Premenstrual Dysphoric Disorder

Premenstrual Dysphoric Disorder

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Premenstrual dysphoric disorder (PMDD) is a diagnosis used to indicate serious premenstrual distress with associated deterioration in functioning.

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.

Nonpharmacologic therapy

Options for nonpharmacologic therapy for PMDD include the following:


Relaxation techniques

Light therapy

Sleep deprivation

Cognitive-behavioral therapy

Pharmacologic therapy

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]

See Treatment and Medication for more detail.

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. [3] Although Frank first described premenstrual syndrome (PMS) in the early 20th century, [4] 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.

Major theories developed to explain the pathophysiology of PMDD include the following [5] :

Ovarian hormone hypothesis

Serotonin hypothesis

Psychosocial hypothesis

Cognitive and social learning theory

Sociocultural 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. [6]

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. [7] 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. [8]

Risk factors for PMDD include the following:

Personal history of a major mood disorder

A family history of mood disorder

Premenstrual depression

Premenstrual mood changes

History of sexual abuse

Past, present, or current domestic violence

Epidemiologic studies indicate that as many as 80% of women in the United States experience emotional, behavioral, or physical premenstrual symptoms. [9] Between 3% and 8% of women meet the diagnostic criteria for PMDD.

Worldwide, PMDD affects 3-8% of women in their reproductive years, [10] imposing an enormous burden on women, their families, and the health care system. A study from India reported a frequency of 6%. [11] A population-based sample of Swiss women from the entire reproductive age range found that 3% of the sample population fulfilled criteria for PMDD. [12] A cross-sectional study of female Nigerian medical students showed that 36% of the respondents met the criteria for the diagnosis of PMDD. [13]

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. [14] White women are more likely than black women to report premenstrual mood changes [15] and weight gain. Pain featured most highly in a sample of Chinese women in Hong Kong. [16]

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.

For patient education resources, see the Women’s Health Center, as well as Premenstrual Syndrome (PMS).

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

WebMD, Sexual Health: Your Guide to Premenstrual Dysphoric Disorder

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Thwe T Htay, MD, FACP Associate Professor of Medicine, Medical Skills Course Director, Department of Medical Education, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Thwe T Htay, MD, FACP is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

KoKo Aung, MD, MPH, FACP Professor of Internal Medicine, Associate Academic Dean, Assistant Vice President, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

KoKo Aung, MD, MPH, FACP is a member of the following medical societies: American College of Physicians, Society of General Internal Medicine

Disclosure: Nothing to disclose.

Iqbal Ahmed, MBBS, FRCPsych(UK) Faculty, Department of Psychiatry, Tripler Army Medical Center; Clinical Professor of Psychiatry, Uniformed Services University of the Health Sciences; Clinical Professor of Psychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych(UK) is a member of the following medical societies: Academy of Psychosomatic Medicine, American Neuropsychiatric Association, American Society of Clinical Psychopharmacology, Royal College of Psychiatrists, American Association for Geriatric Psychiatry, American Psychiatric Association

Disclosure: Nothing to disclose.

Ronald C Albucher, MD Chief Medical Officer, Westside Community Services; Consulting Staff, California Pacific Medical Center

Ronald C Albucher, MD is a member of the following medical societies: American Psychiatric Association

Disclosure: Nothing to disclose.

John Carrick, MD Consulting Staff, Department of Psychiatry, Flagstaff Medical Center

John Carrick, MD is a member of the following medical societies: American Association for Geriatric Psychiatry

Disclosure: Nothing to disclose.

Romeo Papica II MD Staff Physician, Premier Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Premenstrual Dysphoric Disorder

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