex and medial frontal gyrus during cognitive tasks, regardless of hormonal state, suggesting a trait vulnerability. Brain activation differences correlated with symptom severity, especially irritability, which is a hallmark PMDD symptom. The cerebellum also showed heightened activity in PMDD. The disorder’s symptom manifestation requires the fluctuating hormonal environment of the luteal phase, implicating hormone sensitivity as a key pathophysiological factor. Unlike other mood disorders, PMDD’s brain dysfunction is specifically linked to normal hormonal changes rather than baseline abnormalities, explaining the cyclical nature of symptoms.

What are the greatest implications of this review?

This review clarifies that PMDD arises from an interaction between inherent brain vulnerabilities and normal hormonal fluctuations, particularly estradiol and progesterone. It encourages clinicians to view PMDD as a neurobiologically distinct disorder with predictable symptom timing linked to menstrual phases. These insights justify targeted hormonal and neuropharmacological treatments and support ongoing research into brain-based biomarkers and personalized therapies. The findings also highlight the importance of early diagnosis and symptom monitoring to improve patient care and quality of life for affected women.

July 31, 2024

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What was studied?

This cross-sectional study assessed the prevalence of probable premenstrual dysphoric disorder (PMDD) among Hungarian women and examined the relationship between probable PMDD, anxio-depressive symptom severity, and overall well-being. The researchers aimed to validate a retrospective DSM-5-based PMDD screening tool in this population and explore psychological symptom patterns related to PMDD, using standardized questionnaires for depression, anxiety, and well-being.

Who was studied?

The study included 112 women of reproductive age from Hungary with regular menstrual cycles who were not using hormonal contraceptives and had no significant neurological, psychiatric, endocrine, or gynecological disorders. The participants were divided into two groups based on PMDD screening results: a probable PMDD group (n=67) and a non-PMDD group (n=45). They completed validated questionnaires measuring probable PMDD symptoms, anxio-depressive severity, and subjective well-being.

What were the most important findings?

The study revealed a surprisingly high prevalence of probable PMDD at nearly 60%, exceeding international estimates, which the authors attribute partly to retrospective screening limitations and recruitment bias. Women with probable PMDD reported significantly greater depressive and anxiety symptoms and lower well-being than controls, regardless of menstrual cycle phase. Logistic regression confirmed that higher anxiety and depression scores predicted probable PMDD diagnosis. The findings corroborate prior evidence that PMDD involves substantial psychological distress that impacts life quality. Notably, anxiety symptom severity did not vary significantly across cycle phases, suggesting persistent affective symptoms. These results highlight the challenges of accurate PMDD diagnosis, especially given the burden of prospective symptom tracking, and underscore the need for tailored psychological assessment and treatment strategies.

What are the greatest implications of this study?

This study emphasizes that probable PMDD is a prevalent and underrecognized condition that severely affects women's mental health and well-being, even beyond the premenstrual phase. It highlights the utility and limitations of retrospective screening tools in estimating PMDD prevalence and calls for improved diagnostic protocols that balance accuracy with practicality. The findings advocate for personalized mental health support and further research to refine diagnostic tools and treatment approaches tailored to the needs of women with PMDD, especially in underrepresented populations.

June 21, 2024

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What was studied?

This cross-sectional study examined the prevalence of premenstrual dysphoric disorder (PMDD) and its associated factors among high school female students in Finote Selam town, northwest Ethiopia. Using DSM-5 criteria and self-administered questionnaires, the study aimed to quantify PMDD prevalence and identify clinical, psychosocial, and menstrual-related predictors affecting this population's mental health and academic performance.

Who was studied?

The research included 548 high school female students aged 15 to 22 years with regular menstrual cycles, excluding those with serious illness or recent school transfers. Participants completed validated questionnaires assessing PMDD symptoms, depression, perceived stress, social support, menstrual characteristics, and behavioral factors such as substance use.

What were the most important findings?

