Premenstrual Dysphoric Disorder
- Author: Thwe T Htay, MD, FACP; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych(UK) more...
Premenstrual dysphoric disorder (PMDD) is a diagnosis used to indicate serious premenstrual distress with associated deterioration in functioning.
Signs and symptoms
PMDD is characterized by depressed or labile mood, anxiety, irritability, anger, and other symptoms occurring exclusively during the 2 weeks preceding menses. Other symptoms may include the following:
Decreased interest in usual activities (eg, work, school, friends, and hobbies)
Subjective sense of difficulty in concentrating
Lethargy, easy fatigability, or marked lack of energy
Marked change in appetite, overeating, or specific food cravings
Hypersomnia or insomnia
A subjective sense of being overwhelmed or out of control
Other physical symptoms, such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of bloating, or weight gain
The symptoms must be severe enough to interfere with occupational and social functioning, in contrast with the more common PMS. PMDD is a severely distressing and disabling condition that requires treatment.
See Clinical Presentation for more detail.
The initial steps in evaluating a patient for premenstrual dysphoric disorder (PMDD) are aimed at excluding organic syndromes with manifestations similar to those of PMDD, such as thyroid disorders, anemia, perimenopause, and menopause. The role of laboratory studies is limited to screening for medical conditions considered in the differential diagnosis. Although some tests may be needed to reassure the patient, excessive testing can be counterproductive by making the patient more anxious.
Laboratory studies should include the following:
Thyroid function tests
Complete blood count (CBC)
Follicle-stimulating hormone (FSH) level
See Workup for more detail.
Treatment of PMDD includes both nonpharmacologic and pharmacologic therapies.
Options for nonpharmacologic therapy for PMDD include the following:
Options for pharmacologic therapy for PMDD include the following:
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Anxiolytics, antidepressants, and mood stablizers
The combination of drospirenone and ethinyl estradiol is approved by the United States Food and Drug Administration (FDA) for the treatment of PMDD symptoms in women who choose to use an oral contraceptive as their method of contraception.
Buspirone has been shown to be efficacious in the treatment of both premenstrual syndrome (PMS) and PMDD.[1, 2]
Premenstrual dysphoric disorder (PMDD) is a diagnosis used to indicate serious premenstrual distress with associated deterioration in functioning. Clinically significant premenstrual problems with mood and behavior have been recognized since ancient times. Although Frank first described premenstrual syndrome (PMS) in the early 20th century, PMDD is a relatively new concept.
PMDD is characterized by depressed or labile mood, anxiety, irritability, anger, and other symptoms occurring exclusively during the 2 weeks preceding menses. The symptoms must be severe enough to interfere with occupational and social functioning, in contrast with the more common PMS. PMDD is a severely distressing and disabling condition that requires treatment.
In October 1998, a panel of experts evaluated the evidence then available, and a consensus was reached that PMDD was a distinct clinical entity. Subsequently, in November 1999, the US Food and Drug Administration (FDA) Neuropharmacology Advisory Committee supported this concept. Since then, several treatment options for PMDD have been investigated and developed.
Pathophysiology and Etiology
Major theories developed to explain the pathophysiology of PMDD include the following :
Ovarian hormone hypothesis
Cognitive and social learning theory
The ovarian hormone hypothesis suggests that PMDD is caused by an imbalance in the estrogen-to-progesterone ratio, with a relative progesterone deficiency. Accordingly, in the 1960s, PMS patients were treated with progesterone suppositories. However, later studies of estrogen and progesterone levels in women with PMS were inconclusive because of methodologic difficulties. The current consensus seems to be that normal hormonal fluctuations trigger central biochemical events related to PMDD symptoms in some predisposed women.
The serotonin theory hypothesizes that normal ovarian hormone function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system (CNS) and other target tissues.
