Abstract
Premenstrual disorders have been recognized as affecting innumerable women for decades but unlike most other medical conditions universally accepted criteria for definition and diagnosis are not established. Although premenstrual syndrome (PMS) occurs throughout reproductive life, there are some women who become particularly troubled. Those approaching the menopause may also have a mixture of PMS and menopause symptoms, not to mention heavy periods. Furthermore, some of the symptoms are similar in nature and so it is a challenge to identify which set of symptoms belongs to which spectrum. This is an area that has not been explored well. Various classifications have been proposed over the last few decades. A further effort towards the classification was made by an international multidisciplinary group of experts established as the International Society for Premenstrual Disorders (ISPMD) in Montreal in September 2008. Their deliberations resulted in a unified diagnosis, classification of premenstrual disorders (PMD) along with their quantification and guidelines on clinical trial design. This classification of PMS is far more comprehensive and inclusive than previous attempts. PMD in the ISPMD Montreal consensus are divided into two categories: Core and Variant PMD. Core PMD are typical, pure or reference disorders associated with spontaneous ovulatory menstrual cycles while Variant PMD exist where more complex features are present. Further, the consensus group considered that PMD may be subdivided into three subgroups predominantly physical, predominantly psychological and mixed. Variant PMD encompass primarily four different types; premenstrual exacerbation, PMD with anovulatory ovarian activity, PMD with absent menstruation and progestogen-induced PMD.
Introduction
Premenstrual disorders (PMD) have been recognized as affecting innumerable women for decades but unlike most other medical conditions universally accepted criteria for definition and diagnosis are not established.
Clinically significant premenstrual problems with mood and behaviour have been recognized since ancient times. 1 Hippocrates described a group of conditions that occurred prior to the onset of menses, in which women might develop suicidal ideation and other severe symptoms – intermittent ‘agitations’ making their way from the head and expelled via the uterus. In 1931, Frank brought the condition to prominence when he presented his history-making paper, ‘Hormonal Causes of Premenstrual Tension’ at a meeting of the New York Academy of Medicine. 2 Researchers soon realized that ‘tension’, evident during the premenstrual time was only part of what was a wider syndrome, premenstrual syndrome (PMS). This wide spectrum of symptoms understandably made the definition and classification of PMS an extremely complex exercise.
From a medical perspective, physical and psychological experiences associated with the menstrual cycle become symptoms when they appreciably affect quality of life and day-to-day functioning of a woman. Almost 80% of women suffer from mild forms of PMS, while up to a quarter may be affected by moderately severe symptoms. Between 3% and 8% experience an extremely severe form called the premenstrual dysphoric disorder (PMDD). 3
Although PMS occurs throughout reproductive life, there are some women who become particularly troubled. For instance, adolescents are very frequently overlooked and considered difficult teenagers. Those approaching the menopause may also have a mixture of PMS and menopause symptoms, not to mention heavy periods. Furthermore, some of the symptoms are similar in nature and so it is a challenge to identify which set of symptoms belongs to which spectrum. This is an area which has not been explored well. PMS patients are progesterone and progestogen sensitive and so management with cyclical hormonal therapy management may become difficult. Contraception may be also be an additional issue if they feel they need to come off oral contraceptive (OC) pill especially smokers.
Classification of premenstrual disorders
PMS has been the subject of controversy regarding whether it is a physical/medical or psychological/mental disorder. Various classifications have been put forward over the years which try to address and encompass the multitude of symptoms associated with PMD. The American Psychiatric Association has brought forward definitions and classifications from the standpoint of this being a psychiatric disorder. In October 1998, the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM 1V criteria) recognized PMDD as a distinct clinical entity. As opposed to the more common PMS, PMDD is a severely distressing and disabling condition severe enough to interfere with occupational and social functioning and it requires treatment. Minor changes were made to the inclusion criteria in 2000. 4 DSM V is currently under consideration.
This classification is limited by its very restrictive inclusion criteria. It lists 11 (groups of) symptoms and of these 10 out of the 11 are emotional and behavioural in nature. Only one category addresses physical symptoms. It may be superimposed on other psychiatric disorders provided it is not merely an exacerbation of those disorders. It is too prescriptive and excludes many women presenting with predominantly physical premenstrual symptoms and women with premenstrual exacerbation of underlying axis I or II disorders. It is stipulated that the symptoms cause significant impairment. Also, as it requires the presence of at least five symptoms to be present, it again excludes those women with less than five symptoms, which may be quite severe and treatment may be denied on account of this (more relevant in the USA).
The International Statistical Classification of Diseases and Related Health Problems of the World Health Organization, 10th revision (ICD-10) describes a list of physical and psychological symptoms for the diagnosis of PMS. The presence of one distressing symptom from this list is required for an ICD-10 diagnosis of PMS. 5 It does not however specify the severity of symptoms and does not dictate that there should be impairment.
It appears that with ICD-10, too many women are labelled with PMS, while DSM-IV is too restrictive, resulting in under-diagnosis. Both the Royal College of Obstetricians and Gynaecologists (RCOG) and The American College of Obstetricians and Gynaecologists (ACOG) have published criteria that appear to compromise between these extremes. 6,7
The International Society for Premenstrual Disorders 2011 Classification
Much effort and research has gone into defining and classifying these conditions that afflict millions of women across the world transcending their socioeconomic, cultural or ethnic background. Given their widespread nature and also the severity with which they can impact on women's lives it is extremely important to define and classify the conditions properly. A consistent and uniform classification would allow accurate assessment of its prevalence and severity making possible appropriate treatment of the condition and aid further research in the field.
With this aim in mind an international multidisciplinary group of experts met in Montreal in September 2008. The specialists reviewed the current definitions and diagnostic criteria for PMD and this was followed by extensive correspondence, and the consensus group became formally established as the International Society for Premenstrual Disorders (ISPMD). The existing criteria stated in the ICD-10, DSM-1V, RCOG, ACOG along with available research evidence were considered. Their deliberations resulted in a unified diagnosis, classification of PMD along with their quantification and guidelines on clinical design criteria. 8
PMD in the ISPMD Montreal consensus are divided into two categories; Core and Variant PMD. Core PMD are typical, pure or reference disorders associated with spontaneous ovulatory menstrual cycles while Variant PMD exist where more complex features are present.
Core PMD
Core PMD presents with typical features somatic and/or psychological occurring during all or part of the two-week premenstrual phase and resolving during or shortly after menstruation. It is not necessary to confirm that ovulation has occurred. The number of symptoms is not specified, nor their specific nature. It should be noted that over 200 premenstrual symptoms have been reported in the literature. Some of these are however considered characteristic as specified in Box 1. 8 The persistence of symptoms during menstruation does not preclude the diagnosis; however, there must be a clear symptom free period between the end of menstruation and approximate time of ovulation. This cyclical change should occur in most menstrual cycles (typically two out of every three). Suppression of ovulation will result in a major reduction or elimination of symptoms. It should be noted that suppression of ovulation may cause estrogen deficiency with symptoms or side-effects similar to PMD however, they will not be cyclical in nature.
Classification of premenstrual disorders 9
Ovulation dependent Symptoms non-specific Number of symptoms not proscribed Symptoms prospectively rated Psychological and somatic equally important Symptom-free in follicular phase Burden (impairment and distress) Absence of underlying psychiatric disorder
Premenstrual exacerbation – of underlying medical or psychiatric condition PMD with absent menstruation – hysterectomy, endometrial ablation, Lng-IUS Progestogen-induced PMD – Typically cyclical HRT; combined oral contraception PMD with non-ovulatory activity
Lng-IUS, levenorgestrel intrauterine system; HRT, hormone replacement therapy; PMD, premenstrual disorder
Core PMD must not be a premenstrual exacerbation of another psychiatric, physical or medical disorder. Also the severity or impact of symptoms must affect normal daily functioning, interfere with work, school performance or interpersonal relationships or cause significant distress. In other words, they must cause significant impairment.
The different PMD symptoms may have separate causes however the trigger would be the same, i.e. ovulation/progesterone and would respond to treatment by ovarian suppression. Consideration must be given to the existence of symptom-based subcategories of PMD and whether Core PMD should be regarded as a single entity or merely an umbrella term under which different patterns and clusters of symptoms would appear. The consensus group considered that PMD may be subdivided into: (a) predominantly physical, (b) predominantly psychological, (c) mixed. A proportion of b and c may fulfil the criteria for PMDD.
PMS
PMS is defined by the presence of psychological and somatic premenstrual symptoms that cause a negative influence on the daily functioning and levels of distress. Box 2 lists some of these symptoms. The current RCOG and ACOG definitions of PMS meet the criteria of Core PMD. The ICD-10 definition of PMS however does not address the impact or impairment caused by the symptoms, thereby failing to clearly differentiate between PMS and physiological premenstrual symptoms.
Common symptoms of premenstrual disorders 9
Joint pain, muscle pain, back pain Breast tenderness or pain Abdominal swelling or bloating Headaches Skin disorders Swelling of extremities
Changes in appetite, overeating or food cravings Fatigue, lethargy or lack of energy Mood swings (suddenly feeling sad, crying or increased sensitivity to rejection Irritability Anger Sleep disturbances Restlessness Poor concentration Social withdrawal Not in control Lack of interest in usual activities Loneliness Anxiety Depressed mood Confusion Tension Hopelessness
PMDD
As mentioned above in October 1998, the DSM-1V criteria recognized PMDD as a distinct clinical entity when compared with PMS. Their definition of PMDD however meets the criteria of Core PMD. There is particular emphasis on psychological symptoms while physical symptoms are largely not considered. It leads to the exclusion of some women who experience extremely distressing symptoms but do not fit the criteria for PMDD therefore restricting its usefulness in the clinical setting.
Variant PMD
An understanding of the variants of PMD go a long way to helping clinicians understand the complexity of PMD and hence the management of their patients.
Variant PMD encompass primarily four different types:
Premenstrual exacerbation
PMD with anovulatory ovarian activity
PMD with absent menstruation
Progestogen-induced PMD
Premenstrual exacerbation of underlying somatic, psychological or medical conditions during the luteal phase of the ovarian cycle;
Premenstrual symptoms occur with unspecified non-ovulatory ovarian activity;
Symptoms occur in women where menstruation is suppressed at the uterine or endometrial level;
Symptoms can be generated iatrogenically following hormonal therapy in the form of either cyclical hormone replacement therapy (HRT), combined OC pill or progestogen therapeutic regimens.
Premenstrual exacerbation
The profile of symptoms in this variant is similar throughout the cycle but the intensity is significantly greater in the premenstrual phase. Any symptom that exhibits premenstrual exacerbation (whether a common PMD symptom or not) fulfils the criteria for Variant PMD. Examples include diabetes mellitus, migraine, epilepsy, asthma, self-harm and depression. 10 Elimination of the ovarian cycle removes the cyclical component to leave only the underlying condition and this helps to determine the relative contribution of the two components. Women may have coexisting somatic or psychiatric conditions that have no variation during the menstrual cycle and these are termed independent co-morbidities and do not form a part of PMD.
Non-ovulatory premenstrual disorders
Some women do not ovulate but still experience PMD symptoms. The mechanism underlying this condition is not fully understood. Evidence for this is based on clinical and experimental observations in which the symptoms are reproduced on the re-introduction of estrogen or progesterone after ovarian suppression. 11 It is possible that further research in this area may lead to removal of this condition from the list of Variant PMD.
PMD without menstruation
Women may experience PMD despite absent menstruation. This happens where ovulation and ovarian cycle persists and lack of menstruation is due to medical or surgically induced amenorrhoea that targets the endometrium. This is seen in hysterectomy with conservation of ovaries, endometrial ablation and also with insertion of levonorgestrel intrauterine system for contraception or heavy menstrual bleeding.
Progestogen-induced PMD
This is an iatrogenic form of PMD where administration of exogenous progestogen may produce symptoms similar to PMD symptoms. 12 It is often seen in women taking hormonal supplements in the form of postmenopausal HRT or the combined oral contraceptive pill and the symptoms are typically seen in the progestogenic phase of the cycle. In these women, ovulation is either absent or suppressed but the presence of progestogen is believed to introduce de novo or reintroduce PMD-like symptoms. Progestogens given in a continuous manner may also give similar symptoms but these do not form part of PMD as these are not cyclical. This would happen in women receiving progestogen only pills or the levonorgestrel intrauterine system (initial weeks) and is related to sensitivity to progestogen.
This latter group presents a specific management problem for those managing the menopause.
There are however strategies to avoid progestogen induced PMD. These include trying lower dose of progestogen or using it less often. Different progestogens or continuous combined preparations may be tried. See Baker and O'Brien in this issue for a full discussion of this topic. 14
Conclusion
The above classification of PMD encompasses the wide array of symptoms and presentations seen in the general practice surgery and secondary care. The consensus process was a serious effort to arrive at internationally and universally acceptable criteria that could be applied effectively in clinical settings to diagnose correctly as many cases as possible to allow for appropriate treatment. It is essential that those treating the menopause understand this classification as it will be encountered directly or indirectly as a consequence of hormonal therapy on a daily basis.
It was agreed that a prospective, daily, patient recorded symptom rating is currently the only reliable and validated method to diagnose and quantify PMD (Figure 1). It further helps to differentiate PMD from clinical conditions that may have a similar symptom profile but crucially lack the cyclical premenstrual exacerbation seen with PMD. Very frequently the adoption of techniques use to quantify PMD can be used to identify the temporal link between the different phases of combined therapy.
Symptom Chart: Daily Record of Severity of Problems (DSRP)
13
Competing interests
Bayer Schering Pharma provided an unrestricted grant to provide expenses for the meeting of the consensus group of the International Society for Premenstrual Disorders (ISPMD) on Diagnosis, Classification and Clinical Trial Design. Bayer were not involved in the meeting nor did they comment on the manuscript.