premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a dramatic form of Premenstrual syndrome^[1], afflicting 3% to 8% of women PMID 12892987.^[2] It is a diagnosis associated with the luteal phase of the menstrual cycle.

Symptoms

PMDD is premenstrual syndrome (PMS) that is so severe it can be debilitating due to either physical, mental or emotional symptoms. 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 (PMID 11571794). Anxiety, anger, and depression may also occur. The main symptoms, which can be disabling, include^[3]

• feelings of deep sadness or despair, possible suicide ideation
• feelings of tension or anxiety
• panic attacks
• diarrhea
• 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
• yeast infections
• difficulty concentrating
• fatigue
• food cravings or binge eating
• insomnia or hypersomnia
• feeling "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

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

In 2007, the first significant genetic finding in premenstrual dysphoric disorder was reported, which represents an important advance in understanding PMDD.

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.

These findings were published in "Risk for Premenstrual Dysphoric Disorder Is Associated with Genetic Variation in ESR1, the Estrogen Receptor Alpha Gene" by Liang Huo, Richard E. Straub, Peter J. Schmidt, Kai Shi, Radhakrishna Vakkalanka, Daniel R. Weinberger and David R. Rubinow, in Biological Psychiatry, Volume 62, Issue 8 (October 15, 2007), published by Elsevier.

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."^[4][5] 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.^[6]

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.^[7] 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.^[8]

In Australia, although PMDD is recognized by the Therapeutic Goods Administration, SSRIs are not reimbursed for it under the Pharmaceutical Benefits Scheme. ^[9]

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.^[10]

There is objective evidence of a neurological foundation for PMDD distress. In addition to the genetic associated 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) (PMID 16515859).

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 (PMID 16515859).

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.

Treatment

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.^[11] Certain SSRIs provide relief as well.^[12] 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 has expired, but Eli Lilly was able to obtain a new patent for its use in the treatment of PMDD, which has since marketed heavily under the trade name Sarafem.^[13] However Fluoxetine is now 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.^[14]

References

1. ^ "Premenstrual dysphoric disorder (PMDD) is the severe form of PMS." http://patients.uptodate.com/topic.asp?file=endocrin/10662
2. ^ 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
3. ^ "Premenstrual Syndrome" ("What is Premenstrual Dysphoric Disorder (PMDD?)"
4. ^ Laurence, Leslie (1993-05-16). "Psychiatric group scruitinzes categorizing form of PMS". Chicago Tribune. 
5. ^ Lehman, Betsy (1993-05-10). "A little revision is creating a big furor". Boston Globe. 
6. ^ 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
7. ^ Ray Moynihan (2004-02-14). "Controversial disease dropped from Prozac product information". BMJ 328: 7436. doi:10.1136/bmj.328.7436.365. PMID 14962861. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=341379. 
8. ^ European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products (2003-06-13). "Summary Information...for Prozac and associated names". http://www.emea.eu.int/pdfs/human/referral/326303en.pdf. 
9. ^ Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder (PMDD) National Prescribing Service Limited. (Australia)
10. ^ http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030198&ct=1&SESSID=d0c4ae9e966c4ec416e4ea241d60077b | Disease Mongering in Drug Promotion: Do Governments Have a Regulatory Role? Barbara Mintzes Citation: Mintzes B (2006) Disease Mongering in Drug Promotion: Do Governments Have a Regulatory Role? PLoS Med 3(4): e198 doi:10.1371/journal.pmed.0030198 Published: April 11, 2006 Copyright: © 2006 Barbara Mintzes. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Synopsis available: (PMID 16597181) (Noting e.g. Pfizer, the Manufacturer of Lipitor, engaged in attempts to increase Lipitor sales by making more consumers aware of heart disease through marketing and advertising)
11. ^ [1]
12. ^ Premenstrual Syndrome
13. ^ Jennifer Daw (2002-10-09). Is PMDD real?. 33. American Psychological Association Monitor on psychology. http://www.apa.org/monitor/oct02/pmdd.html. 
14. ^ A placebo-controlled study of the effects of L-tryptophan in patients with premenstrual dysphoria. PMID 10721042

Studd, J., Panay N. (2004) Hormones and Depression in Women. Climateric. 2004 Dec: 7(4):338-46. Review. Leather A.T., Studd J.W.W., Watson N.R. Holland E.F.N. (1999) The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo controlled study. Glynecol Endocrinol 13:48-55 Watson N.R., Studd. J.W.W. Savvas M., Garnett T., Baber R.J. (1989). Treatment of severe pre-menstrual syndrome with oestradiol patches and cyclical oral noresthisterone. Lancet ii: 730-734.

See also

• Premenstrual syndrome (PMS)

External links

• 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
• [2] Excellent collection of articles relating to aetiology and treatment of PMDD
• [3] A positive approach Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD)

Possible resource for 8% statistic: American Psychiatric Association. DSM-III-R Diagnostic and Statistical Manual of Mental Disorders. 3rd edition, Revised. American Psychiatric Press, Washington, DC; 1987