Focus Points

• The majority of women with regular ovulatory menstrual cycles (up to 87%) will experience premenstrual symptoms during their lifetime.

• Premenstrual symptoms start in the second half of the menstrual cycle, generally increase in intensity until the onset of menstrual bleeding, then rapidly resolve.

• Premenstrual syndrome is much more common than premenstrual dysphoric disorder.

• In susceptible women, many psychiatric and general medical conditions show premenstrual exacerbations.

• Psychotic conditions with monthly recurrences have been described in adolescents, but probably represent atypical presentation of affective disorders.

Abstract

The concept that mood and behavior changes occur in the premenstruum and abate after menses had been recognized and described in medical literature dating back to the ancient times. The majority of women with regular ovulatory menstrual cycles (up to 87%) experience premenstrual symptoms. Approximately half of these women describe themselves as having premenstrual syndrome and only 3% to 5% meet criteria for premenstrual dysphoric disorder. The most consistent symptoms appear to be anxiety, irritability, and mood lability. Many psychiatric conditions and some general medical conditions may worsen premenstrually. When psychiatric conditions are exacerbated premenstrually, the patient may be at greater risk for suicide. Retrospective recall of premenstrual symptoms is notoriously unreliable, especially when symptoms are present at decreased intensity during the follicular phase. Daily symptom recording by the patient allows for accurate diagnosis, improves patient involvement in managing her condition, and fosters individualized treatment options.

Introduction

Understanding how to diagnose and treat disorders related to the menstrual cycle is clearly an important issue for clinicians treating women of childbearing age. This article describes the three major conditions associated with luteal phase symptom changes—premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation of an existing disorder (PME).

Clinicians are faced with multiple challenges when they recognize that a patient’s condition is changing premenstrually. Whether noticed first by the patient, her family, or in a clinical setting, sorting out the diagnosis requires a bit of detective work for all involved. The concept of changes in mood and behavior occurring in the premenstruum and abating after menses had been recognized and described in medical literature dating back to ancient times. However, PMS did not achieve the status of a cultural icon until the work of Dalton and colleagues1 captured the attention of the lay press, beginning in the 1950s. Since that time, two additional premenstrual syndromes have been described: PMDD and the PME or “premenstrual magnification” of other disorders.2 Since different management strategies are indicated for appropriate clinical management, differentiating between these entities is essential.

Normal Menstrual Cycles

The first half of the menstrual cycle is called the “follicular” phase because that is the time during which follicular development in the ovary occurs. Driven by pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are released from the anterior pituitary and cause predictable changes in the ovary and endometrium. While both estrogen and progesterone are present in variable amounts throughout the cycle, follicular phase is generally described as estrogen dominant. Ovulation marks the end of the follicular phase.

The second half of the menstrual cycle is called the “luteal” phase. It is generally described as progesterone dominant and is fairly rigidly fixed at 14 days in length. By convention, the first day of menstrual bleeding is considered day 1 and the average cycle length is 28 days. If variations in cycle length are noted, the day of ovulation is predicted by subtracting 14 days from the actual cycle length (eg, in a 25-day cycle, ovulation would be expected on day 11; in a 34-day cycle, ovulation would be expected on day 20).

Predicting the day of ovulation is not only essential for those trying to achieve pregnancy, but is also necessary for clinicians evaluating women with recurrent monthly mood symptoms.

Prevalence of Premenstrual Symptoms

The majority of women with regular ovulatory menstrual cycles experience premenstrual symptoms, with one epidemiologic report showing an 87% overall lifetime prevalence. The percentage of women with severe symptoms was low (3.2%), which is consistent with other reported data. The majority of women appeared to have mild symptoms, seeing their symptoms as simply telegraphing the onset of menses. Among women with symptoms of greater magnitude, most chose to self-treat with diet, exercise, and other self-help measures. Only 17% had sought advice from a physician, although 22% were using a drug for symptoms at the time of the survey.3

Premenstrually, women often complain of symptoms that are strikingly similar to affective disorders associated with low serotonin: depressed mood, irritability, self-deprecation, anxiety, aggression, anger, decreased pain threshold, poor impulse control, sleep disturbance, appetite changes such as carbohydrate cravings, and concentration difficulties.4 The most stable symptoms across cycles, both from prospective research and clinical practice, appear to be anxiety, irritability, and mood lability. In prospective ratings, both physical and mood symptoms are remarkably stable across cycles, although mood symptoms account for most of the functional impairment seen among women with premenstrual symptoms.5

Although premenstrual symptoms can occur in ovulatory women of all ages, in clinical practice women tend to seek care in their late 20s and early 30s. Care-seeking women document symptoms ranging from mild to moderate to severe.

