CHAPTER 27 Premenstrual syndrome
Introduction
Premenstrual syndrome (PMS) refers to somatic and psychological symptoms which occur in relation to the luteal phase of the menstrual cycle. Most women of reproductive age will have some symptoms related to the premenstrual phase of the cycle. These are usually very mild and are physiological. Only when the symptoms cause significant disruption to normal functioning are they considered to be PMS. The term ‘premenstrual dysphoric disorder’ (PMDD) is also used and this represents the severe, predominantly psychological form of PMS. It is estimated that 3–8% of women of reproductive age experience debilitating symptoms leading to functional or psychological impairment (Angst et al 2001, Wittchen et al 2002). PMS and PMDD can be debilitating conditions. The impact on society and women’s lives can be very high and comparable to major depressive disorder (Pearlstein et al 2000, Halbriech et al 2003).
Definition
PMS is characterized by symptoms or clusters of symptoms that are associated with the premenstrual phase of the cycle, are recurrent, and are severe enough to cause impairment and distress (Halbriech et al 2007). Any symptom or cluster of symptoms qualify as PMS if they occur during the luteal phase of the menstrual cycle, are alleviated shortly following menses, and are not merely an exacerbation of other underlying conditions. PMDD has similar but separate criteria (Table 27.1, Figures 27.1 and 27.2)
| Type | Definition |
|---|---|
| Physiological premenstrual symptoms | Symptoms occur in the luteal phase of the cycle but are so mild that they are not troublesome. |
| Premenstrual syndrome | PMS symptoms leading up to menstruation and completely relieved by the end of menstruation. |
| Mild | Does not interfere with personal/social and professional life. |
| Moderate | Interferes with personal/social and professional life but still able to function and interact, maybe suboptimally. |
| Severe | Unable to interact personally/socially/professionally, withdraws from social and professional activities (treatment resistant). |
| Premenstrual dysphoric disorder | Currently considered as research criteria, not yet in general use outside the USA, but increasingly addressed in Europe and other countries. This definition of the severe psychological end of the PMS spectrum has been devised by the American Psychiatric Association. |
| Premenstrual exaggeration | Background psychopathology, physical, medical or other condition which worsens premenstrually with incomplete relief of symptoms when menstruation ends. |
| Misattribution | Underlying physical, psychological or psychiatric disorder wrongly labelled as PMS by general practitioner, nurse, gynaecologist, other specialist or patient. |
Adapted from Royal College Obstetricians and Gynaecologists. Management of Premenstrual Syndrome. Green-top guidelines no. 48. London : RCOG, 2007. Available at: http://www.rcog.org.uk/womens-health/clinical-guidance/management-premenstrual-syndrome-green-top-48 (Accessed: Feb 2010).
Symptoms
A woman has PMS if she complains of psychological or somatic symptoms, or both, recurring specifically during the luteal phase of the cycle and resolving by the end of menstruation (Ismail and O’Brien 2005). This separates PMS from psychiatric disorders. The symptoms should be confirmed prospectively by daily ratings during the last two consecutive cycles. This prospective rating is best achieved using the Daily Record of Severity of Problems form (Table 27.2, Box 27.1).
Table 27.2 Commonly reported symptoms in women with premenstrual syndrome
| Psychological symptoms | Irritability, depression, crying/tearfulness, anxiety, tension, mood swings, lack of concentration, confusion, forgetfulness, unsociableness, restlessness, temper outbursts/anger, sadness/blues, loneliness. |
| Pain symptoms | Headache/migraine, breast tenderness/soreness/pain/swelling (collectively know as ‘premenstrual mastalgia’), back pain, abdominal cramps, general pain. |
| Bloatedness | Weight gain, abdominal bloating, oedema of extremities (arms and legs), abdominal swelling and water retention. |
| Appetite symptoms | Increased appetite, food cravings, nausea. |
| Behavioural symptoms | Fatigue, dizziness, sleep/insomnia, decreased efficiency, accident prone, sexual interest changes, increased energy, tiredness. |
Diagnostic criteria for premenstrual syndrome
An international multidisciplinary group of experts who evaluated the definitions of PMS/PMDD recommended the following diagnostic criteria (Halbriech et al 2007):
Aetiology and Pathophysiology
The precise aetiology of PMS/PMDD is unknown. Various theories have been suggested. The current evidence suggests the possibility that both ovarian hormonal and neuroendocrine factors contribute to PMS/PMDD. The majority of women of reproductive age experience mild symptoms which are not troublesome and do not interfere with their daily activities. This should be considered as physiological rather than pathological (Figure 27.3).