The study found a high PMDD prevalence (33%), with physical symptoms like breast tenderness and fatigue being most common. Key factors significantly associated with PMDD included irregular menstrual cycles, depressive symptoms, longer menstruation duration, and high perceived stress. PMDD significantly impacted academic performance, social functioning, and psychological well-being. The findings aligned with prior Ethiopian and African studies but were higher than reports from developed countries, possibly reflecting sociocultural, infrastructural, and menstrual hygiene differences influencing symptom expression and health-seeking behaviors.

What are the greatest implications of this study?

This study highlights PMDD as a prevalent and underrecognized condition adversely affecting adolescent females' mental health and educational outcomes in low-resource settings. It emphasizes the urgent need for early screening, stress reduction interventions, and targeted mental health support within primary healthcare and school systems. Addressing menstrual health education, improving hygiene management, and mitigating psychosocial stressors could reduce PMDD burden and improve quality of life. These insights guide clinicians and policymakers toward culturally sensitive, accessible strategies for PMDD diagnosis and management in similar populations.

May 23, 2024

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What was studied?

This institutional-based cross-sectional study investigated the prevalence and determinants of premenstrual dysphoric disorder (PMDD) among regular undergraduate female students at Hawassa University, Ethiopia. It aimed to quantify PMDD prevalence using a standardized premenstrual symptoms screening tool and to identify socio-demographic, clinical, psychological, gynecological, and behavioral factors associated with PMDD in this population.

Who was studied?

The study included 374 regular female undergraduate students aged 18 and above from the College of Medicine and Health Sciences at Hawassa University. Participants were selected using stratified random sampling and completed a self-administered questionnaire assessing premenstrual symptoms, menstrual characteristics, social support, contraceptive use, and behavioral factors. Students with illnesses or absent during data collection were excluded.

What were the most important findings?

The study found a high PMDD prevalence of approximately 63% among participants, significantly higher than many global estimates. Key factors independently associated with PMDD included severe menstrual pain, irregular menstrual cycles, poor or moderate social support, and contraceptive use. Severe dysmenorrhea exacerbated emotional and behavioral symptoms, while social support appeared protective. These findings indicate that PMDD substantially impairs daily functioning, including academic performance, and is influenced by a complex interplay of physiological, psychological, and social factors. The study emphasizes the importance of early screening and tailored interventions to mitigate PMDD's impact on student well-being and success.

What are the greatest implications of this study?

This study highlights PMDD as a prevalent and underrecognized condition with significant negative effects on young women’s mental health and academic performance in a low-resource setting. It underscores the urgent need for integrating PMDD screening and psychosocial support into university health services, especially focusing on managing menstrual pain, providing social support, and carefully evaluating contraceptive use. These findings advocate for multidisciplinary interventions that address both physical and psychological determinants of PMDD, aiming to improve quality of life and academic outcomes. Moreover, the research supports policymakers and educators in developing targeted health promotion programs and facilitating access to effective treatment for PMDD in similar contexts.

February 10, 2020

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What was studied?

This review analyzed existing literature on the management and treatment challenges of comorbid Premenstrual Dysphoric Disorder (PMDD) in women diagnosed with Bipolar Disorder (BD). It focused on identifying pharmacological and non-pharmacological strategies to manage the complex interaction of mood symptoms in this dual-diagnosed population.

Who was studied?

The review included data from a small number of case reports and case series comprising six women with comorbid BD and PMDD. Additionally, it integrated broader findings from separate research on BD and PMDD to inform treatment hypotheses for this specific comorbid group.

What were the most important findings?

The study emphasized that optimal management requires first stabilizing bipolar symptoms using mood stabilizers such as lithium and lamotrigine, followed by targeted treatment of PMDD symptoms, typically through estroprogestins during euthymic BD phases. Antidepressants may be cautiously used during depressive episodes but carry a risk of inducing manic switches. Atypical antipsychotics may help manage manic episodes and some PMDD symptoms. Psychotherapeutic interventions like cognitive behavioral therapy (CBT), including internet-based delivery, show promise as adjuncts, though evidence specific to comorbid BD/PMDD is limited. Alternative treatments such as lifestyle modifications, supplements (calcium, vitamin B6), and mind-body therapies have been reported anecdotally. The complexity of comorbid BD/PMDD necessitates individualized, multimodal treatment approaches, yet randomized controlled trials (RCTs) in this population remain scarce, highlighting a critical gap in evidence.

