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Premenstrual dysphoric disorder
Premenstrual dysphoric disorder
Premenstrual dysphoric disorder
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Premenstrual dysphoric disorder
Other namesLate luteal phase dysphoric disorder
SpecialtyPsychiatry
SymptomsSevere mood swings, depression, irritability, agitation, uneasiness, change in appetite, severe fatigue, anxiety, anger insomnia/hypersomnia, breast tenderness, decreased interest in usual social activities, reduced interest in sexual activity, difficulty in concentration
Usual onsetCan occur anytime during reproductive years
Duration6 days – 3 weeks of cycle
CausesLikely neuro-sensitivity to reproductive hormones
Risk factorsFamily history, history of violence/trauma, smoking, presence of other mental health disorders
Diagnostic methodBased on symptoms & criteria
Differential diagnosisPremenstrual syndrome, depression, anxiety disorder
TreatmentMedication, counselling, lifestyle change, surgery
MedicationSSRIs, drospirenone-containing oral contraceptives, GnRH analogs, cognitive behavioral therapy (CBT)
FrequencyUp to about 8% of menstruating women

Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms. PMDD causes significant distress or impairment in menstruating females during the luteal phase of the menstrual cycle. The symptoms occur in the luteal phase (between ovulation and menstruation), improve within a few days after the onset of menses, and are minimal or absent in the week after menses.[1] PMDD has a profound impact on an individual's quality of life and dramatically increases the risk of suicidal ideation and even suicide attempts.[2] Many women who menstruate of reproductive age experience discomfort or mild mood changes before menstruation, but 5–8% experience severe premenstrual syndrome (PMS), causing significant distress or functional impairment.[3] Within this population of reproductive age, some will meet the criteria for PMDD.

PMDD's exact cause is unknown. Ovarian hormone levels during the menstrual cycle do not differ between those with PMDD and the general population.[4] But because symptoms are present only during ovulatory cycles and resolve after menstruation, it is believed to be caused by fluctuations in gonadal sex hormones or variations in sensitivity to sex hormones.[5]

In 2017, National Institutes of Health researchers discovered that women with PMDD have genetic changes that make their emotional regulatory pathways more sensitive to estrogen and progesterone, as well as their chemical derivatives. The researchers believe this increased sensitivity may cause PMDD symptoms.[6]

Studies have found that those with PMDD are more at risk of developing postpartum depression after pregnancy.[7] PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013.[1] It has 11 main symptoms, of which five must be present for a PMDD diagnosis.[5] Roughly 20% of females have some PMDD symptoms, but either have fewer than five or do not have functional impairment.[8]

The first-line treatment for PMDD is with selective serotonin reuptake inhibitors (SSRIs), which can be administered continuously throughout the menstrual cycle or intermittently, with treatment only during the symptomatic phase (approximately 14 days per cycle).[9] Hormonal therapy with oral contraceptives that contain drospirenone have also demonstrated efficiency in reducing PMDD symptoms.[10] Cognitive behavioral therapy, whether in combination with SSRIs or alone, has shown to be effective in reducing impairment.[11] Dietary modifications and exercise may also be helpful, but studies investigating these treatments have not demonstrated efficacy in reducing PMDD symptoms.[9]

Signs and symptoms

[edit]

Clinicians consider mood symptoms, physical symptoms, and impact on the patient's life in making the diagnosis of PMDD. Mood symptoms include emotional lability (rapidly changing emotions, sensitivity to rejection, etc.), irritability and anger that may lead to conflict, anxiety, feeling on edge, hopelessness, difficulty concentrating, appetite changes, sleeping more or less than usual, or feeling out of control. The physical symptoms are similar to the symptoms of premenstrual syndrome, such as breast tenderness or swelling, joint pain, muscle pain, weight gain, and bloating.[1]

Because of the broad variety in clinical presentation, the onset of symptoms only during or around the luteal phase is key for diagnosing someone with PMDD rather than any other mood disorders.[12] PMDD follows a predictable, cyclic pattern. Symptoms begin in the late luteal phase of the menstrual cycle (after ovulation) and end or are markedly reduced shortly after menstruation begins.[13] On average, the symptoms last six days but can start up to two weeks before menses, meaning symptoms can be felt for up to three weeks out of a cycle. Severe symptoms can begin and worsen until the onset of menstruation, with many not feeling relief until a few days after menstruation ends. The most intense symptoms occur in the week and days leading up to the first day of menstrual blood flow.[14] The symptoms usually cease shortly after the start of the menstrual period or a few days after it ends.[9][15] Various symptom and severity tracking questionnaires exist to document presence and severity of symptoms throughout consecutive menstrual cycles.[16][12]

The International Society for the Study of Premenstrual Disorders (ISPMD) defines two categories of premenstrual disorders: core PMD and variant PMD.

Core PMD has six characteristics, mainly focusing on the cyclical nature of PMDD and its typical onset pre-menses tracked for more than two menstrual cycles. The four classified variant PMDs involve more unexpected variables that cause the onset of premenstrual distress, such as PMD with absent menstruation or premenstrual exacerbation, wherein the symptoms of another preexisting psychological disorder may be heightened as a result of PMDD onset.[12]

Epidemiology

[edit]

About 5-8% of women who are of reproductive age experience severe premenstrual syndrome; most of them also meet the criteria for PMDD.[14]

Pathophysiology

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PMDD mood symptoms are only present in menstruating women. Thus, symptoms do not occur during pregnancy, after menopause, or in women who have anovulatory cycles. Other mood disorders typically persist across all reproductive life events and are independent of a woman's menstrual cycle.[17]

The current consensus on the cause of PMDD is a combination of heightened sensitivity to fluctuating levels of certain hormones (i.e., the reproductive hormones), environmental stress, and genetic predisposition.[12] The sex steroids—estrogen and progesterone—are neuroactive; they have been noted in rat models to be involved in serotonin pathways.[12] Serotonin is involved in mood regulation alongside estrogen, whose receptors are found in the prefrontal cortex and hippocampus—the regions most known for their involvement in regulating one's mood and cognition overall.[14][12]

While the timing of symptoms suggests hormonal fluctuations as the cause of PMDD, a demonstrable hormonal imbalance in women with PMDD has not been identified. Levels of reproductive hormones and their metabolites in women with and without PMDD are indistinguishable.[18][19][20] It is instead hypothesized that women with PMDD are more sensitive to normal levels of hormone fluctuations, predominantly estrogen and progesterone, which produces biochemical events in the nervous system that cause the premenstrual symptoms.[20] These symptoms are more predominant in women with a predisposition to the disorder.[13]

It is apparent that premenstrual disorders are biologically driven and are not only psychological or cultural phenomena. PMDD has been reported by menstruating women worldwide, indicating a biological basis that is not geographically selective.[14] Most psychologists infer that this disorder is caused by both a reaction to hormone flux and also genetic components. There is evidence of heritability of (retrospectively reported) premenstrual symptoms from several twin and family studies done in the 1990s, with the heritability of PMDD proving to be about 56%.[21][22][23]

Genetic factors

[edit]

Whether or not this disorder has a specific genetic basis is still being discussed in the academic community. The possible genetic factors contributing to PMDD also have yet to be thoroughly researched. However, multiple genetic factors that contribute to the moodiness, depression, irritability, increased appetite, trouble sleeping, acne, fluid retention, headaches, nausea, and other symptoms associated with this disorder have recently been identified.[citation needed]

Many studies have noted that a polymorphism of the brain-derived neurotrophic factor gene (BDNF), a gene that helps support neurons in their function and survival in the brain by creating a protein that helps in the growth, maturation, and maintenance of these cells, may play a role in causing PMDD symptoms. This is because the result of this polymorphism mimics the hallmarks of PMDD: volatile moods, depression, and irritability centered around the menstrual cycle. This gene has been studied extensively in its association with depression and, promisingly for PMDD research, mice homozygous for the BDNF polymorphism exhibited anxiety-like traits that fluctuated and changed around the mice's estrus, analogous to the human's menstruation, therefore mimicking some of the symptoms of PMDD.[24]

