Gonadal Hormones

A deficiency of progesterone or an abnormally high estrogen/progesterone ratio during the luteal phase has been a popular theory as to the cause of PMS for many years. However, studies of hormone levels in women with PMS compared with those in women without the disorder fail to support this hypothesis.²

Prolactin

Prolactin levels peak at the time of ovulation and remain high during the luteal phase. Prolactin excess may be associated with menstrual irregularities, diminished libido, depression, and hostility.³ Some authors suggest that as many as 62% of women with menstrual disorders have some degree of increased prolactin.⁴ Prolactin plays a role in breast stimulation and may be related to premenstrual breast tenderness. However, no consistent abnormalities in prolactin levels have been detected in women with PMS.²

Aldosterone

Aldosterone levels normally increase at the time of ovulation and remain high during the luteal phase of the menstrual cycle. This increase may be responsible for the congestive symptoms of PMS. Some women experience edema, breast swelling, abdominal bloating, weight gain, and headaches. Differences in absolute levels of aldosterone between symptomatic and asymptomatic women have not been found.⁵

Endogenous Opiates

Some researchers have noted an increase in β-endorphin plasma levels after ovulation. It is hypothesized that women with PMS have lower levels of these circulating endogenous opiates, or more sudden withdrawal, causing them to experience increased sensitivity to pain, as well as depression in some cases, in the luteal phase.⁶

A small trial was conducted to determine whether changes in peripheral β-endorphin levels during the periovulatory phase were associated with PMS symptoms. Twenty-one women with PMS and 10 control subjects were enrolled. All participants were in generally good health, with a history of regular menses for at least six cycles and no psychiatric illness. The day of the luteinizing hormone (LH) peak was called day LH-0. β-Endorphin and LH levels were measured with the use of a radioimmunoassay. Blood samples were obtained between 8 and 10 AM daily for 8 days, beginning on the 10th day of the menstrual cycle, for one cycle. β-Endorphin levels were lower throughout the periovulatory phase in the patients with PMS; the greatest differences were noted on LH days 0 and 4.⁷ However, a 1998 study of 10 patients with PMS and 10 control subjects failed to show any differences in levels of β-endorphin, adrenocorticotropic hormone, cortisol, or testosterone after sampling of the subjects’ blood over one complete menstrual cycle.⁸

Vitamin B₆

Vitamin B₆, or pyridoxine, is required for the metabolism of amino acids, carbohydrates, and lipids. The active forms of this vitamin are necessary coenzymes in the decarboxylation of 5-hydroxytryptophan to 5-hydroxytryptamine and dopa to dopamine. Pyridoxine deficiency is associated with increased levels of prolactin and low levels of serotonin and dopamine.⁹ Pyridoxine deficiency can lead to depression, peripheral neuropathy, and mood changes. Vitamin B₆ has been subjected to numerous trials over the years. The evidence supporting pyridoxine deficiency as a cause of PMS symptoms is reviewed later in this chapter.

Magnesium

Although serum levels of magnesium are often normal in women with PMS, researchers have noted lower levels of magnesium in the red blood cells of women with the disorder.¹⁰ Calcium and dairy products may interfere with absorption of magnesium, and refined sugar increases its urinary excretion. Magnesium deficiency can reduce dopamine and thyroid activity (with a resulting increase in the prolactin level) and lead to depression, mood changes, and muscle cramping.

Hypoglycemia

The body appears to be more sensitive to insulin during the luteal phase, leading some researchers to hypothesize that transient hypoglycemia accounts for some PMS symptoms.

Prostaglandins

Prostaglandins are associated with breast pain, fluid retention, abdominal cramping, headaches, irritability, and depression.¹¹ Physical premenstrual complaints and dysmen-orrhea have been shown to respond to prostaglandin inhibitors.

Psychosocial Theory

Emotional and physical stressors have been found to influence the levels of certain hormones and neurotransmitter substances. Travel, illness, stress, weather changes, and other environmental factors may affect ovulation, duration of the menstrual cycle, and the severity of PMS.¹² Cultural, societal, and personal attitudes toward menstruation also appear to play a role in the presence and severity of PMS. The dynamic interplay of environment, spirit, and physiology suggests that an integrated approach to treatment is most effective in many women (Box 3-2).

The American Psychiatric Association has defined diagnostic criteria for premenstrual dysphoric disorder (PMDD), considered by most physicians to be a more severe form of PMS. For this disorder to be diagnosed, a woman must have at least five of the following symptoms on a cyclical basis, and they must be serious enough to interfere with her normal activities:

Feelings of sadness or hopelessness; possible suicidal thoughts

Feelings of tension or anxiety

Mood swings marked by periods of teariness

Persistent irritability or anger

Loss of interest in daily activities and relationships

Trouble concentrating

Fatigue or a low energy level

Food cravings or eating binges

Sleep disturbances

Feelings of being out of control

Physical symptoms, such as bloating, breast tenderness, headaches, and joint or muscle pain

Exercise

The few studies of exercise and PMS that have been conducted have clearly shown that women who engage in regular physical exercise have fewer symptoms than women who do not exercise.¹⁵ The frequency, not the intensity, of exercise apparently relieves the negative mood and physical symptoms that occur during the premenstrual period.¹⁶ It is postulated that exercise reduces symptoms by decreasing estrogen levels, decreasing circulating catecholamines, improving glucose tolerance, and increasing endorphin levels.¹⁷ Given the many health benefits of exercise, practitioners should certainly consider regular exercise a part of the therapeutic approach to PMS.

Diet and Nutrition

A 1983 report found that women with PMS consumed 275% more refined sugar, 79% more dairy products, 78% more sodium, 62% more refined carbohydrates, 77% less manganese, and 53% less iron than women without PMS.¹³ These dietary excesses and deficiencies may help explain some of the symptoms women experience during the premenstrual period. Refined sugars increase the urinary excretion of magnesium.¹⁸ Heavy intake of sugar can increase sodium and water retention as a result of the rapid release of insulin. Dietary salt may exacerbate swelling. Although the data on caffeine and premenstrual breast tenderness are conflicting, many women obtain relief by eliminating or reducing consumption of caffeinated beverages and foods 2 weeks before the onset of menstruation. Consumption of caffeine-containing beverages has been associated with increases in both the prevalence and severity of PMS in college students.¹⁹ A study of Chinese women found that increasing tea consumption was linked to an increasing prevalence of PMS.²⁰ Women experiencing irritability or difficulty sleeping during the premenstrual period should be encouraged to reduce or limit intake of caffeine (Table 3-1).

Table 3-1 Caffeine in common foods and beverages

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