A woman may be said to be suffering from PMS (Pre-Menstrual Syndrome) if she complains of recurrent psychological and somatic symptoms during the luteal phase of the menstrual cycle, which are relieved by the onset of menstruation.

It should fulfill the following criteria: - Not related to any organic lesion - Regularly occurs during the same phase of each menstrual cycle. - Symptom free period during rest of the cycle.

Premenstrual tension is characterized by alteration of personality during the ten days preceding the expected date of menstruation, a change that terminates abruptly with the onset of the flow. The tension begins gradually, the symptoms increasing crescendo-like, and continues progressively accompanied by a foreboding sensation of indescribable insecurity, manifested by the unusual behavior of the woman in the form of restlessness, inability to concentrate, unnatural and extreme annoyance with trifles, unreasonable emotional outbursts, and causeless crying spells, all of which mimic and oncoming mental disease. Headache, backache, and insomnia are frequent accompaniments of this premenstrual syndrome, the monotonous periodicity of which evokes the additional distress attendant upon fearful expectancy.

PHYSIOLOGY OF MENSTRUATION:

1) Ovarian changes during the menstrual cycle (Ovarian cycle)

a) Graafian follicular phase
b) Corpus luteal phase

2) The Uterine Cycle:

It is essentially the changes in endometrium and starts at the onset of menstruation and ends in recurrence of next menses. The first day of menstrual bleeding is the first day of the cycle. The cycle consists of the following phases:-

i) Proliferative phase:

It starts at about the seventh day of the cycle and ends at the fourteenth day. The post-menstrual period before the onset for the proliferative phase is the period of repair which starts almost pari passu with the bleeding phase and is probably complete in 48 hours after the bleeding phase. After reparative phase, there is a short period of resting stage of the endometrium before the proliferative phase. During the proliferative phase, the increasing concentration of oestrogens in blood produces progressive changes in all its elements. The glands becoming gradually longer and sinuous; the epithelium becomes more taller with nuclei showing mitotic divisions. The endometrium also becomes vascular; the endometrial vessels begin to coil. The interstitial tissue of the endometrium becomes oedematous and the stroma cells become more rounded. In some cases, the vascularity of the endometrium becomes so intense at the end of the proliferative phase that intermenstrual bleeding per vagina may occur at the time of ovulation. Histochemically there is an increase of alkaline phosphatase and ribonucleoprotein in the epithelium signifying the production and utilization of protein.

ii) Secretory Phase (premenstrual or progestational stage):

This begins at the ovulation on the fourteenth day and ends before the onset of the menstrual bleeding on the twentyeighth day. The essential changes in the oestrogen-primed proliferated endometrium during this phase are secretory activity of the glands, oedema and further thickening of the endometrium. Towards the early part of this phase, the secretory activity is evidenced by the subnuclear vacuoles filled with glycogen which push up the nuclei of the epithelial cells towards the lumen. During later part of the phase, the glands become corkscrew and the free margins of the epithelial cells become saw-toothed, the nuclei are again pushed to the basal and the cavity of the glands, contain secretion of glycogen and mucus. The spiral endometrial arteries become more spiral and form closely wound perpendicular coils through the mucosa. The stroma cells become more hypertrophied and almost assume the picture of decidua cells of pregnancy. Lymphocytic infiltration also occurs towards the end of this phase. The endometrium is now soft and spongy, oedematous is about ¼” (6mm) thick. Three distinct zones can be distinguished at the later part of the secretory phase as follows:
a) A superficial compact layer with closely packed stroma cells and necks of the glands.
b) Intermediate spongy layer with numerous dilated glands and scanty stroma cells.
c) Deepest basal layer in contact with and often penetrating for short distances the muscularis, is made up of the growing tips of the glands with compact stroma cells. This layer shows little or not change during menstrual cycle and is responsible for growth and regeneration of the endometrium. Superficial and intermediate layers participating in the cyclical changes together comprise the functional layer.

The stage of regression occurs toward the later part of the secretory phase about 2 days before the onset of menstruation and is due to withdrawal of oestrogen and progesterone. The hormonal withdrawal causes shrinkage upto the functional layer of the secretory endometrium with the coiled spiral vessels becoming ‘buckled’ or overcoiled.

Physiology of Premenstrual Syndrome:

PMS may be primary or secondary, depending on the degree of underlying psychopathology.

1) Primary PMS:

This is a disorder of nonspecific somatic, psychological or behavioral symptoms occurring in premenstrual phase of the menstrual cycle. Symptoms resolve completely by the end of menstruation, leaving a symptoms-free week. The symptoms are of sufficient severity to produce social, family or occupational disruption; symptoms must have occurred in at least four to six of the six previous menstrual cycles.