What are the greatest implications of this study?

This review underscores the clinical challenges of managing comorbid BD and PMDD, a condition marked by more severe mood instability and poorer outcomes than either disorder alone. It advocates for careful mood stabilization before addressing PMDD symptoms to prevent exacerbations and cautions regarding antidepressant use in BD due to manic risk. The limited but encouraging data on hormonal treatments and psychotherapy suggest these as valuable components of integrated care. The paucity of RCTs specific to comorbid BD/PMDD calls for urgent research to establish evidence-based protocols. Clinicians must adopt tailored, multidisciplinary strategies combining pharmacological, psychological, and lifestyle interventions to improve quality of life in this vulnerable population.

February 4, 2020

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What was studied?

This review comprehensively examined the role of the neuroactive steroid allopregnanolone (ALLO), a potent positive allosteric modulator of the GAB_A-A receptor (GABA_A-R), in the pathophysiology of premenstrual dysphoric disorder (PMDD). It focused on the evidence supporting altered sensitivity or dysregulation of GABA_A-Rs in response to ALLO fluctuations across the menstrual cycle, linking these neurobiological changes to the characteristic mood symptoms and stress sensitivity of PMDD.

Who was studied?

As a review article, this paper synthesized findings from both human clinical studies and animal models, particularly rodents, to elucidate mechanisms underlying PMDD. Human studies included neuroendocrine and neurophysiological investigations of women diagnosed with PMDD compared to controls, focusing on hormonal dynamics, receptor sensitivity, stress response, and symptomatology. Rodent models primarily involved progesterone or ALLO withdrawal paradigms to mimic PMDD symptoms and investigate GABA_A-R subunit changes and behavior.

What were the most important findings?

The review highlighted that PMDD is not caused by abnormal circulating hormone levels but rather by impaired CNS sensitivity to normal fluctuations of ALLO. In rodent models, rapid withdrawal from progesterone or ALLO induces anxiety- and depression-like behaviors linked to upregulation of the GABA_A-R α4 subunit, implicating receptor plasticity in symptom manifestation. Clinical studies in women with PMDD demonstrated altered GABA_A-R function, such as lack of ALLO-induced sedation during the luteal phase and elevated anxiety-potentiated startle responses, indicating dysfunctional receptor adaptation to hormonal changes. The review also detailed how ALLO modulates the hypothalamic-pituitary-adrenal (HPA) axis, with women with PMDD showing altered stress responsivity likely due to impaired ALLO-GABA_A-R interaction, leading to heightened stress sensitivity during the luteal phase. Importantly, treatments effective in PMDD, including selective serotonin reuptake inhibitors (SSRIs) and novel GABA-modulating drugs appear to normalize ALLO-GABA signaling, further supporting this pathophysiological model.

What are the greatest implications of this study?

This review consolidates strong evidence that PMDD is fundamentally a disorder of impaired neurosteroid modulation of GABA_A-Rs, rather than hormone level abnormalities alone, positioning GABA_A-R plasticity and ALLO sensitivity as central to its pathophysiology. Understanding this mechanism clarifies why PMDD symptoms cyclically align with hormonal fluctuations and why patients experience heightened stress sensitivity. Clinically, this suggests that future therapeutic strategies should target the neurosteroid-GABAergic system directly to restore receptor function or stabilize neurosteroid levels, promising more rapid and effective symptom relief than traditional antidepressants. Moreover, this framework encourages the development and testing of novel GABAergic agents tailored to PMDD and related reproductive mood disorders, enhancing personalized medicine for affected women worldwide.

March 16, 2022

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What was studied?