Risk factors

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Environmental stressors have also been found to increase the risk for PMDD symptoms prospectively.[25][26] Environmental components such as stress, hormonal fluctuation, and epigenetics play a key role in the pathology and onset of the disorder.[6] Some studies have noted evidence of interpersonal trauma (domestic violence, physical or emotional trauma, or substance use) or seasonal changes (making PMDD potentially comorbid with seasonal affective disorder) having an impact on PMDD risk.[9][27] But the most common pre-existing disorder found in those diagnosed with PMDD is major depression, wherein they either had it or were misdiagnosed when they should have only been diagnosed with PMDD.[27] Finally, an easily modifiable risk factor for PMDD is cigarette smoking. One meta-analysis found dramatically increased risk of developing PMDD in menstruating women who smoke.[28]

Relationship to pregnancy and menopause

[edit]

Women with PMDD usually see their symptoms disappear while they are pregnant. Premenstrual dysphoric disorder is primarily a mood disorder that is associated with onset of menstruation; pregnancy, menopause, and hysterectomies all cause menstruation to cease, thereby stopping the proposed sex steroid-/serotonin-caused symptoms from occurring.[29][30] Although one might expect a higher rate of postpartum depression among those with PMDD, a large study of women with prospectively confirmed PMDD did not find a higher prevalence of postpartum depression than in controls.[7][30] If a woman had experienced PPD beforehand, there was found to be a less-than 12% chance of PMDD pathology emerging—hardly any differentiation from the regular population of those who have never experienced postpartum depression.[30] However, PMDD symptoms can get worse following pregnancy or other associated events such as birth and miscarriage.[31]

Mental health comorbidities

[edit]

The lifetime incidence of other psychiatric disorders is high among women with PMDD. An older review article (2002) utilizing the previous edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) which used studies from 1966 to 2002 on PMS and mental health disorders and selected for patients who retrospectively met the diagnostic criteria for PMDD found that major depressive disorder, seasonal affective disorder, and generalized anxiety disorder often co-occur in PMDD.[32] Another systematic review study suggests that patients with bipolar disorder, type I or II, have a higher incidence of PMDD.[33] While the diagnosis of PMDD requires a mental health provider to determine that the symptoms a woman is facing are not due to an underlying mental or physical health condition, it is important to note that other conditions often co-occur and impact the quality of life and treatment plan for people with PMDD. A 2025 study of the Reddit peer support community r/PMDD found that users showed a decrease in associations with depression and anxiety after engaging in the forum, possibly reflecting a reconfiguration of symptom interpretation.[34]

Suicidality

[edit]

Previous links to suicidality and PMS have been made, but women with PMDD are more likely still to consider and attempt suicide even when controlling for mental health comorbidities.[35] Despite the increase in suicidal ideation and attempts in this population, the data currently suggests that suicidal ideation or action is not more likely to occur during the late luteal phase when PMDD symptoms would occur.[36] It is difficult to study whether treatment reduces suicidality because of the multifaceted reasons provided for suicidal ideation. However, treatment has been well documented to reduce physical and emotional symptoms of PMDD.[37][9]

Diagnosis

[edit]

Several expert medical guides provide diagnostic criteria for PMDD. Diagnosis can be supported by having women who are seeking treatment for PMDD use a daily charting method to record their symptoms.[12] Daily charting helps to distinguish when mood disturbances are experienced and allows PMDD to be more easily distinguished from other mood disorders. With PMDD, mood symptoms are present only during the luteal phase, or the last two weeks, of the menstrual cycle.[13] While PMDD mood symptoms are cyclical, other mood disorders are variable or constant over time. Although there is a lack of consensus on the most efficient instrument by which to confirm a PMDD diagnosis, several validated scales for recording premenstrual symptoms include the Calendar of Premenstrual Experiences (COPE), Daily Record of Severity of Problems (DRSP), and Prospective Record of the Severity of Menstruation (PRISM).[38][39] In the context of research, standardized numerical cutoffs are often applied to verify the diagnosis.[38] The difficulty of diagnosing PMDD is one reason that it can be challenging for lawyers to cite the disorder as a defense of crime in the very rare cases where PMDD is allegedly associated with criminal violence.[40]

DSM-5

[edit]

The DSM-5 established seven criteria (A through G) for the diagnosis of PMDD, which are paraphrased below.[1] There is overlap between the criteria for PMDD in the DSM-5 and the criteria found in the Daily Record of Severity of Problems (DRSP).[38][39]

According to the DSM-5, a diagnosis of PMDD requires the presence of at least five of these symptoms, with one of the symptoms being numbers 1–4. These symptoms should occur during the week before menses and remit after initiation of menses. To meet the criteria for the diagnosis, the symptoms should be charted prospectively for two consecutive ovulation cycles to confirm the temporal and cyclical nature of the symptoms. The symptoms should also be severe enough to affect normal work, school, social activities, and/or relationships with others.

The symptoms of Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year and must have caused significant impairment in family, work, school, or social functioning. (Criterion D).

Timing

Criterion A: During most menstrual cycles throughout the past year, at least five of the symptoms outlined in Criterion B and Criterion C must be present in the final week before the onset of menses, must start to improve within a few days after the onset of menses, and become minimal or absent in the week post-menses.

Symptoms

Criterion B: One (or more) of the following symptoms must be present:

  1. Marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection)
  2. Marked irritability or anger or increased interpersonal conflicts
  3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts
  4. Marked anxiety, tension, and/or feelings of being keyed up or on edge

Criterion C: One (or more) of the following symptoms must be present additionally, to reach a total of 5 symptoms when combined with present symptoms from Criterion B above:[1]

  1. Decreased interest in usual activities (e.g., work, school, friends, hobbies).
  2. Subjective difficulty in concentration.
  3. Lethargy, easy fatigability, or marked lack of energy.
  4. Marked change in appetite; overeating; or specific food cravings.
  5. Hypersomnia or insomnia.
  6. A sense of being overwhelmed or out of control.
  7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of "bloating", or weight gain.

Severity

Criterion D: The symptoms observed in Criteria A-C are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).

Consideration of Other Psychiatric Disorders

Criterion E: The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (dysthymia), or a personality disorder—although it may co-occur with any of these disorders.[1]

Confirmation of the Disorder

Criterion F: Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. The diagnosis may be made provisionally before this confirmation.

Criterion G: The symptoms are not attributable to the physiological effects of a substance (e.g., substance use disorder, a medication, other treatments) or another medical condition (e.g., hyperthyroidism).

Multiple scholars have critiqued the criterion of significant distress as being too vague. The DSM-IV does not explicitly define this term, and scholars have viewed this criterion as potentially detrimental for those who have symptoms of depression, anxiety, or other mood disorders because they do not meet the clinical significance requirement.[41][42]

ICD-11

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The diagnostic criteria for PMDD are also included in the ICD-11, which has been in effect since 2022:[43]

GA34.41 Premenstrual dysphoric disorder

Description

During a majority of menstrual cycles within the past year, a pattern of mood symptoms (depressed mood, irritability), somatic symptoms (lethargy, joint pain, overeating), or cognitive symptoms (concentration difficulties, forgetfulness) that begin several days before the onset of menses, start to improve within a few days after the onset of menses, and then become minimal or absent within approximately 1 week following the onset of menses. The temporal relationship of the symptoms and luteal and menstrual phases of the cycle should ideally be confirmed by a prospective symptom diary over at least two symptomatic menstrual cycles. The symptoms are severe enough to cause significant distress or significant impairment in personal, family, social, educational, occupational or other important areas of functioning and do not represent the exacerbation of a mental disorder.

Other criteria sets

[edit]

Other organizations that have published diagnostic criteria for PMDD include the Royal College of Obstetricians and Gynecologists and the International Society for the Study of Premenstrual Disorders (ISPMD).[44][45] The ISPMD was a consensus group established by an international multidisciplinary group of experts. The group's diagnostic criteria for PMDD focus on the cyclic nature of the symptoms occurring during the luteal phase of the menstrual cycle, as well as the symptoms being absent after menstruation and before ovulation and causing significant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or the number of symptoms.[44]

Differential diagnosis

[edit]

Part of diagnosing PMDD is ruling out underlying psychiatric disorders or physical illnesses that can cause similar symptoms. That exhibits premenstrual exacerbation, the menopausal transition, hyperthyroidism, hypothyroidism, as well as other mood disorders. Furthermore, many medical disorders are worsened before menses, but these typically do not present strictly during the luteal phase.