2) Secondary PMS:

Here the psychological and somatic symptoms recur in the premenstrual phase of the cycle and remain following menstruation but significantly improves by the end of menstruation. The symptoms are of sufficient severity to produce social, family or occupational disruption, symptoms must have occurred in at least four of the six previous menstrual cycles.

ETIOLOGY:

The cause of premenstrual syndrome is unknown. Many new neuroendocrine theories have been proposed for PMS. However no single theory is entirely consistent internally, and so single treatment for PMS has been consistently effective. In the 1930 menstrual-related mood symptoms were attributed to an excess production and a decreased excretion of female hormones. With the subsequent burgeoning of radioimmunoassay techniques multitude of hormonal systems have been implicated in the pathogenesis of PMS: the gondal steroids (in particular, a disturbed estrogen-progesterone ratio), prolactin, cortisol, thyroid hormones, prostaglandins, endorphins, and the biogenic amine neurotransmitters. 6

The concept of hormonal imbalance has been popular, but there is no supportive evidence. The hormone status of PMS patients does not appear to differ from that of asymptomatic women.

The range of proposed theories is enormous.

Sodium and water retention:

There can be few articles on PMS which do not refer to premenstrual sodium and water retention. It is surprising, then, to find few scientific data which demonstrate the phenomenon. Women experience an extremely severe subjective sensation of premenstrual bloatedness in the absence of weight increase, changes in abdominal dimensions or any true water or sodium retention (Faratian et al 1984, Hussain 1994). It seems that bloatedness is either perceived or due to gut distension as a result of progesterone-induced relaxation of the gut muscle. Evidence for this is limited though one study demonstrated delay in intestinal transit during the luteal phase of the cycle (Wald et al 1981).

Endocrine effects on fluid and electrolytes:

Lack of a premenstrual water and electrolyte shift is paralleled by a similar lack of difference in those hormones which control sodium and water transport. The factors which could promote water retention include oestrogen, prolactin, antidiuretic hormone, oxyytocin, renin, angiotensin, aldosterone and corticosteroids. Deficiencies of progesterone, atrial natriuretic peptide or renal prostaglandins could also permit water retention by the lack of a natriuretic effect. No clear differences have been demonstrated in any of these, with the exception of atrial natriuretic peptide, which appears to be low in the luteal phase in PMS patients (Hussain et al 1990).

Prostaglandins and essential fatty acids:

The ubiquitous nature of the prostaglandins makes them candidates for an aetiological role in PMS. Inhibition of synthesis and enhancement using precursors (essential fatty acids) have been claimed to relieve PMS. The underlying theory on which essential fatty acid supplementation is based is unconvincing. In the absence of a demonstrable endocrine abnormality in PMS, a differential sensitivity to the endocrine changes of the ovarian cycle has been suggested. In invitro studies, interactions at a cellular and receptor level have been demonstrated between polyunsaturated essential fatty acids and the activity of oestrogen and progesterone. Defective essential fatty acid/ prostaglandin metabolism may give rise to a breakdown in the normal balance or a change in steroid receptor status, allowing an exaggerated response to normal circulating levels of these different hormone systems (Kosikawa et al 1982).

Investigation of essential fatty acid levels in PMS has produced interesting but as yet inconclusive information. Brush and colleagues (1984) have demonstrated abnormalities in essential fatty acid levels in one study. These findings have not been replicated by others (Menden-Vrtovec and Vujic 1992. O’Brien and Massil 1990).

Prolactin:

Prolactin promotes retention of sodium, potassium and water, stimulates the breast and is a so-called stress hormone. Consequently many researchers have investigated its role in PMS. However, prolactin does not undergo change during the cycle: PMS patients have normal levels of prolactin and women with hyperprolactinaemia do not report PMS. Therapeutic studies of bromocriptine show no effect on PMS symptoms, but found limited evidence for treatment of cyclical mastalgia.

Ovarian hormones:

It has long been suggested that fluctuation in mood may be related to ovarian hormone imbalance (Dalton 1977). Research has produced data which could support theories of oestrogen excess, progesterone deficiency, oestrogen/ progesterone imbalance and progesterone excess. None of these has been confirmed and thus, factors other than differences in the levels of individual hormones must be important. Interactions with other endocrine or biochemical systems may operate or differences in receptor status may be relevant.