This review examined the neuroendocrine and neurobiological mechanisms underlying Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD), emphasizing their classification as centrally based disorders influenced by hormonal fluctuations. It also discussed current and novel therapeutic strategies targeting neuroactive steroids and neuroinflammation in PMS/PMDD.

Who was studied?

The review synthesized findings from clinical, neuroimaging, pharmacological, and molecular studies involving women diagnosed with PMS and PMDD across various reproductive stages, incorporating prospective symptom tracking and biochemical assessments to explore hormone-neurotransmitter interactions and brain sensitivity.

What were the most important findings?

The review highlighted that PMS and PMDD are neuro-hormonal disorders marked by increased central nervous system sensitivity to normal cyclical fluctuations of estrogens and progesterone, especially its metabolite allopregnanolone. This neurosteroid modulates GABA_A receptor activity, affecting mood regulation, and its altered function correlates with emotional and behavioral symptoms in PMDD. Impairments in opioid and serotonergic systems also contribute. Neuroinflammation via GABAergic pathways and elevated pro-inflammatory markers may play a role. Treatment focuses on stabilizing hormones, mainly with combined hormonal contraception, and modulating neuroactive steroids. SSRIs reduce symptoms by affecting serotonin pathways. Novel therapies targeting neurosteroid pathways, including progesterone receptor modulators, 5α-reductase inhibitors, and GABA_A receptor antagonists, show promise. However, treatment responses vary depending on hormonal regimens and individual profiles. Emerging evidence also suggests the gut-brain axis and microbiome influence symptom severity through neuroimmune interactions, though further study is needed.

What are the greatest implications of this study?

This review consolidates the understanding of PMS/PMDD as disorders rooted in neuroendocrine and neurochemical dysregulation, shifting the clinical perspective from purely gynecological or psychiatric frameworks to integrated neurobiological models. It underscores the necessity for personalized therapeutic approaches that combine hormonal regulation with neuroactive agents. The identification of neuroinflammation and microbiome influences opens novel research pathways and potential non-hormonal interventions. Clinicians should consider both established and emerging treatments to optimize symptom control, and researchers must prioritize elucidating the gut-brain interactions and refining neurosteroid-targeted therapies for improved patient outcomes.

May 27, 2022

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What was studied?

This cross-sectional pilot study examined the gut microbiota characteristics in women experiencing premenstrual disorders (PMDs) compared to healthy controls, aiming to uncover microbial associations with the severity of premenstrual symptoms and to evaluate inflammatory markers indicative of bacterial translocation.

Who was studied?

The study involved 43 Japanese women aged 20 to 45 years, with 21 women experiencing PMDs severe enough to disrupt social functioning and 22 controls without significant premenstrual symptoms, all selected to exclude confounding factors like recent medication use, neuropsychiatric disorders, and gastrointestinal diseases.

What were the most important findings?

The study revealed that although overall gut microbial diversity did not differ significantly, women with PMDs exhibited lower levels of the Bacteroidetes phylum and reduced abundance of butyrate-producing genera such as Butyricicoccus and Megasphaera, alongside decreased Parabacteroides, a GABA-related genus, while Anaerotaenia was elevated; these microbial shifts correlated with symptom severity, but inflammatory markers linked to endotoxemia showed no group differences, suggesting unique microbiome alterations in PMDs distinct from major depressive disorder.

What are the greatest implications of this study?

These findings suggest that specific gut microbiota alterations, particularly reductions in beneficial butyrate- and GABA-producing bacteria, may underlie premenstrual symptom severity through the gut-brain axis, highlighting potential microbiome-based biomarkers and therapeutic targets for PMDs, and warranting further longitudinal and intervention research to establish causality and clinical applications.

February 1, 2023

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What was reviewed?

This paper conducted a comprehensive review of current research on the effects of dietary and nutritional therapies on premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) symptoms. The authors analyzed data from various studies accessed through major databases like PubMed, ScienceDirect, and Scopus, focusing on dietary patterns, macro- and micronutrients, supplements, and their relationship to PMS symptom severity and management.