Mood disorders – There is potential for patients to have psychiatric disorders with superimposed PMDD or psychiatric disorders. To establish the timeline of symptoms required for a diagnosis of PMDD symptoms need to be tracked using scales like the Calendar of Premenstrual Experiences or the Daily Record of Severity of Problems.[46]

Menopausal transition – affective symptoms associated with the menopausal transition most commonly start when the menstrual cycle starts to become irregular or anovulatory, whereas PMDD symptoms occur during the luteal phase of ovulatory cycles.

Thyroid disorders—Patients with both hyperthyroidism and hypothyroidism may present with affective symptoms. The patient's history is very important to determine whether the provider should suspect thyroid disorders. Patients should also have thyroid hormone levels checked to ensure that no underlying thyroid disorder is present.

Treatment

[edit]

Medication

[edit]

Several medications have been shown to effectively reduce the physical and emotional symptoms of PMDD.

Antidepressant treatment

[edit]

Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication.[13][47][48] Women taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo.[49] Two approaches to dosing have been studied: continuous dosing (daily) and luteal dosing (14 days before menstruation and discontinuing at the onset of menses).[50] Both dosing schedules have similar effectiveness, with some recent studies demonstrating greater symptom control with continuous dosing.[9]

Serotonin-norepinephrine reuptake inhibitors (SNRIs) have also been studied in the treatment of PMDD and shown efficacy in reducing symptoms. These are alternatives for patients who do not respond to SSRIs. However, they are more likely to be dosed continuously due to SNRI discontinuation syndrome - a flu-like feeling caused by dropping blood levels of SNRI.[9]

The rapid onset of anxiolytic and anti-dysphoric effects of SSRIs and SNRIs in PMDD contrast with their delayed efficacy in major depressive disorder (MDD).[51][52] Some SSRI and SNRIs have been demonstrated to induce inhibitory neurosteroid synthesis, with a select few observed to do so at doses inactive on serotonin reuptake.[53][54] It has been proposed that this effect may underlie the accelerated efficacy of SSRIs and SNRIs in PMDD relative to MDD.[52]

Anxiolytics

[edit]

Two medications typically given to reduce acute anxiety have been studied in treatment for PMDD: alprazolam (Xanax) and buspirone. Alprazolam carries a risk of dependence and causes central nervous system depression, and results of clinical trials have not shown benefit to treatment.[9] Buspirone showed lower efficacy than SSRI, but may be used as an adjunctive treatment or alternative if SSRI side effects are intolerable to the patient.[55]

Psychotherapy

[edit]

Cognitive behavioral therapy (CBT) is effective for reducing premenstrual symptoms in women with (retrospectively-reported) PMS.[11] CBT is an evidence-based approach for treating depression and focuses on the link between mood, thoughts, and actions to help women address current issues and symptoms. When CBT was compared to SSRI alone or in combination with SSRI, groups receiving CBT had significant improvement of PMS symptoms.[11] Through the practice of CBT, women are better able to recognize and modify recurrent issues as well as thought and behavior patterns that interfere with functioning well or that make depressive symptoms worse. However, a recent meta-analysis suggests that existing psychotherapies may be primarily useful for reducing impairment (rather than symptom severity) in PMDD.[11]

Hormonal treatment

[edit]

Oral contraceptives have been effective in reducing PMS symptoms, but only certain formulations have proven to be modestly effective in the treatment of PMDD.[49][56] Transdermal estrogen and intrauterine devices containing levonorgestrel have also had modest efficacy.[9]

Another FDA-approved treatment for women with premenstrual dysphoric disorder who have impairments with function is an oral contraceptive with ethinylestradiol and drospirenone (progestin) taken on a 24-4 schedule (24 active pills, 4 inactive pills).[57] Hormonal birth control containing drospirenone and low levels of estrogen (ethinylestradiol) helps relieve severe symptoms related to premenstrual dysphoric disorder, for at least the first three months that it is used. It is not clear if this approach is effective for more than three menstrual cycles.[58] The placebo effect has not been ruled out. The idea behind using oral contraceptives is to suppress ovulation, therefore suppressing sex hormone fluctuations.

Another treatment, typically used when other options have failed, is an injection of a gonadotropin-releasing hormone(GnRH) agonist with adjunctive estrogen and progesterone or tibolone. This is a last resort because GnRH antagonists can cause medical menopause by shutting down the body's pathway for reproductive hormones called the hypothalamic, pituitary, gonadal axis. As a result, GnRH therapy presents an increased risk of osteopenia (decreased bone density) and cardiovascular disease. This therapy is often reserved for patients considering surgical menopause to test the outcome of the surgery.[9]

Surgical menopause

[edit]

In a minority of patient who meet specific criteria and drug-based treatments are ineffective or produce significant side effects, hysterectomy and bilateral oophorectomy followed by estrogen replacement therapy is an option[29] Typically, the uterus is removed during the same surgery, and the woman is prescribed a low-dose estrogen patch to reduce the symptoms produced by surgically induced menopause.[29] There are five guidelines that should be considered before undergoing surgical treatment.[59] The vast majority of women with PMDD will not require surgical treatment to experience the resolution of symptoms.

  • The diagnosis of PMDD must be confirmed
  • GnRH agonist therapy must be the only medical therapy that has been effective, and it must have been effective continuously for a minimum of six months
  • Tolerance of estrogen replacement therapy has been tested
  • The woman does not desire further children
  • The woman's age warrants several more years of therapy

Adjunctive and alternative treatments

[edit]

Other proposed treatments include dietary modification, herbal remedies including St John's Wort and chasteberry, acupuncture, and exercise.[9] Some evidence suggests caffeine, sugar and alcohol intake may increase PMS symptoms.[60] A review article claimed significant improvement of PMS symptoms with herbal treatments and acupuncture but the studies selected for review did not stratify severity of symptoms.[61] Finally, the American College of Obstetricians and Gynecologists recommends regular aerobic exercise to reduce PMS symptoms.[62] The first trials have been approved to study microdosing LSD for the treatment of PMS and PMDD.[63][64]

History

[edit]

In the 18th century, there were early accounts of weeping and other symptoms recurring almost every month,[65] and in 1822 Prichard gave this description: "Many women … display a degree of excitement and irritation … at the period of menstruation; these are chiefly females of very irritable habits. In such instances, … an unusual vehemence of feeling and expression is observed … or there is torpor and dejection of mind with a despondent disposition".[66] In 1827, a German mother was acquitted of infanticide on the grounds of a menstrual mood disorder.[67] Premenstrual tension was also described in the French literature of the early 19th century.[68] Nearly one hundred years later, there were American descriptions of a cyclic personality change appearing 10–14 days before, and ending dramatically at the menses.[69]

The diagnostic category was discussed in the DSM-IIIR (1987), in which the proposed condition was named "Late Luteal Phase Dysphoric Disorder" and was included in the appendix as a proposed diagnostic category needing further study.[70] Preparations for the DSM-IV led to debate about whether to keep the category at all, only keep it in the appendix, or remove it entirely; the reviewers determined that the condition was still too poorly studied and defined, so it was kept in the appendix but elaborated with diagnostic criteria to aid further study.[30][71]

As preparations were underway in 1998 for the DSM-IV-TR, the conversation changed, as Eli Lilly and Company paid for a large clinical trial of fluoxetine as a potential treatment for the condition that was then conducted by Canadian academics and published in the New England Journal of Medicine in 1995.[72] Other studies have been conducted as well, wherein all found that approximately 60% of women with PMDD in the trials improved with the drug; representatives from Lilly & Co. and the FDA participated in the discussion.[30][71]

Various strong stances were taken in the said discussion. Sally Severino, a psychiatrist, argued that because symptoms were more prevalent in the United States, PMDD was a culture-bound syndrome and not a biological condition; she also claimed it unnecessarily pathologized the hormonal changes of the menstrual cycle.[30] Jean Endicott, another psychiatrist and chair of the committee, has argued that it was a valid condition from which women suffer and should be diagnosed and treated, and has claimed that if the symptoms were felt by males, far more effort and research would have been done by that moment. In the end, the committee kept PMDD in the appendix.[30]

The decision has been criticized as being driven by Lilly's financial interests, and possibly by financial interests of members of the committee who had received funding from Lilly.[30] Paula Caplan, a psychologist who had served on the committee for the DSM-IV, noted at the time of the DSM-IV-TR decision that there was evidence that calcium supplements could treat PMDD but the committee gave it no attention. She had also claimed that the diagnostic category is harmful to women with PMDD, leading them to believe they are mentally ill and potentially leading others to mistrust them in situations as important as job promotions or child custody cases.[30] She has called PMDD a fake disorder.[73] Nada Stotland has expressed concern that women with PMDD may have another serious condition like major depressive disorder or may be facing difficult circumstances—such domestic abuse—and therefore may have their true issues remain undiagnosed and mismanaged if their gynecologist diagnoses them with PMDD and gives them drugs to treat it.[30]

The validity of PMDD was once more heavily debated when it came time to create the DSM-5 in 2008.[74][75] In the end it was moved out of the appendix and into the main text as a formal category. A review in the Journal of Clinical Psychiatry published in 2014 examined the arguments against inclusion, which it summarized as:

  1. the PMDD label will harm women economically, politically, legally, and domestically;
  2. there is no equivalent hormone-based medical label for males;
  3. the research on PMDD is faulty;
  4. PMDD is a culture-bound condition;
  5. PMDD is due to situational, rather than biological, factors; and
  6. PMDD was fabricated by pharmaceutical companies for financial gain.[76]

Each argument was addressed, and researchers found:

  1. No evidence of harm;
  2. no equivalent hormone-driven disorder has been discovered in men despite research seeking it;
  3. the research base has matured, and many more reputable studies have been performed;
  4. several cases of PMDD have been reported or identified;
  5. a small minority of women do have the condition; and
  6. While there has been a financial conflict of interest, it has not made the available research unusable.[14][76]

It concluded that women have historically been under-treated and told that they were making their symptoms up, and that the formal diagnostic criteria would spur more funding, research, diagnosis, and treatment for women with PMDD.[76]

References

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Premenstrual dysphoric disorder

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from Grokipedia
Premenstrual dysphoric disorder (PMDD) is a cyclic characterized by severe affective symptoms—including marked , depression, or anxiety—accompanied by cognitive and somatic complaints, that emerge in the late of the and resolve abruptly within days of menses onset, causing significant functional impairment. The condition requires at least five symptoms across emotional, behavioral, and physical domains, with one core mood disturbance, confirmed prospectively over two cycles to distinguish it from exacerbations of other psychiatric conditions. PMDD affects an estimated 3% to 8% of menstruating individuals, though prospective cohort studies yield lower prevalence rates around 1.6% to 3.2% after excluding comorbidities like major depression, highlighting methodological challenges in retrospective self-reports. supports its validity through consistent cyclicity, biological markers of hormone sensitivity, and response to targeted interventions, countering historical that viewed it as an extension of normal premenstrual variability rather than a distinct . The underlying mechanisms involve heightened sensitivity to progesterone-derived neurosteroids like , which modulate GABA-A receptors, alongside serotonin dysregulation, rather than absolute hormone level abnormalities. Effective treatments include intermittent or continuous selective serotonin reuptake inhibitors (SSRIs) and specific combined oral contraceptives that suppress , with surgical options like bilateral reserved for refractory cases. Despite robust evidence, diagnostic controversies persist regarding its psychiatric versus gynecological framing, potential overmedicalization of menstrual cycles, and barriers to recognition in clinical practice.

Clinical Presentation

Signs and Symptoms

To contextualize the symptoms of premenstrual dysphoric disorder (PMDD), it is helpful to review typical mood variations across the menstrual cycle phases in individuals without the disorder. These variations are influenced by fluctuating levels of estrogen and progesterone. In the follicular phase, from the end of menstruation to ovulation, rising estrogen levels generally lead to improved mood, increased energy, motivation, confidence, and libido, which peaks around ovulation due to effects on dopamine and serotonin systems. During ovulation, estrogen reaches its peak before declining as progesterone begins to rise, often associated with high energy and outgoing behavior. In the luteal phase, from ovulation to the start of menstruation, progesterone dominates, which can commonly cause premenstrual syndrome (PMS) symptoms such as irritability, low mood, fatigue, and reduced motivation. During menstruation, both estrogen and progesterone levels are low, typically resulting in mood stabilization or improvement for many, although libido often decreases. Premenstrual dysphoric disorder manifests as a severe, cyclical pattern of emotional, behavioral, and physical symptoms confined to the of the , typically intensifying in the week prior to menses onset and remitting within a few days after begins, with minimal or absent symptoms during the . Diagnosis per requires prospective confirmation of at least five symptoms over two consecutive cycles, including at least one core affective symptom, causing marked interference in work, social activities, or relationships, and not merely an exacerbation of another disorder. Core affective symptoms include:
  • Markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts.
  • Marked anxiety, tension, or a sense of being "keyed up" or "on edge."
  • Affective lability, such as sudden tearfulness, sadness, or heightened sensitivity to rejection.
  • Persistent , , or increased interpersonal conflicts.
The symptom of persistent anger, irritability, and increased interpersonal conflicts can lead to considerable strain in romantic relationships. Recent research indicates that PMDD is associated with lower relationship quality for both individuals with the disorder and their partners, particularly in domains such as satisfaction, intimacy, trust, and passion, though levels of love and commitment remain comparable to those without the condition. In online support communities such as r/PMDD and r/PMDDpartners, individuals with PMDD and their partners commonly describe a recurring "breakup cycle" during the luteal phase. This pattern involves intense urges to end relationships, driven by amplified negative emotions, irritability, and heightened relationship dissatisfaction or perceived flaws in the partner. Manifestations include frequent arguments, breakup threats, temporary separations, repeated breakups followed by reconciliations, and, in some cases, permanent termination of relationships due to accumulated strain. Community members attribute this cyclical pattern to the hormonal fluctuations characteristic of PMDD, which exacerbate mood disturbances and alter perceptions of interpersonal dynamics. Associated behavioral and cognitive symptoms comprise decreased interest in usual activities, subjective difficulty concentrating, or easy fatigability, marked appetite changes with or cravings, or , and a subjective sense of being overwhelmed or out of control. Physical symptoms, while not required for , often accompany the affective disturbances and include tenderness or swelling, headaches, or muscle , bloating, and transient . These somatic complaints mirror those in but occur alongside severe mood symptoms that distinguish PMDD, with overall symptom severity rated as moderate to severe and peaking approximately two days before menses.

Distinction from Premenstrual Syndrome

PMS is generally manageable without major interference to daily life, whereas PMDD is debilitating and often requires medical intervention. Premenstrual dysphoric disorder (PMDD) represents a severe subtype of premenstrual symptoms, distinguished from (PMS) primarily by the intensity and predominance of affective disturbances that substantially impair social, occupational, or other important functioning. While PMS affects approximately 47.8% of menstruating individuals globally with mostly physical manifestations such as bloating, breast tenderness, and , PMDD occurs in 3-8% and requires marked emotional symptoms alongside physical ones, occurring cyclically in the and remitting shortly after menses onset. The distinction underscores PMDD's classification in the as a depressive disorder with perimenstrual exacerbation, emphasizing its potential for greater psychosocial disability compared to PMS. Symptom profiles overlap in physical domains but diverge sharply in psychological severity; PMS typically features mild or mood changes secondary to somatic complaints, whereas PMDD mandates at least five symptoms during the final luteal week, including one core affective symptom such as extreme , affective lability, marked depression, or anxiety, often leading to hopelessness or in severe cases. Common shared symptoms include lethargy, appetite changes, and sleep disturbances, but PMDD uniquely amplifies behavioral and cognitive elements like concentration difficulties or interpersonal conflicts, which resolve post-menses and are absent in the . This pattern must be confirmed prospectively over at least two cycles to differentiate from chronic mood disorders.
AspectPMSPMDD
Primary SymptomsPredominantly physical (e.g., bloating, headaches, breast pain); mild mood effects possibleSevere mood/cognitive (e.g., intense anger, depression, anxiety) plus physical; at least one mood symptom required
Diagnostic ThresholdNo formal DSM criteria; based on symptom history and cyclicity criteria: ≥5 symptoms (≥1 affective), luteal-phase timing, functional impairment, exclusion of other disorders
ImpactRarely disrupts daily life significantlyOften causes substantial interference in work/social roles; higher risk
PrevalenceUp to 47.8% of menstruating women3-8% of menstruating women
PMS lacks codified emotional benchmarks, allowing diagnosis via retrospective recall of milder, tolerable symptoms, whereas PMDD's criteria demand rigorous documentation to rule out comorbidities like major depressive disorder, highlighting its distinct neurobiological underpinnings involving heightened sensitivity to hormonal fluctuations. Failure to distinguish can lead to undertreatment of PMDD's disabling features, as evidenced by studies showing PMDD patients report more profound quality-of-life decrements than those with PMS alone.