A link with ovarian hormone changes, particularly progesterone, seems likely, however, since the temporal relationship between progesterone secretion and symptoms is so close. Ablation of the ovarian endocrine cycle by oophorectomy or more conveniently by the administration of analogues of GnRH is associated with the parallel elimination of PMS symptoms (Hussain et al 1992). In women whose ovarian cycles have ceased (due to the menopause or bilateral oophorectomy) and who subsequently receive HRT, a significant percentage re-develop PMS symptoms during the progesterone phase of theory (Hammarback et al 1985).

In a pilot study, women with severe PMS who had undergone hysterectomy and bilateral salpingo-oophorectomy were recruited to assess the effects of hormone replacement on their PMS symptoms (Henshaw et al 1993). During oestrogen only replacement therapy they remained asymptomatic; when progesterone was administered PMS symptoms recurred demonstrating fairly clearly that patients remained sensitive to the effects of progesterone.

Investigations of the metabolites of progesterone have shown that women with PMS had lower levels of the progesterone metabolite allopregnanolone in the luteal phase (Rapkin et al 1997). This provides a plausible theory because allopregnanolone has ???aminobutyric acid (GABA)- ergic activity; deficiency may lose this, giving rise to PMS.

Opioids:

Diminished levels of luteal phase ? -endorphin have been shown (Chuong et al 1985, Rapkin et al 1996). Symptoms such as anxiety, food craving and physical discomfort have been associated with a significant premenstrual decline in ?-endorphin levels (Giannini et al 1994).

The role of serotonin in depression has been extended into PMS research. Low serotonin levels in red cells and platelets (Rapkin 1992) have been demonstrated in PMS patients. This serotonin deficiency has been proposed to enhance sensitivity to progesterone (Rapkin et al 1997). Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and sertraline, have been shown to be an extremely efficacious treatment for-severe PMS/PMDD (Dimmock et al 2000). This gives further support to the involvement of serotonin in PMS aetiology. Vitamin B6 (pyridoxine) is a co-factor in the final step in the synthesis of serotonin and dopamine from tryptophan. However, no data have yet demonstrated consistent abnormalities either of brain amine synthesis or deficiency of co-factors such as vitamin B6.

Other neurotransmitters may have relevance to PMS, for example GABA, dopamine and acetylcholine, although research data are less convincing for these in comparison to ?-endorphin and serotonin.

If these theories are true, it would seem that PMS is not caused by an endocrine imbalance. However, it appears that there is increased sensitivity to normal circulating level of ovarian hormones, particularly progesterone following ovulation, secondary to a neuroendocrine disturbance, probably serotonin deficiency. 19

BIOLOGICAL THEORIES:

Where scientists have failed to provide proof, practitioners have seldom, failed to provide theories. The list of biological theories is impressive:

1. Low progesterone levels
2. High estrogen levels
3. Failing estrogen levels
4. Changes in estrogen: progesterone ratios
5. Increased aldosterone activity
6. Increased renin-angiotensin activity
7. Increased adrenal activity
8. Endogenous endorphin withdrawal
9. Subclinical hypoglycemia
10. Central changes in catecholamines
11. Response to prostaglandins
12. Vitamin deficiencies
13. Excess prolactin secretion

GENETIC FACTORS:

One study found that 70 percent of daughters of mothers with premenstrual tension also had premenstrual dysphoric disorder symptoms compared with only 37 percent of daughters of unaffected mothers. Another study found that symptoms of premenstrual dysphoric disorder are likely to occur in both monozygotic twins if the symptoms occur in one twin. Concordance rates were significantly higher in monozygotic twins (93 percent) than in dizygotic twins (44 percent) or in sibling controls (31 percent). The difference between dizygotic twins and sibling controls was not significant.

PSYCHOPHYSIOLOGICAL FACTORS:

Early psychoanalytic formulations posited that premenstrual symptoms are derivative of conflicts over the feminine role and that menstruation is a stimulus that threatens repressed conflict. Detailed observations, however, indicate that premenstrual dysphoric disorder symptoms begin to ameliorate with the onset of menses, contrary to the theory. Studies have not consistently shown any specific psychological profiles of personality traits correlated with symptom severity. A large proportion of women with premenstrual dysphoric disorder have normal personalities. As in other medical and psychiatric disorders, premenstrual dysphoric disorder symptoms often exacerbate under stress. Evidence indicates a greater reactivity to stress and higher levels of arousal during the premenstrual period than during other phases of the cycle.

CLINICAL FEATURES:

Over 150 symptoms have been attributed to PMS

Commonly reported symptoms groups in women with PMS

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/ breast pain/ breast swelling (collectively known as premenstrual mastalgia)
back pain
abdominal cramps
general pain.
Bloatedness, Weight gain
abdominal bloating
oedema of extremities (arms and legs) abdominal swelling
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.

PMS -Diet and Regimen