Who was reviewed?

The review synthesized findings from multiple clinical and observational studies involving women of reproductive age experiencing PMS, encompassing diverse populations and dietary behaviors. The included studies examined correlations between specific nutrients, food groups, supplements, and premenstrual symptom patterns.

What were the most important findings?

The review emphasized that while diet plays an important role in modulating PMS symptoms, the scientific evidence remains limited and inconsistent, especially regarding macronutrient intake—no strong correlations were found between protein, fat, carbohydrates, or fiber consumption and PMS symptoms. However, micronutrients such as calcium, magnesium, vitamin D, and B vitamins showed potential benefits in symptom reduction. Specifically, calcium and vitamin D supplementation were linked to decreased PMS symptom severity and improved quality of life, although definitive clinical recommendations require further trials. The role of vitamin B6 and broad-spectrum micronutrient supplementation was also noted, with both showing some efficacy in managing PMS-related psychological symptoms. Herbal supplements like evening primrose oil and curcumin demonstrated mixed results and warrant additional research. The review also highlighted the influence of dietary patterns, showing Western diets rich in processed foods and refined sugars positively associate with increased PMS symptoms, whereas traditional and healthy diets rich in fruits, vegetables, and whole foods correlate with reduced symptom severity.

What are the greatest implications of this review?

This review underscores the potential of nutritional therapy as a complementary approach to PMS symptom management. It calls for increased awareness among healthcare providers to educate women on adopting balanced dietary habits that may mitigate symptoms. Given the current limitations in evidence, it encourages personalized nutritional counseling and advocates for further research integrating microbiome and metabolomic insights to refine diet-based interventions. This can potentially facilitate the development of microbiome-targeted dietary strategies to improve PMS and PMDD outcomes.

March 5, 2025

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What was studied?

This study conducted a cross-sectional analysis to examine the association between dietary patterns and premenstrual disorders (PMDs), including premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), among young women in China. Using data from 1382 female college students, dietary intake and PMD symptoms were assessed to identify how regional and specific dietary patterns influence the prevalence and severity of PMDs.

Who was studied?

The participants were female medical and health science students aged 17–30 years from Sichuan University in China. Among them, 24.4% met the criteria for PMDs, with 22.2% classified as PMS and 2.17% as probable PMDD. The study evaluated their dietary habits via food frequency questionnaires, assessed PMD symptoms using a validated tool, and controlled for lifestyle, psychological, and demographic factors.

What were the most important findings?

The study identified three main dietary patterns: Traditional North China Diet (TNCD), Traditional South China Diet (TSCD), and Lacto-ovo Vegetarian Diet (LVD). The TSCD, characterized by high intake of rice, red meat, poultry, and fresh vegetables, showed a statistically significant inverse association with PMDs. This means higher adherence to TSCD correlated with reduced PMD prevalence and symptom severity across both PMS and PMDD subtypes. Notably, rice consumption alone was inversely associated with PMDs, potentially due to its effects on brain serotonin regulation and mood stabilization. While animal protein sources like red meat and poultry provided essential micronutrients linked to lower PMD risks, such as vitamin D, B vitamins, iron, and zinc, their role remains complex due to variability in hormonal content and potential metabolic effects. The study also found that this dietary association was independent of comorbid depression/anxiety, BMI, and other confounders, and was robust across different symptom severities and onset timings. The findings suggest that localized dietary patterns may play a crucial role in managing or preventing PMDs, although causal inferences are limited by the cross-sectional design.

What are the greatest implications of this study?