Epidemiology

Prevalence and Incidence

The prevalence of premenstrual dysphoric disorder (PMDD) among menstruating women varies by diagnostic method, with confirmed cases—requiring prospective daily symptom tracking over at least two cycles—yielding lower estimates than provisional diagnoses based on retrospective self-reports, which are prone to recall bias and overestimation. A 2024 systematic review and meta-analysis of 44 studies encompassing 50,659 participants reported a pooled prevalence of 3.2% (95% CI: 1.7%-5.9%) for confirmed PMDD and 7.7% (95% CI: 5.3%-11.0%) for provisional PMDD; in community-based samples, confirmed prevalence was 1.6% (95% CI: 1.0%-2.5%). These figures align with earlier clinical estimates of 3% to 8% in reproductive-age women, though methodological heterogeneity, including differences in assessment tools and population sampling, contributes to variability. Incidence data, reflecting new-onset cases, remain scarce due to the disorder's chronic nature and reliance on studies rather than longitudinal cohorts tracking first episodes. PMDD symptoms typically emerge during reproductive years, with onset around age 26, though they may appear as early as late and often peak in severity between ages 25 and 35. This pattern suggests development tied to ovulatory cycles post-menarche, but without established annual incidence rates per population at risk.

Demographic and Risk Factors

PMDD primarily affects women of reproductive age, from through , with an estimated prevalence of 5-8% among this demographic in the United States. The disorder is characterized by cyclic symptoms tied to the , limiting its occurrence to individuals with intact ovarian function, including women and some individuals retaining ovaries. Limited data exist on ethnic or racial disparities, though one study among ethnic minority women in the U.S. found associations with nativity status, duration of U.S. residence, and age at , suggesting potential cultural or environmental influences on symptom reporting or expression. Established risk factors include cigarette smoking, with current smokers exhibiting a (RR) of 2.1 and former smokers an RR of 1.8 compared to never smokers. confers additional risk, particularly for (BMI) ≥35 kg/m² (RR 1.66), alongside a 3% increased risk per 1 kg/m² increment. History of traumatic events and preexisting anxiety disorders are also linked to PMDD development, potentially through heightened stress sensitivity or altered neurobiological responses. Comorbid psychiatric conditions, such as (present in approximately 50% of PMDD cases), and self-reported depressive symptoms elevate risk, with moderate or higher depression associated with a prevalence ratio (PR) of 2.81 in one study of medical students. Genetic factors may contribute, evidenced by estimates and associations with variants in serotonergic receptors (e.g., 5HT1A) and genes (ESR1), though these remain speculative pending larger confirmatory studies. Other potential modifiers include early (inversely related to risk in some cohorts) and consumption (>3 times weekly), but evidence is inconsistent across populations and requires further validation. Higher has been inversely associated with vulnerability in select research, possibly reflecting differences in symptom awareness or coping mechanisms.

Pathophysiology

Hormonal and Neurosteroid Mechanisms

Premenstrual dysphoric disorder (PMDD) is characterized by an abnormal central nervous system response to normal ovarian hormone fluctuations rather than absolute deficiencies or excesses in estrogen or progesterone levels, which remain within physiological norms across the menstrual cycle in affected women. Symptoms typically manifest during the luteal phase, coinciding with the post-ovulatory rise in progesterone and its metabolites, suggesting a heightened vulnerability to these cyclic changes that triggers affective dysregulation. Early conceptualizations emphasized dysregulated estrogen-progesterone interactions, but empirical data indicate that ovulation itself initiates the hormonal cascade implicated in symptom onset, as suppression via gonadotropin-releasing hormone (GnRH) agonists often ameliorates symptoms. Progesterone, synthesized in the after , serves as a precursor to neuroactive steroids, including allopregnanolone (ALLO), which exerts potent effects on neuronal excitability. ALLO acts as a positive of the GABA_A receptor, typically promoting inhibitory and effects by enhancing GABA binding affinity. In PMDD, however, rapid luteal-phase elevations in ALLO levels—despite being comparable to those in women—elicit paradoxical negative mood responses, such as and anxiety, potentially due to altered GABA_A receptor subunit composition or sensitivity that disrupts the expected neuroinhibitory balance. This hypersensitivity is evidenced by studies showing exacerbated emotional reactivity to ALLO challenges in PMDD patients, contrasting with its calming influence in controls. Supporting evidence includes hormone manipulation trials: administration of progesterone or its analogs exacerbates symptoms in susceptible individuals, while luteal-phase ALLO infusions provoke selectively in those with PMDD, underscoring a causal role for neurosteroid-GABA_A interactions over peripheral levels alone. Genetic polymorphisms in ALLO-metabolizing enzymes, such as , or GABA_A receptor genes (e.g., δ-subunit variants) may underlie this differential sensitivity, though direct causation remains under investigation through and pharmacogenomic studies. These mechanisms highlight PMDD as a disorder of steroid- evoked signaling rather than endocrine pathology, with ALLO's failure to mitigate stress responses linking hormonal cues to core neuropsychiatric features.

Neurobiological and Genetic Factors

Twin and family studies have established a genetic component to premenstrual dysphoric disorder (PMDD), with estimates ranging from 35% to 56% based on analyses of menstrual and premenstrual symptoms. Probandwise concordance rates for , a related condition, are higher among monozygotic twins (0.81) than dizygotic twins (0.67), supporting additive genetic influences over shared environment. Candidate gene studies have identified inconsistent associations with polymorphisms in genes (ESR1 and ESR2) and the serotonin 1A receptor (HTR1A C(-1019)G variant), suggesting potential genetic vulnerabilities in signaling and mood regulation pathways, though replication is limited. Neurobiologically, PMDD is characterized by an abnormal sensitivity to normal fluctuations in progesterone-derived neuroactive steroids, particularly (ALLO), a positive of GABA_A receptors that enhances inhibitory . Peripheral ALLO levels do not differ significantly between women with PMDD and controls, but affected individuals demonstrate dysregulated GABA_A receptor plasticity, including upregulated α4 subunit expression in response to luteal-phase ALLO withdrawal, which correlates with heightened anxiety and mood instability. Lower cortical GABA concentrations in mood-relevant regions during the luteal phase further indicate impaired inhibitory function in PMDD. Serotonergic dysregulation also contributes, with evidence of reduced whole-blood serotonin levels and altered 5-HT_{1A} receptor binding in women with PMDD, potentially exacerbating affective symptoms during the . reveals cycle-phase-specific alterations, including enhanced reactivity to emotional stimuli, diminished prefrontal cortical activation, and greater cerebellar gray matter volume, reflecting deficient top-down regulation of salience and emotion-processing networks. These findings support a model where genetic predispositions interact with hormonal triggers to disrupt and serotonergic systems, yielding exaggerated neuroinflammatory and stress responses in susceptible individuals.

