Chapter 202 Premenstrual Syndrome
Diagnostic Summary
• Recurrent signs and symptoms that develop during the late luteal phase of the menstrual cycle and disappear by the end of the full flow of menses
• Symptoms typically including decreased energy, tension, irritability, depression, headache, altered sex drive, breast pain, backache, abdominal bloating, and edema of the fingers and ankles
General Considerations
Premenstrual syndrome (PMS) refers to the cyclic constellation of troublesome symptoms that appears during the luteal phase of the menstrual cycle—more so in the late luteal phase—disappear by the end of the full flow of menses, and do not appear during the follicular phase.1 Although some 150 symptoms have been listed as premenstrual, the most common symptoms are as follows (Box 202-1):
PMS is estimated to affect between 30% and 40% of menstruating women; 80% of women experience premenstrual emotional or physical changes but do not have much difficulty. Peak occurrence is among women in their 30s and 40s. In most cases symptoms are relatively mild; however, in about 2.5% to 5% of women symptoms can be severe enough to have a negative impact on their lives, putting home life and work in jeopardy. Severe PMS with depression, irritability, and severe mood swings is referred to as premenstrual dysphoric disorder (PMDD)2 and has a separate diagnostic category in the fourth edition of the American Psychological Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
Although PMS has been a well-defined clinical entity for more than 60 years, some physicians still argue that it really does not exist.3 Therefore, many women suffering from PMS do not receive proper treatment. Until the advent of therapy with selective serotonin reuptake inhibitors (SSRIs), conventional mainstream medicine had not been able to offer women a known cause for PMS, nor has it been able to offer satisfactory interventions. Women were by and large left to self-care or to seek the advice of alternative medicine practitioners.
The etiology of PMS has not yet been fully understood, but endocrine studies have clarified that the premenstrual symptoms are not a result of a simple excess or deficiency of any given hormone.4 Several theories have been proposed to explain the causes of PMS; currently strongest is an interaction between the ovarian steroids and the brain’s neurotransmitters. Genetic predispositions and sociocultural beliefs about menstruation may also influence what women experience. At present, the dominant thinking is that cyclic changes in the ovarian steroids estrogen and progesterone cause changes in many body systems, including brain neurotransmitters, which then have emotional and physical manifestations.5 Therefore, normal ovarian function, and not a true hormonal imbalance, triggers the central nervous system and predisposes a woman to hormone-induced instability.6 We do not currently know why women differ in their sensitivity to the changes in ovarian steroid-induced neurotransmitters. Of the neurotransmitters studied, serotonin is the principal one implicated in the pathogenesis of PMS and PMDD.7,8 Whether PMS and PMDD are related to absolute levels or reduced blood levels of serotonin or to serotonin transport remains unclear.9
Diagnosis and Classification
Therapeutic Considerations
Estrogen Metabolism
In the early 1940s, Morton Biskind observed an apparent relationship between B-vitamin deficiency and PMS.10,11 He postulated that PMS, as well as excessive menstruation and fibrocystic breast disease, was due to an excess in estrogen levels caused by decreased detoxification and elimination in the liver as a result of B-vitamin deficiency. The liver uses various B vitamins to detoxify estrogen and excrete it in the bile.
Cholestasis can be caused by a large number of factors besides estrogen excess (Box 202-2). The presence of cholestasis may be a predisposing factor in PMS, because with cholestasis there is reduced estrogen detoxification and clearance. Hence, a positive feedback scenario is produced. The high incidence of gallstones is a clear indication that many American women suffer from cholestasis.
Again, even though elevated serum estrogen values cannot be confirmed in PMS studies, it is interesting to note that estrogen excess during the luteal phase affects endorphin levels negatively. One study found a direct correlation between an increased estrogen/progesterone ratio and endorphin activity in the brain.12 In essence, when the estrogen/progesterone ratio was increased, there was a decline in endorphin levels. This reduction is significant considering the known ability of endorphins to normalize or improve mood. Other studies have shown that low endorphin levels during the luteal phase are common in women with PMS.13 Endorphins are lowered by stress and raised by exercise. The role of endorphins is discussed further later.