This research highlights that adherence to regional dietary patterns, particularly the Traditional South China Diet, may serve as an effective, culturally relevant approach to reduce PMD burden in young women. While the study does not directly involve microbiome signatures, the dietary patterns identified align with diets known to influence gut microbial composition and function, suggesting an indirect link whereby diet modulates PMD symptoms, potentially via the gut-brain axis and microbiome-related pathways. Clinicians should consider dietary counseling tailored to local food practices as part of holistic PMD management. Furthermore, the study underscores the need for prospective and mechanistic research to confirm these associations and explore how dietary modulation of the gut microbiome can be leveraged to develop targeted microbiome-based interventions for PMDs. Such insights could pave the way for non-pharmacological strategies that complement existing therapies, improving patient outcomes through diet and microbiome health.

References

Premenstrual dysphoric disorder-an undervalued diagnosis? A cross-sectional study in Hungarian women. Pataki B, Kiss BL, Kálmán S, Kovács I.. (Compr Psychoneuroendocrinol. 2024 Jul 31;20:100256.)
Premenstrual dysphoric disorder: General overview, treatment strategies, and focus on sertraline for symptom-onset dosing. Andrade C.. (Indian J Psychiatry. 2016 Jul-Sep;58(3):329-331.)
Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Hantsoo, L., & Epperson, C. N. (2015). (Current Psychiatry Reports, 17(11), 87.)
Premenstrual disorders and PMDD - a review. Cary, E., & Simpson, P. (2023). (Best Practice & Research Clinical Endocrinology & Metabolism, 38(1), 101858.)
Premenstrual dysphoric disorder and the brain. Epperson CN.. (Am J Psychiatry. 2013 Mar;170(3):248-52)
Biological rhythms in premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Nexha, A., Caropreso, L., de Azevedo Cardoso, T. et al.. (BMC Women’s Health 24, 551 (2024))
Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Hantsoo, L., & Epperson, C. N. (2015). (Current Psychiatry Reports, 17(11), 87.)
Premenstrual dysphoric disorder: General overview, treatment strategies, and focus on sertraline for symptom-onset dosing. Andrade C.. (Indian J Psychiatry. 2016 Jul-Sep;58(3):329-331.)
Premenstrual disorders and PMDD - a review. Cary, E., & Simpson, P. (2023). (Best Practice & Research Clinical Endocrinology & Metabolism, 38(1), 101858.)
Premenstrual dysphoric disorder-an undervalued diagnosis? A cross-sectional study in Hungarian women. Pataki B, Kiss BL, Kálmán S, Kovács I.. (Compr Psychoneuroendocrinol. 2024 Jul 31;20:100256.)
Premenstrual dysphoric disorder: General overview, treatment strategies, and focus on sertraline for symptom-onset dosing. Andrade C.. (Indian J Psychiatry. 2016 Jul-Sep;58(3):329-331.)
Determinants of premenstrual dysphoric disorder and associated factors among regular undergraduate students at Hawassa University Southern, Ethiopia, 2023: institution-based cross-sectional study.. Chekol AT, Reta Y, Ayinewa F, Hailu L, Tesema M, Wale MA.. (BMC Public Health. 2024 May 23;24(1):1390)
Premenstrual Dysphoric Disorder: Etiology, Risk Factors and Biomarkers. In: Martin, C.R., Preedy, V.R., Patel, V.B., Rajendram, R. (eds) Handbook of the Biology and Pathology of Mental Disorders.. Keijser, R., Hysaj, E., Opatowski, M., Yang, Y., Lu, D. (2024). (Springer, Cham.)
Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle. Hantsoo L, Epperson CN.. (Neurobiol Stress. 2020 Feb 4;12:100213)
Premenstrual dysphoric disorder and the brain. Epperson CN.. (Am J Psychiatry. 2013 Mar;170(3):248-52)
The Role of Serotonin in Premenstrual Syndrome. RAPKIN, ANDREA J. MD.. (Clinical Obstetrics and Gynecology 35(3):p 629-636, September 1992)