Common patterns of symptom presentation have been identified (Figure).6 In the most common pattern, women report symptoms occurring only in the latter part of the luteal phase, with rapid resolution after the onset of menses. Also common is the brief interjection of symptoms around the time of ovulation, a return to baseline, and then recurrence of symptoms in the late luteal phase.6 Other patterns are less common, and probably represent the premenstrual exacerbation of an underlying mood or anxiety disorder. It is quite common for women to recognize their premenstrual symptoms without realizing that similar symptoms are occurring throughout the cycle.7


Defining Premenstrual Syndromes

Premenstrual Syndrome

Symptoms of PMS begin in the second half of the menstrual cycle (luteal phase), generally increase in intensity until the onset of bleeding, then rapidly resolve, leaving a clear symptom-free interval in the first half of the cycle (follicular phase). Symptoms typical of PMS are defined by the American College of Obstetricians and Gynecologists (ACOG; Table 1).8 Theoretically, just having one symptom, even a physical symptom such as breast tenderness, could be coded as PMS (International Classification of Diseases, 9th Edition [ICD-9] code 625.4),9 although that is seldom done. In common use, PMS almost always refers to affective symptoms. PMS symptoms are generally considered to be shorter in duration and of milder intensity than symptoms associated with PMDD or PME.

For reasons that have not been clearly elucidated, some women using oral contraceptives, even monophasic pills, experience recurrent monthly symptoms that are strikingly similar to PMS. Although the ACOG criterion specifically excludes those women, in clinical practice they are often diagnosed and treated like other women with PMS.

Premenstrual Dysphoric Disorder

In recent years, the medical community and literature has focused more on PMDD than PMS, but it is important to recognize that PMDD is a narrowly defined entity at the extreme end of the spectrum for premenstrual symptoms.

The American Psychiatric Association specifies that the PMDD diagnosis requires a minimum of five luteal phase symptoms, at least one of which must be a mood symptom. Symptoms must have a cyclic relationship to the luteal phase, although the “disease-free interval” is not explicitly defined. Symptoms must cause functional impairment in work, school, or relationships. In addition, the complex of symptoms cannot be the premenstrual anexacerbation of another disorder; this is documented by prospective daily ratings for at least two menstrual cycles.2

The criteria set for PMDD (Table 2) remains in Appendix B (“Criteria Sets and Axes Provided for Further Study”) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision,2 although PMDD has now been included as an example of a “Depressive Disorder Not Otherwise Specified” (ICD-9 code 311).10


Premenstrual Exacerbation of Another Disorder

A wide range of general medical and psychiatric conditions worsen premenstrually. Some occur so commonly that reference to the menstrual cycle has become part of the nomenclature, eg, premenstrual asthma,11 menstrual migraine,12 and catamenial epilepsy.-13 Many psychiatric conditions also worsen during the luteal phase in susceptible women. Increased incidences of psychiatric admissions and suicide attempts have long been documented to begin during the last few days before the onset of menses and extend through the first 4 days of menstrual bleeding.14

As treatment strategies evolve using complimentary alternative medicine or intermittent doses of serotonin-containing antidepressants, it is precisely that worsening of suicide risk which mandates prospective daily symptom ratings (eg, diary) for the diagnosis of premenstrual disorders. Women often identify with the premenstrual intensification of their symptoms, ignoring lesser symptoms prevalent during the first half of the cycle. In clinical settings dedicated to the treatment of premenstrual symptoms, up to 40% of patients who initially self-identify as having PMS or PMDD can be diagnosed with mood or anxiety disorders.15

Interpreting the medical literature regarding the PME of other conditions is difficult, because of the variety of conditions that worsen premenstrually and the relative paucity of prospective data. Common conditions that worsen premenstrually are shown in Table 3.16-51 There are no high-quality, randomized, double-blind, placebo-controlled trials in this area of interest. However, there is always practical difficulty in women with affective disorders. For example, if a woman is stable in the maintenance phase of treatment but has teary, anxious, and irritable days just before her menses, is she just premenstrual or is she having worsening of her mood disorder? If abiding by strict criteria, one would have to choose the latter. From the standpoint of etiology, however, her symptoms may be more reflective of her menstrual phase than her mood disorder.