PMDD shares many of the phenomenologic features of depression and anxiety states that have been linked to serotonergic dysregulation. A growing body of evidence suggests that serotonin (5-hydroxytryptamine [5-HT]) also may be important in the etiology of PMDD. Decreased serotonergic activity in women with PMDD has also been implied by the observation of reduced platelet uptake of serotonin and serotonin levels in peripheral blood.
In women with PMDD, sensitivity to perturbations of the central serotonin system is altered premenstrually. The administration of the serotonin agonist m -chlorophenylpiperazine may induce mood elevation. Agents that transiently diminish serotonin activity have been associated with behavioral changes, including irritability and social withdrawal.
The psychosocial theory hypothesizes that PMDD or PMS is a conscious manifestation of a woman’s unconscious conflict about femininity and motherhood. Psychoanalysts proposed that premenstrual physical changes reminded the woman that she was not pregnant and therefore was not fulfilling her traditional feminine role. Obviously, proving this theory through scientific evidence is quite difficult.
The cognitive and social learning theory hypothesizes that the onset of menses is an aversive psychological event for women susceptible to PMDD. Moreover, these women might have had negative and extreme thoughts that further reinforce the aversiveness of premenstrual symptoms.
Consequently, these women develop maladaptive coping strategies (eg, lability of mood, absence from school or work, and overeating) in an attempt to reduce the immediate stress. The immediate reduction of stress acts as a reinforcement, leading to the regular recurrence of symptoms during the premenstrual period.
Finally, the sociocultural theory hypothesizes that PMDD is a manifestation of the conflict between the dual roles society expects women to fill simultaneously—namely, productive workers and child-rearing mothers. PMDD is postulated to be a cultural expression of women’s discontent with the traditional role of women in the society.
Of these 5 theories, the serotonin theory is perhaps the most popular at present. Although genetic predisposition and societal expectations may play a role, the strongest scientific data implicate serotonin as the primary neurotransmitter whose levels are affected by ovarian steroid levels. Other neurotransmitter systems that have been implicated include the opioid, adrenergic, and gamma-aminobutyric acid (GABA) systems.
Risk factors for PMDD include the following:
Personal history of a major mood disorder
A family history of mood disorder
Premenstrual mood changes
History of sexual abuse
Past, present, or current domestic violence
United States statistics
Epidemiologic studies indicate that as many as 80% of women in the United States experience emotional, behavioral, or physical premenstrual symptoms. Between 3% and 8% of women meet the diagnostic criteria for PMDD.
Worldwide, PMDD affects 3-8% of women in their reproductive years, imposing an enormous burden on women, their families, and the health care system. A study from India reported a frequency of 6%. A population-based sample of Swiss women from the entire reproductive age range found that 3% of the sample population fulfilled criteria for PMDD. A cross-sectional study of female Nigerian medical students showed that 36% of the respondents met the criteria for the diagnosis of PMDD.
Age- and race-related demographics
Apparently, women in the late third to middle fourth decades of life are most vulnerable to experiencing PMDD. Although premenstrual clinics are reported to be almost exclusively attended by white women, community-based studies found no difference between black women and white women with respect to the prevalence or severity of premenstrual symptoms.
Some isolated reports indicate variations in individual symptoms—though not in the overall prevalence of premenstrual symptoms—among different racial groups. Black women tend to have a higher prevalence of food cravings than white women. White women are more likely than black women to report premenstrual mood changes and weight gain. Pain featured most highly in a sample of Chinese women in Hong Kong.
PMDD is a multifactorial syndrome that occurs with varying degrees of severity and thus may have a range of potential adverse effects on work, social activities, and interpersonal relationships.
Upon treatment, symptoms tend to improve rapidly. After cessation of treatment, symptoms recur rapidly, and their reemergence is more predictable than that with major depressive disorder or dysthymia. After oophorectomy, however, symptoms usually do not recur.
Educate women to seek help for PMDD. Emphasize the following reasons why they should do so:
Problems tend to recur each cycle
Problems may become more severe over time
Problems can be quite disabling for women and their families
Problems may not go away if ignored
Problems can be readily diagnosed and effectively treated.
