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Premenstrual dysphoric disorder
Classification and external resources
ICD-9 Controversial. Either 311,[1] 625.4, or none[2]
eMedicine article/293257

Premenstrual dysphoric disorder (PMDD) is an illness associated with the luteal phase of the menstrual cycle. It is characterized by severe irritability, anxiety and anger. It is similar to premenstrual syndrome (PMS), but differs from it in severity and in that it requires treatment, because it interferes in a woman's ability to function in her environment. It has been proposed as a disorder requiring further study by the American Psychiatric Association in the DSM-IV-TR. .


The cause of PMDD is not known, but several theories exist. One theory suggests it is due to the lack of serotonin (a neurotransmitter in the brain) and mediated by the levels of the level of sex hormones (progesterone and estrogen) in the luteal phase of the menstrual cycle. A common treatment for PMDD is selective serotonin reuptake inhibitors (SSRIs), specially fluoxetine (Sarafem, also known as Prozac).


The comdition is thought to afflicting 3% to 8% of women.[3] It is a diagnosis associated with the luteal phase of the menstrual cycle.


PMDD is a severe form of premenstrual syndrome (PMS).

Like less severe forms of 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.[4]

Emotional symptoms are generally present, and in PMDD, mood symptoms are dominant.[4] Substantial disruption to personal relationships is typical for women with PMDD.[4] Anxiety, anger, and depression may also occur. The main symptoms, which can be disabling, include[5]

  • 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 feelings of being out of control
  • increase or decrease in sex drive
  • increased need for emotional closeness

Common physical symptoms include:

  • breast tenderness or swelling, heart palpitations, headaches, joint or muscle pain, swollen face and nose
  • 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.

Genetic links and possible causes

In 2007, the first significant genetic finding in premenstrual dysphoric disorder was reported.[6][7] 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.

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 be significantly correlated with the concomitant worsening of their brain serotonin precursors, measured by positron emission tomography (PET).[8]

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.[8]

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.

Women with PMDD but have never experienced major depressive disorder (MDD) have lower sensitivity and response to stress and pain than people with MDD.[9] This suggests that PMDD is a separate disease from MDD.

Unipolar depression, anxiety disorders, and other Axis I disorders are more common in women with premenstrual dysphoric disorder (PMDD) than in women without PMDD.[10]

Status 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. It is not recognized as a disorder in the DSM-IV. PMDD was moved from a position the DSM-IV in the appendix of the manual to a "disorder requiring further study."[11][12]

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.[13] 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.[14]

In Australia, although PMDD is recognized by the Therapeutic Goods Administration, SSRIs are not reimbursed for it under the Pharmaceutical Benefits Scheme.[15]

Some commentators suggest that PMDD (along with heart disease, borderline high blood pressure, mild hypercholesterolemia, social anxiety disorder, restless leg syndrome, and female sexual dysfunction) has been marketed by pharmaceutical companies in order to increase the demand for treatments.[16] Some psychiatrists and women's groups say that labeling this severe form of PMS as a psychiatric disorder, rather than a physical disorder, is stigmatizing. Psychologist Peggy Kleinplatz has criticized the diagnosis as part of a trend in medicalization of normal human behavior.[17]


The primary goal of treatment is to reduce the woman's suffering and the disruption to her social relationships.

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 can alleviate symptoms.[18]

Certain SSRIs provide relief as well.[19] The U.S. Food and Drug Administration (FDA) has approved four medications for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil) and escitalopram oxalate (Lexapro).

L-tryptophan, a serotonin precursor, was found in two studies to provide significant relief when supplemented daily in a large dose.[20]

See also

Premenstrual stress syndrome (PMS)


  1. Halbreich U (December 2004). The diagnosis of premenstrual syndromes and premenstrual dysphoric disorder--clinical procedures and research perspectives. Gynecol. Endocrinol. 19 (6): 320–34.
  2. Endicott J, McLaughlin TP, Grudzinski AN (December 2003). Comparison of managed care charges among patients treated with selective serotonin reuptake inhibitors for premenstrual dysphoric disorder. J Clin Psychiatry 64 (12): 1511–6.
  3. PMDD affects "... 3-8% of women of reproductive age. Assessment of published reports demonstrate that the prevalence of clinically relevant dysphoric premenstrual disorder is probably higher. 13-18% of women of reproductive age may have premenstrual dysphoric symptoms severe enough to induce impairment and distress, though the number of symptoms may not meet the arbitrary count of 5 symptoms on the PMDD list." PMID 12892987
  4. 4.0 4.1 4.2 Steiner, Pearlstein, et al. "Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs." J Womens Health (Larchmt). 2006 Jan-Feb;15(1):57-69 PMID 16417420
  5. Premenstrual Syndrome: "What is Premenstrual Dysphoric Disorder (PMDD?)"
  6. Huo L, Straub RE, Roca C, Schmidt PJ, Shi K, Vakkalanka R, Weinberger DR, Rubinow DR (October 2007). Risk for premenstrual dysphoric disorder is associated with genetic variation in ESR1, the estrogen receptor alpha gene. Biol. Psychiatry 62 (8): 925–33.
  7. "UNC Center for Women's Mood Disorders"
  8. 8.0 8.1 Eriksson O, Wall A, Marteinsdottir I, et al. (March 2006). Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria. Psychiatry Res 146 (2): 107–16.
  9. Klatzkin RR, Lindgren ME, Forneris CA, Girdler SS (May 2010). Histories of major depression and premenstrual dysphoric disorder: Evidence for phenotypic differences. Biol Psychol 84 (2): 235–47.
  10. Kim DR, Gyulai L, Freeman EW, Morrison MF, Baldassano C, Dubé B (February 2004). Premenstrual dysphoric disorder and psychiatric co-morbidity. Arch Womens Ment Health 7 (1): 37–47.
  11. includeonly>Laurence, Leslie. "Psychiatric group scruitinzes categorizing form of PMS", Chicago Tribune, 1993-05-16.
  12. includeonly>Lehman, Betsy. "A little revision is creating a big furor", Boston Globe, 1993-05-10.
  13. Ray Moynihan (2004-02-14). Controversial disease dropped from Prozac product information. BMJ 328 (7436): 7436.
  14. European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products. Summary Information...for Prozac and associated names.
  15. Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder (PMDD) National Prescribing Service Limited. (Australia)
  16. Mintzes B (April 2006). Disease mongering in drug promotion: do governments have a regulatory role?. PLoS Med. 3 (4): e198.
  17. Offman A, Kleinplatz PJ (2004). Does PMDD Belong in the DSM? Challenging the Medicalization of Women's Bodies. The Canadian Journal of Human Sexuality, Vol. 13
  19. Premenstrual Syndrome
  20. Steinberg S, Annable L, Young SN, Liyanage N (1999). A placebo-controlled study of the effects of L-tryptophan in patients with premenstrual dysphoria. Adv. Exp. Med. Biol. 467: 85–8.

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