Figure 27.3 Aetiological theories which have been proposed for premenstrual syndrome/premenstrual dysphoric disorder.
Ovarian hormones
PMS only occurs in women of reproductive age during the luteal phase of the cycle; symptoms classically disappear when ovulation is absent. PMS is absent before puberty, during pregnancy and following the menopause. Suppression of ovulation with gonadotrophin-releasing hormone (GnRH) analogues (Hussain et al 1992) or following bilateral oophorectomy typically eliminates the symptoms. Conversely, postmenopausal women on sequential combined hormone replacement therapy can redevelop PMS-/PMDD-like symptoms during the progestogen phase of therapy (Hammarback et al 1985).
Previously, it was believed that hormonal or progesterone imbalances during ovulatory cycles may trigger the symptoms. However, administration of progesterone during this phase does not abolish symptoms (Wyatt et al 2001), and differences in oestrogen or progesterone levels have not been demonstrated between PMS patients and asymptomatic controls. Alternative hypotheses include the proposal that symptoms may be triggered by a preovulatory peak in oestradiol level or a postovulatory increase in progesterone level (Magos et al 1986, Schmidt et al 1998). These hypotheses do not explain why some women only develop symptoms in the late luteal phase.
As there is no clear evidence to implicate different levels of oestrogen or progesterone in inducing PMS, an attractive and convincing theory, partially supported by good evidence, is that an enhanced responsiveness or sensitivity exists to normal levels of these fluctuating hormones (Yonkers et al 2008) (Figures 27.4 and 27.5).
Serotonergic system
Studies undertaken on the rat model demonstrate that serotonin receptor concentrations vary with changes in oestrogen and progesterone levels (Biegen et al 1980). Serotonin depletion affects the sex-steroid-dependent behaviour; this suggests that the role of serotonin is to modulate behavioural changes by interacting with serotonin transmission, which has been demonstrated in studies performed on rodents (Carlsson and Carlsson 1988, Rubinow et al 1998) and non-human primates (Bethea et al 2002).
Selective serotonin reuptake inhibitors (SSRIs), serotonin receptor agonists (Landén et al 2001), serotonin precursors (Steinberg et al 1999) and serotonin-enhancing agents effectively dampen premenstrual symptoms. Impairment of serotonin transmission by serotonin receptor antagonists (Roca et al 2002) or a tryptophan-free diet provokes symptoms (Menkes et al 1994). Women with PMS have a low platelet concentration of serotonin and this concentration varies during the menstrual cycle (Ashby et al 1998). This suggests that serotonin may play an important role in the pathophysiology of PMS/PMDD.
There is limited research on the genetics of serotonin in PMDD, but there does appear to be a difference in specific serotonin receptor polymorphism in PMDD sufferers (Dhingra et al 2007).
The GABAergic system
The GABA transmitter is a major inhibitory system in the central nervous system. GABA levels are low in the plasma and cerebrospinal fluid of individuals with mood disorders (Brambilla et al 2003). GABA levels have also been found to be decreased in women with PMDD during the late luteal phase compared with normal women whose plasma levels increase from the midfollicular phase (Halbriech et al 1996).
Allopregnanolone is a metabolite of progesterone, and levels vary in parallel with progesterone levels during the menstrual cycle (Genazzani et al 1998). In women with PMS, allopregnanolone levels are low in the follicular and luteal phases (Rapkin et al 1997, Bicíková et al 1998). Allopregnanolone is a positive modulator of the GABA receptor and a potent neurotransmitter with effects on mood, behaviour and cognitive function. Allopregnanolone has a bimodal effect on mood symptoms similar to benzodiazepines, barbiturates and alcohol. However, in some women with PMS, the plasma levels of allopregnanolone are low, suggesting that GABA receptor dysfunction might play a role in these women (Girdler et al 2001) (Table 27.3).
Theories related to sodium and fluid retention
Women with PMS report various somatic symptoms in the form of breast tenderness, bloating and swelling. Studies have failed to demonstrate weight gain, changes in abdominal dimensions, or any true water or sodium retention, even in women who experience bloatedness (Faratian et al 1984). There is no evidence to suggest that a shift in premenstrual water and electrolytes occurs; this is paralleled by a lack of similar changes in the hormones which influence potassium and water transport, such as components of atrial natriuretic peptide and the renin–angiotensin system. Studies have consistently shown that evidence is lacking to support this hypothesis.
Prolactin
Box 27.2 Differential diagnoses of PMS