Comorbidities and Suicidality

Premenstrual dysphoric disorder (PMDD) exhibits high rates of with psychiatric conditions, especially s. A 2025 and of 28 studies reported pooled estimates of comorbidity between PMDD or (PMS) and mood disorders ranging from 42% (95% CI: 30%-55%) for to higher figures for any mood disorder, with consistency across community and clinical samples. These associations extend to anxiety disorders, somatoform disorders, and , where comorbid PMDD correlates with earlier bipolar onset, more frequent acute mood episodes, and elevated rapid-cycling rates. Such overlaps may reflect shared neurobiological vulnerabilities, including serotonin dysregulation, though causal directions remain under investigation. Suicidality represents a critical risk in PMDD, independent of comorbid conditions. A 2021 of seven studies found women with PMDD face nearly sevenfold higher odds of suicide attempts (OR: 6.97; 95% CI: 2.98-16.29) and fourfold higher odds of (OR: 3.90; 95% CI: 1.72-8.82) relative to those without premenstrual disturbances. Another corroborated elevated (OR: 2.34; 95% CI: 1.50-3.18) and plans, with no significant heterogeneity across studies. These risks underscore the need for routine suicidality screening in PMDD , as severe premenstrual mood exacerbation can precipitate acute crises. Longitudinal data suggest PMDD's cyclic symptom pattern amplifies baseline vulnerabilities, contributing to lifetime self-injurious behaviors in up to 20-30% of affected individuals in some cohorts.

Diagnosis

Diagnostic Criteria

The diagnosis of premenstrual dysphoric disorder (PMDD) follows the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), where it is classified as a depressive disorder. These criteria emphasize the cyclic timing of symptoms tied to the menstrual cycle, requiring prospective documentation to distinguish PMDD from chronic mood disorders. Criterion A specifies that, in most menstrual cycles during the past year, at least five symptoms must be present for most of the final week before menses onset, begin to remit within a few days after menses begins, and become minimal or absent during the week following menses. At least one of the five symptoms must meet Criterion B, consisting of the following core affective or mood symptoms:
  • Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).
  • Marked or or increased interpersonal conflicts.
  • Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.
  • Marked anxiety, tension, and/or feelings of being keyed up or on edge.
The remaining symptoms to reach a total of five (per Criterion C) may include one or more of:
  • Decreased interest in usual activities (e.g., work, school, friends, hobbies).
  • Subjective difficulty in concentration.
  • , easy fatigability, or marked lack of energy.
  • Marked change in appetite; ; or specific food cravings.
  • or .
  • A of being overwhelmed or out of control.
  • Physical symptoms such as breast tenderness or swelling, joint or muscle , a sensation of , or .
Criterion D requires that the symptoms cause clinically significant distress or marked interference with work, school, usual social activities, or relationships (e.g., avoidance of social activities, decreased productivity at work or school). Criterion E stipulates that the disturbance is not merely an exacerbation of the symptoms of another disorder, such as , , or a , though PMDD may coexist with such conditions if the cyclic pattern is distinct. Prospective daily ratings of symptoms (Criterion F) must confirm Criterion A for at least two symptomatic cycles, typically using tools like the Daily Record of Severity of Problems; a provisional may be made prior to this confirmation if retrospective accounts are suggestive. Finally, Criterion G excludes symptoms attributable to the physiological effects of a substance (e.g., drug abuse, ) or another medical condition (e.g., ). The , includes similar criteria under code GA34.41, aligning closely with in requiring at least five symptoms (including affective lability, , or depression) confined to the in most cycles, with prospective verification recommended.

Differential Diagnosis and Challenges

Differentiating premenstrual dysphoric disorder (PMDD) from other conditions requires confirming that symptoms are cyclically tied to the of the , with remission in the , typically verified through at least two cycles of prospective daily symptom ratings. Common differentials include (MDD), where PMDD symptoms resolve post-menstrually unlike persistent MDD symptoms, and , which may present with premenstrual exacerbations but lacks the strict cyclicity of PMDD. Anxiety disorders such as generalized anxiety or can mimic PMDD's affective components but do not remit with menses onset. Medical conditions like , , or perimenopause must be ruled out via tests, as they can cause similar , , and mood changes without menstrual linkage. Premenstrual syndrome (PMS) overlaps but features milder physical symptoms without the severe meeting PMDD's threshold for functional impairment. High rates of psychiatric , such as 50-70% of PMDD patients also meeting criteria for MDD or anxiety disorders, complicate differentiation, as premenstrual worsening of an underlying condition may be mistaken for primary PMDD. poses particular risks, with studies showing up to 20% , where rapid cycling or mixed states can resemble PMDD's irritability and lability, necessitating trials or longitudinal tracking to distinguish. Other considerations include substance use disorders exacerbating symptoms or personality disorders like borderline contributing to emotional instability, requiring comprehensive psychiatric evaluation. Diagnostic challenges stem from reliance on self-reported prospective charting, which demands patient compliance and can yield if retrospective data is used, leading to over- or under-diagnosis. In adolescents, overlapping puberty-related mood volatility and irregular cycles hinder confirmation, with symptoms often dismissed as normative. Underdiagnosis is prevalent due to stigma, normalization of severe premenstrual symptoms as "just PMS," and provider unfamiliarity, with surveys indicating delays of 10-20 years from symptom onset to diagnosis. Comorbidities amplify misattribution, as primary treatment of co-occurring depression may mask PMDD without cycle-specific assessment, while biological markers like sensitivity remain investigational and unavailable for routine use. These factors underscore the need for multidisciplinary approaches, including gynecology and , to avoid conflating PMDD with exacerbations of chronic disorders.

Treatment

Pharmacological Interventions

Selective serotonin reuptake inhibitors (SSRIs) represent the first-line pharmacological treatment for premenstrual dysphoric disorder (PMDD), with strong evidence from randomized controlled trials and meta-analyses demonstrating significant reductions in core mood symptoms such as , affective lability, and anxiety. Common agents include at 20 mg/day, sertraline at 50-150 mg/day, and at 12.5-25 mg/day, administered either continuously throughout the or intermittently during the (typically starting 14 days before menses). Intermittent dosing achieves comparable efficacy to continuous regimens for most symptoms while minimizing exposure and side effects like , , and insomnia, though it may be less effective for persistent physical symptoms or sleep disturbances in some cases. Response rates exceed 60% in meta-analyses involving thousands of patients, with rapid onset often within days of luteal-phase initiation, distinguishing PMDD treatment from protocols. Hormonal therapies, particularly combined oral contraceptives (COCs) containing and (e.g., 3 mg/20 μg in a 24/4 regimen), are recommended as an alternative or adjunct for PMDD, especially when contraception is desired or SSRIs are contraindicated. These suppress and stabilize fluctuations, yielding moderate of benefit for overall premenstrual symptoms, including and tenderness, though effects on severe depressive or irritability symptoms are inconsistent across trials. The U.S. approved this formulation specifically for PMDD in 2006 based on pivotal studies showing superior symptom relief compared to . Risks include venous thromboembolism, necessitating careful patient selection and monitoring. For refractory cases, (GnRH) agonists such as leuprolide (3.75 mg monthly depot) offer high efficacy by inducing and halting cyclic hormone changes, with studies reporting near-complete symptom resolution in small cohorts. However, long-term use risks menopausal-like side effects (e.g., hot flashes, loss), requiring concomitant "add-back" hormone replacement. Aldosterone antagonists like (25-100 mg/day in ) may alleviate physical symptoms such as fluid retention but lack robust data for mood improvement. Anxiolytics (e.g., 0.25-0.5 mg as needed) provide limited, short-term relief for acute anxiety but are not recommended as monotherapy due to dependency risks and weak evidence. Treatment selection should prioritize individualized response, with prospective symptom tracking to confirm efficacy.