It is important to educate not only the patient but also the partner and family; this disorder has an impact on the entire family context. Useful Web sites for patients and their families include the following:
MedlinePlus, Premenstrual dysphoric disorder
American Family Physician, Diagnosis and Treatment of Premenstrual Dysphoric Disorder
Wyatt K, Dimmock P, O'Brien PMS. Premenstrual syndrome. Clin Evid. 2000. 4:1121-33.
Rickels K, Freeman E, Sondheimer S. Buspirone in treatment of premenstrual syndrome. Lancet. 1989 Apr 8. 1(8641):777. [Medline].
Endicott J. History, evolution, and diagnosis of premenstrual dysphoric disorder. J Clin Psychiatry. 2000. 61 Suppl 12:5-8. [Medline].
Frank RT. The hormonal causes of premenstrual tension. Arch Neurol Psych. 1931. 26:1053-57.
Klock SC. Premenstrual dysphoric disorder. Ryan KJ, ed. Kistner's Gynecology and Women's Health. 7th ed. 520-4.
Steiner M, Pearlstein T. Premenstrual dysphoria and the serotonin system: pathophysiology and treatment. J Clin Psychiatry. 2000. 61 Suppl 12:17-21. [Medline].
Mueller EA, Murphy DL, Sunderland T. Neuroendocrine effects of M-chlorophenylpiperazine, a serotonin agonist, in humans. J Clin Endocrinol Metab. 1985 Dec. 61(6):1179-84. [Medline].
Ling FW. Recognizing and treating premenstrual dysphoric disorder in the obstetric, gynecologic, and primary care practices. J Clin Psychiatry. 2000. 61 Suppl 12:9-16. [Medline].
Boyle CA, Berkowitz GS, Kelsey JL. Epidemiology of premenstrual symptoms. Am J Public Health. 1987 Mar. 77(3):349-50. [Medline].
Grady-Weliky TA. Clinical practice. Premenstrual dysphoric disorder. N Engl J Med. 2003 Jan 30. 348(5):433-8. [Medline].
Banerjee N, Roy KK, Takkar D. Premenstrual dysphoric disorder--a study from India. Int J Fertil Womens Med. 2000 Sep-Oct. 45(5):342-4. [Medline].
Tschudin S, Bertea PC, Zemp E. Prevalence and predictors of premenstrual syndrome and premenstrual dysphoric disorder in a population-based sample. Arch Womens Ment Health. 2010 Dec. 13(6):485-94. [Medline].
Issa BA, Yussuf AD, Olatinwo AW, Ighodalo M. Premenstrual dysphoric disorder among medical students of a Nigerian university. Ann Afr Med. 2010 Jul-Sep. 9(3):118-22. [Medline].
Stout AL, Grady TA, Steege JF, et al. Premenstrual symptoms in black and white community samples. Am J Psychiatry. 1986 Nov. 143(11):1436-9. [Medline].
Woods NF, Most A, Dery GK. Prevalene of perimenstrual symptoms. Am J Public Health. 1982 Nov. 72(11):1257-64. [Medline].
Chang AM, Holroyd E, Chau JP. Premenstrual syndrome in employed Chinese women in Hong Kong. Health Care Women Int. 1995 Nov-Dec. 16(6):551-61. [Medline].
The American Psychiatric Association. Diagnostic and statistical manual of mental disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000. 717-8.
Bhatia SC, Bhatia SK. Depression in women: diagnostic and treatment considerations. Am Fam Physician. 1999 Jul. 60(1):225-34, 239-40. [Medline].
Baca-Garcia E, Diaz-Sastre C, Ceverino A, García Resa E, Oquendo MA, Saiz-Ruiz J, et al. Premenstrual symptoms and luteal suicide attempts. Eur Arch Psychiatry Clin Neurosci. 2004 Oct. 254(5):326-9. [Medline].