Estrogen Impairs Vitamin B6
The way in which estrogen levels during the luteal phase negatively affect neurotransmitter and endorphin levels may be secondary to impairment of the action of vitamin B6. It is well known that estrogens affect vitamin B6 function negatively. Vitamin B6 levels are typically quite low in depressed patients, especially women taking estrogens (birth control pills or conjugated estrogens [Premarin]).14,15 Vitamin B6 supplementation has been shown to have positive effects on all PMS symptoms, particularly depression, in many women (discussed in greater detail later). This improvement is achieved via a combination of a reduction in midluteal estrogen levels and an increase in midluteal progesterone levels.
Dietary Considerations
Women suffering from PMS typically eat a diet that is even worse than the standard American diet. Abraham16 reports that, compared with symptom-free women, PMS patients consume the following substances:
A diet that is higher in dairy products may also contribute to some PMS symptoms. A survey of 39 women with PMS and 14 women without reported that the women with PMS consumed fivefold more dairy products and threefold more refined sugar than the women without PMS.17 Another study observed that women with PMS also have an increased intake of dietary fat, carbohydrates, and simple sugars and decreased protein intake.18
Food cravings are often also higher in women with PMS; this may in part be due to a decrease in serotonin during the luteal phase in PMS sufferers. Therefore, serotonergic treatments may be helpful in controlling such food cravings.19
Another nutritional factor in PMS is the effect of refined sugars on rapid increases in insulin, which then causes the retention of sodium and subsequent water retention, with swelling in the hands and feet, abdominal bloating, and breast engorgement. Sugar has several detrimental actions in PMS. Eating foods high in simple sugars increases insulin secretion and can be harmful to blood sugar control, especially if the patient is hypoglycemic or diabetic. Sugar, especially combined with caffeine, also has a detrimental effect on PMS and mood (discussed later).20 A high intake of sugar also impairs estrogen metabolism. The evidence is based on the higher frequency of PMS symptoms in women consuming a high-sugar diet and the fact that a high sugar intake is also associated with higher estrogen levels.21 One study found that a low-fat, high-complex-carbohydrate diet alleviated premenstrual breast tenderness.22
C-reactive protein, a marker of inflammation, has been correlated with the severity of both physical and psychological symptoms of PMS.23 A diet that stimulates inflammatory pathways includes sugar, poultry, eggs, cheese, milk, white flour, white rice, and partially hydrogenated oils. Foods that can reduce inflammation include fresh fruits, especially berries, green leafy vegetables, fish, nuts, seeds, turmeric, garlic, and onions.
Vegetarian women have been shown to excrete two to three times more estrogen in their feces and to have 50% lower levels of free estrogen in their blood than omnivores.24,25 These differences are thought to be due to the lower fat and higher fiber intake of the vegetarian women. These dietary differences may also explain the lower incidence of breast cancer, endometriosis, and uterine cancer in vegetarian women. They may also play a role in PMS.
Decreasing the percentage of calories as fat, in particular saturated fat, has dramatic effects on the reduction of circulating estrogen.26,27 In one study, when 17 women switched from the standard American diet (composed of 40% of calories as fat and only 12 g as fiber daily) to a low-fat, high-fiber diet (consisting of 25% of calories as fat and 40 g as fiber daily), there was a 36% reduction in blood estrogen levels, with 16 out of the 17 women demonstrating significant reductions in only 8 to 10 weeks.28
It should be noted that not all nutrition research shows a clear-cut association with PMS. In the Study of Women’s Health Across the Nation, a cross-sectional analysis was conducted of PMS symptoms in a multiethnic sample of 3302 midlife women.29
They sought to determine if the frequency of physical or emotional premenstrual symptoms was associated with dietary intake of phytoestrogens/fiber/fat or calcium, consumption of alcohol or caffeine, cigarette exposure, lack of physical exercise, and race/ethnicity or socioeconomic status. In this study, most dietary factors were not related to PMS. Fat intake was negatively associated with craving and bloating. Fiber intake was positively associated with breast pain. Alcohol intake was negatively associated with anxiety, mood changes, and headaches. Cigarette smoke exposure, whether passive or active, was positively associated with cramps and back pain. Ethnic differences in the reporting of symptoms and comorbidity associations were observed as well.