Diagnosing Premenstrual Symptoms

Many women seeking care for premenstrual complaints can list the symptoms that are most bothersome to them and can estimate the duration of their symptoms. Unfortunately, this retrospective recall has consistently been shown to be unreliable.52 Practitioners familiar with the retrospective recall data generalize it to mean that women are not good at identifying premenstrual symptoms. In reality, women are excellent at identifying the presence of premenstrual symptoms. However, they do less well remembering backwards and tend to ignore less-troubling follicular phase symptoms.7

When comparing the patient’s history to her subsequently produced daily symptoms diary, discrepancies are noted in three areas: First, the history generally under-reports the number of symptoms shown in the daily diary. Second, the history generally over-reports the duration of symptoms shown on the daily diary. Third, and most important, when follicular phase symptoms are present they may not be reported.7

Clinically, stigma associated with mental illness appears to perpetuate the patient’s belief that they are just premenstrual even when confronted with proof to the contrary, such as their own daily ratings indicating symptoms throughout the menstrual cycle. It is also probable that the affective quality of the follicular symptoms causes so much less difficulty than those in the luteal phase that the woman would not have sought care for follicular phase symptoms. She may also not understand why treatment across the whole cycle is important.

Daily symptom diaries are relatively simple and effective tools which can easily differentiate PMS from PMDD and PME. Many centers specializing in the care of women with premenstrual symptoms mail a diary form in advance of the scheduled appointment, which facilitates a timely confirmation of a diagnosis. Table 4 shows a sample diary; however, a variety of prospective symptom rating devices are available in the medical literature, lay press, and on the Internet.

Review of the patient’s diary requires a symptom-free interval in order to consider a diagnosis of PMS or PMDD. The number of symptoms noted, the severity of those symptoms, and the extent to which symptoms interfere with function will distinguish PMS from PMDD. If there is no symptom-free interval, the patient is experiencing the premenstrual exacerbation of another disorder, most likely a mood or anxiety disorder.

Benefits of prospective daily symptom ratings are accurate diagnosis, fostering of patient involvement, improved patient adherence to a management strategy, and a means for assessing response to treatment.

Practitioners who resist prospective symptom charting often contend that it is time consuming, may result in delay of needed intervention (and thus can be perceived by the patient as a lack of empathy), necessitates more patient visits (thus increases healthcare cost), and frequently does not change the management choices. In clinical settings, the patient-recorded diary actually saves time for the practitioner. It also markedly increases one’s ability to individualize treatment options based on accuracy of diagnosis, quality of symptoms, and duration of symptoms.

Psychotic Conditions in the Premenstruum

Psychotic conditions that recur premenstrually have been described and are occasionally seen in clinical practice. They are most commonly seen in adolescent females and appear to represent a heterogeneous group of affective disorders (major depression with psychotic features, bipolar disorder, brief psychotic episodes).53,54 Prospective data are lacking and treatment is individually determined.55 Similar symptoms have been described in adolescent males.54

Conclusion

PMS, PMDD, and PME are terms used to describe mood and physical symptoms that consistently recur in the luteal phase of the menstrual cycle and abate (PMS, PMDD) or lessen (PME) after menstruation. The majority of ovulating women experience premenstrual symptoms, but do not seek care for those symptoms. Among women seeking care who experience moderate and severely distressing mood and emotional symptoms premenstrually, the majority have PMS or PME, not PMDD.

Even among women who suffer disruptions in interpersonal relationships and diminished quality of life, many do not directly seek medical care. Thus, clinicians should proactively assess women for premenstrual symptoms as a part of routine care, both in general practice and in psychiatry.

Prospective daily symptom charting is essential to precise diagnosis and will readily determine whether a patient has PMS/PMDD or is suffering from PME, which could put her at increased risk for harm in the second half of her menstrual cycle. Daily symptom rating diaries are available from multiple sources. A daily symptom diary is needed to differentiate premenstrual diagnoses, since retrospective recall is notoriously unreliable (patients know more about their luteal phase symptoms than their follicular phase symptoms) and because most psychiatric (and somatic) conditions get worse premenstrually. PP

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Dr. Dell is assistant clinical professor in the Departments of Psychiatry and OB/GYN at Duke University Medical Center in Durham, North Carolina.

Disclosure: Dr. Dell is a consultant to Eli Lilly and Pfizer; is on the speaker’s bureaus of Berlex, Eli Lilly, Forest, GlaxoSmithKline, Pfizer, TAP, and Wyeth; and has received research support from Berlex, GlaxoSmithKline, and Pfizer.

Please direct all correspondence to: Diana L. Dell, MD, FACOG, Duke University Medical Center, DUMC Box 3263, Durham, NC 27710; Tel: 919-668-2570; Fax: 919-684-6243; E-mail: dell0001@mc.duke.edu.