Kim SY, Park HJ, Lee H, Lee H. Acupuncture for premenstrual syndrome: a systematic review and meta-analysis of randomised controlled trials. BJOG. 2011 Jul. 118(8):899-915. [Medline].
Jang SH, Kim DI, Choi MS. Effects and treatment methods of acupuncture and herbal medicine for premenstrual syndrome/premenstrual dysphoric disorder: systematic review. BMC Complement Altern Med. 2014 Jan 10. 14:11. [Medline].
Goodale IL, Domar AD, Benson H. Alleviation of premenstrual syndrome symptoms with the relaxation response. Obstet Gynecol. 1990 Apr. 75(4):649-55. [Medline].
Lam RW, Carter D, Misri S, et al. A controlled study of light therapy in women with late luteal phase dysphoric disorder. Psychiatry Res. 1999 Jun 30. 86(3):185-92. [Medline].
Krasnik C, Montori VM, Guyatt GH, Heels-Ansdell D, Busse JW. The effect of bright light therapy on depression associated with premenstrual dysphoric disorder. Am J Obstet Gynecol. 2005 Sep. 193(3 Pt 1):658-61. [Medline].
Parry BL, Cover H, Mostofi N, et al. Early versus late partial sleep deprivation in patients with premenstrual dysphoric disorder and normal comparison subjects. Am J Psychiatry. 1995 Mar. 152(3):404-12. [Medline].
Blake F, Salkovskis P, Gath D, et al. Cognitive therapy for premenstrual syndrome: a controlled trial. J Psychosom Res. 1998 Oct. 45(4):307-18. [Medline].
Busse JW, Montori VM, Krasnik C, Patelis-Siotis I, Guyatt GH. Psychological intervention for premenstrual syndrome: a meta-analysis of randomized controlled trials. Psychother Psychosom. 2009. 78(1):6-15. [Medline].
Lustyk MK, Gerrish WG, Shaver S, Keys SL. Cognitive-behavioral therapy for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Arch Womens Ment Health. 2009 Apr. 12(2):85-96. [Medline].
drospirenone and ethinyl estradiol (YAZ®) [package insert]. Wayne, NJ: Bayer Health Care Phamaceuticals. 2007. Available at [Full Text].
Pearlstein T, Steiner M. Non-antidepressant treatment of premenstrual syndrome. J Clin Psychiatry. 2000. 61 Suppl 12:22-7. [Medline].
Andersen AN, Larsen JF, Steenstrup OR, Svendstrup B, Nielsen J. Effect of bromocriptine on the premenstrual syndrome. A double-blind clinical trial. Br J Obstet Gynaecol. 1977 May. 84(5):370-4. [Medline].
Kullander S, Svanberg L. Bromocriptine treatment of the premenstrual syndrome. Acta Obstet Gynecol Scand. 1979. 58(4):375-8. [Medline].
Graham JJ, Harding PE, Wise PH, Berriman H. Prolactin suppression in the treatment of premenstrual syndrome. Med J Aust. 1978 Nov 4. 2(3 Suppl):18-20. [Medline].
Werch A, Kane RE. Treatment of premenstrual tension with metolazone: a double-blind evaluation of a new diuretic. Curr Ther Res Clin Exp. 1976 Jun. 19(6):565-72. [Medline].
Harrison WM, Endicott J, Nee J. Treatment of premenstrual dysphoria with alprazolam. A controlled study. Arch Gen Psychiatry. 1990 Mar. 47(3):270-5. [Medline].
Schmidt PJ, Grover GN, Rubinow DR. Alprazolam in the treatment of premenstrual syndrome. A double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1993 Jun. 50(6):467-73. [Medline].
Eriksson E. Serotonin reuptake inhibitors for the treatment of premenstrual dysphoria. Int Clin Psychopharmacol. 1999 May. 14 Suppl 2:S27-33. [Medline].
The Medical Letter. Which SSRI?. Med Lett Drugs Ther. 2003 Nov 24. 45(1170):93-5. [Medline].