Non-Pharmacological and Surgical Options

Non-pharmacological interventions for premenstrual dysphoric disorder (PMDD) primarily encompass lifestyle modifications, , and complementary therapies, which aim to alleviate symptoms through behavioral and environmental adjustments rather than medication. performed most days of the week has been associated with reduced PMDD symptoms, including mood disturbances, in clinical guidelines derived from observational and interventional data. Dietary changes, such as decreasing intake of , , salt, and alcohol while increasing complex carbohydrates and protein, may mitigate physical and emotional symptoms by stabilizing blood glucose and serotonin levels, though evidence from randomized trials remains limited to smaller cohorts. techniques, including relaxation training and , are commonly recommended as adjuncts, with surveys of clinicians indicating their frequent use alongside counseling for milder cases. Cognitive behavioral therapy (CBT) represents a core evidence-based psychotherapeutic approach, demonstrating efficacy comparable to selective serotonin reuptake inhibitors in reducing PMDD symptom severity and associated distress. Randomized controlled trials have shown that both individual and couple-based CBT significantly decrease premenstrual mood symptoms, anxiety, and functional impairment, with effects persisting post-treatment in follow-up assessments. Internet-delivered CBT variants have also yielded substantial reductions in symptom severity and disability, offering accessibility for remote patients. Guidelines endorse CBT as a routine first-line option, particularly for women preferring non-drug strategies or those with comorbid psychological factors. Complementary therapies include bright light therapy and , with varying levels of supporting evidence from controlled trials. Bright light exposure, typically 30 minutes daily of 2500-10,000 lux during the , has reduced depressive symptoms and premenstrual tension in multiple randomized trials, potentially via normalization and serotonin enhancement. , administered in the or cyclically, showed superior symptom relief compared to sham interventions in some randomized controlled trials for (PMS) and PMDD, though systematic reviews note methodological limitations and inconsistent replication. Nutritional supplements are considered as a complementary option for managing PMDD symptoms. Systematic reviews of randomized controlled trials provide consistent evidence that calcium (≥1,000 mg/day) and vitamin B6 (≥50 mg/day) improve psychological symptoms such as depression, irritability, anxiety, and mood swings. Zinc (≥30 mg/day) also shows consistent positive effects. Magnesium has some supportive evidence, particularly in combination with vitamin B6. In contrast, evening primrose oil lacks strong evidence and is generally considered ineffective, with systematic reviews of clinical trials finding no significant benefit over placebo. Surgical options, reserved for severe, refractory PMDD unresponsive to conservative measures, involve hysterectomy combined with bilateral salpingo-oophorectomy (BSO) to eliminate ovarian hormone fluctuations driving symptoms. This procedure has provided complete symptom resolution in case series and prospective studies of selected patients, with follow-up data indicating sustained benefits when paired with to manage induced . However, it carries risks including , , and loss of , necessitating thorough preoperative evaluation and long-term estrogen-progestin replacement. Such interventions are considered only after exhaustive trials of pharmacological and non-pharmacological alternatives, with success rates approaching 90% in appropriately screened cohorts but limited to women who have completed childbearing.

Controversies and Debates

Validity as a Distinct Disorder

Premenstrual dysphoric disorder (PMDD) was formally recognized as a distinct diagnostic entity in the (2013), transitioning from its prior status in the DSM-IV appendix as "premenstrual dysphoric disorder" (formerly late dysphoric disorder), based on accumulating empirical evidence of its unique cyclic symptom pattern tied to the of the . This classification requires prospective daily symptom tracking over at least two cycles to confirm that affective and somatic symptoms—such as marked irritability, depression, and anxiety—emerge reliably in the week before menses and remit shortly after onset, distinguishing PMDD from chronic mood disorders like or , where symptoms lack this phasic specificity. Validation studies employing and Guze criteria, including familial aggregation and course delineation, support PMDD's nosologic independence, with heritability estimates around 50-60% from twin studies indicating a genetic underpinning separate from general (PMS). Biological markers further substantiate PMDD's distinctiveness, revealing an abnormal sensitivity rather than atypical hormone levels; women with PMDD exhibit heightened brain responses to progesterone-derived fluctuations, which modulate GABA-A receptors and serotonin systems, leading to dysphoric symptoms absent in unaffected individuals despite comparable ovarian steroid profiles. Neuroimaging evidence shows altered and activation during provocation in PMDD patients, correlating with symptom severity, while treatment responses—such as luteal-phase-only selective serotonin reuptake inhibitors (SSRIs) yielding rapid symptom relief without full-cycle dosing needs—differentiate it from non-cyclic depressions. These findings counter earlier dismissals equating PMDD with PMS amplification or misattributed mood instability, as prospective designs rule out retrospective and confirm at 3-8% among reproductive-age women, far exceeding PMS's milder manifestations in 20-30%. Debates persist regarding overpathologization of variations, with some critiques from the early arguing insufficient separation from underlying depressions or cultural influences on symptom reporting, potentially inflating diagnostic boundaries. However, recent systematic reviews affirm validity through consistent exclusion of comorbidities via stringent criteria and replicated treatment specificity, though underdiagnosis remains prevalent due to clinician unfamiliarity and overlap risks with bipolar spectrum disorders. Longitudinal data indicate PMDD's course aligns more closely with neuroendocrinological vulnerabilities than stressors alone, positioning it as a legitimate, hormone-triggered neuropsychiatric condition rather than a mere variant of PMS.

Influences on Recognition and Treatment

The recognition of premenstrual dysphoric disorder (PMDD) has been impeded by societal stigma associated with and women's complaints, leading to underreporting and dismissal of symptoms as mere emotional volatility. Cultural attitudes exacerbating this include menstrual taboos that discourage open discussion, particularly in regions with conservative gender norms, such as the , where women face compounded stigma for both reproductive and psychological symptoms. Additionally, exposure to Western cultural environments has correlated with elevated PMDD symptoms among ethnic minority women, attributed to diminished traditional like familial cohesion and , which buffer against stress in more collectivist societies. Diagnostic challenges further delay recognition, as confirmation requires prospective daily symptom charting over at least two menstrual cycles to establish cyclicity, a process many patients find burdensome and providers often overlook amid time constraints. Structural barriers in healthcare systems, including limited training on women's cyclic disorders and historical research biases favoring male-centric models, contribute to frequent misattribution of PMDD symptoms to primary mood disorders like major depression, resulting in diagnostic overshadowing. In clinical settings, this manifests as provisional diagnoses persisting without cycle-specific validation, with studies indicating that up to 20-30% of women seeking care for premenstrual complaints receive alternative psychiatric labels instead. Treatment paradigms have been shaped by pharmaceutical developments, particularly the U.S. Food and Drug Administration's approval of (branded as Sarafem) for PMDD in July 2000, which preceded its full inclusion as a distinct disorder in in 2013 and expanded access to selective serotonin reuptake inhibitors (SSRIs) via targeted marketing. This regulatory step, supported by industry-sponsored trials demonstrating SSRI efficacy in alleviating mood symptoms during the , shifted guidelines toward pharmacological interventions as first-line options, despite initial of these agents. Consequently, SSRIs like sertraline and gained specific licensing for PMDD in regions such as the U.S., influencing provider preferences and expectations, though continuous dosing regimens remain debated for their impact on somatic symptoms versus intermittent luteal-phase administration. These advancements, while evidence-based in reducing symptom severity by 50-70% in randomized trials, have also prompted critiques of potential overmedicalization, underscoring the interplay between empirical data and commercial incentives in standardizing care.

