Annu. Rev. Med. 1997. 48:447–55 Copyright © 1997 by Annual Reviews Inc. All rights reserved
PREMENSTRUAL SYNDROMES Meir Steiner, MD, PhD, FRCPC St. Joseph’s Hospital, McMaster Psychiatric Unit, McMaster University, Hamilton, Ontario, Canada L8N 4A6; e-mail:
[email protected] KEY WORDS: premenstrual dysphoric disorder, premenstrual magnification, etiology, diagnosis, treatment
ABSTRACT The recent inclusion of research criteria for premenstrual dysphoric disorder in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders should help physicians recognize women with symptoms of irritability, tension, dysphoria, and lability of mood that seriously interfere with their lifestyle. Premenstrual dysphoric disorder can be differentiated from premenstrual syndrome, which is primarily reserved for milder physical symptoms and minor mood changes. The use of criteria from the Diagnostic and Statistical Manual in conjunction with prospective daily charting for at least two menstrual cycles is now accepted as common practice in confirming the diagnosis. Treatment options range from the conservative (lifestyle and stress management) to treatment with psychotropic medications and hormonal or surgical interventions to eliminate ovulation for the more extreme cases. Results from several randomized, placebo-controlled trials have clearly demonstrated that selective serotonin reuptake inhibitors, as well as medical or surgical oophorectomy, are effective in treating premenstrual dysphoric disorder. Taken together, these data indicate that treatment may be accomplished by either eliminating the hormonal trigger or by reversing the sensitivity of the serotonergic system.
Introduction The inclusion of diagnostic criteria for late luteal phase dysphoric disorder in the third revised edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR) (1) and the more recent inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in the appendix of the fourth edition (DSM-IV) (2) validates the findings that some women in their
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reproductive years have extremely distressing emotional and behavioral symptoms premenstrually. At the same time, these strict criteria establish the fact that not all women who have premenstrual symptoms necessarily have a mental illness. Through the use of the DSM-IV criteria, PMDD can be differentiated from premenstrual syndrome (PMS), which has milder physical symptoms such as breast tenderness, bloating, headache, and minor mood changes (3), as well as from premenstrual magnification, which occurs when physical and/or psychological symptoms of a concurrent psychiatric and/or medical disorder are magnified during the premenstruum (4).
Epidemiology Epidemiologic surveys have estimated that as many as 75% of women with regular menstrual cycles experience some symptoms of PMS (5). The majority of these women do not require medical or psychiatric interventions. PMS has been featured in the popular press for many years now; thus, the more effective self-management techniques are usually accessed by women through the media or through their peers. Women who feel they are unable to self-manage their PMS are most often seen in primary care settings and by gynecologists. PMDD, on the other hand, is much less common. It affects only 3–8% of women in this age group (6–11), but it is much more severe and exerts a much greater psychological toll. These women report premenstrual symptoms of irritability, tension, dysphoria, and lability of mood that seriously interfere with their lifestyle and relationships (12, 13). These women do not usually respond to conservative and conventional interventions, and they often require the expertise of a mental health professional. Premenstrual tension syndrome has, in the past, been defined as a diversity of symptoms that appear during the week prior to menstruation and that resolve within a week of onset of menstruation. More than 100 physical and psychological symptoms have been attributed to the premenstruum (14). A diagnosis of PMS differs from that of PMDD in that neither a minimum number of symptoms nor functional impairment is required. PMDD as defined by the DSM-IV is much stricter in its delineation. In order to apply the DSM-IV criteria, women must chart symptoms daily for two cycles, and their chief complaints must include one of the four core symptoms (irritability, tension, dysphoria, and lability of mood) and at least 5 of the 11 total symptoms. The symptoms should have occurred with most menstrual cycles during the last year and have interfered with social or occupational roles. In addition, the charting of troublesome symptoms should demonstrate clear worsening premenstrually and remit within a few days after the onset of menstruation. There should be at least a 30% change in symptoms from the follicular to the
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luteal phase to make a diagnosis of PMDD (15), and to warrant pharmacologic treatment, worsening should increase by at least 50% (16). Also, it is important to exclude the possibility that the presentation is of a different major psychiatric or medical problem with premenstrual onset. The relationship between PMDD and other psychiatric disorders is further complicated by the observation that a high proportion of women presenting with PMDD have a history of previous episodes of mood disorders, and that women with continuing mood disorders report premenstrual magnification of symptoms and an emergence of new symptoms (17–24).
