Premenstrual dysphoric disorder

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

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome,[3] for about 2% [4] of women. One publication from 2003 claimed that at that time it was estimated that 3-8% of women of reproductive age meet the PMDD criteria. "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."[5] It is a diagnosis associated primarily with the luteal phase of the menstrual cycle, and results in behavioral and somatic symptoms.[6] Up to one-third of women diagnosed with PMDD report residual symptoms into the first 2 or 3 days of the follicular phase.[7]


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.[8] 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.[9]

Emotional symptoms are generally present, and in PMDD, mood symptoms are dominant.[8] Substantial disruption to personal relationships is typical for women with PMDD.[8] Anxiety, anger, and depression may also occur. The main symptoms, which can be disabling, include[10]

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.[10]


In 2007, the first significant genetic finding in premenstrual dysphoric disorder was reported.[11][12] 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).[13] A tryptophan-depleted diet significantly worsened premenstrual symptoms.[14]

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.[13]

Supporting the hypothesized important role of serotonin, a number of selective serotonin reuptake inhibitors (SSRIs) have been shown[8] 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.[15] Although PMDD is classified as a depressive disorder,[4] 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.[16]

General life stress is also associated with the prevalence of PMDD and the severity of symptoms.[17] Research shows that perceived discrimination is a stressor associated with the lifetime prevalence of PMDD.[17] The experience of subtle forms of gender and race discrimination is correlated with PMDD among ethnic minority women.[17]


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."[18][19] In the DSM-5 (publication May 2013,) premenstrual dysphoric disorder has been moved from Appendix B to the main body of DSM-5.[20]

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,[21] 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.[22] 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.[23]

In Australia, although PMDD is recognized by the Therapeutic Goods Administration, SSRIs are not reimbursed for it under the Pharmaceutical Benefits Scheme.[24]


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.[25] Several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that the SSRIs have excellent efficacy and minimal side effects.[26][27] 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.[6] 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.[28]

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.[29] There is some evidence that vitamin B6 can alleviate symptoms.[30][31]

See also[edit]


  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. doi:10.1080/0951590400018215. PMID 15724807. 
  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. doi:10.4088/JCP.v64n1216. PMID 14728114. 
  3. ^ "Premenstrual dysphoric disorder (PMDD) is the a form of PMS."
  4. ^ a b Nolen-Hoeksema, Susan (2014). Abnormal Psychology (Sixth edition. ed.). 2 Penn Plaza, New York, NY 10121: McGraw-Hill Education. p. 180. ISBN 978-0-07-803538-8. 
  5. ^ PMID 12892987
  6. ^ a b "Treatment of premenstrual dysphoric disorder.". National Center for Biotechnology Information. 
  7. ^ Yonkers KA, Pearlstein T, Fayyad R, Gillespie JA. Luteal phase treatment of premenstrual dysphoric disorder improves symptoms that continue into the postmenstrual phase. J Affect Disord. 2005 Apr;85(3):317-21. doi:10.1016/j.jad.2004.10.006 PMID 15780701
  8. ^ a b c d Steiner M, Pearlstein T, Cohen LS, et al. (2006). "Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs". J Womens Health (Larchmt) 15 (1): 57–69. doi:10.1089/jwh.2006.15.57. PMID 16417420. 
  9. ^ Biggs, WS.; Demuth, RH. (Oct 2011). "Premenstrual syndrome and premenstrual dysphoric disorder.". Am Fam Physician 84 (8): 918–24. PMID 22010771. 
  10. ^ a b Premenstrual Syndrome: "What is Premenstrual Dysphoric Disorder (PMDD?)"
  11. ^ 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. doi:10.1016/j.biopsych.2006.12.019. PMC 2762203. PMID 17599809. 
  12. ^ "UNC Center for Women's Mood Disorders"
  13. ^ a b 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. doi:10.1016/j.pscychresns.2005.02.012. PMID 16515859. 
  14. ^ Menkes, DB1; Coates DC; Fawcett JP (1994). "Acute tryptophan depletion aggravates premenstrual syndrome.". J Affect Disord. 32 (Sep.): 37–44. doi:10.1016/0165-0327(94)90059-0. PMID 7798465. Retrieved 2 March 2014. 
  15. ^ 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. doi:10.1016/j.biopsycho.2010.01.018. PMC 2877489. PMID 20138113. 
  16. ^ 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. doi:10.1007/s00737-003-0027-3. PMID 14963731. 
  17. ^ a b c Pilver, C, Desai, R, Kasl, S & Levy, B, 2011, ‘Lifetime Discrimination Associated with Greater Likelihood of Premenstrual Dysphoric Disorder’, Journal of Women’s Health, vol. 20, no. 6, pp. 923-931.
  18. ^ Laurence, Leslie (1993-05-16). "Psychiatric group scrutinizes categorizing form of PMS". Chicago Tribune. 
  19. ^ Lehman, Betsy (1993-05-10). "A little revision is creating a big furor". Boston Globe. 
  20. ^
  21. ^ Premenstrual Dysphoric Disorder (PMDD); Retrieved July. 13, 2013
    Severe form of premenstrual syndrome considered as a distinct clinical entity, characterized by prominent symptoms of irritability, anger, internal tension, dysphoria and mood lability. Diagnosis requires a prospective symptom diary documenting specific cyclic symptoms associated with the luteal and menstrual phases of the cycle, and evidence of socioeconomic dysfunction.
  22. ^ Ray Moynihan (2004-02-14). "Controversial disease dropped from Prozac product information". BMJ 328 (7436): 7436. doi:10.1136/bmj.328.7436.365. PMC 341379. PMID 14962861. 
  23. ^ European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products (2003-06-13). "Summary Information...for Prozac and associated names". 
  24. ^ Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder (PMDD) National Prescribing Service Limited. (Australia)
  25. ^ Steiner M, Pearlstein T, Cohen LS, et al. (2006). "Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs". J Womens Health (Larchmt) 15 (1): 57–69. doi:10.1089/jwh.2006.15.57. PMID 16417420. 
  26. ^ Steiner M, Pearlstein T (2000). "Premenstrual dysphoria and the serotonin system: pathophysiology and treatment". J Clin Psychiatry. 61 Suppl 12: 17–21. PMID 11041380. 
  27. ^ Premenstrual Syndrome
  28. ^ Lopez, LM.; Kaptein, AA.; Helmerhorst, FM. (2012). "Oral contraceptives containing drospirenone for premenstrual syndrome.". Cochrane Database Syst Rev 2: CD006586. doi:10.1002/14651858.CD006586.pub4. PMID 22336820. 
  29. ^ 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. Advances in Experimental Medicine and Biology 467: 85–8. doi:10.1007/978-1-4615-4709-9_11. ISBN 978-0-306-46204-7. PMID 10721042. 
  30. ^
  31. ^ Wyatt, Katrina; Paul Dimmock; Peter Jones; P M Shaughn O'Brien (22 May 1999). "Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review". BMJ 318 (7195): 1375–1381. doi:10.1136/bmj.318.7195.1375. PMC 27878. PMID 10334745. 

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