Steiner M. Recognition of premenstrual dysphoric disorder and its treatment. Lancet. 2000 Sep 30. 356(9236):1126-7. [Medline].
Brown J, O' Brien PM, Marjoribanks J, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. 2009 Apr 15. CD001396. [Medline].
Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual dysphoria. Canadian Fluoxetine/Premenstrual Dysphoria Collaborative Study Group. N Engl J Med. 1995 Jun 8. 332(23):1529-34. [Medline].
The Medical Letter. Fluoxetine (Sarafem) for premenstrual dysphoric disorder. Med Lett Drugs Ther. 2001 Jan 22. 43(1096):5-6. [Medline].
Yonkers KA, Halbreich U, Freeman E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. JAMA. 1997 Sep 24. 278(12):983-8. [Medline].
Young SA, Hurt PH, Benedek DM, Howard RS. Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: a randomized, double-blind, placebo-controlled crossover trial. J Clin Psychiatry. 1998 Feb. 59(2):76-80. [Medline].
Steiner M, Hirschberg AL, Bergeron R, et al. Luteal phase dosing with paroxetine controlled release (CR) in the treatment of premenstrual dysphoric disorder. Am J Obstet Gynecol. 2005. 193:352-60. [Medline].
Steiner M, Ravindran AV, LeMelledo JM, Carter D, Huang JO, Anonychuk AM, et al. Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women. J Clin Psychiatry. 2008 Jun. 69(6):991-8. [Medline].
Freeman EW, Rickels K, Sondheimer SJ, et al. Nefazodone in the treatment of premenstrual syndrome: a preliminary study. J Clin Psychopharmacol. 1994 Jun. 14(3):180-6. [Medline].
Freeman EW, Rickels K, Yonkers KA, et al. Venlafaxine in the treatment of premenstrual dysphoric disorder. Obstet Gynecol. 2001 Nov. 98(5 Pt 1):737-44. [Medline].
Freeman EW, Sondheimer SJ, Sammel MD, et al. A preliminary study of luteal phase versus symptom-onset dosing with escitalopram for premenstrual dysphoric disorder. J Clin Psychiatry. 2005. 66:769-73. [Medline].
Shah NR, Jones JB, Aperi J, Shemtov R, Karne A, Borenstein J. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis. Obstet Gynecol. 2008 May. 111(5):1175-82. [Medline].
Kayatekin ZE, Sabo AN, Halbreich U. Levetiracetam for treatment of premenstrual dysphoric disorder: a pilot, open-label study. Arch Womens Ment Health. 2008 Jul. 11(3):207-11. [Medline].
Wyatt KM, Dimmock PW, Jones PW, Shaughn O''Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999 May 22. 318(7195):1375-81. [Medline].
Thys-Jacobs S, Starkey P, Bernstein D, Tian J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol. 1998 Aug. 179(2):444-52. [Medline].
Facchinetti F, Borella P, Sances G, Fioroni L, Nappi RE, Genazzani AR. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 1991 Aug. 78(2):177-81. [Medline].
Walker AF, De Souza MC, Vickers MF, Abeyasekera S, Collins ML, Trinca LA. Magnesium supplementation alleviates premenstrual symptoms of fluid retention. J Womens Health. 1998 Nov. 7(9):1157-65. [Medline].
Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome?. Control Clin Trials. 1996 Feb. 17(1):60-8. [Medline].
Brauser D. Progesterone, Anxiety Affect Premenstrual Dysphoric Disorder. Available at http://www.medscape.com/viewarticle/812792. Accessed: October 28, 2013.
Dell DL. Premenstrual Syndrome, Premenstrual Dysphoric Disorder, and Premenstrual Exacerbation of Another Disorder. Clin Obstet Gynecol. 2004 Sep. 47(3):568-575. [Medline].
Gingnell M, Morell A, Bannbers E, Wikström J, Sundström Poromaa I. Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder. Horm Behav. 2012 Sep. 62(4):400-6. [Medline].