Etiology The etiology of PMS and PMDD is still largely unknown. Attempts have been made to explain the phenomena in terms of biology, psychology, or psychosocial factors, but most of these explanations have failed to be confirmed by laboratory and treatment-based studies. As is true for all female-specific mood disorders, the role of female sex hormones in PMDD has been considered of central importance. To date, however, studies attempting to attribute the disorder to an excess of estrogen, a deficit of progesterone, a withdrawal of estrogen, or changes in estrogen-toprogesterone ratio have been unable to find specific differences between women with PMDD and those without the disorder (25). Treatment studies have suggested that progesterone and progestagens may actually provoke, rather than ameliorate, the cyclical symptom changes of PMDD (26). The hypothesis that ovarian cyclicity is important in the etiology of PMDD is, nevertheless, supported by studies in which suppression of ovulation with estradiol patches and cyclical oral norethisterone, with the gonadotrophin-releasing hormone agonist buserelin, or by a bilateral oophorectomy resulted in the disappearance of premenstrual symptoms (27–36). An alternative strategy to measuring various hormone plasma levels in an attempt to discern the etiology of PMDD has been to search for endocrine abnormalities that have been repeatedly associated with various other forms of psychopathology. The main advantage of this approach is its potential to help further our understanding of PMDD as well as its relation to other psychiatric disorders, especially mood disorders. The current literature suggests that thyroid dysfunction may be found in a small group of women with PMDD, but that PMDD should not be viewed as a masked form of hypothyroidism (37–39). The current consensus seems to be that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target tissues. A psychoneuroendocrine mechanism triggered by the normal endocrine events of
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the ovarian cycle seems the most plausible explanation (40). This viewpoint is attractive in that it encourages investigation of the neuroendocrine-modulated central neurotransmitters and the role of hypothalamic-pituitary-gonadal axis in PMDD. Of all the neurotransmitters studied to date, increasing evidence suggests that serotonin (5-HT) may be important in the pathogenesis of PMDD (41–45). PMDD shares many of the features of other mood and anxiety disorders (46–48). In addition, reduced platelet uptake of serotonin has been shown during the week before menstruation in women with the premenstrual syndrome (49), and women with this disorder also have demonstrated a lowered level of platelet serotonin content (50). The serotonergic system is in close reciprocal relationship with gonadal hormones (51, 52). Previous studies have shown that serum levels of androgens are higher in women with premenstrual irritability and dysphoria (53), and more recently, there is evidence that reduced central 5-HT turnover is associated with impulsivity and high testosterone concentrations in male offenders (54). Women with PMDD may be behaviorly or biochemically sub- or supersensitive to biological challenges of the serotonergic system (55). It is not yet clear whether these women present with a trait or state marker of PMDD (45, 56).
Diagnosis The DSM-IV (2) multiaxial classification system includes five axes, each a different domain of information that may help the physician in the comprehensive and systematic evaluation of the patient. It draws attention to the various major mental disorders (axis I), to personality disorders (axis II), to general medical conditions (axis III), and to psychosocial and environmental factors (axis IV) and provides a global assessment of functioning (axis V). In utilizing the DSM-IV criteria for PMDD, a certain familiarity with the multiaxial system is assumed. Thus, for PMDD, any current axis I, II, or III illness or episode must be excluded. The other essential features of the DSM-IV PMDD criteria are the “on-offness” of symptoms and the emphasis on core mood symptoms, the requirement that the symptoms must interfere markedly with lifestyle and, most importantly, that the disorder must be confirmed prospectively by daily ratings for at least two menstrual cycles. Upon completion of the two-cycle prospective diagnostic assessment phase, women will usually fit into one of four diagnostic categories. Most women will not meet DSM-IV criteria for PMDD (2) but will meet criteria from the International Statistical Classification of Diseases and Related Health Problems (tenth revision) (3) for PMS, which includes mild
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psychological discomfort and, mostly, feelings of bloating and weight gain, breast tenderness and swelling, swelling of hands and feet, various aches and pains, poor concentration, sleep disturbance, and change in appetite. Only one of these symptoms is required for this diagnosis, although the symptoms must be restricted to the luteal phase of the menstrual cycle, reach a peak shortly before menstruation, and cease with the menstrual flow or soon after. Fewer women will meet DSM-IV criteria for PMDD. Although these women must not have a current psychiatric disorder, they may have a history of a past psychiatric disorder (and often do) (17, 18, 22). Some women will have premenstrual magnification of a current major psychiatric disorder or an unstable medical condition. In addition, there will be some women with a current psychiatric disorder who do not demonstrate premenstrual magnification. Women meeting criteria for intermittent depressive disorder, or cyclothymia, often fall into this category, as the cyclical nature of their symptoms do not necessarily match the phases of their menstrual cycle. Applying these diagnostic criteria to women who seek help for premenstrual complaints will facilitate the clinician in planning treatment interventions.