History

Early Observations and Formal Recognition

Early reports of severe mood disturbances linked to the menstrual cycle date back to ancient civilizations, with describing symptoms such as agitation and preceding menses around 400 BCE. Similar observations appeared in sporadically over centuries, often attributing premenstrual emotional volatility to humoral imbalances, though these were not systematically studied or differentiated from general . In the modern era, American gynecologist Robert T. Frank provided one of the first detailed clinical descriptions in 1931, coining the term "premenstrual tension" to characterize cyclic irritability, depression, and fatigue in a subset of women, based on observations of patients whose symptoms resolved post-menses. British physician Katharina Dalton advanced recognition in the 1950s through her work on progesterone therapy, documenting severe premenstrual syndromes including mood swings and behavioral changes in hundreds of cases, which she termed premenstrual syndrome (PMS) to encompass both physical and psychological manifestations. Despite these accounts, skepticism persisted in medical communities, with symptoms often dismissed as psychosomatic or exaggerated until prospective daily rating scales in the 1980s confirmed their cyclic nature and prevalence in 3-8% of menstruating women. Formal diagnostic criteria for what became known as premenstrual dysphoric disorder (PMDD) emerged in 1987 with the inclusion of "late dysphoric disorder" (LLPDD) as a proposed diagnostic category in the appendix of the DSM-III-R, requiring at least five symptoms—including marked affective lability, , and anxiety—confined to the and absent in the . This marked the first psychiatric acknowledgment of severe premenstrual mood disorders as distinct from PMS, emphasizing functional impairment. In 1994, the DSM-IV renamed it PMDD and retained it in the appendix as criteria for further study, specifying prospective documentation over two cycles to distinguish it from comorbidities like major depression. Full integration into the in 2013 elevated PMDD to a standalone depressive disorder diagnosis, reflecting accumulated evidence from blinded, placebo-controlled trials validating its neurobiological basis. International recognition followed in the effective 2022, codifying PMDD under mood disorders.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK532307/
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC4890701/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC10711063/
  4. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1458114/full
  5. https://www.ox.ac.uk/news/2024-01-30-new-data-shows-prevalence-premenstrual-dysphoric-disorder
  6. https://pubmed.ncbi.nlm.nih.gov/11883723/
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC9564553/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC7716347/
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC9790166/
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC10193729/
  11. https://flo.health/menstrual-cycle/health/emotions/menstrual-cycle-phases-and-moods
  12. https://www.everydayhealth.com/womens-health/how-your-menstrual-cycle-affects-your-behavior.aspx
  13. https://healthy.kaiserpermanente.org/health-wellness/healtharticle.phases-of-the-menstrual-cycle
  14. https://www.raleighob.com/phases-of-the-menstrual-cycle/
  15. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-premenstrual-syndrome-and-premenstrual-dysphoric-disorder
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC12017513/
  17. https://www.reddit.com/r/PMDD/comments/183u75f/im_over_wanting_to_break_up_every_month/
  18. https://www.reddit.com/r/PMDD/comments/194dxs2/does_pmdd_cause_anyone_else_to_hate_their_partner/
  19. https://www.mayoclinic.org/diseases-conditions/premenstrual-syndrome/expert-answers/pmdd/faq-20058315
  20. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1363875/full
  21. https://www.psychdb.com/mood/pmdd
  22. https://www.apa.org/topics/women-girls/pms-vs-pmdd
  23. https://www.aafp.org/pubs/afp/issues/2016/0801/p236.html
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC10673441/
  25. https://bestpractice.bmj.com/topics/en-us/419
  26. https://www.aafp.org/pubs/afp/afp-community-blog/entry/dont-miss-the-diagnosis-of-premenstrual-dysphoric-disorder.html
  27. https://www.sciencedirect.com/science/article/pii/S0165032724000764
  28. https://pubmed.ncbi.nlm.nih.gov/38199397/
  29. https://www.riversideonline.com/en/patients-and-visitors/healthy-you-blog/blog/u/understanding-premenstrual-dysphoric-disorder
  30. https://www.sciencedirect.com/science/article/abs/pii/S1083318806002798
  31. https://www.newportinstitute.com/resources/mental-health/premenstrual-dysphoric-disorder/
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC3068238/
  33. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0278702
  34. https://pmc.ncbi.nlm.nih.gov/articles/PMC2992541/
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC10176022/
  36. https://pmc.ncbi.nlm.nih.gov/articles/PMC7231988/
  37. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1140796/full
  38. https://www.nature.com/articles/s41398-023-02424-3
  39. https://pubmed.ncbi.nlm.nih.gov/40518728/
  40. https://www.sciencedirect.com/science/article/abs/pii/S0301008213000671
  41. https://pubmed.ncbi.nlm.nih.gov/21962135/
  42. https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/systematic-review-and-metaanalysis-on-the-comorbidity-of-premenstrual-dysphoric-disorder-or-premenstrual-syndrome-with-mood-disorders-prevalence-clinical-and-neurobiological-correlates/963893C74FCB4CE0D9CB6502BEBC58A9
  43. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.719241/full
  44. https://www.tandfonline.com/doi/full/10.2147/NDT.S202881
  45. https://journals.sagepub.com/doi/abs/10.1089/jwh.2021.0185
  46. https://pubmed.ncbi.nlm.nih.gov/34488087/
  47. https://pmc.ncbi.nlm.nih.gov/articles/PMC8721500/
  48. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-022-03851-0
  49. https://www.ncbi.nlm.nih.gov/books/NBK279045/
  50. https://pubmed.ncbi.nlm.nih.gov/12892988/
  51. https://www.psychiatrist.com/jcp/bipolar-disorder-pmdd-comorbidity-conundrum/
  52. https://www.ccjm.org/content/ccjom/71/4/303.full.pdf
  53. https://emedicine.medscape.com/article/293257-differential
  54. https://www.sciencedirect.com/science/article/pii/S0924933817305928
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC8423998/
  56. https://www.psychiatrictimes.com/view/premenstrual-dysphoric-disorder-and-psychiatric-comorbidity
  57. https://pmc.ncbi.nlm.nih.gov/articles/PMC11281859/
  58. https://pubmed.ncbi.nlm.nih.gov/40251463/
  59. https://pmc.ncbi.nlm.nih.gov/articles/PMC8785767/
  60. https://pubmed.ncbi.nlm.nih.gov/39070312/
  61. https://journals.lww.com/greenjournal/fulltext/2023/12000/management_of_premenstrual_disorders__acog.34.aspx
  62. https://www.sciencedirect.com/science/article/pii/S108707922500022X
  63. https://emedicine.medscape.com/article/293257-treatment
  64. https://www.exxcellence.org/list-of-pearls/management-of-premenstrual-dysphoric-disorder-pmdd/?categoryName=&searchTerms=&featured=False&bookmarked=False&sortColumn=date&sortDirection=Descending
  65. https://www.hopkinsmedicine.org/health/conditions-and-diseases/premenstrual-dysphoric-disorder-pmdd
  66. https://onlinelibrary.wiley.com/doi/full/10.1002/pcn5.234
  67. https://womensmentalhealth.org/specialty-clinics/pms-and-pmdd/
  68. https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-021-01589-7
  69. https://www.sciencedirect.com/science/article/pii/S1521690X23001343
  70. https://pubmed.ncbi.nlm.nih.gov/10482337/
  71. https://pmc.ncbi.nlm.nih.gov/articles/PMC6614973/
  72. https://pubmed.ncbi.nlm.nih.gov/24410911/
  73. https://pmc.ncbi.nlm.nih.gov/articles/PMC6422848/
  74. https://www.bmj.com/content/318/7195/1375
  75. https://www.sciencedirect.com/science/article/pii/S0301211525003586
  76. https://pubmed.ncbi.nlm.nih.gov/8721802/
  77. https://academic.oup.com/humrep/article/19/9/2152/782265
  78. https://pubmed.ncbi.nlm.nih.gov/2301479/
  79. https://www.verywellhealth.com/surgical-management-of-premenstrual-dysphoria-disorder-4138313
  80. https://pmc.ncbi.nlm.nih.gov/articles/PMC3462360/
  81. https://womensmentalhealth.org/posts/etiology-premenstrual-dysphoric-disorder/
  82. https://www.apa.org/monitor/oct02/pmdd
  83. https://pmc.ncbi.nlm.nih.gov/articles/PMC11345297/
  84. https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-025-01557-9
  85. https://www.health.harvard.edu/blog/premenstrual-dysphoria-disorder-its-biology-not-a-behavior-choice-2017053011768
  86. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1458114/pdf
  87. https://link.springer.com/article/10.1007/s43032-025-01861-3
  88. https://www.jsonline.com/story/news/investigations/2016/11/16/one-condition-drugs-came-before-disorder/93823042/
  89. https://www.cochrane.org/evidence/CD001396_what-are-benefits-and-risks-treating-premenstrual-syndrome-and-premenstrual-dysphoric-disorder
  90. https://pubmed.ncbi.nlm.nih.gov/9411273/
  91. https://pubmed.ncbi.nlm.nih.gov/11041378/
  92. https://emedicine.medscape.com/article/293257-overview
  93. https://time.com/6963199/menstrual-mood-disorder-pmdd-essay/
  94. https://www.iapmd.org/dsm-iii-r-dsm-iv
  95. https://www.ncbi.nlm.nih.gov/books/NBK519704/table/ch3.t24/
  96. https://www.theravive.com/therapedia/premenstrual-dysphoric-disorder-dsm--5-625.4-%28n94.3%29
  97. https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.14360
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