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Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms. PMDD can cause significant distress and impairment during the luteal phase of the menstrual cycle (between ovulation and menstruation). Symptoms typically improve within a few days after the onset of menses, and are minimal or absent in the week after menses. PMDD has a profound impact on an individual's quality of life and dramatically increases the risk of suicidal ideation and even suicide attempts. Many women experience discomfort or mild mood changes before menstruation, but 5–8% experience severe premenstrual syndrome (PMS), causing significant distress or functional impairment. <!-- Cause and diagnosis -->

PMDD's exact cause is unknown. Ovarian hormone levels during the menstrual cycle do not differ between those with PMDD and the general population. 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.

PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Roughly 20% of females have some PMDD symptoms, but either have fewer than five or do not have functional impairment.

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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). Hormonal therapy with oral contraceptives that contain drospirenone have also demonstrated efficiency in reducing PMDD symptoms. Cognitive behavioral therapy, whether in combination with SSRIs or alone, has shown to be effective in reducing impairment. Dietary modifications and exercise may also be helpful, but studies investigating these treatments have not demonstrated efficacy in reducing PMDD symptoms. 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. 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. The symptoms usually cease shortly after the start of the menstrual period or a few days after it ends. Various symptom and severity tracking questionnaires exist to document presence and severity of symptoms throughout consecutive menstrual cycles.

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. 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.

Genetic factors

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.

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.

Risk factors

Environmental stressors have also been found to increase the risk for PMDD symptoms prospectively. Environmental components such as stress, hormonal fluctuation, and epigenetics play a key role in the pathology and onset of the disorder. 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. 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.

Relationship to pregnancy and menopause

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. PMDD symptoms can get worse following pregnancy or other associated events such as birth and miscarriage.

Studies on the association between PMDD and postpartum depression (PPD) have provided conflicting results. While one large study of women with prospectively confirmed PMDD did not find a higher prevalence of postpartum depression in that population than in controls, have found a positive association, and one study found a bidirectional relationship between PMDD and PPD (meaning that previous history of PMDD raises the risk of future PPD, and vice versa).

Mental health comorbidities

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. Another systematic review study suggests that patients with bipolar disorder, type I or II, have a higher incidence of PMDD. 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.

Suicidality

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. 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. 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.

DSM-5

The DSM-5 established seven criteria (A through G) for the diagnosis of PMDD, which are paraphrased below.

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).

<u>Timing</u>

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.

<u>Symptoms</u>

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:

ICD-11

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

  • Affective, somatic, or cognitive symptoms occur regularly in conjunction with menstruation, beginning several days before the onset of menstruation.
  • The symptoms include at least one affective symptom and at least one additional somatic or cognitive symptom.
  • The symptoms are not a manifestation of another medical condition or mental disorder.
  • The symptoms cause significant distress.

Other criteria sets

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). 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.

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

Medication

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

Antidepressant treatment

Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication. Women taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo. Two approaches to dosing have been studied: continuous dosing (daily) and luteal dosing (14 days before menstruation and discontinuing at the onset of menses). Both dosing schedules have similar effectiveness, with some recent studies demonstrating greater symptom control with continuous dosing. 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. It has been proposed that this effect may underlie the accelerated efficacy of SSRIs and SNRIs in PMDD relative to MDD.

Psychotherapy

Cognitive behavioral therapy (CBT) is effective for reducing premenstrual symptoms in women with (retrospectively-reported) PMS. 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. Transdermal estrogen and intrauterine devices containing levonorgestrel have also had modest efficacy. 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. 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 among last resorts 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. 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.

  • 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 children
  • The woman's age warrants several more years of therapy

Adjunctive and alternative treatments

Other proposed treatments include dietary modification, herbal remedies including St John's Wort and chasteberry, acupuncture, and exercise. 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. Finally, the American College of Obstetricians and Gynecologists recommends regular aerobic exercise to reduce PMS symptoms. The first trials have been approved to study microdosing LSD for the treatment of PMS and PMDD.

History

In the 18th century, there were early accounts of weeping and other symptoms recurring almost every month, 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". In 1827, a German mother was acquitted of infanticide on the grounds of a menstrual mood disorder. Premenstrual tension was also described in the French literature of the early 19th century. 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.

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. 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.

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. 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. 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. 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.

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.