Treatment Therapeutic interventions for premenstrual syndromes range from the conservative (lifestyle and stress management) to treatment with psychotropic medications and hormonal therapy or surgical procedures to eliminate ovulation or ovarian function (for the more extreme cases). While all of these treatments are successful in relieving symptoms for some of the women treated, to date no one intervention has proven to be effective for all. Most therapies are now being tested in randomized controlled trials (RCTs), and what has become obvious is that the intervention alone cannot predict efficacy. More consideration is now being given to past psychiatric history as well as to family psychiatric history, especially of mood disorders in the families of women with PMDD (57–59). Lifestyle and stress management is a necessary adjunct to any therapeutic intervention, and patients should be educated and encouraged to practice these principles. Included under this rubric is the elimination or reduction of caffeine, alcohol, and tobacco, and adopting a diet composed of frequent highprotein and low-refined–sugar meals. Patients should be encouraged to decrease excess sodium in the diet when edema or fluid retention occurs and, if possible, to reduce weight to within 20% of their ideal. Regular exercise is important and particularly effective when combined with the regular practice of stress management techniques.
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Naturopathic remedies are increasing in popularity; however, limited efficacy has been reported in clinical trials of pyridoxine (vitamin B6) (60), and primrose evening oil has been deemed ineffective in a recent meta-analysis (61). Therapeutic interventions for women who meet the criteria for PMDD usually include treatment of symptoms or manipulation of the menstrual cycle. Selective serotonin reuptake inhibitors (SSRI), as well as clomipramine, continue to be efficacious in women with PMDD who have failed conservative treatment (16, 62–64). These interventions have demonstrated excellent efficacy and minimal side effects. Recent investigations of SSRI have also demonstrated success at low doses (16, 62, 63). Most investigators now suggest that if efficacy has not been attained after several dosing increases, other treatment options should be considered. There is also increasing evidence that response to treatment with SSRI or clomipramine will be relatively immediate in this population; therefore, if there is no change in symptomatology, an alternate therapy should be considered within two to three menstrual cycles. Alprazolam and buspirone have also been successful in the reduction of psychological symptoms in RCTs (for review, see 65); however, side effects and possible dependence inhibit their use. There is also evidence of success with estradiol implants, gonadotrophin-releasing hormone analogues, ovariectomy, danazol, and oral contraceptives (27–36, 66, 67). Unfortunately, many women are unable to tolerate the side effects of these interventions. Women who manifest severe physical symptoms or a psychiatric disorder with premenstrual magnification should be treated for their primary condition. Premenstrual symptoms usually remit considerably with successful treatment of the primary condition, and residual symptoms can be treated as indicated. For women who do not meet criteria for PMS, PMDD, or other physical and psychological disorders, conservative treatments are appropriate, and management without pharmacologic interventions should be encouraged. Stressful life events should be queried and monitored. These patients may best respond to individual or group psychotherapy in combination with diet and lifestyle changes. Patients should also be taught to review their own monthly diaries and identify triggers to symptom exacerbation.
Summary The etiology of PMS is still unknown. However, we are now able to identify and classify those women who present with severe psychological symptoms and to determine whether these symptoms are attributable only to the premenstruum or are a magnification of a physical or psychiatric disorder. Women who do not have a concurrent disorder and who meet criteria for PMS but not PMDD should be treated conservatively. Women who meet criteria for PMDD can be treated successfully with low-dose clomipramine or SSRI.
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ACKNOWLEDGMENT I thank Ms. Annette Wilkins for her advice and comments and Mrs. Marianne Jaszek for her editorial assistance and final preparation of the manuscript.
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