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Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome, afflicting about 2% of women. It is a diagnosis associated primarily with the luteal phase of the menstrual cycle, and results in behavioral and somatic symptoms. Up to one-third of women diagnosed with PMDD report residual symptoms into the first 2 or 3 days of the follicular phase.

Symptoms
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). Like PMS, premenstrual dysphoric disorder follows a predictable, cyclic pattern. Symptoms begin in the late luteal phase of the menstrual cycle (after ovulation) and end shortly after menstruation begins. On average, the symptoms last six days, with the most intense symptoms happening in the two days before through the day of the start of menstrual blood flow.

Emotional symptoms are generally present, and in PMDD, mood symptoms are dominant. Substantial disruption to personal relationships is typical for women with PMDD. Anxiety, anger, and depression may also occur. The main symptoms, which can be disabling, include


 * Feelings of sadness or despair, or even thoughts of suicide
 * Feelings of tension or anxiety
 * Panic attacks
 * Mood swings or frequent crying
 * Lasting irritability or anger that affects other people
 * Lack of interest in daily activities and relationships
 * Trouble thinking or focusing
 * Tiredness or low energy
 * Food cravings or binge eating
 * Trouble sleeping
 * Feeling out of control
 * Physical symptoms, such as bloating, breast tenderness, headaches, and joint or muscle pain

The symptoms occur during the week before menstruation, and go away once it starts. A diagnosis of PMDD requires the presence of at least five of these symptoms.

Cause
In 2007, the first significant genetic finding in premenstrual dysphoric disorder was reported. Variants in the estrogen receptor alpha gene are associated with PMDD. Women with these genetic variants were more likely to suffer from PMDD. They also discovered that this association is seen only in women with a variant form of another gene, Catechol-O-methyl transferase also known as COMT, which is involved in regulating the function of the prefrontal cortex, a critical regulator of mood.

Previously, research showed that women with PMDD have an abnormal response to normal hormone levels, and, thus, are differentially sensitive to their own natural hormone changes.

There is objective correlational evidence of a neurological connection for PMDD distress. The self-rated cardinal mood symptoms of women suffering premenstrual dysphoria was found to increase with a decrease in brain trapping of 5-hydroxytryptophan, the immediate precursor of serotonin, as measured by positron emission tomography (PET). A tryptophan-depleted diet significantly worsened premenstrual symptoms.

While the cause of PMDD has not been definitively established, a leading theory suggests it is due to the lack of serotonin (a neurotransmitter) and mediated by the fluctuations of the levels of sex hormones (progesterone, estrogen, and testosterone) in the luteal phase of the menstrual cycle.

Supporting the hypothesized important role of serotonin, a number of selective serotonin reuptake inhibitors (SSRIs) have been shown in clinical trials to effectively treat the mood component of PMDD when taken during the dysphoric phase, as detailed in the treatment section below.

Women with PMDD who have never experienced major depressive disorder (MDD) have lower sensitivity and response to stress and pain than people with a MDD. Although PMDD is classified as a depressive disorder, this suggests that PMDD is a separate disease from MDD.

Bipolar depression, anxiety disorders, and other Axis I disorders are more common in women with premenstrual dysphoric disorder (PMDD) than in women without PMDD.

General life stress is also associated with the prevalence of PMDD and the severity of symptoms. Research shows that perceived discrimination is a stressor associated with the lifetime prevalence of PMDD. The experience of subtle forms of gender and race discrimination is correlated with PMDD among ethnic minority women.

Diagnosis
Originally called late luteal phase dysphoric disorder (LLPDD), the disorder was renamed PMDD by the American Psychiatric Association in its May 1993 revision of the DSM-IV. In 1993, PMDD was not yet recognized as a disorder in the DSM-IV, but was noted in appendix B, "Criteria Sets and Axes Provided for Further Study." In the DSM-5 (publication May 2013,) premenstrual dysphoric disorder has been moved from Appendix B to the main body of DSM-5.

PMDD is accepted as an illness by the Food and Drug Administration (FDA) but has not as yet been listed as a separate disorder in the World Health Organization's International Classification of Diseases (ICD-10). Listing may be imminent, however, since the current beta draft of ICD-11 extends recognition, albeit in a way lacking the clinical sophistication of the DSM-5.

In 2003, the manufacturer of Prozac (fluoxetine) was required by the Committee for Proprietary Medicinal Products to remove PMDD from the list of indications for fluoxetine sold in Europe. Reflecting the approach of the ICD-10, the committee found that "...PMDD is not a well-established disease entity across Europe... There was considerable concern that women with less severe pre-menstrual symptoms might erroneously receive a diagnosis of PMDD resulting in widespread inappropriate short and long-term use of fluoxetine."

In Australia, although PMDD is recognized by the Therapeutic Goods Administration, SSRIs are not reimbursed for it under the Pharmaceutical Benefits Scheme.

Treatment
The primary goal of treatment is to reduce the patient's suffering and the disruption to their social relationships.

Selective serotonin reuptake inhibitors (SSRIs) have emerged as first-line therapy. Several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that the SSRIs have excellent efficacy and minimal side effects. 'However, just as PMDD is cyclical, treatment for it is cyclical as well. Unlike treatments for other depressive disorders, SSRIs do not need to be taken daily but instead can be taken only in the luteal phase or for the duration of PMDD symptoms'. The U.S. Food and Drug Administration (FDA) has approved four SSRIs for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil) and escitalopram oxalate (Lexapro).

Hormonal birth control containing drospirenone and low levels of estrogen helps relieve severe PMDD symptoms, for at least the first three months it is used.

Lifestyle changes such as regular exercise and a well balanced diet may ameliorate some of the effects of PMDD. L-tryptophan, a serotonin precursor, was found to provide significant relief (p = 0.004) when supplemented daily in a large dose of 6 grams per day. There is some evidence that vitamin B6 can alleviate symptoms.