Premenstrual disorders affect many women in the United States. These disorders range in severity from the mild, bothersome symptoms that occur in more than 75% of women with regular menstrual cycles, to premenstrual syndrome (PMS) and, finally, to the most severe and disabling, premenstrual dysphoric disorder (PMDD). Nearly 5 million American women have PMDD.
The disability associated with premenstrual disorders is substantial. Women with PMS have significantly higher absenteeism from work and more ambulatory health care visits.1 In addition, women with premenstrual disorders have an average increase of $59 in direct annual health care costs and $4333 in indirect costs.2
Many women are reluctant to seek medical attention for premenstrual disorders, and many do not believe that treatment will help them. A survey of 455 US women found that 83% had premenstrual bloating, 79% had fatigue, and 77% had appetite changes, but only 45% of the women with severe symptoms had sought care.3
Some health care providers fail to recognize the symptoms of PMS and PMDD. In a Canadian study, 322 physicians were asked to diagnose PMS in a patient scenario with typical symptoms. Although 73% correctly diagnosed PMS, fewer than 1% would have required a 2-month prospective diary.4 Women with PMS reported that they had seen on average 4 physicians over a period of more than 5 years before the syndrome was correctly diagnosed.5 Up to 89% of women with PMDD do not receive a diagnosis.6
In this article, we review the diagnostic criteria for premenstrual disorders, and we discuss effective treatment approaches.
The etiology of premenstrual disorders is multifactorial; it is a complex interaction that involves genetic predisposition, the CNS, gonadal hormones, and other modulators.
Some women clearly have a genetic predisposition to the development of premenstrual symptoms. These women probably have an amplified sensitivity to cyclical changes in steroid hormones or a varied response to neurotransmitters. Although no single gene is responsible for premenstrual symptoms, twin studies have demonstrated that premenstrual symptoms such as depression and anxiety are heritable.7 In addition, a genetic predisposition to PMS is also associated with a predisposition to other psychiatric disorders.8
Many studies on the causes of PMS and PMDD have focused on reproductive hormones. Research has not shown that estrogen levels, follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels, or lack of progesterone are associated with premenstrual disorders.
Conclusive research on the role of reproductive hormones is complicated by constantly fluctuating serum levels. However, studies that have included many blood samples during the course of the day have been able to detect some differences between women with PMS and women without the syndrome. Facchinetti and colleagues9 found that women with PMS had increased pulse frequency of progesterone in the luteal phase compared with controls. Also, the amplitude of the progesterone pulses was significantly lower in the PMS group. An analysis of LH pulsatility demonstrated the same finding.
Although levels of the gonadal steroids are the same in patients with and without PMS, the patients’ responses to fluctuating levels of hormones are different. A study in which women were given gonadotropin-releasing hormone (GnRH) to induce “temporary menopause” demonstrated this finding. The women with PMS had decreased symptoms after administration of GnRH, but the symptoms returned when the estrogen and progesterone were replaced. Women without PMS had no change in symptoms when the same protocol was followed.10
Another area of research in the etiology of premenstrual disorders has centered on neurotransmitters, including γ-aminobutyric acid (GABA) and serotonin. Studies have demonstrated that a progesterone metabolite, allopregnanolone, affects the GABA receptor and probably plays a role in PMS symptoms. When allopregnanolone binds to the GABAA receptor, it acts similarly to benzodiazepines and barbiturates by changing the frequency and duration of the chloride channel. There is evidence that luteal-phase allopregnanolone levels are significantly lower in women with PMS compared with controls.11,12 Lower levels of this progesterone metabolite may affect the inhibitory action of GABA, leading to PMS symptoms.
Serotonin has also been implicated in the development of premenstrual symptoms. Rapkin and colleagues13 found that women with PMS have significantly lower serotonin levels during the mid and late luteal phases. A more recent study of 15 patients also found potential differences in serotonin and metabolite (5-hydroxyindoleacetic acid, or 5- HIAA) levels between controls and patients with PMS or PMDD.14
Another area of research focus has been the renin-angiotensinaldosterone system (RAAS). Many premenstrual symptoms, including bloating, breast swelling, and weight gain, are caused by fluid retention. Estrogen increases angiotensinogen production, which in turn leads to increased aldosterone levels and increased fluid retention. Under normal circumstances, progesterone competes with aldosterone and prevents fluid retention; however, in the late luteal phase, there is a decline in progesterone levels, which leads to an increase in the effect of estrogen.
Symptoms. More than 100 physical and behavioral symptoms have been described in premenstrual disorders, including fatigue, irritability, “bloating,” breast tenderness, and mood lability. The symptoms are confined to the luteal phase of the menstrual cycle and resolve after the onset of menses.
The most important consideration in diagnosing premenstrual disorders concerns the timing of the symptoms. In order to accurately determine the severity and timing of the symptoms, prospective recording of symptoms for at least 2 consecutive months is required. Because symptom severity may vary significantly from month to month, patients may need to record their symptoms for more than 2 months.
Specific criteria. Specific criteria have been developed for the diagnosis of both PMS and PMDD. The PMS criteria were established by the American College of Obstetricians and Gynecologists (ACOG) in 2000.15 For a diagnosis of PMS, patients must have at least 1 somatic or affective symptom (these symptoms are listed in Table 1). The symptom must start within 5 days preceding menses, resolve by day 4 of menses, and be absent until at least day 12 of the next menstrual cycle. The symptoms must cause socioeconomic dysfunction, and they must not be attributable to another cause.
PMDD is diagnosed using the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) criteria.16 As with PMS, the diagnosis of PMDD relies on prospective charting for at least 2 consecutive menstrual cycles. The symptoms of PMDD must interfere with work, school, or other usual activities. Patients must have at least 5 symptoms, and 1 of these must be a core symptom:
•Feelings of sadness or hopelessness, or self-deprecating thoughts.
•Feeling tense, anxious, or “on edge.”
•Marked mood lability.
•Persistent irritability, anger, and increased interpersonal conflicts.
The other symptoms include the following:
•Change in sleep or eating patterns.
•Difficulty with concentration.
•Decreased interest in usual activities.
•Feeling overwhelmed or out of control.
•Other physical symptoms, such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of bloating, and weight gain.
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Therapeutic Agents in This Article
Drospirenone 3 mg/ethinyl estradiol
20 μg (Yaz)
Paroxetine, controlled-release (Paxil CR)
*Available in a generic formulation.