Premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome ["Premenstrual dysphoric disorder (PMDD) is the severe form of PMS." http://patients.uptodate.com/topic.asp?file=endocrin/10662 ] , afflicting 3% to 8% of women. [" ... PMDD affects only 3 to 8 percent of women." http://patients.uptodate.com/topic.asp?file=endocrin/10662] It is a mood disorder associated with the luteal phase of the menstrual cycle.

ymptoms

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 [ [http://www.4women.gov/FAQ/pms.htm "Premenstrual Syndrome" ("What is Premenstrual Dysphoric Disorder (PMDD?)] "]

* feelings of deep sadness or despair, possible suicide ideation
* feelings of tension or anxiety
* panic attacks
* mood swings, crying
* lasting irritability or anger, increased interpersonal conflicts
* apathy or disinterest in daily activities and relationships
* 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

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

Linked To Genetics

In 2007, the first significant genetic finding in premenstrual dysphoric disorder was reported, which represents an importance 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 an "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." [cite news| author=Laurence, Leslie | title=Psychiatric group scruitinzes categorizing form of PMS | publisher=Chicago Tribune | date=1993-05-16 ] [cite news| author=Lehman, Betsy | title=A little revision is creating a big furor |publisher=Boston Globe| date=1993-05-10] 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.

PMDD is accepted as 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. [cite journal| url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=341379 | title=Controversial disease dropped from Prozac product information| author=Ray Moynihan | journal = BMJ | volume=328 | date=2004-02-14 | pages = 7436 | pmid=14962861 | doi=10.1136/bmj.328.7436.365] 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. [cite web| url=http://www.emea.eu.int/pdfs/human/referral/326303en.pdf | title=Summary Information...for Prozac and associated names| author=European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products| date=2003-06-13]

PMDD is not listed on the Australian Pharmaceutical Benefits Scheme. [ [http://www.npsradar.org.au/site.php?page=1&content=/npsradar/content/sertraline.html Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder (PMDD)] National Prescribing Service Limited. (Australia)]

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. [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.0030198Published: April 11, 2006Copyright: © 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)]

There is evidence of a neurological foundation for PMDD distress. The self-rated cardinal mood symptoms of women suffering premenstrual dysphoria was found to be strongly correlated with the concomitant worsening of their brain serotonin precursors, measured objectively 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 proven in clinical trials to effectively treat the mood component of PMDD when taken during the dysphoric phase.

Treatment

Lifestyle changes may ameliorate some of the effects of PMDD, and certain SSRIs provide relief as well. [ [http://www.4women.gov/FAQ/pms.htm Premenstrual Syndrome ] ] 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.cite journal| url=http://www.apa.org/monitor/oct02/pmdd.html |publisher=American Psychological Association Monitor on psychology | title=Is PMDD real?| author=Jennifer Daw| volume=33| date=2002-10-09] 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. [A placebo-controlled study of the effects of L-tryptophan in patients with premenstrual dysphoria. PMID 10721042 ]

Another alternative is hormone therapy; the simplest treatment is the Pill, which may lessen or even eliminate symptoms. The Pill can also make some women's symptoms worse as it contains progesterons and many women with PMS and particularly PMDD are intolerant to progesterones (their own and synthetic ones). There is evidence to show that progesterones may be at the root of their PMDD and PMS (Watson et al 1989; Leather et al 1999; Studd et al 2004).

The only complete cure is removal of the ovaries or menopause. However, hormone therapy is usually then needed to mimic natural hormone levels.

References

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

* [http://www.emedicine.com/med/topic3357.htm eMedicine on PMDD]
* [http://www.pmdd.factsforhealth.org/ Madison Institute of Medicine (a non-profit organization) on PMDD]
* [http://www.thenation.com/doc/20051017/moynihan A Disease for Every Pill] , an article in The Nation questioning the reality of PMDD
* [http://www.med.unc.edu/psych/wmd/htm/research_studies.htm PMDD Research] Current research studies at The University of North Carolina at Chapel Hill for women with PMDD
* [http://www.studd.co.uk/pms.php] Excellent collection of articles relating to aetiology and treatment of 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