Biological rhythms in premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Nexha, A., Caropreso, L., de Azevedo Cardoso, T. et al.. (BMC Women’s Health 24, 551 (2024))
Premenstrual disorders and PMDD - a review. Cary, E., & Simpson, P. (2023). (Best Practice & Research Clinical Endocrinology & Metabolism, 38(1), 101858.)
Characteristics of the gut microbiota in women with premenstrual symptoms: A cross-sectional study. Takeda T, Yoshimi K, Kai S, Ozawa G, Yamada K, Hiramatsu K.. (PLoS One. 2022 May 27;17(5):e0268466)
Comorbid Premenstrual Dysphoric Disorder in Women with Bipolar Disorder: Management Challenges. Sepede G, Brunetti M, Di Giannantonio M.. (Neuropsychiatr Dis Treat. 2020 Feb 10;16:415-426)
Comorbid Premenstrual Dysphoric Disorder in Women with Bipolar Disorder: Management Challenges. Sepede G, Brunetti M, Di Giannantonio M.. (Neuropsychiatr Dis Treat. 2020 Feb 10;16:415-426)
Premenstrual Syndrome and Premenstrual Dysphoric Disorder as Centrally Based Disorders. Nappi, R. E., Cucinella, L., Bosoni, D., Righi, A., Battista, F., Molinaro, P., Stincardini, G., Piccinino, M., Rossini, R., & Tiranini, L. (2022).. (Endocrines, 3(1), 127-138)
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Association of Premenstrual Syndrome and Premenstrual Dysphoric Disorder with Bulimia Nervosa and Binge-eating Disorder in a Nationally Representative Epidemiological Sample. Nobles, Carrie J., Jennifer J. Thomas, Sarah E. Valentine, Monica W. Gerber, Adin S. Vaewsorn, and Luana Marques. (The International Journal of Eating Disorders 49, no. 7 (2016): 641. Accessed May 20, 2025)
Premenstrual Syndrome and Premenstrual Dysphoric Disorder as Centrally Based Disorders. Nappi, R. E., Cucinella, L., Bosoni, D., Righi, A., Battista, F., Molinaro, P., Stincardini, G., Piccinino, M., Rossini, R., & Tiranini, L. (2022).. (Endocrines, 3(1), 127-138)
Premenstrual Syndrome and Premenstrual Dysphoric Disorder as Centrally Based Disorders. Nappi, R. E., Cucinella, L., Bosoni, D., Righi, A., Battista, F., Molinaro, P., Stincardini, G., Piccinino, M., Rossini, R., & Tiranini, L. (2022).. (Endocrines, 3(1), 127-138)
Characteristics of the gut microbiota in women with premenstrual symptoms: A cross-sectional study. Takeda T, Yoshimi K, Kai S, Ozawa G, Yamada K, Hiramatsu K.. (PLoS One. 2022 May 27;17(5):e0268466)
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Characteristics of the gut microbiota in women with premenstrual symptoms: A cross-sectional study. Takeda T, Yoshimi K, Kai S, Ozawa G, Yamada K, Hiramatsu K.. (PLoS One. 2022 May 27;17(5):e0268466)
Lactobacillus Paragasseri OLL2809 Improves Premenstrual Psychological Symptoms in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Study. Sato, Asako, Akika Fukawa-Nagira, and Toshihiro Sashihara.. (Nutrients 15, no. 23 (2023): 4985. Accessed May 22, 2025)
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Association between dietary patterns and premenstrual disorders: A cross-sectional analysis of 1382 college students in China.. Shi, X., Chen, M., Pan, Q., Zhou, J., Liu, Y., Jiang, T., Lin, Y., Huang, J., Shen, X., Lu, D., & Li, Y. (2024).. (Food & Function, 15(4), 4170–4179.)
Impact of nutritional diet therapy on premenstrual syndrome.. Siminiuc, R., & Ţurcanu, D. (2023).. (Frontiers in Nutrition, 10, 1079417.)
Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments. Microorganisms. Martinelli S, Nannini G, Cianchi F, Staderini F, Coratti F, Amedei A.. (2023 Sep 27;11(10):2407)
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Premenstrual Dysphoric Disorder (PMDD)

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Microbiome Signature: Premenstrual Dysphoric Disorder (PMDD)

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