Thyroid Function
Low thyroid function (hypothyroidism) has been shown to affect a large proportion of women with PMS.30,31 For example, in one study, 51 of 54 subjects with PMS demonstrated low thyroid status compared with 0 of 12 in the control group.30 In another study, 7 of 10 subjects in the PMS group had low thyroid status compared with 0 of 9 in the control group.31 Other studies have also shown hypothyroidism to be only slightly more common in women with PMS than in controls.32,33 Many women with PMS and confirmed hypothyroidism who are given thyroid hormone experience complete relief of symptoms.30 For more information, see Chapter 177.
Stress, Coping Style, and Depression
Study of the interaction of stress/serotonin and PMS has shown that serotonin levels in women with PMS fall after ovulation. Those without PMS had much higher levels of serotonin during the last half of the menstrual cycle. In a holistic/natural medicine approach to PMS, the identification of stressors and stress management should not be overlooked.34 Many women with PMS tend to employ “negative” coping styles,35 examples of which are listed in Box 202-3. It is important to identify the manner in which the patient deals with stress and to counsel her on more positive ways of coping.
There are some important relationships between PMS and depression. Depression is a common feature in many cases of PMS, and PMS symptoms are typically more severe in depressed women.1 The reason appears to be a decrease in the brain level of various neurotransmitters, with serotonin and GABA being the most significant.36,37 The most common class of prescription medications recommended for moderate to severe PMS/PMDD is an SSRI. When they are used for chronic depression, SSRIs must be taken daily. When used for PMS/PMDD, they can be taken just on the days of the month when the symptoms are the most problematic. This would suggest that when used in this way, they are not really increasing neurotransmitter levels but work by altering the neurophysiology and electrical conduction in the brain. Several SSRIs have been used, including fluoxetine, sertraline, and paroxetine. However, various psychotherapy methods have been equally if not more successful in improving the psychological aspects of PMS. In particular, biofeedback and short-term individual counseling (especially cognitive therapy) have documented clinical efficacy.38,39 One of the advantages of cognitive therapy over antidepressant drug therapy in the treatment of PMS is that learning techniques such as cognitive-behavioral coping skills can produce excellent results that are maintained over time.
Exercise
Several studies have shown that women engaged in a regular exercise program do not suffer from PMS nearly as often as sedentary women.40–42 In one of the more thorough studies, mood and physical symptoms during the menstrual cycle were assessed in 97 women who exercised regularly and in a second group of 159 women who did not exercise.40 Mood scores and physical symptoms assessed throughout the menstrual cycle showed significant effects of exercise on negative mood states and physical symptoms. The regular exercisers obtained significantly lower scores for impaired concentration, negative mood, behavior change, and pain.
In another study, 143 women were monitored for 5 days in each of the three phases of their cycles (midcycle, premenstrual, and menstrual).41 The women were 35 competitive athletes, two groups of exercisers (33 high-frequency exercisers and 36 low-frequency exercisers), and 39 sedentary women. The high-frequency exercisers experienced the greater positive mood scores and sedentary women the least. The high-frequency exercisers also reported the least depression and anxiety. The differences were most apparent during the premenstrual and menstrual phases. These results are consistent with the belief that women who exercise frequently (but not competitive athletes) are protected from PMS symptoms. In particular, regular exercise protects against the deterioration of mood before and during menstruation.
These studies provide evidence that women with PMS should partake of the benefits of exercise. Exercise may reduce PMS symptoms by elevating endorphin values, improving glucose tolerance, decreasing catecholamines, and modulating estrogen levels.43