Premenstrual dysphoric disorder (PMDD) is a severe form of Premenstrual syndrome, afflicting 3% to 8% of women. It is a diagnosis associated with the luteal phase of the menstrual cycle.

PMDD is premenstrual syndrome (PMS) that is so severe it can be debilitating due to either physical, mental or emotional symptoms.

The hallmark feature of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) is the predictable, cyclic nature of symptoms or distinct on/offness that begins in the late luteal phase of the menstrual cycle and remits shortly after the onset of menstruation. PMDD is distinguished from PMS by the severity of symptoms, predominance of mood symptoms, and role dysfunction, particularly in personal relationships and marital/family domains.

Treatment is recommended because PMDD interferes with the sufferer's ability to function in her social or occupational life. The cardinal symptom???surfacing between ovulation and menstruation, and disappearing within a few days after the onset of the bleeding???is irritability. Anxiety, anger, and depression may also occur. The main symptoms, which can be disabling, include

• feelings of deep sadness or despair, possible suicide ideation

• feelings of tension or anxiety

• increased sensitivity to rejection or criticism

• panic attacks

• mood swings, crying

• lasting irritability or anger, increased interpersonal conflicts. Typically sufferers are unaware of the impact they have on those close to them

• apathy or disinterest in daily activities and relationships

• difficulty concentrating

• fatigue

• food cravings or binge eating

• insomnia or hypersomnia; sleeping more than usual, or (in a smaller group of sufferers) being unable to sleep

• feeling overwhelmed or "out of control"

• increase or decrease in sex drive

• increased need for emotional closeness

• physical symptoms: bloating, heart palpitations, breast tenderness, headaches, joint or muscle pain, swollen face and nose

Other symptoms that are common and more specific to PMDD include:

• physical symptoms such as breast tenderness or swelling, headaches, joint or muscle pain.

• an altered view of one's body - a sensation of 'bloating', feeling fat or actual weight gain.

Five or more of these symptoms may indicate PMDD. Symptoms occur during the 2 weeks before the menstrual cycle and disappear within a few days after the onset of the bleeding.

In a recent study published in the journal Biological Psychology and led by Susan Girdler, Ph.D., professor of psychiatry at the University of North Carolina at Chapel Hill School of Medicine, demonstrated that PMDD women had greater sensitivity and respond to stress and pain.

In 2007, the first significant genetic finding in premenstrual dysphoric disorder was reported.

Previously, researchers have shown that women with PMDD have an abnormal response to normal hormone levels, and, thus, are differentially sensitive to their own hormone changes. In a study, Dr. Liang Huo and colleagues, found variants in the estrogen receptor alpha gene that 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???methyltransferase (COMT), which is involved in regulating the function of the prefrontal cortex, a critical regulator of mood.

Background and controversy

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. PMDD was moved from a position in the appendix of the manual to a "disorder requiring further study." While no one denies the reality of the suffering caused by PMDD, or advocates withholding treatment if a woman desires it, some psychiatrists and women's groups object to the labeling of a severe form of PMS as a psychiatric disorder. Psychologist Peggy Kleinplatz has criticized the diagnosis as part of a trend in medicalization of normal human behavior.

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 . 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. 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.

Some commentators suggest that PMDD (along with heart disease, social anxiety disorder, restless leg syndrome, and female sexual dysfunction) has been marketed by pharmaceutical companies in order to increase the demand for treatments.

There is objective correlational evidence of a neurological connection for PMDD distress. In addition to the genetic association noted in the section above, the self-rated cardinal mood symptoms of women suffering premenstrual dysphoria was found to be significantly correlated with the concomitant worsening of their brain serotonin precursors, measured by Positron emission tomography (PET).

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.

Psychiatric comorbidity

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

Lifestyle changes such as regular exercise and a well balanced diet may ameliorate some of the effects of PMDD. There is some evidence that vitamin B₆ in doses up to 100 mg can alleviate symptoms. Certain SSRIs provide relief as well. The U.S. Food and Drug Administration (FDA) has approved four medications for the treatment of PMDD: Fluoxetine (also known as Prozac), was approved by the U.S. Food and Drug administration for PMDD in 2000. Sertraline (Zoloft) was approved in 2002, Paroxetine HCI (Paxil) and also Escitalopram oxalate (Lexapro) has also been approved by the FDA. The patent for Fluoxetine expired in 2001, but Eli Lilly was able to extend patent protection until 2007 for its use in the treatment of PMDD, and thereafter marketed it heavily for this use under the trade name Sarafem. Fluoxetine is available as a generic in the same doses used in Sarafem, with the generic price generally a fraction of the cost for branded Sarafem. L-tryptophan, a serotonin precursor, was found in two studies to provide significant relief when supplemented daily in a large dose of (six grams) per day.

• Premenstrual syndrome (PMS)

• eMedicine on PMDD

• Madison Institute of Medicine (a non-profit organization) on PMDD

• A Disease for Every Pill , an article in The Nation questioning the reality of PMDD

• PMDD Research Current research studies at The University of North Carolina at Chapel Hill for women with PMDD

• Excellent collection of articles relating to aetiology and treatment of PMDD

• A positive approach Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD)