Premenstrual dysphoric disorder and premenstrual syndrome : an overview

Premenstrual dysphoric disorder (PMDD) affects 38% of women in the reproductive age group, while premenstrual syndrome (PMS) has a prevalence of 20-30%. PMS and PMDD are associated with significant reduction in quality of life and decreased work productivity. This review examines the current literature regarding the epidemiology, aetiology, diagnosis, burden of illness and management of PMDD and PMS.


Introduction
Premenstrual syndrome (PMS) is defined as recurrent moderate psychological and physical symptoms that occur during late luteal phase of menstrual cycles and resolves during menstruation (1).Premenstrual dysphoric disorder (PMDD) is a severe form of PMS that affects many women of reproductive age across the world.PMDD is characterised by affective, cognitive, behavioural, and somatic symptoms.PMDD and PMS have a negative impact on work attendance, productivity and relationships (2).Table 1 lists the symptoms associated with these two disorders.A better understanding of PMS and PMDD would help early identification and management of this disorder.The objective of this review was to describe the epidemiology, aetiology, symptoms, burden of illness and management of PMS and PMDD.

Epidemiology
PMDD is a severe form of the premenstrual symptom spectrum with a prevalence of 3-8%, while PMS has a prevalence of 20-30% (5).Sveindottir et al in their prospective study of 250 women in Iceland reported that 6% of the women met criteria for PMDD (6).Another prospective study of 1194 women in the United States reported a PMDD prevalence of 4.7% (7).Retrospective studies of severe premenstrual symptoms also reported similar rates of 2-6% (5).A community study of 1091 women in Germany reported that 5.8% of those surveyed met criteria for PMDD (8).
Studies from India have reported similar results.Banerjee et al reported a prevalence of 6.4% among Indian women (9).A higher rate of 10% was reported by Joshi et al in 2010, from Mumbai (10).

Aetiology
PMDD and PMSS are closely linked to the function of hypothalamic pituitary gonadal axis (11).It is hypothesised that PMDD is the result of heightened central nervous system sensitivity to normal cyclical changes in hormone levels, resulting in reduced levels of the neurotransmitter serotonin or 5-hydroxy tryptamine (5-HT) (12).The dorsolateral prefrontal cortex and medial frontal cortex are particularly sensitive to these hormonal changes.As women with PMDD enter the late luteal phase of their menstrual cycle, the levels of 5-HT are reduced, triggering symptoms associated with 5-HT depletion such as irritability, dysphoria, impulsivity, and carbohydrate craving (11).Another explanation offered for PMDD is the hormonal theory; here it is argued that women with PMS/PMDD develop depressive symptoms in response to either progesterone or oestradiol, and a resolution of these symptoms occur with increase of gonadotropin releasing hormone agonist (GnRH) levels (13).However this theory is disputed, with some studies offering evidence to the contrary (12).
While dysregulation of serotonin appears to be the primary cause of PMDD symptoms, there is evidence that other neurotransmitters may play a significant role.
During the late luteal phase of the menstrual cycle, levels of gamma aminobutyric acid (GABA) are low in patients with PMDD and PMS.This may contribute towards the irritability and lability of mood seen during this time (14).
The use of selective serotonin reuptake inhibitor (SSRI) medications in PMDD has led to another theory regarding the aetiology of this disorder.It has been noted that SSRIs are effective in PMDD, and the response time is usually shorter than for depression, panic disorder, or obsessive-compulsive disorder.Therefore some argue that SSRIs exert their action in PMDD via a different mechanism compared to its action in depression or anxiety.It is hypothesised that SSRIs work in PMDD by indirectly increasing synthesis of allopregnanolone from progesterone.Allopregnanolone, a neurosteroid, has high affinity to GABA receptors and potently facilitates GABA action at these receptors, leading to rapid relief of PMDD symptoms such as dysphoria and anxiety (13,15).
Central sensitivity rather than peripheral hormonal abnormality seems to be the cause of the symptoms of PMDD.This has implications for treatment, suggesting that the focus should be on correcting or compensating for the central sensitivity, rather than peripheral modification of menstrual cycle hormones.

Diagnosis
The

The burden of illness
PMDD is a chronic illness and does not completely remit until menopause.PMDD has a significant negative impact on quality of life.Yang et al. reported that the burden of PMDD on health-related quality of life was greater than the burden associated with back pain, and was similar to Type II diabetes, hypertension, rheumatoid arthritis and somewhat similar to depression [18].Heinemann, Minh, Filonenko, and Uhl-Hochgraber concluded that PMDD is associated with impaired work productivity and absenteeism, thus resulting in a potential reduction of female economic productivity (19).
Working women who were classified as having moderate to severe PMS/PMDD, when compared to women with no/mild symptoms, had higher rates of productivity impairment and absenteeism (20).

Treatment
Symptom relief is the goal of treatment of PMS and PMDD (Table 3).Mild premenstrual symptoms may respond to non-pharmacological interventions, such as education on sleep hygiene, exercise, relaxation therapy, and cognitive-behavioural therapy.Dietary modifications, including reduction of salty foods, caffeine, red meat, and alcohol, along with increased consumption of fruits, legumes, whole grains, and water, as well as consumption of smaller and more frequent meals high in carbohydrates, have been reported to improve tension and depressive symptoms (17).
Calcium (not exceeding 1,500 mg/day) and vitamin D may reduce the risk of moderate to severe premenstrual symptoms, while also reducing the risk of osteoporosis (17).Ghanbari et al reported that calcium at a dose of 500 mg twice daily reduced fatigability, changes in appetite and depression in women with PMS (21).
Pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) has shown good efficacy for moderate to severe PMDD (22).The most evidence is available for fluoxetine and sertraline, with an average response rate of 60% in controlling symptoms (22).Continuous pharmacological treatment (i.e., throughout the month) is best for women with comorbid depressive or anxiety disorders and for women who have difficulty adhering to intermittent therapy regimens.Intermittent treatment with SSRIs is best for patients who have symptoms that are clearly localised to the premenstrual days, and who experience side-effects due to SSRIs (17).
Premenstrual dysphoric disorder and premenstrual syndrome

(N94.3)
A. In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, must start to improve within a few days after the onset of menses, and become minimal or absent in the week postmenses.
B. One (or more) of the following symptoms must be present: 1. Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).Contraceptive pill types containing ethinyl oestradiol and drospirenone may represent another effective treatment for PMDD (2).Not all evidence supports the use of contraceptives, but they could be considered as first-line pharmaceutical interventions for women with PMDD who also require contraception (23).
Cognitive behaviour therapy (CBT) is also a proven strategy for management of PMDD.Combination of CBT along with SSRIs has been proven more efficacious than SSRIs alone (2).
Although medical and psychological treatment provides excellent symptomatic relief to many women, a small proportion of women may experience poor therapeutic response or adverse effects.In such cases oophorectomy (with concomitant hysterectomy) followed by low-dose oestrogen therapy has been shown to be an effective alternative (24).
Evidence suggests that up to 8% women meet diagnostic criteria for PMDD in their lifetime.The key factor in diagnosis is the demonstration of a pattern of PMDD symptoms that recurs during the late luteal phase of the menstrual cycle and remits soon after menses, which occurs over at least 2 menstrual cycles, and which are associated with significant dysfunction.Other psychiatric disorders that may mimic PMDD need to be considered as differential diagnosis.Current theories suggest that severe PMS and PMDD are due to CNS sensitivity to hormonal cycling rather than due to abnormality of hormone levels.
SSRIs and oral contraceptives are the current mainstay of the treatment of PMDD.Measures such as lifestyle modification, dietary supplements and dietary modification maybe helpful in mild PMS, but have limited proven efficacy in severe PMDD.